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1

Endogenous Molecules Induced by a Pathogen-Associated Molecular Pattern (PAMP) Elicit Innate Immunity in Shrimp  

PubMed Central

Invertebrates rely on an innate immune system to combat invading pathogens. The system is initiated in the presence of cell wall components from microbes like lipopolysaccharide (LPS), ?-1,3-glucan (?G) and peptidoglycan (PG), altogether known as pathogen-associated molecular patterns (PAMPs), via a recognition of pattern recognition protein (PRP) or receptor (PRR) through complicated reactions. We show herein that shrimp hemocytes incubated with LPS, ?G, and PG caused necrosis and released endogenous molecules (EMs), namely EM-L, EM-?, and EM-P, and found that shrimp hemocytes incubated with EM-L, EM-?, and EM-P caused changes in cell viability, degranulation and necrosis of hemocytes, and increased phenoloxidase (PO) activity and respiratory burst (RB) indicating activation of immunity in vitro. We found that shrimp receiving EM-L, EM-?, and EM-P had increases in hemocyte count and other immune parameters as well as higher phagocytic activity toward a Vibrio pathogen, and found that shrimp receiving EM-L had increases in proliferation cell ratio and mitotic index of hematopoietic tissues (HPTs). We identified proteins of EMs deduced from SDS-PAGE and LC-ESI-MS/MS analyses. EM-L and EM-P contained damage-associated molecular patterns (DAMPs) including HMGBa, HMGBb, histone 2A (H2A), H2B, and H4, and other proteins including proPO, Rab 7 GPTase, and Rab 11 GPTase, which were not observed in controls (EM-C, hemocytes incubated in shrimp salt solution). We concluded that EMs induced by PAMPs contain DAMPs and other immune molecules, and they could elicit innate immunity in shrimp. Further research is needed to identify which individual molecule or combined molecules of EMs cause the results, and determine the mechanism of action in innate immunity. PMID:25517999

Chen, Yu-Yuan; Chen, Jiann-Chu; Lin, Yong-Chin; Kitikiew, Suwaree; Li, Hui-Fang; Bai, Jia-Chin; Tseng, Kuei-Chi; Lin, Bo-Wei; Liu, Po-Chun; Shi, Yin-Ze; Kuo, Yi-Hsuan; Chang, Yu-Hsuan

2014-01-01

2

Cell Death-Associated Molecular-Pattern Molecules: Inflammatory Signaling and Control  

PubMed Central

Apoptosis, necroptosis, and pyroptosis are different cellular death programs characterized in organs and tissues as consequence of microbes infection, cell stress, injury, and chemotherapeutics exposure. Dying and death cells release a variety of self-proteins and bioactive chemicals originated from cytosol, nucleus, endoplasmic reticulum, and mitochondria. These endogenous factors are named cell death-associated molecular-pattern (CDAMP), damage-associated molecular-pattern (DAMP) molecules, and alarmins. Some of them cooperate or act as important initial or delayed inflammatory mediators upon binding to diverse membrane and cytosolic receptors coupled to signaling pathways for the activation of the inflammasome platforms and NF-?B multiprotein complexes. Current studies show that the nonprotein thiols and thiol-regulating enzymes as well as highly diffusible prooxidant reactive oxygen and nitrogen species released together in extracellular inflammatory milieu play essential role in controlling pro- and anti-inflammatory activities of CDAMP/DAMP and alarmins. Here, we provide an overview of these emerging concepts and mechanisms of triggering and maintenance of tissue inflammation under massive death of cells. PMID:25140116

Sangiuliano, Beatriz; Pérez, Nancy Marcela; Moreira, Dayson F.; Belizário, José E.

2014-01-01

3

The role of damage associated molecular pattern molecules in acetaminophen-induced liver injury in mice.  

PubMed

The idiosyncratic nature, severity and poor diagnosis of drug-induced liver injury (DILI) make these reactions a major safety issue during drug development, as well as the most common cause for the withdrawal of drugs from the pharmaceutical market. Elucidation of the underlying mechanism(s) is necessary for identifying predisposing factors and developing strategies in the treatment and prevention of DILI. Acetaminophen (APAP) is a widely used over the counter therapeutic that is known to be effective and safe at therapeutic doses. However, in overdose situations fatal and non-fatal hepatic necrosis can result. Evidence suggests that the chemically reactive metabolite of the drug initiates hepatocyte damage and that inflammatory innate immune responses also occur within the liver, leading to the exacerbation and progression of tissue injury. Here we investigate whether following APAP-induced liver injury (AILI) damaged hepatocytes release "danger" signals or damage associated molecular pattern (DAMP) molecules, which induce pro-inflammatory activation of hepatic macrophages, further contributing to the progression of liver injury. Our study demonstrated a clear activation of Kupffer cells following early exposure to APAP (1h). Activation of a murine macrophage cell line, RAW cells, was also observed following treatment with liver perfusate from APAP-treated mice, or with culture supernatant of APAP-challenged hepatocytes. Moreover, in these media, the DAMP molecules, heat-shock protein-70 (HSP-70) and high mobility group box-1 (HMGB1) were detected. Overall, these findings reveal that DAMP molecules released from damaged and necrotic hepatocytes may serve as a crucial link between the initial hepatocyte damage and the activation of innate immune cells following APAP-exposure, and that DAMPs may represent a potential therapeutic target for AILI. PMID:19931603

Martin-Murphy, Brittany V; Holt, Michael P; Ju, Cynthia

2010-02-15

4

Detecting Molecular Fingerprints in Single Molecule Force Spectroscopy Using Pattern Recognition  

E-print Network

manipulation of the protein of interest [see Fig. 1(b)]. An example of a force-extension trace obtained with such a modular fusion protein is shown in Fig. 1(b). The protein was engineered such that a single green fluorescent protein (GFP) molecule is flanked by several modules of Dictyostelium discoideum filamin (Dd

5

Damage Associated Molecular Pattern Molecule-Induced microRNAs (DAMPmiRs) in Human Peripheral Blood Mononuclear Cells  

PubMed Central

Endogenous damage associated molecular pattern molecules (DAMPs) released from necrotic, damaged or stressed cells are associated with an inflammatory response. Whether the microRNA (miR) expression signature of this response is different from that of a pathogen associated molecular pattern (PAMP)-stimulated inflammatory response is unknown. We report here that miR-34c and miR-214 are significantly expressed in fresh human peripheral blood mononuclear cells (PBMCs) exposed to DAMP-containing freeze-thaw lysates, or to conditioned media from serum-starved and glucose-deprived cells (p<6×10?4 and p<3.7×10?3), respectively. Interestingly, only miR-34c expression was differentially expressed in PBMCs exposed to freeze-thaw lysates or conditioned media from wildtype High Mobility Group B1 (HMGB1+/+) mouse embryonic fibroblast (MEF) cells, when compared to cultures exposed to lysates or conditioned media from HMGB1?/? MEFs. miR-155 expression in these cultures was negligible, but was significantly expressed in PBMCs stimulated with Lipopolysaccahride (LPS) or most other Toll-like receptor (TLR) ligands, making it the prototypic “PAMPmiR”. Exposure to a damaged human colorectal carcinoma cell line lysate (HCT116) similarly resulted in increased miR-34c and miR-214 levels. When PBMCs were pre-transfected with anti-miR-34c and then exposed to lysate, expression levels of IKK? mRNA, a putative target of miR-34c, increased, while protein levels of IKK? in cultures transfected with a pre-miR-34c were abrogated. Levels of miR-34c expression (as well as pro-inflammatory cytokines, IL-1? and TNF?) decreased when PBMC cultures were briefly pre-incubated with the K+ channel (inflammasome) inhibitor, glybenclamide, suggesting that inflammasome activation is upstream of miR-34c expression in response to DAMPs. Our findings demonstrate that a specific microRNA expression signature is associated with the inflammatory response to damaged/injured cells and carries implications for many acute and chronic inflammatory disorders. PMID:22745684

Unlu, Sebnem; Tang, Siuwah; Wang, E. na; Martinez, Ivan; Tang, Daolin; Bianchi, Marco E.; Zeh, Herbert J.; Lotze, Michael T.

2012-01-01

6

Molecular biomechanics of collagen molecules  

E-print Network

Collagenous tissues, made of collagen molecules, such as tendon and bone, are intriguing materials that have the ability to respond to mechanical forces by altering their structures from the molecular level up, and convert ...

Chang, Shu-Wei

7

Programmable motion and patterning of molecules on solid surfaces  

PubMed Central

Adsorbed on a solid surface, a molecule can migrate and carry an electric dipole moment. A nonuniform electric field can direct the motion of the molecule. A collection of the same molecules may aggregate into a monolayer island on the solid surface. Place such molecules on a dielectric substrate surface, beneath which an array of electrodes is buried. By varying the voltages of the electrodes individually, it is possible to program molecular patterning, direct an island to move in a desired trajectory, or merge several islands into a larger one. The dexterity may lead to new technologies, such as reconfigurable molecular patterning and programmable molecular cars. This paper develops a phase field model to simulate the molecular motion and patterning under the combined actions of dipole moments, intermolecular forces, entropy, and electrodes. PMID:15138299

Suo, Z.; Hong, W.

2004-01-01

8

Molecular cloning, relative expression, and structural analysis of pattern recognition molecule ?-glucan binding protein from mangrove crab Episesarma tetragonum.  

PubMed

A full-length cDNA of a ?-glucan binding protein (?-GBP) gene was identified from the mangrove crab Episesarma tetragonum. The open reading frame of the E. tetragonum ?-GBP (Epte ?-GBP) is 1,167 bp long, encoding a polypeptide of 389 amino acids. The deduced amino acid sequence of Epte ?-GBP gene has conserved a potential recognition motif for ?-1,3 linkages of polysaccharides and putative RGD (Arg-Gly-Asp) cell adhesion sites. Phylogenetic analysis of the Epte ?-GBP gene showed the similarity with ?-GBPs of other crustaceans and arthropods. Quantitative RT-PCR results showed the upregulation of Epte ?-GBP gene expression in E. tetragonum hemocytes following a 12-H challenge in response to ?-glucan (?-G). Epte ?-GBP was involved in the regulation and activation of the prophenoloxidase cascade. A three-dimensional structure of active Epte ?-GBP was modeled by homology modeling and refined with molecular dynamics simulations. A structural aspect of the protein is discussed based on experimental and theoretical results obtained. PMID:25066826

Sivakamavalli, Jeyachandran; Selvaraj, Chandrabose; Singh, Sanjeev Kumar; Vaseeharan, Baskaralingam

2014-07-27

9

Molecular spintronics using single-molecule magnets  

Microsoft Academic Search

A revolution in electronics is in view, with the contemporary evolution of the two novel disciplines of spintronics and molecular electronics. A fundamental link between these two fields can be established using molecular magnetic materials and, in particular, single-molecule magnets. Here, we review the first progress in the resulting field, molecular spintronics, which will enable the manipulation of spin and

Lapo Bogani; Wolfgang Wernsdorfer

2008-01-01

10

Molecular Cloning, Expression Pattern, and Immunocytochemical Localization of a Gonadotropin-Releasing Hormone-like Molecule in the Gastropod Mollusk, Aplysia californica  

PubMed Central

Successful reproduction in vertebrates depends upon the actions of gonadotropin-releasing hormone (GnRH). Despite the wide presence of GnRH in Phylum Chordata, GnRH has not been isolated in protostomes other than the common octopus. To provide information on the evolution of this critical hormone, we isolated the full-length cDNA of a GnRH-like molecule from the central nervous system of a gastropod mollusk, the sea hare Aplysia californica. The open reading frame of this cDNA encodes a protein of 147 amino acids. The molecular architecture of the deduced protein is highly homologous to that reported for the prepro-octopus GnRH (oct-GnRH) and consists of a putative signal peptide, a GnRH dodecapeptide, a downstream processing site, and a GnRH-associated peptide (GAP). The deduced amino acid sequence of the Aplysia GnRH (ap-GnRH) is QNYHFSNGWYAG and differs from oct-GnRH by only two amino acids. The transcript for ap-GnRH is widely expressed in the central nervous system (CNS), the ovotestis, and the atrial gland, an exocrine gland. Immunocytochemistry (ICC) using an antiserum against oct-GnRH detected immunoreactive neurons in all CNS ganglia examined, and the staining was abolished by the preadsorption of the antiserum with synthetic ap-GnRH. In sum, ap-GnRH sequence is the first gastropod GnRH-like molecule to be elucidated. Further, it represents one of the only two GnRH-like molecules found outside Phylum Chordata. These data refute the possibility that oct-GnRH arose singly in cephalopods by convergent evolution and provide valuable support for an ancient origin of GnRH during metazoan evolution. PMID:18178211

Zhang, Lihong; Tello, Javier A.; Zhang, Weimin; Tsai, Pei-San

2008-01-01

11

Tiling patterns from ABC star molecules: 3-colored foams?  

PubMed

We present coarse-grained simulations of the self-assembly of 3-armed ABC star polyphiles. In systems of star polyphiles with two arms of equal length the simulations corroborate and expand previous findings from related miktoarm star terpolymer systems on the formation of patterns containing columnar domains whose sections are 2D planar tilings. However, the systematic variation of face topologies as the length of the third (unequal) arm is varied differs from earlier findings regarding the compositional dependence. We explore 2D 3-colored foams to establish the optimal patterns based on interfacial energy alone. A generic construction algorithm is described that accounts for all observed 2D tiling patterns and suggests other patterns likely to be found beyond the range of the simulations reported here. Patterns resulting from this algorithm are relaxed using Surface Evolver calculations to form 2D foams with minimal interfacial length as a function of composition. This allows us to estimate the interfacial enthalpic contributions to the free energy of related star molecular assemblies assuming strong segregation. We compare the resulting phase sequence with a number of theoretical results from particle-based simulations and field theory, allowing us to tease out relative enthalpic and entropic contributions as a function of the chain lengths making up the star molecules. Our results indicate that a richer polymorphism is to be expected in systems not dominated by chain entropy. Further, analysis of corresponding planar tiling patterns suggests that related two-periodic columnar structures are unlikely hypothetical phases in 4-arm star polyphile melts in the absence of sufficient arm configurational freedom for minor domains to form lens-shaped di-gons, which require higher molecular weight polymeric arms. Finally, we discuss the possibility of forming a complex tiling pattern that is a quasi-crystalline approximant for 3-arm star polyphiles with unequal arm lengths. PMID:25026461

Kirkensgaard, Jacob J K; Pedersen, Martin C; Hyde, Stephen T

2014-10-01

12

Rotation and Anisotropic Molecular Orbital Effect in a Single H2TPP Molecule Transistor  

NASA Astrophysics Data System (ADS)

Electron transport through a single molecule is determined not only by the intrinsic properties of the molecule but also by the configuration of the molecule with respect to the lead electrodes. Here, we show how electron transport through a single H2TPP molecule is modulated by changes in the configuration. The Coulomb stability diagram of a single H2TPP molecule transistor exhibited a few different patterns in different measurement scans. Furthermore, the sample exhibited negative differential resistance, the magnitude of which changed with the pattern in the Coulomb stability diagram. Such behavior can be explained by the rotation of the molecule with anisotropic molecular orbitals in the gap electrodes induced by electrical stress. Moreover, we find that the energy separations between molecular orbitals are also affected by the rotation, confirming that the metal-molecule interface configuration renormalizes the electronic levels in the molecule.

Sakata, Shuichi; Yoshida, Kenji; Kitagawa, Yuichi; Ishii, Kazuyuki; Hirakawa, Kazuhiko

2013-12-01

13

Molecular cloning, expression pattern, and immunocytochemical localization of a gonadotropin-releasing hormone-like molecule in the gastropod mollusk, Aplysia californica  

Microsoft Academic Search

Successful reproduction in vertebrates depends upon the actions of gonadotropin-releasing hormone (GnRH). Despite the wide presence of GnRH in Phylum Chordata, GnRH has not been isolated in protostomes other than the common octopus. To provide information on the evolution of this critical hormone, we isolated the full-length cDNA of a GnRH-like molecule from the central nervous system of a gastropod

Lihong Zhang; Javier A. Tello; Weimin Zhang; Pei-San Tsai

2008-01-01

14

Laser Induced Molecular Micro-Jet Implantation of Perylene Molecules through Water or Diiodomethane Layers  

NASA Astrophysics Data System (ADS)

Laser-induced molecular micro-jets of perylene molecules have been successfully generated in water and diiodomethane layers. The perylene molecules were ejected from a thin film of perylene molecules used as a source by photoexcitation using 4-ns laser pulses onto a borosilicate glass substrate used as a target. The gap between the source and the target was filled with water or diiodomethane. After the ejection, the perylene molecules passed through the liquid layer and were implanted into the target. The focusing of the molecular micro-jet and consequently the shape of the implanted molecular dots depends on the molecular species and type of liquid. This novel technique can be used for the fabrication of a pattern of functional molecular dots on a designated region of hard materials and can be used to manufacture molecular devices, molecular sensors, and optoelectronic devices.

Goto, Masahiro; Pihosh, Yuriy; Kasahara, Akira; Tosa, Masahiro

2008-06-01

15

Receptor-mediated signalling in plants: molecular patterns and programmes  

PubMed Central

A highly evolved surveillance system in plants is able to detect a broad range of signals originating from pathogens, damaged tissues, or altered developmental processes, initiating sophisticated molecular mechanisms that result in defence, wound healing, and development. Microbe-associated molecular pattern molecules (MAMPs), damage-associated molecular pattern molecules (DAMPs), virulence factors, secreted proteins, and processed peptides can be recognized directly or indirectly by this surveillance system. Nucleotide binding-leucine rich repeat proteins (NB-LRR) are intracellular receptors and have been targeted by breeders for decades to elicit resistance to crop pathogens in the field. Receptor-like kinases (RLKs) or receptor like proteins (RLPs) are membrane bound signalling molecules with an extracellular receptor domain. They provide an early warning system for the presence of potential pathogens and activate protective immune signalling in plants. In addition, they act as a signal amplifier in the case of tissue damage, establishing symbiotic relationships and effecting developmental processes. The identification of several important ligands for the RLK-type receptors provided an opportunity to understand how plants differentiate, how they distinguish beneficial and detrimental stimuli, and how they co-ordinate the role of various types of receptors under varying environmental conditions. The diverse roles of extra-and intracellular plant receptors are examined here and the recent findings on how they promote defence and development is reviewed. PMID:19628572

Tör, Mahmut; Lotze, Michael T.; Holton, Nicholas

2009-01-01

16

Optical spectroscopy of molecular-rotor molecules adsorbed on cellulose.  

PubMed

Steady-state and time-resolved emission techniques were used to study the fluorescence properties of two molecular rotors, thioflavin-T and auramine-O adsorbed on cellulose powder. Molecular rotors are known for their weak fluorescence intensity and short fluorescence lifetime when dissolved in liquids of low viscosity. We found that these molecular-rotor molecules when adsorbed on cellulose exhibit a rather strong steady-state fluorescence spectrum as well as long emission lifetime. We explain these results by the inhibition of segmental intramolecular rotation when these molecules are adsorbed on cellulose. PMID:25185064

Simkovitch, Ron; Huppert, Dan

2014-09-25

17

Advanced molecular self-assemblies facilitated by simple molecules.  

PubMed

Advanced materials are often based on smart molecular self-assemblies that either respond to external stimuli or have hierarchical structures. Approaches to this goal usually stem from complicated molecular design and difficult organic synthesis. In this invited feature article, we demonstrate that desired molecular self-assemblies can be made conveniently by introducing simple functional molecules into amphiphilic systems. We show that upon introducing specific small molecules which serve as responders, modulators, or even building blocks, smart supramolecular architectures can be achieved which avoid complicated organic synthesis. We expect that this could be a general and economical way to produce advanced materials in the near future. PMID:24870151

Wu, Zheng; Yan, Yun; Huang, Jianbin

2014-12-01

18

A random rotor molecule: Vibrational analysis and molecular dynamics simulations  

NASA Astrophysics Data System (ADS)

Molecular structures that permit intramolecular rotational motion have the potential to function as molecular rotors. We have employed density functional theory and vibrational frequency analysis to study the characteristic structure and vibrational behavior of the molecule (4',4??-(bicyclo[2,2,2]octane-1,4-diyldi-4,1-phenylene)-bis-2,2':6',2?-terpyridine. IR active vibrational modes were found that favor intramolecular rotation. To demonstrate the rotor behavior of the isolated single molecule, ab initio molecular dynamics simulations at various temperatures were carried out. This molecular rotor is expected to be thermally triggered via excitation of specific vibrational modes, which implies randomness in its direction of rotation.

Li, Yu; Zhang, Rui-Qin; Shi, Xing-Qiang; Lin, Zijing; Van Hove, Michel A.

2012-12-01

19

Molecular modeling of phosphonate molecules onto barium sulfate terraced surfaces.  

PubMed

The adsorption of phosphonate molecules onto mineral surfaces is of interest due to their use as scale inhibitors. Molecular modeling is an important tool that can aid the fundamental understanding of how these inhibitors operate. This paper presents an empirical molecular mechanics study of the adsorption of a series of straight chain phosphonate molecules onto barium sulfate. It has been found that inhibition can be predicted for this straight chain series of molecules, which differ by the number of phosphonate groups present as well as by the chain length. Even more importantly, the modeling results can predict which faces will be preferred, and this has been verified by scanning and transmission electron microscopy on the resultant barite particles. It has been found that, in general, lattice matching results in the lowest replacement energy for all of the organic molecules investigated. The agreement between the experiment and the model confirms that the dominant mechanism of interaction for the additives on barium sulfate is via the deprotonated phosphonate groups with the barium ions on the surface. PMID:16599519

Jones, Franca; Richmond, William R; Rohl, Andrew L

2006-04-13

20

Molecular Design of Branched and Binary Molecules at Ordered Interfaces  

SciTech Connect

This study examined five different branched molecular architectures to discern the effect of design on the ability of molecules to form ordered structures at interfaces. Photochromic monodendrons formed kinked packing structures at the air-water interface due to the cross-sectional area mismatch created by varying number of alkyl tails and the hydrophilic polar head group. The lower generations formed orthorhombic unit cell with long range ordering despite the alkyl tails tilted to a large degree. Favorable interactions between liquid crystalline terminal groups and the underlying substrate were observed to compel a flexible carbosilane dendrimer core to form a compressed elliptical conformation which packed stagger within lamellae domains with limited short range ordering. A twelve arm binary star polymer was observed to form two dimensional micelles at the air-water interface attributed to the higher polystyrene block composition. Linear rod-coil molecules formed a multitude of packing structures at the air-water interface due to the varying composition. Tree-like rod-coil molecules demonstrated the ability to form one-dimensional structures at the air-water interface and at the air-solvent interface caused by the preferential ordering of the rigid rod cores. The role of molecular architecture and composition was examined and the influence chemically competing fragments was shown to exert on the packing structure. The amphiphilic balance of the different molecular series exhibited control on the ordering behavior at the air-water interface and within bulk structures. The shell nature and tail type was determined to dictate the preferential ordering structure and molecular reorganization at interfaces with the core nature effect secondary.

Kirsten Larson Genson

2005-12-27

21

Molecular design of branched and binary molecules at ordered interfaces  

NASA Astrophysics Data System (ADS)

This study examined five different branched molecular architectures to discern the effect of design on the ability of molecules to form ordered structures at interfaces. Photochromic monodendrons formed kinked packing structures at the air-water interface due to the cross sectional area mismatch created by varying number of alkyl tails and the hydrophilic polar head group. The lower generations formed orthorhombic unit cell with long range ordering despite the alkyl tails tilted to a large degree. Favorable interactions between liquid crystalline terminal groups and the underlying substrate were observed to compel a flexible carbosilane dendrimer core to form a compressed elliptical conformation which packed stagger within lamellae domains with limited short range ordering. A twelve arm binary star polymer was observed to form two dimensional micelles at the air-water interface attributed to the higher polystyrene block composition. Linear rod-coil molecules formed a multitude of packing structures at the air-water interface due to the varying composition. Tree-like rod-coil molecules demonstrated the ability to form one-dimensional structures at the air-water interface and at the air-solvent interface caused by the preferential ordering of the rigid rod cores. The role of molecular architecture and composition was examined and the influence chemically competing fragments was shown to exert on the packing structure. The amphiphilic balance of the different molecular series exhibited control on the ordering behavior at the air-water interface and within bulk structures. The shell nature and tail type was determined to dictate the preferential ordering structure and molecular reorganization at interfaces with the core nature effect secondary.

Genson, Kirsten Larson

22

Molecular patterning of the mammalian dentition  

PubMed Central

Four conserved signaling pathways, including the bone morphogenetic proteins (Bmp), fibroblast growth factors (Fgf), Sonic hedgehog (Shh), and Wingless-related (Wnt) pathways, are each repeatedly used throughout tooth development. Inactivation of any of these resulted in early tooth developmental arrest in mice. The mutations identified thus far in human patients with tooth agenesis also affect these pathways. Recent studies show that these signaling pathways interact through positive and negative feedback loops to regulate not only morphogenesis of individual teeth but also tooth number, shape, and spatial pattern. Increased activity of each of the Fgf, Shh, and canonical Wnt signaling pathways revitalizes development of the physiologically arrested mouse diastemal tooth germs whereas constitutive activation of canonical Wnt signaling in the dental epithelium is able to induce supernumerary tooth formation even in the absence of Msx1 and Pax9, two transcription factors required for normal tooth development beyond the early bud stage. Bmp4 and Msx1 act in a positive feedback loop to drive sequential tooth formation whereas the Osr2 transcription factor restricts Msx1-mediated expansion of the mesenchymal odontogenic field along both the buccolingual and anteroposterior axes to pattern mouse molar teeth in a single row. Moreover, the ectodermal-specific ectodysplasin (EDA) signaling pathway controls tooth number and tooth shape through regulation of Fgf20 expression in the dental epithelium, whereas Shh suppresses Wnt signaling through a negative feedback loop to regulate spatial patterning of teeth. In this article, we attempt to integrate these exciting findings in the understanding of the molecular networks regulating tooth development and patterning. PMID:24355560

Lan, Yu; Jia, Shihai; Jiang, Rulang

2014-01-01

23

Commensurability and Mobility in Two-Dimensional Molecular Patterns on Graphite  

Microsoft Academic Search

Two-dimensional molecular patterns were obtained by the adsorption of long-chain alkanes, alcohols, fatty acids, and a dialkylbenzene from organic solutions onto the basal plane of graphite. In sim scanning tunneling microscopy (STM) studies revealed that these molecules organize in lamellae with the extended alkyl chains oriented parallel to a lattice axis within the basal plane of graphite. The planes of

Jurgen P. Rabe; Stefan Buchholz

1991-01-01

24

Localization of molecular orbitals: from fragments to molecule.  

PubMed

Conspectus Localized molecular orbitals (LMO) not only serve as an important bridge between chemical intuition and molecular wave functions but also can be employed to reduce the computational cost of many-body methods for electron correlation and excitation. Therefore, how to localize the usually completely delocalized canonical molecular orbitals (CMO) into confined physical spaces has long been an important topic: It has a long history but still remains active to date. While the known LMOs can be classified into (exact) orthonormal and nonorthogonal, as well as (approximate) absolutely localized MOs, the ways for achieving these can be classified into two categories, a posteriori top-down and a priori bottom-up, depending on whether they invoke the global CMOs (or equivalently the molecular density matrix). While the top-down approaches have to face heavy tasks of minimizing or maximizing a given localization functional typically of many adjacent local extrema, the bottom-up ones have to invoke some tedious procedures for first generating a local basis composed of well-defined occupied and unoccupied subsets and then maintaining or resuming the locality when solving the Hartree-Fock/Kohn-Sham (HF/KS) optimization condition. It is shown here that the good of these kinds of approaches can be combined together to form a very efficient hybrid approach that can generate the desired LMOs for any kind of gapped molecules. Specifically, a top-down localization functional, applied to individual small subsystems only, is minimized to generate an orthonormal local basis composed of functions centered on the preset chemical fragments. The familiar notion for atomic cores, lone pairs, and chemical bonds emerges here automatically. Such a local basis is then employed in the global HF/KS calculation, after which a least action is taken toward the final orthonormal localized molecular orbitals (LMO), both occupied and virtual. This last step is very cheap, implying that, after the CMOs, the LMOs can be obtained essentially for free. Because molecular fragments are taken as the basic elements, the approach is in the spirit of "from fragments to molecule". Two representatives of highly conjugated molecules, that is, C12H2 and C60, are taken as showcases for demonstrating the success of the proposed approach. The use of the so-obtained LMOs will lead naturally to low-order scaling post-HF/KS methods for electron correlation or excitation. In addition, the underlying fragment picture allows for easy and pictorial interpretations of the correlation/excitation dynamics. PMID:25019464

Li, Zhendong; Li, Hongyang; Suo, Bingbing; Liu, Wenjian

2014-09-16

25

Molecular spectral line surveys and the organic molecules in the interstellar molecular clouds  

NASA Astrophysics Data System (ADS)

It is known that more than 140 interstellar and circumstellar molecules have so far been detected, mainly by means of the radio astronomy observations. Many organic molecules are also detected, including alcohols, ketons, ethers, aldehydes, and others, that are distributed from dark clouds and hot cores in the giant molecular clouds. It is believed that most of the organic molecules in space are synthesized through the grain surface reactions, and are evaporated from the grain surface when they are heated up by the UV radiation from adjacent stars. On the other hand the recent claim on the detection of glycine have raised an important issue how difficult it is to confirm secure detection of weak spectra from less abundant organic molecules in the interstellar molecular cloud. I will review recent survey observations of organic molecules in the interstellar molecular clouds, including independent observations of glycine by the 45 m radio telescope in Japan, and will discuss the procedure to securely identify weak spectral lines from organic molecules and the importance of laboratory measurement of organic species.

Ohishi, Masatoshi

2008-10-01

26

Apparatus and method of determining molecular weight of large molecules  

DOEpatents

A mass spectrometer determines the mass of multiply charged high molecular weight molecules. This spectrometer utilizes an ion detector which is capable of simultaneously measuring the charge z and transit time of a single ion as it passes through the detector. From this transit time, the velocity of the single ion may then be derived, thus providing the mass-to-charge ratio m/z for a single ion which has been accelerated through a known potential. Given z and m/z, the mass m of the single ion can then be calculated. Electrospray ions with masses in excess of 1 MDa and charge numbers greater than 425 e.sup.- are readily detected. The on-axis single ion detection configuration enables a duty cycle of nearly 100% and extends the practical application of electrospray mass spectrometry to the analysis of very large molecules with relatively inexpensive instrumentation.

Fuerstenau, Stephen (Montrose, CA); Benner, W. Henry (Danville, CA); Madden, Norman (Livermore, CA); Searles, William (Fremont, CA)

1998-01-01

27

Apparatus and method of determining molecular weight of large molecules  

DOEpatents

A mass spectrometer determines the mass of multiply charged high molecular weight molecules. This spectrometer utilizes an ion detector which is capable of simultaneously measuring the charge z and transit time of a single ion as it passes through the detector. From this transit time, the velocity of the single ion may then be derived, thus providing the mass-to-charge ratio m/z for a single ion which has been accelerated through a known potential. Given z and m/z, the mass m of the single ion can then be calculated. Electrospray ions with masses in excess of 1 MDa and charge numbers greater than 425 e{sup {minus}} are readily detected. The on-axis single ion detection configuration enables a duty cycle of nearly 100% and extends the practical application of electrospray mass spectrometry to the analysis of very large molecules with relatively inexpensive instrumentation. 14 figs.

Fuerstenau, S.; Benner, W.H.; Madden, N.M.; Searles, W.

1998-06-23

28

Molecular dynamics simulation of paracetamol molecules ordering around glycogen  

NASA Astrophysics Data System (ADS)

By the use of classical atomistic molecular dynamics simulations, we demonstrate that paracetamol molecules exist in a highly ordered phase in the presence of a glycogen substrate at 317K whereas the paracetamol fluid exists in an isotropic phase in the absence of the glycogen substrate at the same temperature. This result further validates the studies made on polysaccharide regarding its abilities to promote nucleation of paracetamol via liquid preordering. As little is known regarding liquid ordering induced by a polymeric substrate, we seek to explore the ordering mechanism from an energy perspective. This is accomplished using conformation mappings. Our analysis shows that the conformation space accessible to the paracetamol molecule at 317K in the vicinity of glycogen is smaller than the one in the absence of glycogen. An investigation on the orientation of the dipole moments of the glycogen monomers and paracetamol molecules were carried out as well. From the investigations, we show that dipolar interactions play an important role in the ordering process. These studies bear significance to the understanding of the ordering process as well as the promotion and effective control of the nucleation rate.

Lim, Wilber; Feng, Yuan Ping; Liu, X. Y.

2005-05-01

29

Polarizable Atomic Multipole-based Molecular Mechanics for Organic Molecules  

PubMed Central

An empirical potential based on permanent atomic multipoles and atomic induced dipoles is reported for alkanes, alcohols, amines, sulfides, aldehydes, carboxylic acids, amides, aromatics and other small organic molecules. Permanent atomic multipole moments through quadrupole moments have been derived from gas phase ab initio molecular orbital calculations. The van der Waals parameters are obtained by fitting to gas phase homodimer QM energies and structures, as well as experimental densities and heats of vaporization of neat liquids. As a validation, the hydrogen bonding energies and structures of gas phase heterodimers with water are evaluated using the resulting potential. For 32 homo- and heterodimers, the association energy agrees with ab initio results to within 0.4 kcal/mol. The RMS deviation of hydrogen bond distance from QM optimized geometry is less than 0.06 Å. In addition, liquid self-diffusion and static dielectric constants computed from molecular dynamics simulation are consistent with experimental values. The force field is also used to compute the solvation free energy of 27 compounds not included in the parameterization process, with a RMS error of 0.69 kcal/mol. The results obtained in this study suggest the AMOEBA force field performs well across different environments and phases. The key algorithms involved in the electrostatic model and a protocol for developing parameters are detailed to facilitate extension to additional molecular systems. PMID:22022236

Ren, Pengyu; Wu, Chuanjie; Ponder, Jay W.

2011-01-01

30

MAMP (microbe-associated molecular pattern) triggered immunity in plants  

PubMed Central

Plants are sessile organisms that are under constant attack from microbes. They rely on both preformed defenses, and their innate immune system to ward of the microbial pathogens. Preformed defences include for example the cell wall and cuticle, which act as physical barriers to microbial colonization. The plant immune system is composed of surveillance systems that perceive several general microbe elicitors, which allow plants to switch from growth and development into a defense mode, rejecting most potentially harmful microbes. The elicitors are essential structures for pathogen survival and are conserved among pathogens. The conserved microbe-specific molecules, referred to as microbe- or pathogen-associated molecular patterns (MAMPs or PAMPs), are recognized by the plant innate immune systems pattern recognition receptors (PRRs). General elicitors like flagellin (Flg), elongation factor Tu (EF-Tu), peptidoglycan (PGN), lipopolysaccharides (LPS), Ax21 (Activator of XA21-mediated immunity in rice), fungal chitin, and ?-glucans from oomycetes are recognized by plant surface localized PRRs. Several of the MAMPs and their corresponding PRRs have, in recent years, been identified. This review focuses on the current knowledge regarding important MAMPs from bacteria, fungi, and oomycetes, their structure, the plant PRRs that recognizes them, and how they induce MAMP-triggered immunity (MTI) in plants. PMID:23720666

Newman, Mari-Anne; Sundelin, Thomas; Nielsen, Jon T.; Erbs, Gitte

2013-01-01

31

ION AND MOLECULE SENSORS USING MOLECULAR RECOGNITION IN LUMINESCENT, CONDUCTIVE POLYMERS  

EPA Science Inventory

This program integrates three individual, highly interactive projects that will use molecular recognition strategies to develop sensor technology based on luminescent, conductive polymers that contain sites for binding specific molecules or ions in the presence of related molecul...

32

Exploration of target molecules for molecular imaging of inflammatory bowel disease  

SciTech Connect

Highlights: {sup {yields}18}F-FDG PET could discriminate each inflamed area of IBD model mice clearly. {sup {yields}18}F-FDG PET could not discriminate the difference of pathogenic mechanism. {yields} Cytokines and cytokine receptors expression was different by pathogenic mechanism. {yields} Cytokines and cytokine receptors would be new target molecules for IBD imaging. -- Abstract: Molecular imaging technology is a powerful tool for the diagnosis of inflammatory bowel disease (IBD) and the efficacy evaluation of various drug therapies for it. However, it is difficult to elucidate directly the relationships between the responsible molecules and IBD using existing probes. Therefore, the development of an alternative probe that is able to elucidate the pathogenic mechanism and provide information on the appropriate guidelines for treatment is earnestly awaited. In this study, we investigated pathognomonic molecules in the intestines of model mice. The accumulation of fluorine-18 fluorodeoxyglucose ({sup 18}F-FDG) in the inflamed area of the intestines of dextran sulfate sodium (DSS)- or indomethacin (IND)-induced IBD model mice was measured by positron emission tomography (PET) and autoradiography to confirm the inflamed area. The results suggested that the inflammation was selectively induced in the colons of mice by the administration of DSS, whereas it was induced mainly in the ilea and the proximal colons of mice by the administration of IND. To explore attractive target molecules for the molecular imaging of IBD, we evaluated the gene expression levels of cytokines and cytokine receptors in the inflamed area of the intestines of both model mice. We found that the expression levels of cytokines and cytokine receptors were significantly increased during the progression of IBD, whereas the expression levels were decreased as the mucosa began to heal. In particular, the expression levels of these molecules had already changed before the symptoms of IBD appeared. In addition, the alterations of cytokine and cytokine receptor expression levels indicated differences in the expression pattern depending on the pathogenic mechanism or the region of inflammation (e.g., TNF-{alpha}). Our results suggest that these cytokines or cytokine receptors participate in the pathogenesis of IBD and are valuable biomarkers for the detection of the different circumstances underlying inflammation by the molecular imaging method. Finally, the development of an imaging probe for our target molecules is expected to improve our understanding of the inflammatory conditions of IBD.

Higashikawa, Kei; Akada, Naoki; Yagi, Katsuharu [Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama 700-8530 (Japan)] [Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama 700-8530 (Japan); Watanabe, Keiko; Kamino, Shinichiro; Kanayama, Yousuke; Hiromura, Makoto [Multiple Molecular Imaging Research Laboratory, RIKEN Center for Molecular Imaging Science, Kobe 650-0047 (Japan)] [Multiple Molecular Imaging Research Laboratory, RIKEN Center for Molecular Imaging Science, Kobe 650-0047 (Japan); Enomoto, Shuichi, E-mail: senomoto@pharm.okayama-u.ac.jp [Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama 700-8530 (Japan) [Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama 700-8530 (Japan); Multiple Molecular Imaging Research Laboratory, RIKEN Center for Molecular Imaging Science, Kobe 650-0047 (Japan)

2011-07-08

33

The long pentraxin PTX3: a paradigm for humoral pattern recognition molecules.  

PubMed

Pattern recognition molecules (PRMs) are components of the humoral arm of innate immunity; they recognize pathogen-associated molecular patterns (PAMP) and are functional ancestors of antibodies, promoting complement activation, opsonization, and agglutination. In addition, several PRMs have a regulatory function on inflammation. Pentraxins are a family of evolutionarily conserved PRMs characterized by a cyclic multimeric structure. On the basis of structure, pentraxins have been operationally divided into short and long families. C-reactive protein (CRP) and serum amyloid P component are prototypes of the short pentraxin family, while pentraxin 3 (PTX3) is a prototype of the long pentraxins. PTX3 is produced by somatic and immune cells in response to proinflammatory stimuli and Toll-like receptor engagement, and it interacts with several ligands and exerts multifunctional properties. Unlike CRP, PTX3 gene organization and regulation have been conserved in evolution, thus allowing its pathophysiological roles to be evaluated in genetically modified animals. Here we will briefly review the general properties of CRP and PTX3 as prototypes of short and long pentraxins, respectively, emphasizing in particular the functional role of PTX3 as a prototypic PRM with antibody-like properties. PMID:23527487

Mantovani, Alberto; Valentino, Sonia; Gentile, Stefania; Inforzato, Antonio; Bottazzi, Barbara; Garlanda, Cecilia

2013-05-01

34

Complete Photo-Induced Breakup of the H2 Molecule as a Probe ofMolecular Electron Correlation  

SciTech Connect

Despite decades of progress in quantum mechanics, electron correlation effects are still only partially understood. Experiments in which both electrons are ejected from an oriented hydrogen molecule by absorption of a single photon have recently demonstrated a puzzling phenomenon: The ejection pattern of the electrons depends sensitively on the bond distance between the two nuclei as they vibrate in their ground state. Here we report a complete numerical solution of the Schrodinger equation for the double photoionization of H2. The results suggest that the distribution of photoelectrons emitted from aligned molecules reflects electron correlation effects that are purely molecular in origin.

Vanroose, Wim; Martin, Fernando; Rescigno, Thomas N.; McCurdy, C.William

2005-11-17

35

Sensing of protein molecules through nanopores: a molecular dynamics study  

NASA Astrophysics Data System (ADS)

Solid-state nanopores have been shown to be suitable for single molecule detection. While numerous modeling investigations exist for DNA within nanopores, there are few simulations of protein translocations. In this paper, we use atomistic molecular dynamics to investigate the translocation of proteins through a silicon nitride nanopore. The nanopore dimensions and profile are representative of experimental systems. We are able to calculate the change in blockade current and friction coefficient for different positions of the protein within the pore. The change in ionic current is found to be negligible until the protein is fully within the pore and the current is lowest when the protein is in the pore center. Using a simple theory that gives good quantitative agreement with the simulation results we are able to show that the variation in current with position is a function of the pore shape. In simulations that guide the protein through the nanopore we identify the effect that confinement has on the friction coefficient of the protein. This integrated view of translocation at the nanoscale provides useful insights that can be used to guide the design of future devices.

Kannam, Sridhar Kumar; Kim, Sung Cheol; Rogers, Priscilla R.; Gunn, Natalie; Wagner, John; Harrer, Stefan; Downton, Matthew T.

2014-04-01

36

Electron transport through heterocyclic molecule: ab initio molecular orbital theory  

Microsoft Academic Search

We have calculated the electron transport properties of molecule wires by an ab initio molecule orbital theory on the basis of the first-principles density functional theory (DFT) and the non-equilibrium Green function (NEGF) technique. The wires are made of heterocyclic molecule (furan, thiophene, and pyrrole, shown in first figure), in contact with the atomic scale Au electrodes. The results of

W. W. Cheng; Y. X. Liao; H. Chen; H. Mizuseki; Y. Kawazoe

2004-01-01

37

Experimental and numerical analysis of DNA nanostrand array formation by molecular combing on microwell-patterned surface  

NASA Astrophysics Data System (ADS)

DNA molecules can be stretched and immobilized onto a solid surface containing surface microstructures, to form a well-defined array by dewetting the surface with DNA solution. However, the mechanism of DNA stretching, immobilizing and patterning in this molecular combing process is not well understood. In this study, we demonstrated the generation of stretched DNA nanostrand arrays with different orientations and morphologies by controlling the dewetting direction on a microwell-patterned surface. We also simulated the dewetting process based on a deforming body-fitted grid approach. The simulation results provide insights for explaining the stretching, immobilizing and patterning of DNA molecules observed in the experiments.

Lin, C. H.; Guan, J.; Chau, S. W.; Lee, L. J.

2009-01-01

38

Chains of quantum dot molecules grown on Si surface pre-patterned by ion-assisted nanoimprint lithography  

NASA Astrophysics Data System (ADS)

An original approach based on the combination of nanoimprint lithography and ion irradiation through mask has been developed for fabrication of large-area periodical pattern on Si(100). Using the selective etching of regions amorphized by ion irradiation ordered structures with grooves and ridges were obtained. The shape and depth of the relief were governed by ion energy and by the number of etching stages as well. Laterally ordered chains of Ge quantum dots were fabricated by molecular beam epitaxy of Ge on the pre-patterned Si substrates. For small amount of Ge deposited chains contain separate quantum dot molecules. The increase of deposition amount leads to overlapping of quantum dot molecules with formation of dense homogeneous chains of quantum dots. It was shown that the residual irradiation-induced bulk defects underneath the grooves suppress nucleation of Ge islands at the bottom of grooves. On pre-patterned substrates with whole defect regions, etched quantum dots grow at the bottom of grooves. The observed location of Ge quantum dots is interpreted in terms of local strain-mediated surface chemical potential which controls the sites of islands nucleation. The local chemical potential is affected by additional strain formed by the residual defects. It was shown by molecular dynamics calculations that these defects form the compressive strain at the bottom of grooves.

Smagina, Zh. V.; Stepina, N. P.; Zinovyev, V. A.; Novikov, P. L.; Kuchinskaya, P. A.; Dvurechenskii, A. V.

2014-10-01

39

Time-Resolved Molecular Frame Dynamics of Fixed-in-Space CS2 Molecules  

SciTech Connect

Random orientation of molecules within a sample leads to blurred observationsof chemical reactions studied from the laboratory perspective. Methodsdeveloped for the dynamic imaging of molecular structures and processesstruggle with this, as measurements are optimally made in the molecular frame.Here we uselaser alignment to transiently fix CS2 molecules in space longenough to elucidate, in the molecular reference frame, details of ultrafast electronic vibrationaldynamics during a photochemical reaction. These three-dimensional photoelectron imaging results, combined with ongoing efforts in molecular alignment and orientation, presage a wide range of insights obtainable fromtime-resolved studies in the molecular frame.

Bisgaard, Christer; Clarkin, Owen; Wu, Guorong; Lee, Anthony; Gessner, Oliver; Hayden, Carl; Stolow, Albert

2009-04-02

40

Elements of the theory of molecular spectra. [multiatomic molecules  

NASA Technical Reports Server (NTRS)

The basic aspects of the theory concerning the spectra of multiatomic molecules are presented. The classification of the forms of motions in a molecule, the methods for determining the corresponding Schroudinger levels, the spectral types and the selection rules are discussed in order to identify their presence and state in outer space.

Gribov, L. A.

1979-01-01

41

M-ficolin, an innate immune defence molecule, binds patterns of acetyl groups and activates complement.  

PubMed

Ficolins play a role in the innate immune defence as pathogen-associated molecular pattern recognition molecules. Three ficolins are found in humans: H-ficolin, L-ficolin and M-ficolin. L-ficolin and H-ficolin circulate in blood in complexes with mannan-binding lectin-associated serine proteases (MASPs) and are capable of activating the complement system. L-ficolin shows affinity for acetylated compounds and binds to various capsulated strains of bacteria. H-ficolin has been shown to bind Aerococcus viridans. Less is known about M-ficolin, but it is thought to be present only on monocytes. We have synthesized recombinant M-ficolin and find that it, in a manner similar to L-ficolin, is able to bind to acetylated compounds and to associate with recombinant MASP-2. Upon binding to M-ficolin ligands, the associated MASP-2 zymogen is activated and cleaves C4, thus triggering the complement system. We developed a monoclonal rat anti-human-M/L-ficolin antibody and verified by flow cytometric analysis the presence of ficolin on the surface of peripheral blood monocytes. PMID:16305643

Frederiksen, P D; Thiel, S; Larsen, C B; Jensenius, J C

2005-11-01

42

Organic molecules as chemical fossils - The molecular fossil record  

NASA Technical Reports Server (NTRS)

The study of biochemical clues to the early earth and the origin of life is discussed. The methods used in such investigation are described, including the extraction, fractionation, and analysis of geolipids and the analysis of kerogen. The occurrence of molecular fossils in the geological record is examined, discussing proposed precursor-product relationships and the molecular assessment of deep sea sediments, ancient sediments, and crude petroleums. Alterations in the molecular record due to diagenesis and catagenesis are considered, and the use of microbial lipids as molecular fossils is discussed. The results of searches for molecular fossils in Precambrian sediments are assessed.

Eglinton, G.

1983-01-01

43

Progress in Biophysics & Molecular Biology 74 (2000) 115140 Twisting and stretching single DNA molecules  

E-print Network

Progress in Biophysics & Molecular Biology 74 (2000) 115­140 Review Twisting and stretching single and tools for the study of single-molecule biophysics. Methods as diverse as optical and magnetic tweezers

Levine, Alex J.

44

Molecular Physiology of Protein Kinases (and Phosphatases): Molecules, mechanisms, medicines  

NSDL National Science Digital Library

This powerpoint presentation from the 2011 EB Refresher Course on CellPhysiology:Intracellular Signaling addressed protein kinase structure, conformational changes, molecular domains, activation, and inhibition.

Michael Eck (Harvard University)

2011-04-09

45

Molecular Physiology of Protein Kinases (and Phosphatases): Molecules, mechanisms, medicines  

NSDL National Science Digital Library

This recorded presentation from the 2011 EB Refresher Course on CellPhysiology:Intracellular Signaling addressed protein kinase structure, conformational changes, molecular domains, activation, and inhibition.

Michael Eck (Harvard University)

2011-04-09

46

Building foundations for molecular electronics: Growth of organic molecules on alkali halides as prototypical insulating substrates  

Microsoft Academic Search

The epitaxy and growth of a series of organic molecules deposited on insulating surfaces were investigated by noncontact atomic force microscopy (nc-AFM). The molecules studied, C60, 3,4,9,10-perylene tetracarboxylic dianhydride (PTCDA), 3,4,9,10-perylene tetracarboxlylic diimide (PTCDI), and copper (II) phthalocyanine (CuPc), were selected to investigate the effect of different molecular geometries, charge distributions and intermolecular interactions and as interesting candidates in molecular

Sarah A. Burke

2009-01-01

47

Critical Roles of Metal-Molecule Contacts in Electron Transport Through Molecular-wire Junctions  

Microsoft Academic Search

We use non-equilibrium Green's function DFT methods (TranSIESTA) to study the bonding-site dependence of the transmission through metal-molecule contacts in molecular junctions of type M-S-mol-S-M for a number of different molecular systems, mainly short molecules with DTB as a reference system, and also OPVn, n=3-5. For all systems on Au(111) surfaces the transmission is quite insensitive to the bonding site.

Anton Grigoriev; Zeljko Crljen

2005-01-01

48

Heteroduplex molecules cause sexing errors in a standard molecular protocol for avian sexing.  

PubMed

Molecular methods are a necessary tool for sexing monomorphic birds. These molecular approaches are usually reliable, but sexing protocols should be evaluated carefully because biochemical interactions may lead to errors. We optimized laboratory protocols for genetic sexing of a monomorphic shorebird, the upland sandpiper (Bartramia longicauda), using two independent sets of primers, P2/P8 and 2550F/2718R, to amplify regions of the sex-linked CHD-Z and CHD-W genes. We discovered polymorphisms in the region of the CHD-Z intron amplified by the primers P2/P8 which caused four males to be misidentified as females (n = 90 mated pairs). We cloned and sequenced one CHD-W allele (370 bp) and three CHD-Z alleles in our population: Z° (335 bp), Z' (331 bp) and Z? (330 bp). Normal (Z°Z°) males showed one band in agarose gel analysis and were easily differentiated from females (Z°W), which showed two bands. However, males heterozygous for CHD-Z alleles (Z'Z?) unexpectedly showed two bands in a pattern similar to females. While the Z' and Z? fragments contained only short deletions, they annealed together during the polymerase chain reaction (PCR) process and formed heteroduplex molecules that were similar in size to the W fragment. Errors previously reported for molecular sex-assignment have usually been due to allelic dropout, causing females to be misidentified as males. Here, we report evidence that events in PCRs can lead to the opposite error, with males misidentified as females. We recommend use of multiple primer sets and large samples of known-sex birds for validation when designing protocols for molecular sex analysis. PMID:21564567

Casey, Ashley E; Jones, Kenneth L; Sandercock, Brett K; Wisely, Samantha M

2009-01-01

49

I. Molecular magnetism and single-molecule magnets The research in the area of molecular magnetism is focused on molecular assemblies containing a  

E-print Network

are attributed to the MS2 and MS1 metastable states observed experimentally. 4. Magnetic anisotropy of spin-frustrated1 Research: I. Molecular magnetism and single-molecule magnets The research in the area of molecular magnetism is focused on molecular assemblies containing a finite number of exchange coupled

Vardi, Amichay

50

A Novel Pictorial Approach to Teaching Molecular Motions in Polyatomic Molecules.  

ERIC Educational Resources Information Center

Describes a procedure for teaching the "generator orbital" (GO) approach of molecular orbital bonding in polyatomic molecules. Explains how the GO can be utilized with students in generating the vibrational, rotational, and translational modes of molecules in a completely pictorial manner. (ML)

Verkade, John G.

1987-01-01

51

Molecular dynamics simulations of flexible liquid crystal molecules using a Gay-Berne/Lennard-Jones model  

E-print Network

Molecular dynamics simulations of flexible liquid crystal molecules using a Gay for liquid crystal molecules composed of two Gay-Berne particles connected by an eight-site Lennard layers. The latter is seen through the temperature dependence of the Gay-Berne radial distribution

Wilson, Mark R.

52

The Virtual Museum of Minerals and Molecules: Molecular Visualization in a Virtual Hands-On Museum  

ERIC Educational Resources Information Center

The Virtual Museum of Minerals and Molecules (VMMM) is a web-based resource presenting interactive, 3-D, research-grade molecular models of more than 150 minerals and molecules of interest to chemical, earth, plant, and environmental sciences. User interactivity with the 3-D display allows models to be rotated, zoomed, and specific regions of…

Barak, Phillip; Nater, Edward A.

2005-01-01

53

Laser Induced Molecular MicroJet Implantation of Perylene Molecules through Water or Diiodomethane Layers  

Microsoft Academic Search

Laser-induced molecular micro-jets of perylene molecules have been successfully generated in water and diiodomethane layers. The perylene molecules were ejected from a thin film of perylene molecules used as a source by photoexcitation using 4-ns laser pulses onto a borosilicate glass substrate used as a target. The gap between the source and the target was filled with water or diiodomethane.

Masahiro Goto; Yuriy Pihosh; Akira Kasahara; Masahiro Tosa

2008-01-01

54

Reducing false positives in molecular pattern recognition.  

PubMed

In the search for new cancer subtypes by gene expression profiling, it is essential to avoid misclassifying samples of unknown subtypes as known ones. In this paper, we evaluated the false positive error rates of several classification algorithms through a 'null test' by presenting classifiers a large collection of independent samples that do not belong to any of the tumor types in the training dataset. The benchmark dataset is available at www2.genome.rcast.u-tokyo.ac.jp/pm/. We found that k-nearest neighbor (KNN) and support vector machine (SVM) have very high false positive error rates when fewer genes (<100) are used in prediction. The error rate can be partially reduced by including more genes. On the other hand, prototype matching (PM) method has a much lower false positive error rate. Such robustness can be achieved without loss of sensitivity by introducing suitable measures of prediction confidence. We also proposed a cluster-and-select technique to select genes for classification. The nonparametric Kruskal-Wallis H test is employed to select genes differentially expressed in multiple tumor types. To reduce the redundancy, we then divided these genes into clusters with similar expression patterns and selected a given number of genes from each cluster. The reliability of the new algorithm is tested on three public datasets. PMID:15706518

Ge, Xijin; Tsutsumi, Shuichi; Aburatani, Hiroyuki; Iwata, Shuichi

2003-01-01

55

The Molecule Calculator: A Web Application for Fast Quantum Mechanics-Based Estimation of Molecular Properties  

NASA Astrophysics Data System (ADS)

A new web-server called The Molecule Calculator (MolCalc) is presented. The entry page is a molecular editor (JSmol) for interactive molecule building. The resulting structure can then be used to estimate molecular properties such as heats of formation and other thermodynamic properties, vibrational frequencies and vibrational modes, and molecular orbitals and orbital energies. These properties are computed using the GAMESS program at either the RHF/STO-3G (orbitals and orbital energies) or PM3 level of theory (all other properties) in a matter of seconds or minutes depending on the size of the molecule. The results, though approximate, can help students develop a "chemical intuition" about how molecular structure affects molecular properties, without performing the underlying calculations by hand, a near impossible task for all but the simplest chemical systems.

Jensen, Jan H.; Kromann, Jimmy C.

2013-08-01

56

Molecular recognition of chromophore molecules to amine terminated surfaces  

NASA Astrophysics Data System (ADS)

We report the design and characterization of quartz surfaces that can bind to three retinal based chromophores. The amine terminated surfaces were engineered in order to mimic the environment of the opsin protein that accommodates binding of chromophore molecules in the human eye. Each surface coupling step was characterized by water contact angle measurements, ellipsometry, atomic force microscopy, X-ray photoelectron spectroscopy, and transmission infrared spectroscopy. The spectroscopic techniques confirmed that the three chromophore molecules can bind to the surface using a Schiff base mode. Our data suggests that the availability of the amine groups on the surface is critical in the accommodation of the binding of different chromophores.

Flores-Perez, Rosangelly; Ivanisevic, Albena

2007-02-01

57

Role of hydrogen interaction in two-dimensional molecular packing with strong molecule-substrate bonding  

SciTech Connect

Calixarene molecules deposited on Au(110) self-organize giving rise to a (19x6) coincidence cell with the substrate. Using grazing incidence x-ray diffraction, the structure has been completely resolved: gold reconstructs with a (1x3) missing-row structure while the molecules form a (19/6x6) surface cell containing two molecules. This study opens perspectives to create long-range ordered molecular templates to be used as receptors for other species providing an example of collaborative self-arrangement through a metallic substrate acting as guide and molecular flexibility.

Langlais, V.; Torrelles, X.; Gauthier, Y.; De Santis, M. [Laboratoire de Cristallographie, CNRS, Boite Postal 166 X, 38 042 Grenoble Cedex 9 (France); Departament de Fisica, Universitat Autonoma de Barcelona, 08193 Bellaterra (Spain); Institut de Ciencia de Materials de Barcelona, CSIC-Campus de la UAB, 08193 Bellaterra (Spain)

2007-07-15

58

Role of hydrogen interaction in two-dimensional molecular packing with strong molecule-substrate bonding  

NASA Astrophysics Data System (ADS)

Calixarene molecules deposited on Au(110) self-organize giving rise to a (19×6) coincidence cell with the substrate. Using grazing incidence x-ray diffraction, the structure has been completely resolved: gold reconstructs with a (1×3) missing-row structure while the molecules form a (19/6×6) surface cell containing two molecules. This study opens perspectives to create long-range ordered molecular templates to be used as receptors for other species providing an example of collaborative self-arrangement through a metallic substrate acting as guide and molecular flexibility.

Langlais, V.; Torrelles, X.; Gauthier, Y.; de Santis, M.

2007-07-01

59

Research Update: Molecular electronics: The single-molecule switch and transistor  

SciTech Connect

In order to design and realize single-molecule devices it is essential to have a good understanding of the properties of an individual molecule. For electronic applications, the most important property of a molecule is its conductance. Here we show how a single octanethiol molecule can be connected to macroscopic leads and how the transport properties of the molecule can be measured. Based on this knowledge we have realized two single-molecule devices: a molecular switch and a molecular transistor. The switch can be opened and closed at will by carefully adjusting the separation between the electrical contacts and the voltage drop across the contacts. This single-molecular switch operates in a broad temperature range from cryogenic temperatures all the way up to room temperature. Via mechanical gating, i.e., compressing or stretching of the octanethiol molecule, by varying the contact's interspace, we are able to systematically adjust the conductance of the electrode-octanethiol-electrode junction. This two-terminal single-molecule transistor is very robust, but the amplification factor is rather limited.

Sotthewes, Kai; Heimbuch, René, E-mail: r.heimbuch@utwente.nl; Kumar, Avijit; Zandvliet, Harold J. W. [Physics of Interfaces and Nanomaterials, MESA Institute for Nanotechnology, University of Twente, P.O. Box 217, 7500AE Enschede (Netherlands); Geskin, Victor [Service de Chimie des Materiaux Nouveaux, University of Mons, Mons (Belgium)

2014-01-01

60

High-order harmonic spectroscopy for molecular imaging of polyatomic molecules.  

PubMed

High-order harmonic generation is a powerful and sensitive tool for probing atomic and molecular structures, combining in the same measurement an unprecedented attosecond temporal resolution with a high spatial resolution of the order of an angstrom. Imaging of the outermost molecular orbital by high-order harmonic generation has been limited for a long time to very simple molecules, like nitrogen. Recently we demonstrated a technique that overcame several of the issues that have prevented the extension of molecular orbital tomography to more complex species, showing that molecular imaging can be applied to a triatomic molecule like carbon dioxide. Here we report on the application of such a technique to nitrous oxide (N2O) and acetylene (C2H2). This result represents a first step towards the imaging of fragile compounds, a category which includes most of the fundamental biological molecules. PMID:25415258

Negro, M; Devetta, M; Faccialá, D; De Silvestri, S; Vozzi, C; Stagira, S

2014-01-01

61

Molecular polarizability in quantum defect theory: polar molecules  

SciTech Connect

The reduced-added Green's function technique in the quantum defect theory combines the advantages of analytical and ab initio methods in calculating frequency-dependent (dynamic) polarizabilities of atoms and molecules, providing an exact account for the high-excited and continuum electronic states. In the present paper this technique is modified to take into account the long-range dipole potential of a polar molecule core. The method developed is applied to calculation of the dynamic polarizability tensors of alkali-metal hydrides LiH and NaH as well as to some fluorides (CaF and BF) in the frequency range up to the first resonances. The results are in good agreement with ab initio calculations available for some frequencies.

Akindinova, E. V.; Chernov, V. E.; Kretinin, I. Yu.; Zon, B. A. [Voronezh State University, Voronezh RU-394693 (Russian Federation)

2010-04-15

62

Immunopathological Roles of Cytokines, Chemokines, Signaling Molecules, and Pattern-Recognition Receptors in Systemic Lupus Erythematosus  

PubMed Central

Systemic lupus erythematosus (SLE) is an autoimmune disease with unknown etiology affecting more than one million individuals each year. It is characterized by B- and T-cell hyperactivity and by defects in the clearance of apoptotic cells and immune complexes. Understanding the complex process involved and the interaction between various cytokines, chemokines, signaling molecules, and pattern-recognition receptors (PRRs) in the immune pathways will provide valuable information on the development of novel therapeutic targets for treating SLE. In this paper, we review the immunopathological roles of novel cytokines, chemokines, signaling molecules, PRRs, and their interactions in immunoregulatory networks and suggest how their disturbances may implicate pathological conditions in SLE. PMID:22312407

Yu, Shui-Lian; Kuan, Woon-Pang; Wong, Chun-Kwok; Li, Edmund K.; Tam, Lai-Shan

2012-01-01

63

Immunopathological roles of cytokines, chemokines, signaling molecules, and pattern-recognition receptors in systemic lupus erythematosus.  

PubMed

Systemic lupus erythematosus (SLE) is an autoimmune disease with unknown etiology affecting more than one million individuals each year. It is characterized by B- and T-cell hyperactivity and by defects in the clearance of apoptotic cells and immune complexes. Understanding the complex process involved and the interaction between various cytokines, chemokines, signaling molecules, and pattern-recognition receptors (PRRs) in the immune pathways will provide valuable information on the development of novel therapeutic targets for treating SLE. In this paper, we review the immunopathological roles of novel cytokines, chemokines, signaling molecules, PRRs, and their interactions in immunoregulatory networks and suggest how their disturbances may implicate pathological conditions in SLE. PMID:22312407

Yu, Shui-Lian; Kuan, Woon-Pang; Wong, Chun-Kwok; Li, Edmund K; Tam, Lai-Shan

2012-01-01

64

New Materials, Methods, and Molecules for Microelectronic and Molecular Electronic Devices  

NASA Astrophysics Data System (ADS)

This dissertation reports a variety of new methods and materials for the fabrication of electronic devices. Particular emphasis is placed on low-cost, solution based methods for flexible electronic device fabrication, and new substrates and molecules for molecular electronic tunnel junctions. Chapter 2 reports a low-cost, solution based method for depositing patterned metal circuitry onto a variety of flexible polymer substrates. Microcontact printing an aluminum (III) porphyrin complex activates selected areas of an oxidized polymer substrate to electroless copper metallization. Chapter 3 reports a new transparent conductive electrode for use in optoelectronic devices. A highly conductive, transparent silver nanowire network is embedded at the surface of an optical adhesive, which can be applied to a variety of rigid and flexible polymer substrates. Chapter 4 describes a new approach to the self-assembly of mesoscale components into two-dimensional arrays. Unlike most previously reported self-assembly motifs, this method is completely dry; eliminating solvent makes this method compatible with the assembly of electronic components. Chapter 5 describes a new class of self-assembled monolayer (SAM) on gold formed from dihexadecyldithiophosphinic acid ((C16) 2DTPA) adsorbate molecules. The binding and structure (C16) 2DTPA SAMs is dependent upon the roughness and morphology of the underlying gold substrate. Chapter 6 investigates the influence of chain length on the binding and structure of dialkyl-DTPA SAMs on smooth, template-stripped (TS) gold. Binding of the DTPA head group is independent of the length of the alkyl chain, while the structure of the organic layer has a counter-intuitive dependence: As the length of the alkyl chain increases, these SAMs become more disordered and liquid-like. Chapter 7 describes the fabrication of ultra smooth gold substrates using chemical mechanical polishing (CMP). These substrates are smooth, uniform, and prove to be ideal candidates for bottom electrodes within SAM-based molecular electronic tunnel junctions. Chapter 8 investigates the charge transport properties of new diphenyldithiophosphinic acid (Ph 2DTPA) SAMs on TS gold within metal-SAM//Ga2O3/EGaIn molecular tunnel junctions. A computational investigation provides insight into the electronic structure of the junction.

Miller, Michael Stephen

65

Molecular topology analysis of the differences between drugs, clinical candidate compounds, and bioactive molecules.  

PubMed

A new method to decompose molecules is proposed and used to analyze drugs, clinical candidate compounds and bioactive molecules. The method classifies a set of molecules into a few well-defined classes based on their molecular framework. It is then possible to use these classes to investigate differences between drugs, clinical candidates and bioactive molecules. The analysis shows that in comparison with clinical candidates and bioactive compounds, drugs have a higher fraction of compounds with only one ring system. This conclusion is still valid after correcting for lipophilicity (ClogP) and molecular size, as well as any potential protein target bias in the data sets. Furthermore the molecular bridge part of compounds in the drug set has on average fewer ring systems than molecules from the other sets. The ring system complexity (RSC) was also investigated and for most topological classes drugs have a lower RSC than the clinical candidates and bioactive molecules. Hence, this study highlights differences in topology between drugs, clinical candidate compounds and bioactive molecules. PMID:21077637

Chen, Hongming; Yang, Yidong; Engkvist, Ola

2010-12-27

66

Pattern formation in Langmuir-Blodgett films of tricycloquinazoline based discotic liquid crystal molecules  

NASA Astrophysics Data System (ADS)

The assembly of molecules on the surface has drawn considerable attention because of its potential to tailor the physicochemical, electronic, and magnetic properties of materials. The structure of aggregates of molecules can be influenced by the molecular interactions and the external parameters like temperature, pressure and ion contents. We have found a stable Langmuir monolayer of amphiphilic tricycloquinazoline based discotic liquid crystal (AmTCQ) molecules at air-water (A-W) interface. The monolayer exhibits gas phase, low density liquid phase and high density liquid phase. The structural evolution in Langmuir-Blodgett (LB) films of the AmTCQ molecules as a function of target surface pressure is studied using an atomic force microscope. We found aggregation of the discotic molecules leading to nucleation sites at a lower surface pressure. With the increasing surface pressure, each nucleation site grows to form a stable triangular structure. The shape and size of the triangular structure remain stable till the target surface pressure for LB films deposition exceeds the equilibrium surface pressure of the AmTCQ molecules. The number of triangles in the film increases with increasing target surface pressure of LB deposition. The target surface pressure of LB deposition acts as a controlling parameter for obtaining desired number of triangular domains in the film.

Karthik, C.; Manjuladevi, V.; Gupta, R. K.; Kumar, Sandeep

2014-07-01

67

A barrier-free molecular radical-molecule reaction:  

Microsoft Academic Search

The reaction of 3C2 (a3?) radical with O2 (X3?) molecule has been studied theoretically using ab initio Quantum Chemistry method. Both singlet and triplet potential energy surfaces (PES) are calculated at the CCSD(T)\\/aug-cc-pVDZ\\/\\/B3LYP\\/6-311+G(d)\\u000a + ZPE and G3B3 levels of theory. On the singlet PES of the title reaction, it is shown that the most feasible pathway should\\u000a be the O-atom

Ming-Hui Zuo; Ji-Lai Li; Xu-Ri Huang; Hui-Ling Liu; Cai-Yun Geng; Fei Li; Chia-Chung Sun

2007-01-01

68

Using the first steps of hydration for the determination of molecular conformation of a single molecule.  

PubMed

Determination of the exact structure of individual molecules is the ultimate goal of high-resolution microscopy. However, the resolution of scanning tunneling microscopy (STM) is intrinsically limited to the extent of molecular orbitals, which frequently do not differ for small changes in the molecular conformation. Here we use the position of water molecules during the first hydration steps of an azobenzene derivative on Au(111) to determine not only the orientation of the end groups with respect to the phenyl rings but also the orientation of the two phenyl rings with respect to the azo group. We investigate the co-adsorption of 4,4'-hydroxy-azobenzene and water molecules on Au(111) by low-temperature STM. The water molecules are attached exclusively to the hydroxyl end groups of the azobenzene derivatives. Predominantly the trans-azobenzene molecule with the two hydroxyl groups pointing into opposite directions is adsorbed. As corroborated by the attachment of a single water molecule to 4-anilino-4'-nitro azobenzene on the same inert surface, the method is generally applicable for structure determination of molecules with appropriate end groups. Our study thus gives unprecedented information about the intramolecular orientation based on the first real space observation of the hydration of a functional molecule. PMID:25180814

Henzl, Jörg; Boom, Konrad; Morgenstern, Karina

2014-09-24

69

The Role of Damage-Associated Molecular Patterns in Human Diseases  

PubMed Central

There is increasing interest by physicians in the impact of the innate immune system on human diseases. In particular, the role of the molecules that initiate and amplify innate immune pathways, namely damage-associated molecular patterns (DAMPs), is of interest as these molecules are involved in the pathogenesis of many human disorders. The first part of this review identifies five classes of cell stress/tissue injury-induced DAMPs that are sensed by various recognition receptor-bearing cells of the innate immune system, thereby mounting inflammation, promoting apoptosis and shaping adaptive immune responses. The DAMPs activate and orchestrate several innate immune machineries, including inflammasomes and the unfolded protein response that synergistically operates to induce inflammatory, metabolic and adaptive immune pathologies. Two examples of autoimmune diseases are discussed as they represent a typical paradigm of the intimate interplay between innate and adaptive immune responses.

Land, Walter G.

2015-01-01

70

Molecular beam study of the scattering behavior of water molecules from a graphite surface.  

PubMed

Gas flow in nanospaces is greatly affected by the scattering behavior of gas molecules on solid surfaces, resulting in unique mass transport properties. In this paper, the molecular beam scattering experiment of water molecules on a graphite surface was conducted to understand their scattering dynamics in an incident energy range that corresponds to their thermal velocity distribution at room temperature (35-130 meV). Because of the large adsorption energy (?100 meV), the scattering behavior is quite sensitive to the incident energy even within this narrow energy range. For relatively large incident energies, the direct-inelastic and trapping-desorption channels have comparable contributions to the scattering process on the surface at 300 K. In contrast, when the incident energy decreases well below the adsorption energy on the surface, the trapping-desorption channel becomes dominant, changing the scattering pattern from directional to diffusive scattering. As a result, the tangential momentum accommodation coefficient (TMAC), which significantly impacts the mass transport in nanospaces, largely depends on the incident energy. A decrease in the incident energy from 130 to 35 meV doubles the TMAC (0.42 to 0.86). In addition to the incident energy, the TMAC shows a strong dependence on the surface temperature. With increasing the surface temperature from 300 to 500 K, the scattering becomes more directional because of the increasing contribution of the direct-inelastic channel, which reduces the TMAC for the incident beam energy of 35 meV to 0.48. PMID:24901371

Miyoshi, Nobuya; Osuka, Kenichi; Kinefuchi, Ikuya; Takagi, Shu; Matsumoto, Yoichiro

2014-07-01

71

Molecular dynamics simulation study of the ejection of polymer molecules and generation of molecular balloons in matrix-assisted  

E-print Network

of molecular balloons in matrix-assisted pulsed laser evaporation Leonid V. Zhigilei*, Elodie Leveugle, Aaron by the Matrix-Assisted Pulsed Laser Evaporation (MAPLE) technique. The simulations of MAPLE are performed for polymer concentrations up to 6 wt.% and a broad range of laser fluences. The polymer molecules are found

Zhigilei, Leonid V.

72

Millimeter-Wave Spectroscopic and Collisional Studies of Molecules and Molecular Ions  

NASA Astrophysics Data System (ADS)

Molecular spectroscopy in the millimeter- and submillimeter-wave regions is an important tool in molecular physics. Information on molecular motions and interactions is obtained from spectroscopic studies of energy levels and collisions. This information and the data from which it is derived are essential in remote sensing of the atmosphere and the interstellar medium. Remote sensing at submillimeter wavelengths is now possible, making higher frequency and quantum number measurements of known interstellar species like water, propionitrile and ethyl alcohol necessary. Remote sensing improvements have also facilitated the need for spectral data on suspected interstellar molecules like propylene. The desire to extract quantitative information from atmospheric remote sensing has resulted in the need for a better understanding of the molecular interactions that cause pressure broadening. The use of a cold molecular ion to magnify the effects of intermolecular interactions has serious implications for pressure broadening theory. The measurement and analysis of rotational spectra of the asymmetric rotors water and propionitrile and the internal rotors propylene and ethyl alcohol are presented. These investigations provide the data and analysis necessary for astronomical observation. The ethyl alcohol investigation is the first experimental millimeter-wave study of a molecule with an asymmetric internal rotor. This study provides the data necessary for detailed theoretical modeling of this type of problem. A novel new experimental technique for generating and studying molecular ions is presented. The first temperature dependent microwave pressure broadening study of a molecular ion colliding with a neutral molecule, HCO^{+} on H_2 , is presented.

Pearson, John Christoffersen

1995-01-01

73

A quantum mechanical/molecular mechanical approach to the investigation of particle-molecule interactions  

NASA Astrophysics Data System (ADS)

A quantum mechanical/molecular mechanical aerosol model is developed to describe the interaction between gas phase molecules and atmospheric particles. The model enables the calculation of interaction energies and time-dependent properties. We use the model to investigate how a succinic acid molecule interacts with an aqueous particle. We show how the interaction energies and linear response properties (excitation energies, transition moments, and polarizabilities) depend on the distance between aerosol particle and molecule and on their relative orientation. The results are compared with those obtained previously using a dielectric continuum model [Sloth et al., J. Phys. Chem. (submitted)].

Sloth, Marianne; Bilde, Merete; Mikkelsen, Kurt V.

2003-06-01

74

Molecular level studies on binding modes of labeling molecules with polyalanine peptides  

NASA Astrophysics Data System (ADS)

In this work, the binding modes of typical labeling molecules (thioflavin T (ThT), Congo red (CR) and copper(ii) phthalocyanine tetrasulfonic acid tetrasodium salt (PcCu(SO3Na)4)) on pentaalanine, which is a model peptide segment of amyloid peptides, have been resolved at the molecular level by using scanning tunneling microscopy (STM). In the STM images, ThT molecules are predominantly adsorbed parallel to the peptide strands and two binding modes could be identified. It was found that ThT molecules are preferentially binding on top of the peptide strand, and the mode of intercalated between neighboring peptides also exists. The parallel binding mode of CR molecules can be observed with pentaalanine peptides. Besides the binding modes of labeling molecules, the CR and PcCu(SO3Na)4 display different adsorption affinity with the pentaalanine peptides. The results could be beneficial for obtaining molecular level insight of the interactions between labeling molecules and peptides.In this work, the binding modes of typical labeling molecules (thioflavin T (ThT), Congo red (CR) and copper(ii) phthalocyanine tetrasulfonic acid tetrasodium salt (PcCu(SO3Na)4)) on pentaalanine, which is a model peptide segment of amyloid peptides, have been resolved at the molecular level by using scanning tunneling microscopy (STM). In the STM images, ThT molecules are predominantly adsorbed parallel to the peptide strands and two binding modes could be identified. It was found that ThT molecules are preferentially binding on top of the peptide strand, and the mode of intercalated between neighboring peptides also exists. The parallel binding mode of CR molecules can be observed with pentaalanine peptides. Besides the binding modes of labeling molecules, the CR and PcCu(SO3Na)4 display different adsorption affinity with the pentaalanine peptides. The results could be beneficial for obtaining molecular level insight of the interactions between labeling molecules and peptides. Electronic supplementary information (ESI) available. See DOI: 10.1039/c0nr00782j

Mao, Xiaobo; Wang, Chenxuan; Ma, Xiaojing; Zhang, Min; Liu, Lei; Zhang, Lan; Niu, Lin; Zeng, Qindao; Yang, Yanlian; Wang, Chen

2011-04-01

75

Carbon Nanotube Biosensors for Space Molecule Detection and Clinical Molecular Diagnostics  

NASA Technical Reports Server (NTRS)

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.

Han, Jie

2001-01-01

76

Binding at molecule/gold transport interfaces. V. Comparison of different metals and molecular bridges  

NASA Astrophysics Data System (ADS)

The geometric and electronic structural properties of symmetric and asymmetric metal cluster-molecule-cluster' complexes have been explored. The metals include Au, Ag, Pd, and Al, and both benzenedithiol and the three isometric forms of dicyanobenzene are included as bridging molecules. Calculated properties such as cluster-molecule interface geometry, electronic state, degree of metal ? molecule charge transfer, metal-molecule mixing in the highest occupied molecular orbital-lowest unoccupied molecular orbital (HOMO-LUMO) energy region, the HOMO-LUMO gap, cluster ? cluster' charge transfer as a function of external field strength and direction, and the form of the potential profile across such complexes have been examined. Attempts are made to correlate charge transport with the characteristics of the cluster-complex systems. Indications of rectification in complexes that are asymmetric in the molecule, clusters, and molecule-cluster interfaces are discussed. The results obtained here are only suggestive because of the limitations of the cluster-complex model as it relates to charge transport.

Basch, Harold; Ratner, Mark A.

2005-12-01

77

Binding at molecule/gold transport interfaces. V. Comparison of different metals and molecular bridges.  

PubMed

The geometric and electronic structural properties of symmetric and asymmetric metal cluster-molecule-cluster' complexes have been explored. The metals include Au, Ag, Pd, and Al, and both benzenedithiol and the three isometric forms of dicyanobenzene are included as bridging molecules. Calculated properties such as cluster-molecule interface geometry, electronic state, degree of metal --> molecule charge transfer, metal-molecule mixing in the highest occupied molecular orbital-lowest unoccupied molecular orbital (HOMO-LUMO) energy region, the HOMO-LUMO gap, cluster --> cluster' charge transfer as a function of external field strength and direction, and the form of the potential profile across such complexes have been examined. Attempts are made to correlate charge transport with the characteristics of the cluster-complex systems. Indications of rectification in complexes that are asymmetric in the molecule, clusters, and molecule-cluster interfaces are discussed. The results obtained here are only suggestive because of the limitations of the cluster-complex model as it relates to charge transport. PMID:16392941

Basch, Harold; Ratner, Mark A

2005-12-15

78

Fabrication of a highly oriented line structure on an aluminum surface and the nanoscale patterning on the nanoscale structure using highly functional molecules  

SciTech Connect

The surface of an Al plate was treated with a combination of chemical and electrochemical processes for fabrication of surface nanoscale structures on Al plates. Chemical treatments by using acetone and pure water under supersonic waves were conducted on an Al surface. Additional electrochemical process in H{sub 2}SO{sub 4} solution created a finer and oriented nanoscale structure on the Al surface. Dynamic force microscopy (DFM) measurement clarified that the nanoscale highly oriented line structure was successfully created on the Al surface. The line distance was estimated approximately 30-40 nm. At the next stage, molecular patterning on the highly oriented line structure by functional molecules such as copper phthalocyanine (CuPc) and fullerene C{sub 60} was also conducted. CuPc or C{sub 60} molecules were deposited on the highly oriented line structure on Al. A toluene droplet containing CuPc molecules was cast on the nanostructured Al plate and was extended on the surface. CuPc or C{sub 60} deposition on the nanostructured Al surface proceeded by evaporation of toluene. DFM and x-ray photoemission spectroscopy measurements demonstrated that a unique molecular pattern was fabricated so that the highly oriented groove channels were filled with the functional molecules.

Watanabe, Y.; Kato, H.; Takemura, S.; Watanabe, H.; Hayakawa, K.; Kimura, S.; Okumura, D.; Sugiyama, T.; Hiramatsu, T.; Nanba, N.; Nishikawa, O.; Taniguchi, M. [Department of Electrical, Electronic and Information Engineering, College of Engineering, Kanto Gakuin University, 1-50-1 Mutsuurahigashi, Kanazawa-ku, Yokohama 236-8501 (Japan); Department of Biology and Chemistry, Kanazawa Institute of Technology, 7-1 Ohgigaoka, Nonoichi, Ishikawa 921-8501 (Japan)

2009-07-15

79

Molecular models for the smectic A smectic C phase transition in a system of biaxial molecules  

NASA Astrophysics Data System (ADS)

A molecular theory of the smectic A-smectic C transition in a system of biaxial molecules is developed in the mean-field approximation. The influence of molecular biaxiality on the transition is considered in detail and it is demonstrated how the biaxial order parameters are induced by the tilt. It is shown that the ordering of biaxial molecules of low symmetry in the smectic C phase is generally described by ten independent orientational order parameters, and there exist three different tilt angles which specify the tilt of three ordering tensors. The order parameters are calculated numerically as functions of temperature for two models of biaxial molecules: molecules with two principal axes and molecules with a pair of off-center transverse dipoles. A substantial difference between the three tilt angles is found, which makes impossible a strict definition of a unique director in the smectic C phase. It is also shown that biaxial interactions may lead to an anomalously weak layer contraction in the smectic C phase. Finally, it is demonstrated that the smectic A-smectic C phase transition may be directly driven by biaxial intermolecular interactions. In this case, the tilt of long molecular axes is not a primary order parameter, and its temperature dependence is very different from convention.

Gorkunov, Maxim V.; Osipov, Mikhail A.

2008-07-01

80

The use of chlorobenzene as a probe molecule in molecular dynamics simulations.  

PubMed

We map ligand binding sites on protein surfaces in molecular dynamics simulations using chlorobenzene as a probe molecule. The method was validated on four proteins. Two types of affinity maps that identified halogen and hydrophobic binding sites on proteins were obtained. Our method could prove useful for the discovery and development of halogenated inhibitors. PMID:24910248

Tan, Yaw Sing; Spring, David R; Abell, Chris; Verma, Chandra

2014-07-28

81

Hydration shells of molecules in molecular association: A mechanism for biomolecular recognition  

PubMed Central

It has become clear that water should not be treated as an inert environment, but rather as an integral and active component of molecules. Here, we consider molecules and their hydration shells together as single entities. We show that: (1) the rate of association of molecules should be determined by the energetic barriers arising from interactions between their hydration shells; (2) replacing non-polar atoms of molecular surfaces with polar atoms increases these barriers; (3) reduction of the hydration shells during molecular association is the driving force for association not only of non-polar, but of polar molecules as well; (4) in most cases the dehydration of polar atoms during molecular association thermodynamically counteracts association; (5) on balance the thermodynamic stability of associated complexes is basically determined by the action of these two opposing factors: reduction of the hydration shells and dehydration of polar atoms; (6) molecular crowding reduces the energetic barriers counteracting association and changes the thermodynamic stability of associated complexes. These results lead to a mechanism for biomolecular recognition in the context of which the formation of unique structures is provided by rapidly forming kinetic traps with a biologically necessary lifetime but with a marginal thermodynamic stability. The mechanism gives definitive answers to questions concerning the heart of specific interactions between biomolecules, their folding and intracellular organization. Predictions are given that can be subjected to direct experimental tests. PMID:22365908

Lim, Valery I.; Curran, James F.; Garber, Maria B.

2013-01-01

82

Resonance enhanced multiphoton ionization spectra of molecules and molecular fragments. Technical report, January 1990--December 1990  

SciTech Connect

The objective of our effort is to carry out theoretical studies of resonance enhanced multiphoton ionization processes in molecules and molecular fragments. These studies are designed to provide a quantitatively robust analysis and prediction of key spectral features of interest in several ongoing experimental studies and applications of this technique.

NONE

1997-07-01

83

Ultra high resolution molecular beam cars spectroscopy with application to planetary atmospheric molecules  

NASA Technical Reports Server (NTRS)

The measurement of high resolution pulsed and continuous wave (CW) coherent anti-Stokes Raman spectroscopy (CARS) measurements in pulsed and steady state supersonic expansions were demonstrated. Pulsed molecular beam sources were characterized, and saturation of a Raman transition and, for the first time, the Raman spectrum of a complex molecular cluster were observed. The observation of CW CARS spectra in a molecular expansion and the effects of transit time broadening is described. Supersonic expansion is established as a viable technique for high resolution Raman spectroscopy of cold molecules with resolutions of 100 MH2.

Byer, R. L.

1982-01-01

84

Single-molecule chemical reaction reveals molecular reaction kinetics and dynamics.  

PubMed

Understanding the microscopic elementary process of chemical reactions, especially in condensed phase, is highly desirable for improvement of efficiencies in industrial chemical processes. Here we show an approach to gaining new insights into elementary reactions in condensed phase by combining quantum chemical calculations with a single-molecule analysis. Elementary chemical reactions in liquid-phase, revealed from quantum chemical calculations, are studied by tracking the fluorescence of single dye molecules undergoing a reversible redox process. Statistical analyses of single-molecule trajectories reveal molecular reaction kinetics and dynamics of elementary reactions. The reactivity dynamic fluctuations of single molecules are evidenced and probably arise from either or both of the low-frequency approach of the molecule to the internal surface of the SiO2 nanosphere or the molecule diffusion-induced memory effect. This new approach could be applied to other chemical reactions in liquid phase to gain more insight into their molecular reaction kinetics and the dynamics of elementary steps. PMID:24963600

Zhang, Yuwei; Song, Ping; Fu, Qiang; Ruan, Mingbo; Xu, Weilin

2014-01-01

85

Molecular Threading: Mechanical Extraction, Stretching and Placement of DNA Molecules from a Liquid-Air Interface  

PubMed Central

We present “molecular threading”, a surface independent tip-based method for stretching and depositing single and double-stranded DNA molecules. DNA is stretched into air at a liquid-air interface, and can be subsequently deposited onto a dry substrate isolated from solution. The design of an apparatus used for molecular threading is presented, and fluorescence and electron microscopies are used to characterize the angular distribution, straightness, and reproducibility of stretched DNA deposited in arrays onto elastomeric surfaces and thin membranes. Molecular threading demonstrates high straightness and uniformity over length scales from nanometers to micrometers, and represents an alternative to existing DNA deposition and linearization methods. These results point towards scalable and high-throughput precision manipulation of single-molecule polymers. PMID:23935923

Kemmish, Kent; Hamalainen, Mark; Bowell, Charlotte; Bleloch, Andrew; Klejwa, Nathan; Lehrach, Wolfgang; Schatz, Ken; Stark, Heather; Marblestone, Adam; Church, George; Own, Christopher S.; Andregg, William

2013-01-01

86

Molecular Nanoshearing: An Innovative Approach to Shear off Molecules with AC-Induced Nanoscopic Fluid Flow  

PubMed Central

Early diagnosis of disease requires highly specific measurement of molecular biomarkers from femto to pico-molar concentrations in complex biological (e.g., serum, blood, etc.) samples to provide clinically useful information. While reaching this detection limit is challenging in itself, these samples contain numerous other non-target molecules, most of which have a tendency to adhere to solid surfaces via nonspecific interactions. Herein, we present an entirely new methodology to physically displace nonspecifically bound molecules from solid surfaces by utilizing a newly discovered “tuneable force”, induced by an applied alternating electric field, which occurs within few nanometers of an electrode surface. This methodology thus offers a unique ability to shear-off loosely bound molecules from the solid/liquid interface. Via this approach, we achieved a 5-fold reduction in nonspecific adsorption of non-target protein molecules and a 1000-fold enhancement for the specific capture of HER2 protein in human serum. PMID:24430114

Shiddiky, Muhammad J. A.; Vaidyanathan, Ramanathan; Rauf, Sakandar; Tay, Zhikai; Trau, Matt

2014-01-01

87

Molecular Nanoshearing: An Innovative Approach to Shear off Molecules with AC-Induced Nanoscopic Fluid Flow  

NASA Astrophysics Data System (ADS)

Early diagnosis of disease requires highly specific measurement of molecular biomarkers from femto to pico-molar concentrations in complex biological (e.g., serum, blood, etc.) samples to provide clinically useful information. While reaching this detection limit is challenging in itself, these samples contain numerous other non-target molecules, most of which have a tendency to adhere to solid surfaces via nonspecific interactions. Herein, we present an entirely new methodology to physically displace nonspecifically bound molecules from solid surfaces by utilizing a newly discovered ``tuneable force'', induced by an applied alternating electric field, which occurs within few nanometers of an electrode surface. This methodology thus offers a unique ability to shear-off loosely bound molecules from the solid/liquid interface. Via this approach, we achieved a 5-fold reduction in nonspecific adsorption of non-target protein molecules and a 1000-fold enhancement for the specific capture of HER2 protein in human serum.

Shiddiky, Muhammad J. A.; Vaidyanathan, Ramanathan; Rauf, Sakandar; Tay, Zhikai; Trau, Matt

2014-01-01

88

Molecular release from patterned nanoporous gold thin films  

NASA Astrophysics Data System (ADS)

Nanostructured materials have shown significant potential for biomedical applications that require high loading capacity and controlled release of drugs. Nanoporous gold (np-Au), produced by an alloy corrosion process, is a promising novel material that benefits from compatibility with microfabrication, tunable pore morphology, electrical conductivity, well-established gold-thiol conjugate chemistry, and biocompatibility. While np-Au's non-biological applications are abundant, its performance in the biomedical field is nascent. In this work, we employ a combination of techniques including nanoporous thin film synthesis, quantitative electron microscopy, fluorospectrometry, and electrochemical surface characterization to study loading capacity and molecular release kinetics as a function of film properties and discuss underlying mechanisms. The sub-micron-thick sputter-coated nanoporous gold films provide small-molecule loading capacities up to 1.12 ?g cm-2 and molecular release half-lives between 3.6 hours to 12.8 hours. A systematic set of studies reveals that effective surface area of the np-Au thin films on glass substrates plays the largest role in determining loading capacity. The release kinetics on the other hand depends on a complex interplay of micro- and nano-scale morphological features.Nanostructured materials have shown significant potential for biomedical applications that require high loading capacity and controlled release of drugs. Nanoporous gold (np-Au), produced by an alloy corrosion process, is a promising novel material that benefits from compatibility with microfabrication, tunable pore morphology, electrical conductivity, well-established gold-thiol conjugate chemistry, and biocompatibility. While np-Au's non-biological applications are abundant, its performance in the biomedical field is nascent. In this work, we employ a combination of techniques including nanoporous thin film synthesis, quantitative electron microscopy, fluorospectrometry, and electrochemical surface characterization to study loading capacity and molecular release kinetics as a function of film properties and discuss underlying mechanisms. The sub-micron-thick sputter-coated nanoporous gold films provide small-molecule loading capacities up to 1.12 ?g cm-2 and molecular release half-lives between 3.6 hours to 12.8 hours. A systematic set of studies reveals that effective surface area of the np-Au thin films on glass substrates plays the largest role in determining loading capacity. The release kinetics on the other hand depends on a complex interplay of micro- and nano-scale morphological features. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr01288g

Kurtulus, Ozge; Daggumati, Pallavi; Seker, Erkin

2014-05-01

89

Distribution patterns of small-molecule ligands in the protein universe and implications for origin of life and drug discovery  

PubMed Central

Background Extant life depends greatly on the binding of small molecules (such as ligands) with macromolecules (such as proteins), and one ligand can bind multiple proteins. However, little is known about the global patterns of ligand-protein mapping. Results By examining 2,186 well-defined small-molecule ligands and thousands of protein domains derived from a database of druggable binding sites, we show that a few ligands bind tens of protein domains or folds, whereas most ligands bind only one, which indicates that ligand-protein mapping follows a power law. Through assigning the protein-binding orders (early or late) for bio-ligands, we demonstrate that the preferential attachment principle still holds for the power-law relation between ligands and proteins. We also found that polar molecular surface area, H-bond acceptor counts, H-bond donor counts and partition coefficient are potential factors to discriminate ligands from ordinary molecules and to differentiate super ligands (shared by three or more folds) from others. Conclusion These findings have significant implications for evolution and drug discovery. First, the chronology of ligand-protein binding can be inferred by the power-law feature of ligand-protein mapping. Some nucleotide-containing ligands, such as ATP, ADP, GDP, NAD, FAD, dihydro-nicotinamide-adenine-dinucleotide phosphate (NDP), nicotinamide-adenine-dinucleotide phosphate (NAP), flavin mononucleotide (FMN) and AMP, are found to be the earliest cofactors bound to proteins, agreeing with the current understanding of evolutionary history. Second, the finding that about 30% of ligands are shared by two or more domains will help with drug discovery, such as in finding new functions from old drugs, developing promiscuous drugs and depending more on natural products. PMID:17727706

Ji, Hong-Fang; Kong, De-Xin; Shen, Liang; Chen, Ling-Ling; Ma, Bin-Guang; Zhang, Hong-Yu

2007-01-01

90

Identifying Molecular Dynamics in Single-Molecule FRET Experiments with Burst Variance Analysis  

PubMed Central

Histograms of single-molecule Förster resonance energy transfer (FRET) efficiency are often used to study the structures of biomolecules and relate these structures to function. Methods like probability distribution analysis analyze FRET histograms to detect heterogeneities in molecular structure, but they cannot determine whether this heterogeneity arises from dynamic processes or from the coexistence of several static structures. To this end, we introduce burst variance analysis (BVA), a method that detects dynamics by comparing the standard deviation of FRET from individual molecules over time to that expected from theory. Both simulations and experiments on DNA hairpins show that BVA can distinguish between static and dynamic sources of heterogeneity in single-molecule FRET histograms and can test models of dynamics against the observed standard deviation information. Using BVA, we analyzed the fingers-closing transition in the Klenow fragment of Escherichia coli DNA polymerase I and identified substantial dynamics in polymerase complexes formed prior to nucleotide incorporation; these dynamics may be important for the fidelity of DNA synthesis. We expect BVA to be broadly applicable to single-molecule FRET studies of molecular structure and to complement approaches such as probability distribution analysis and fluorescence correlation spectroscopy in studying molecular dynamics. PMID:21402040

Torella, Joseph P.; Holden, Seamus J.; Santoso, Yusdi; Hohlbein, Johannes; Kapanidis, Achillefs N.

2011-01-01

91

Theoretical Study of Donor - Spacer - Acceptor Structure Molecule for Molecular Rectifier  

NASA Astrophysics Data System (ADS)

Recently, the molecular electronics has attracted strong attention as a ``post-silicone technology'' to establish a future nanoscale electronic devices. To realize this molecular device, unimolecular rectifiering function is one of the most important constituents in nanotechnology [C. Majumder, H. Mizuseki, and Y. Kawazoe, Molecular Scale Rectifier: Theoretical Study, J. Phys. Chem. A, 105 (2001) 9454-9459.]. In the present study, the geometric and electronic structure of alkyl derivative C37H50N4O4 (PNX) molecule, (donor - spacer - acceptor), a leading candidate of molecular rectifying device, has been investigated theoretically using ab initio quantum mechanical calculation. The results suggest that in such donor-acceptor molecular complexes, while the lowest unoccupied orbital concentrates on the acceptor subunit, the highest occupied molecular orbital is localized on the donor subunit. The approximate potential differences for optimized PNX molecule have been estimated at the B3PW91/6-311g++(d,p) level of theory, which achieves quite good agreement with experimentally reported results. This study was performed through Special Coordination Funds for Promoting Science and Technology of the Ministry of Education, Culture, Sports, Science and Technology of the Japanese Government.

Mizuseki, Hiroshi; Kenji, Niimura; Belosludov, Rodion; Farajian, Amir; Kawazoe, Yoshiyuki

2003-03-01

92

Molecular release from patterned nanoporous gold thin films.  

PubMed

Nanostructured materials have shown significant potential for biomedical applications that require high loading capacity and controlled release of drugs. Nanoporous gold (np-Au), produced by an alloy corrosion process, is a promising novel material that benefits from compatibility with microfabrication, tunable pore morphology, electrical conductivity, well-established gold-thiol conjugate chemistry, and biocompatibility. While np-Au's non-biological applications are abundant, its performance in the biomedical field is nascent. In this work, we employ a combination of techniques including nanoporous thin film synthesis, quantitative electron microscopy, fluorospectrometry, and electrochemical surface characterization to study loading capacity and molecular release kinetics as a function of film properties and discuss underlying mechanisms. The sub-micron-thick sputter-coated nanoporous gold films provide small-molecule loading capacities up to 1.12 ?g cm(-2) and molecular release half-lives between 3.6 hours to 12.8 hours. A systematic set of studies reveals that effective surface area of the np-Au thin films on glass substrates plays the largest role in determining loading capacity. The release kinetics on the other hand depends on a complex interplay of micro- and nano-scale morphological features. PMID:24842586

Kurtulus, Ozge; Daggumati, Pallavi; Seker, Erkin

2014-06-21

93

Molecular Dynamics Simulation of Multivalent-Ion Mediated Attraction between DNA Molecules  

NASA Astrophysics Data System (ADS)

All atom molecular dynamics simulations with explicit water were done to study the interaction between two parallel double-stranded DNA molecules in the presence of the multivalent counterions putrescine (2+), spermidine (3+), spermine (4+) and cobalt hexamine (3+). The inter-DNA interaction potential is obtained with the umbrella sampling technique. The attractive force is rationalized in terms of the formation of ion bridges, i.e., multivalent ions which are simultaneously bound to the two opposing DNA molecules. The lifetime of the ion bridges is short on the order of a few nanoseconds.

Dai, Liang; Mu, Yuguang; Nordenskiöld, Lars; van der Maarel, Johan R. C.

2008-03-01

94

Microfluidic parallel patterning and cellular delivery of molecules with a nanofountain probe.  

PubMed

This brief report describes a novel tool for microfluidic patterning of biomolecules and delivery of molecules into cells. The microdevice is based on integration of nanofountain probe (NFP) chips with packaging that creates a closed system and enables operation in liquid. The packaged NFP can be easily coupled to a micro/nano manipulator or atomic force microscope for precise position and force control. We demonstrate here the functionality of the device for continuous direct-write parallel patterning on a surface in air and in liquid. Because of the small volume of the probes (~3 pL), we can achieve flow rates as low as 1 fL/s and have dispensed liquid drops with submicron to 10 µm diameters in a liquid environment. Furthermore, we demonstrate that this microdevice can be used for delivery of molecules into single cells by transient permeabilization of the cell membrane (i.e., electroporation). The significant advantage of NFP-based electroporation compared with bulk electroporation and other transfection techniques is that it allows for precise and targeted delivery while minimizing stress to the cell. We discuss the ongoing development of the tool toward automated operation and its potential as a multifunctional device for microarray applications and time-dependent single-cell studies. PMID:23897012

Kang, Wonmo; McNaughton, Rebecca L; Yavari, Fazel; Minary-Jolandan, Majid; Safi, Asmahan; Espinosa, Horacio D

2014-02-01

95

Proton Fingerprints Portray Molecular Structures: Enhanced Description of the 1H NMR Spectra of Small Molecules  

PubMed Central

The characteristic signals observed in NMR spectra encode essential information on the structure of small molecules. However, extracting all of this information from complex signal patterns is not trivial. This report demonstrates how computer-aided spectral analysis enables the complete interpretation of 1D 1H NMR data. The effectiveness of this approach is illustrated with a set of organic molecules, for which replicas of their 1H NMR spectra were generated. The potential impact of this methodology on organic chemistry research is discussed. PMID:24007197

Napolitano, José G.; Lankin, David C.; McAlpine, James B.; Niemitz, Matthias; Korhonen, Samuli-Petrus; Chen, Shao-Nong; Pauli, Guido F.

2013-01-01

96

Tungsten polyoxometalate molecules as active nodes for dynamic carrier exchange in hybrid molecular/semiconductor capacitors  

SciTech Connect

In this work we study the utilization of molecular transition metal oxides known as polyoxometalates (POMs), in particular the Keggin structure anions of the formula PW{sub 12}O{sub 40}{sup 3?}, as active nodes for potential switching and/or fast writing memory applications. The active molecules are being integrated in hybrid Metal-Insulator/POM molecules-Semiconductor capacitors, which serve as prototypes allowing investigation of critical performance characteristics towards the design of more sophisticated devices. The charging ability as well as the electronic structure of the molecular layer is probed by means of electrical characterization, namely, capacitance-voltage and current-voltage measurements, as well as transient capacitance measurements, C (t), under step voltage polarization. It is argued that the transient current peaks observed are manifestations of dynamic carrier exchange between the gate electrode and specific molecular levels, while the transient C (t) curves under conditions of molecular charging can supply information for the rate of change of the charge that is being trapped and de-trapped within the molecular layer. Structural characterization via surface and cross sectional scanning electron microscopy as well as atomic force microscopy, spectroscopic ellipsometry, UV and Fourier-transform IR spectroscopies, UPS, and XPS contribute to the extraction of accurate electronic structure characteristics and open the path for the design of new devices with on-demand tuning of their interfacial properties via the controlled preparation of the POM layer.

Balliou, A., E-mail: aballiou@imel.demokritos.gr [Institute of Nanoscience and Nanotechnology, NCSR Demokritos, Aghia Paraskevi, Athens 15310 (Greece); Department of Chemical Engineering, NTUA, Zographou Campus, Athens 15773 (Greece); Douvas, A. M.; Normand, P.; Argitis, P.; Glezos, N. [Institute of Nanoscience and Nanotechnology, NCSR Demokritos, Aghia Paraskevi, Athens 15310 (Greece); Tsikritzis, D.; Kennou, S. [Department of Chemical Engineering, University of Patras, University Campus, Patras 26504 (Greece)

2014-10-14

97

Tungsten polyoxometalate molecules as active nodes for dynamic carrier exchange in hybrid molecular/semiconductor capacitors  

NASA Astrophysics Data System (ADS)

In this work we study the utilization of molecular transition metal oxides known as polyoxometalates (POMs), in particular the Keggin structure anions of the formula PW12O403-, as active nodes for potential switching and/or fast writing memory applications. The active molecules are being integrated in hybrid Metal-Insulator/POM molecules-Semiconductor capacitors, which serve as prototypes allowing investigation of critical performance characteristics towards the design of more sophisticated devices. The charging ability as well as the electronic structure of the molecular layer is probed by means of electrical characterization, namely, capacitance-voltage and current-voltage measurements, as well as transient capacitance measurements, C (t), under step voltage polarization. It is argued that the transient current peaks observed are manifestations of dynamic carrier exchange between the gate electrode and specific molecular levels, while the transient C (t) curves under conditions of molecular charging can supply information for the rate of change of the charge that is being trapped and de-trapped within the molecular layer. Structural characterization via surface and cross sectional scanning electron microscopy as well as atomic force microscopy, spectroscopic ellipsometry, UV and Fourier-transform IR spectroscopies, UPS, and XPS contribute to the extraction of accurate electronic structure characteristics and open the path for the design of new devices with on-demand tuning of their interfacial properties via the controlled preparation of the POM layer.

Balliou, A.; Douvas, A. M.; Normand, P.; Tsikritzis, D.; Kennou, S.; Argitis, P.; Glezos, N.

2014-10-01

98

Small molecules make big differences: molecular doping effects on electronic and optical properties of phosphorene.  

PubMed

Systematical computations on the density functional theory were performed to investigate the adsorption of three typical organic molecules, tetracyanoquinodimethane (TCNQ), tetracyanoethylene (TCNE) and tetrathiafulvalene (TTF), on the surface of phosphorene monolayers and thicker layers. There exist considerable charge transfer and strong non-covalent interaction between these molecules and phosphorene. In particular, the band gap of phosphorene decreases dramatically due to the molecular modification and can be further tuned by applying an external electric field. Meanwhile, surface molecular modification has proven to be an effective way to enhance the light harvesting of phosphorene in different directions. Our results predict a flexible method toward modulating the electronic and optical properties of phosphorene and shed light on its experimental applications. PMID:25665596

Jing, Yu; Tang, Qing; He, Peng; Zhou, Zhen; Shen, Panwen

2015-03-01

99

Implantation of Perylene Molecules into Glass Plates through a Water Layer Using a Laser Induced Molecular Micro-Jet  

NASA Astrophysics Data System (ADS)

Perylene molecules have been successfully implanted onto borosilicate glass plates, forming fluorescent features of 420 nm in diameter, using a method involving laser induced molecular micro-jet ejection through a water layer. The technique utilises a polymer source film in which perylene molecules are dispersed, a borosilicate glass substrate as a target and a pulsed laser. The space gap between the source film and the target is filled with liquid water. Perylene molecules dispersed in the polymer source films are photo-excited using 4-ns laser pulses resulting in the ejection of the molecules from the source matrix after which they become implanted into the target after passing through the water layer. This new advanced implantation method, using a laser induced molecular micro-jet through water, gives fine spatial control for fixing functional organic molecules in a designated region on hard dielectric materials and will have application in the fabrication of molecular devices, molecular sensors, and opto-electronics.

Goto, Masahiro; Pihosh, Yuriy; Kasahara, Akira; Tosa, Masahiro

2006-09-01

100

Single-molecule toroics in Ising-type lanthanide molecular clusters.  

PubMed

Single-molecule toroics (SMTs) are defined, by analogy with single-molecule magnets, as bistable molecules with a toroidal magnetic state, and seem to be most promising for future applications in quantum computing and information storage and use as multiferroic materials with magnetoelectric effect. As an interdisciplinary research area that spans chemistry, physics and material sciences, synthetic chemists have produced systems suitable for detailed study by physicists and materials scientists, while ab initio calculations have been playing a major role in the detection of toroidal magnetization and the advancement of this field. In this tutorial review, we demonstrate the research developed in the fascinating and challenging field of molecular-based SMTs with particular focus on how recent studies tend to address the issue of toroidal arrangement of the magnetic moment in these systems. Herein, nine typical SMTs are summarized, showing that the assembly of wheel-shaped complexes with the high symmetry of the molecule unit and strong intra-molecular dipolar interactions using strong anisotropy metal ions represents the most promising route toward the design of a toroidal moment. Furthermore, the linkage of such robust toroidal moment units with ferromagnetic type through appropriate bridging ligands enhances the toroidal magnetic moment per unit cell. PMID:24975197

Ungur, Liviu; Lin, Shuang-Yan; Tang, Jinkui; Chibotaru, Liviu F

2014-10-21

101

Solvation chemical shifts of perylenic antenna molecules from molecular dynamics simulations.  

PubMed

Solvation-induced shifts in molecular properties can be realistically simulated by employing a dynamic model with explicit solvent molecules. In this work, (13)C NMR chemical shifts of various candidate antenna molecules for dye-sensitised solar cells have been studied by using density-functional theory calculations both in vacuo and by employing a dynamic solvation model. The solvent effects were investigated using instantaneous molecular dynamics snapshots containing the antenna molecule and surrounding acetonitrile solvent molecules. Such calculations take into account the main mechanisms of solvation-induced chemical shifts. We have analysed the contributions to the solvent shift due to the solvent susceptibility anisotropy, changes in the density of the virtual orbital space and the accessibility of the excited states to the pronouncedly local magnetic hyperfine operator. We present Lorentzian-broadened chemical shift stick spectra in which a comparison of the in vacuo and dynamic-solvation model results is graphically illustrated. The results show that the solvent-accessible atoms at the perimeter of the solute are influenced by the virtual states of the solvent molecules, which are visible to the hyperfine operators of the perimeter nuclei. This enables efficient coupling of the ground state of the solute to the magnetically allowed excited states, resulting in a positive chemical shift contribution of the perimeter nuclei. As a result of solvation, the chemical shift signals of perimeter nuclei are found to be displaced towards larger chemical shift values, whereas the nuclei of the inner region of the solute molecules show the opposite trend. The solvent susceptibility anisotropy is found to cause a small and practically constant contribution. PMID:25222796

Özcan, Nergiz; Mareš, Ji?í; Sundholm, Dage; Vaara, Juha

2014-10-28

102

Molecular features determining different partitioning patterns of papain and bromelain in aqueous two-phase systems.  

PubMed

The partitioning patterns of papain (PAP) and bromelain (BR), two well-known cysteine-proteases, in polyethyleneglycol/sodium citrate aqueous two-phase systems (ATPSs) were determined. Polyethyleneglycols of different molecular weight (600, 1000, 2000, 4600 and 8000) were assayed. Thermodynamic characterization of partitioning process, spectroscopy measurements and computational calculations of protein surface properties were also carried out in order to explain their differential partitioning behavior. PAP was observed to be displaced to the salt-enriched phase in all the assayed systems with partition coefficients (KpPAP) values between 0.2 and 0.9, while BR exhibited a high affinity for the polymer phase in systems formed by PEGs of low molecular weight (600 and 1000) with partition coefficients (KpBR) values close to 3. KpBR values resulted higher than KpPAP in all the cases. This difference could be assigned neither to the charge nor to the size of the partitioned biomolecules since PAP and BR possess similar molecular weight (23,000) and isoelectric point (9.60). The presence of highly exposed tryptophans and positively charged residues (Lys, Arg and His) in BR molecule would be responsible for a charge transfer interaction between PEG and the protein and, therefore, the uneven distribution of BR in these systems. PMID:23831382

Rocha, Maria Victoria; Nerli, Bibiana Beatriz

2013-10-01

103

Building foundations for molecular electronics: Growth of organic molecules on alkali halides as prototypical insulating substrates  

NASA Astrophysics Data System (ADS)

The epitaxy and growth of a series of organic molecules deposited on insulating surfaces were investigated by noncontact atomic force microscopy (nc-AFM). The molecules studied, C60, 3,4,9,10-perylene tetracarboxylic dianhydride (PTCDA), 3,4,9,10-perylene tetracarboxlylic diimide (PTCDI), and copper (II) phthalocyanine (CuPc), were selected to investigate the effect of different molecular geometries, charge distributions and intermolecular interactions and as interesting candidates in molecular electronic applications. As it is known that the properties of molecules are influenced by their structural arrangements, an understanding of the interactions of molecules with substrates of interest as well as the dominant processes involved in growth are of great interest. Model insulating substrates KBr and NaCl were used for growth studies, due to the necessity of insulators in electrically isolating device regions. Dewetting processes were observed in several of these systems: C 60 on KBr and NaCl, PTCDA on NaCl and PTCDI on NaCl. The specific influences of de- wetting are discussed for each system, in particular the morphological impact of dewetting and the driving of dewetting by strained metastable monolayers. For C60 deposits, interesting branched structures are formed in the process of dewetting which are remarkably stable once formed, yet do not represent the equilibrium growth morphology. A determination of the large cell coincident epitaxy reveals a small, yet significant discrepancy between the observed overlayer and calculated stable adsorption sites indicating a dominance of the intermolecular interaction over the molecule---substrate interaction. For both PTCDA and PTCDI on NaCl, strained metastable monolayer epitaxies were observed giving rise to a transition in both interface structure and morphology: a dewetting transition. A comparison of the observed molecular scale structures and growth modalities is made in order to build a framework for understanding the prevalence of dewetting for molecules on ionic surfaces. Finally, in order to better understand the connection between molecular scale structures and interesting opto-electronic properties, the application of a hybrid-electrostatic characterization technique by nc-AFM is discussed. Using this technique, the opto-electrostatic response of three different PTCDA arrangements on a nanotemplated NaCl surface are shown to differ according to the degree of intermolecular interaction permitted by the structure.

Burke, Sarah A.

104

Single-molecule study of molecular mobility in the cytoplasm of Escherichia coli  

NASA Astrophysics Data System (ADS)

The cytoplasm of bacterial cells is filled with individual molecules and molecular complexes that rely on diffusion to bring them together for interaction. The mobility of molecules in the cytoplasm has been characterized by several techniques mainly using fluorescent probes and ensemble methods. In order to probe the microenvrionment inside the cytoplasm as viewed by an individual molecule, we have studied single green fluorescent proteins (GFPs) diffusing in the cytoplasm of Escherichia coli cells at observation at rates ranging from 60 to 1000 Hz. Over long times the diffusion shows confinement due to the geometry of the cells themselves. A simulation in model cells using the actual distribution of cell sizes found in the experiments describes accurately the experimental results as well as reveals a short time diffusion coefficient that agrees well with that determined by ensemble methods. Higher short time diffusion coefficients can be obtained by filling the simulated cell with small spheres modeling cytoplasmic molecules and, depending on the density of particles included in the modeled cytoplasm, can approach the diffusion coefficient of GFPs found in water. Thus, single-molecule tracking combined with analysis using simple simulation of Brownian motion is able to reveal the main contributors to the GFP mobility in the cytoplasm of E. coli.

Lill, Yoriko; Kaserer, Wallace A.; Newton, Salete M.; Lill, Markus; Klebba, Phillip E.; Ritchie, Ken

2012-08-01

105

Exploring the aqueous vertical ionization of organic molecules by molecular simulation and liquid microjet photoelectron spectroscopy.  

PubMed

To study the influence of aqueous solvent on the electronic energy levels of dissolved organic molecules, we conducted liquid microjet photoelectron spectroscopy (PES) measurements of the aqueous vertical ionization energies (VIEaq) of aniline (7.49 eV), veratrole alcohol (7.68 eV), and imidazole (8.51 eV). We also reanalyzed previously reported experimental PES data for phenol, phenolate, thymidine, and protonated imidazolium cation. We then simulated PE spectra by means of QM/MM molecular dynamics and EOM-IP-CCSD calculations with effective fragment potentials, used to describe the aqueous vertical ionization energies for six molecules, including aniline, phenol, veratrole alcohol, imidazole, methoxybenzene, and dimethylsulfide. Experimental and computational data enable us to decompose the VIEaq into elementary processes. For neutral compounds, the shift in VIE upon solvation, ?VIEaq, was found to range from ?-0.5 to -0.91 eV. The ?VIEaq was further explained in terms of the influence of deforming the gas phase solute into its solution phase conformation, the influence of solute hydrogen-bond donor and acceptor interactions with proximate solvent molecules, and the polarization of about 3000 outerlying solvent molecules. Among the neutral compounds, variability in ?VIEaq appeared largely controlled by differences in solute-solvent hydrogen-bonding interactions. Detailed computational analysis of the flexible molecule veratrole alcohol reveals that the VIE is strongly dependent on molecular conformation in both gas and aqueous phases. Finally, aqueous reorganization energies of the oxidation half-cell ionization reaction were determined from experimental data or estimated from simulation for the six compounds aniline, phenol, phenolate, veratrole alcohol, dimethylsulfide, and methoxybenzene, revealing a surprising constancy of 2.06 to 2.35 eV. PMID:25516011

Tentscher, Peter R; Seidel, Robert; Winter, Bernd; Guerard, Jennifer J; Arey, J Samuel

2015-01-01

106

Extracellular matrix molecules exhibit unique expression pattern in the climbing fiber-generating precerebellar nucleus, the inferior olive.  

PubMed

Extracellular matrix (ECM) accumulates around different neuronal compartments of the central nervous system (CNS) or appears in diffuse reticular form throughout the neuropil. In the adult CNS, the perineuronal net (PNN) surrounds the perikarya and dendrites of various neuron types, whereas the axonal coats are aggregations of ECM around the individual synapses, and the nodal ECM is localized at the nodes of Ranvier. Previous studies in our laboratory demonstrated on rats that the heterogeneous distribution and molecular composition of ECM is associated with the variable cytoarchitecture and hodological organization of the vestibular nuclei and may also be related to their specific functions in gaze and posture control as well as in the compensatory mechanisms following vestibular lesion. Here, we investigated the ECM expression pattern in the climbing fiber-generating inferior olive (IO), which is functionally related to the vestibular nuclei. By using histochemical and immunohistochemical methods, the most characteristic finding was the lack of PNNs, presumably due to the absence of synapses on the perikarya and proximal dendrites of IO neurons. On the other hand, the darkly stained dots or ring-like structures in the neuropil might represent the periaxonal coats around the axon terminals of olivary synaptic glomeruli. We have observed positive ECM reaction for the hyaluronan, tenascin-R, hyaluronan and proteoglycan link protein 1 (HAPLN1) and various chondroitin sulfate proteoglycans. The staining intensity and distribution of ECM molecules revealed a number of differences between the functionally different subnuclei of IO. We hypothesized that the different molecular composition and intensity differences of ECM reaction is associated with different control mechanisms of gaze and posture control executed by the visuomotor-vestibular, somatosensory and integrative subnuclei of the IO. PMID:25445196

Kecskes, S; Gaál, B; Rácz, E; Birinyi, A; Hunyadi, A; Matesz, C

2015-01-22

107

Molecular dynamics simulations on aqueous two-phase systems - Single PEG-molecules in solution  

PubMed Central

Background Molecular Dynamics (MD) simulations are a promising tool to generate molecular understanding of processes related to the purification of proteins. Polyethylene glycols (PEG) of various length are commonly used in the production and purification of proteins. The molecular mechanisms behind PEG driven precipitation, aqueous two-phase formation or the effects of PEGylation are however still poorly understood. Results In this paper, we ran MD simulations of single PEG molecules of variable length in explicitly simulated water. The resulting structures are in good agreement with experimentally determined 3D structures of PEG. The increase in surface hydrophobicity of PEG of longer chain length could be explained on an atomic scale. PEG-water interactions as well as aqueous two-phase formation in the presence of PO4 were found to be correlated to PEG surface hydrophobicity. Conclusions We were able to show that the taken MD simulation approach is capable of generating both structural data as well as molecule descriptors in agreement with experimental data. Thus, we are confident of having a good in silico representation of PEG. PMID:22873343

2012-01-01

108

High-resolution single-molecule recognition imaging of the molecular details of ricin-aptamer interaction  

Technology Transfer Automated Retrieval System (TEKTRAN)

The molecular details of DNA aptamer-ricin interactions were investigated. The toxic protein ricin molecules were immobilized on Au(111) surface using N-hydroxysuccinimide (NHS) ester to specifically react with lysine residues located on the ricin B chains. A single ricin molecule was visualized in ...

109

Implantation of Perylene Molecules into Glass Plates through a Water Layer Using a Laser Induced Molecular MicroJet  

Microsoft Academic Search

Perylene molecules have been successfully implanted onto borosilicate glass plates, forming fluorescent features of 420 nm in diameter, using a method involving laser induced molecular micro-jet ejection through a water layer. The technique utilises a polymer source film in which perylene molecules are dispersed, a borosilicate glass substrate as a target and a pulsed laser. The space gap between the

Masahiro Goto; Yuriy Pihosh; Akira Kasahara; Masahiro Tosa

2006-01-01

110

Manipulating molecular quantum states with classical metal atom inputs: demonstration of a single molecule NOR logic gate.  

PubMed

Quantum states of a trinaphthylene molecule were manipulated by putting its naphthyl branches in contact with single Au atoms. One Au atom carries 1-bit of classical information input that is converted into quantum information throughout the molecule. The Au-trinaphthylene electronic interactions give rise to measurable energy shifts of the molecular electronic states demonstrating a NOR logic gate functionality. The NOR truth table of the single molecule logic gate was characterized by means of scanning tunnelling spectroscopy. PMID:21291281

Soe, We-Hyo; Manzano, Carlos; Renaud, Nicolas; de Mendoza, Paula; De Sarkar, Abir; Ample, Francisco; Hliwa, Mohamed; Echavarren, Antonio M; Chandrasekhar, Natarajan; Joachim, Christian

2011-02-22

111

Micron and submicron patterning of dicyanopyrazine-linked porphyrin molecules using micro-contact printing and Langmuir-Blodgett assembly.  

PubMed

We describe a method to conveniently fabricate micron- and submicron-sized patterns of well-ordered and densely-packed dicyanopyrazine-linked porphyrin (4-TDCPP) molecules by using micro-contact printing (micro-CP) in conjunction with Langmuir-Blodgett (LB) deposition. SEM and AFM images reveal that the sizes and shapes of the 4-TDCPP patterns are well-matched with the geometric features of the polydimethylsiloxane (PDMS) stamps used for micro-CP. Fluorescence images show strong, red emission from the 4-TDCPP patterns. However, the thicknesses of the 4-TDCPP patterns transferred onto a silicon substrate by micro-CP are not the same, even though the same amount of 4-TDCPP layers are deposited on the surface of PDMS stamps in the LB process. The thicknesses of the 10 microm line, 2 microm dot and 300 nm line patterns of 10-layered 4-TDCPP molecules are 34.6, 26.7 and 5.9 nm, respectively. These differences may be due to variations in adhesion forces between the silicon substrate and 4-TDCPP on PDMS stamps having different size patterns. Larger patterns have greater contact areas compared to smaller patterns. This phenomenon can cause stronger adhesion forces, resulting in greater pattern thickness. PMID:21137959

Cho, Jaepil; Ahn, Heejoon

2010-11-01

112

Mitochondrial damage-associated molecular patterns activate ?? T-cells.  

PubMed

Gamma delta T-cells have been shown to be important in the early immunoinflammatory response to injury, which can be independent of infection. This sterile inflammatory response is believed to be, in part, associated with danger-associated molecular patterns (DAMPs). Mitochondrial DAMPs (MTDs) have been shown to be important in trauma-induced neutrophil activation, but it is unknown whether MTDs activate other innate immune cells, such as ?? T-cells. To study this, splenic CD3(+) ?? T-cells were isolated from ?? T-cell-deficient C57BL/6 mice and mitochondria isolated from wild type mouse livers. MTDs were isolated from mitochondria by sonication and centrifugation. Gamma delta T-cells were incubated with various concentrations of MTDs (0-500?µg/ml) for 24?h. T-cells were phenotyped for TLR expression by flow cytometry and the supernatants assayed for cytokine and growth factor content. MTDs caused a dose-dependent increase in TLR2 and TLR4 expression by ?? T-cells. Both the percentage of cells positive for TLRs and the degree of expression increased. MTDs also induced the production of IL-1?, IL-6, IL-10, RANTES, fibroblast growth factor-basic and vascular endothelial growth factor by ?? T-cells. These findings support the concept that the MTDs released after tissue/cellular injury are capable of activating ?? T-cells, thus initiating sterile inflammation, as well as subsequent healing processes. PMID:23757324

Schwacha, Martin G; Rani, Meenakshi; Zhang, Qiong; Nunez-Cantu, Oliver; Cap, Andre P

2014-04-01

113

Small Molecule Activators of the Heat Shock Response: Chemical Properties, Molecular Targets, and Therapeutic Promise  

PubMed Central

All cells have developed various mechanisms to respond and adapt to a variety of environmental challenges, including stresses that damage cellular proteins. One such response, the heat shock response (HSR), leads to the transcriptional activation of a family of molecular chaperone proteins that promote proper folding or clearance of damaged proteins within the cytosol. In addition to its role in protection against acute insults, the HSR also regulates lifespan and protects against protein misfolding that is associated with degenerative diseases of aging. As a result, identifying pharmacological regulators of the HSR has become an active area of research in recent years. Here, we review progress made in identifying small molecule activators of the HSR, what cellular targets these compounds interact with to drive response activation, and how such molecules may ultimately be employed to delay or reverse protein misfolding events that contribute to a number of diseases. PMID:22799889

West, James D.; Wang, Yanyu; Morano, Kevin A.

2012-01-01

114

Molecular orbital tomography for adsorbed molecules: is a correct description of the final state really unimportant?  

NASA Astrophysics Data System (ADS)

The application of the ‘orbital tomography’ technique to obtain direct images of molecular orbitals of adsorbed molecules from angle-resolved photoemission data, first proposed by Puschnig et al (2009 Science 326 702), is an extremely attractive idea, but is based on the assumption that the photoemission can be described by a plane wave final state. It is well known that this neglect of the spherical-wave nature of the initial emission and of the role of final state scattering both within the molecule and from the substrate can lead to serious errors. Despite this, in the albeit simple systems studied so far the method appears to work reasonably well. Here we provide a detailed critique of this problem, highlight situations in which the orbital tomography approach is likely to lead to major errors, and propose test experiments that could provide clear information on the extent of these problems.

Bradshaw, A. M.; Woodruff, D. P.

2015-01-01

115

Molecular dynamics simulations of water molecule-bridges in polar domains of humic acids.  

PubMed

The stabilizing effect of water molecule bridges on polar regions in humic substances (HSs) has been investigated by means of molecular dynamics (MD) simulations. The purpose of these investigations was to show the effect of water molecular bridges (WAMB) for cross-linking distant locations of hydrophilic groups. For this purpose, a tetramer of undecanoid fatty acids connected to a network of water molecules has been constructed, which serve as a model for spatially fixed aliphatic chains in HSs terminated by a polar (carboxyl) group. The effect of environmental polarity has been investigated by using solvents of low and medium polarity in force-field MD. A nonpolar environment simulated by n-hexane was chosen to mimic the stability of WAMB in a hydrophilic hotspot surrounded by a nonpolar environment, while the more polar acetonitrile environment was chosen to simulate a more even distribution of polarity around the carboxylic groups and the water molecules. The dynamics simulations show that the rigidity of the oligomer chains is significantly enhanced as soon as the water cluster is large enough to comprise all four carboxyl groups. Increasing the temperature leads to evaporization processes which destabilize the rigidity of the tetramer-water cluster. Embedding it into the nonpolar environment introduces a pronounced cage effect which significantly impedes removal of water molecules from the cluster region. On the other hand, a polar environment facilitates their diffusion from the polar region. One important consequence of these simulations is that although the local water network is the stabilizing factor for the organic matter matrix, the degree of stabilization is additionally affected by the presence of nonpolar surroundings. PMID:21863811

Aquino, Adelia J A; Tunega, Daniel; Pasali?, Hasan; Schaumann, Gabriele E; Haberhauer, Georg; Gerzabek, Martin H; Lischka, Hans

2011-10-01

116

Circular dichroism in molecular-frame photoelectron angular distributions in the dissociative photoionization of H2 and D2 molecules  

NASA Astrophysics Data System (ADS)

The presence of net circular dichroism in the photoionization of nonchiral homonuclear molecules has been put in evidence recently through the measurement of molecular-frame photoelectron angular distributions in dissociative photoionization of H2 [Dowek et al., Phys. Rev. Lett. 104, 233003 (2010), 10.1103/PhysRevLett.104.233003]. In this work we present a detailed study of circular dichroism in the photoelectron angular distributions of H2 and D2 molecules, oriented perpendicularly to the propagation vector of the circularly polarized light, at different photon energies (20, 27, and 32.5 eV). Circular dichroism in the angular distributions at 20 and to a large extent 27 eV exhibits the usual pattern in which inversion symmetry is preserved. In contrast, at 32.5 eV, the inversion symmetry breaks down, which eventually leads to total circular dichroism after integration over the polar emission angle. Time-dependent ab initio calculations support and explain the observed results for H2 in terms of quantum interferences between direct photoionization and delayed autoionization from the Q1 and Q2 doubly excited states into ionic states (1 s ?g and 2 p ?u ) of different inversion symmetry. Nevertheless, for D2 at 32.5 eV, there is a particular case where theory and experiment disagree in the magnitude of the symmetry breaking: when D+ ions are produced with an energy of around 5 eV. This reflects the subleties associated to such simple molecules when exposed to this fine scrutiny.

Pérez-Torres, J. F.; Sanz-Vicario, J. L.; Veyrinas, K.; Billaud, P.; Picard, Y. J.; Elkharrat, C.; Poullain, S. Marggi; Saquet, N.; Lebech, M.; Houver, J. C.; Martín, F.; Dowek, D.

2014-10-01

117

Onset of Patterns in an Ocillated Granular Layer: Continuum and Molecular Dynamics Simulations  

E-print Network

Onset of Patterns in an Ocillated Granular Layer: Continuum and Molecular Dynamics Simulations J of continuum equations to Navier­Stokes order and molecular dynam­ ics (MD) simulations, we find that standing for ordered standing waves is approximately 10% higher in molecular dynamics simulations than in the continuum

Texas at Austin. University of

118

Onset of patterns in an oscillated granular layer: Continuum and molecular dynamics simulations  

E-print Network

Onset of patterns in an oscillated granular layer: Continuum and molecular dynamics simulations J significantly between the models. The delay in the onset of order in molecular dynamics simulations-Stokes order and 3D inelastic hard-sphere molecular dynamics MD simulations to investigate the onset of stand

Texas at Austin. University of

119

NKp44 and Natural Cytotoxicity Receptors as Damage-Associated Molecular Pattern Recognition Receptors  

PubMed Central

Natural killer (NK) cells are a key constituent of the innate immune system, protecting against bacteria, virally infected cells, and cancer. Recognition and protective function against such cells are dictated by activating and inhibitory receptors on the surface of the NK cell, which bind to specific ligands on the surface of target cells. Among the activating receptors is a small class of specialized receptors termed the natural cytotoxicity receptors (NCRs) comprised of NKp30, NKp46, and NKp44. The NCRs are key receptors in the recognition and termination of virally infected and tumor cells. Since their discovery over 10?years ago, ligands corresponding to the NCRs have largely remained elusive. Recent identification of the cellular ligands for NKp44 and NKp30 as exosomal proliferating cell nuclear antigen (PCNA) and HLA-B-associated transcript 3 (BAT3), respectively, implicate that NCRs may function as receptors for damage-associated molecular pattern (DAMP) molecules. In this review, we focus on NKp44, which surprisingly recognizes two distinct ligands resulting in either activation or inhibition of NK cell effector responses in response to tumor cells. The inhibitory function of NKp44 requires further study as it may play a pivotal role in placentation in addition to being exploited by tumors as a mechanism to escape NK cell killing. Finally, we suggest that the NCRs are a class of pattern recognition receptors, which recognize signals of genomic instability and cellular stress via interaction with the c-terminus of DAMP molecules localized to the surface of target cells by various co-ligands.

Horton, Nathan C.; Mathew, Porunelloor A.

2015-01-01

120

Time reversible and symplectic integrators for molecular dynamics simulations of rigid molecules.  

PubMed

Molecular dynamics integrators are presented for translational and rotational motion of rigid molecules in microcanonical, canonical, and isothermal-isobaric ensembles. The integrators are all time reversible and are also, in some approaches, symplectic for the microcanonical ensembles. They are developed utilizing the quaternion representation on the basis of the Trotter factorization scheme using a Hamiltonian formalism. The structure is similar to that of the velocity Verlet algorithm. Comparison is made with standard integrators in terms of stability and it is found that a larger time step is stable with the new integrators. The canonical and isothermal-isobaric molecular dynamics simulations are defined by using a chain thermostat approach according to generalized Nosé-Hoover and Andersen methods. PMID:15974658

Kamberaj, H; Low, R J; Neal, M P

2005-06-01

121

On the separability of the extended molecule: Constructing the best localized molecular orbitals for an organic molecule bridging two model electrodes.  

PubMed

Based on a quantum chemical valence formalism that allows the rigorous construction of best-localized molecular orbitals on specific parts of an extended system, we examined the separability of individual components of model systems relevant to the description of electron transport in molecular devices. We started by examining how to construct the maximally localized electronic density at the tip of a realistic model of a gold electrode. By varying the number of gold atoms included in the local region where to project the total electronic density, we quantitatively assess how many molecular orbitals are entirely localized in that region. We then considered a 1,4-benzene-di-thiol molecule connected to two model gold electrodes and examined how to localize the electronic density of the total system in the extended molecule, a fractional entity comprising the organic molecule plus an increasing number of the closest metal atoms. We were able to identify in a rigorous manner the existence of three physically different electronic populations, each one corresponding to a distinct set of molecular orbitals. First, there are those entirely localized in the extended molecule, then there is a second group of those completely distributed in the gold atoms external to that region, and, finally, there are those delocalized over the entire system. This latter group can be associated to the shared electronic population between the extended molecule and the rest of the system. We suggest that the treatment here presented could be useful in the theoretical analysis of the electronic transport in nanodevices whenever the use of localized molecular states are required by the physics of the specific problem, such as in cases of weak coupling and super-exchange limits. PMID:25273466

Moreira, Rodrigo A; de Melo, Celso P

2014-09-28

122

On the separability of the extended molecule: Constructing the best localized molecular orbitals for an organic molecule bridging two model electrodes  

NASA Astrophysics Data System (ADS)

Based on a quantum chemical valence formalism that allows the rigorous construction of best-localized molecular orbitals on specific parts of an extended system, we examined the separability of individual components of model systems relevant to the description of electron transport in molecular devices. We started by examining how to construct the maximally localized electronic density at the tip of a realistic model of a gold electrode. By varying the number of gold atoms included in the local region where to project the total electronic density, we quantitatively assess how many molecular orbitals are entirely localized in that region. We then considered a 1,4-benzene-di-thiol molecule connected to two model gold electrodes and examined how to localize the electronic density of the total system in the extended molecule, a fractional entity comprising the organic molecule plus an increasing number of the closest metal atoms. We were able to identify in a rigorous manner the existence of three physically different electronic populations, each one corresponding to a distinct set of molecular orbitals. First, there are those entirely localized in the extended molecule, then there is a second group of those completely distributed in the gold atoms external to that region, and, finally, there are those delocalized over the entire system. This latter group can be associated to the shared electronic population between the extended molecule and the rest of the system. We suggest that the treatment here presented could be useful in the theoretical analysis of the electronic transport in nanodevices whenever the use of localized molecular states are required by the physics of the specific problem, such as in cases of weak coupling and super-exchange limits.

Moreira, Rodrigo A.; de Melo, Celso P.

2014-09-01

123

Bicelles: A natural ‘molecular goniometer’ for structural, dynamical and topological studies of molecules in membranes  

PubMed Central

Major biological processes occur at the biological membrane. One of the great challenges is to understand the function of chemical or biological molecules inside the membrane; as well of those involved in membrane trafficking. This requires obtaining a complete picture of the in situ structure and dynamics as well as the topology and orientation of these molecules in the membrane lipid bilayer. These led to the creation of several innovative models of biological membranes in order to investigate the structure and dynamics of amphiphilic molecules, as well as integral membrane proteins having single or multiple transmembrane segments. Because the determination of the structure, dynamics and topology of molecules in membranes requires a macroscopic alignment of the system, a new membrane model called ‘bicelles’ that represents a crossover between lipid vesicles and classical micelles has become very popular due to its property of spontaneous self-orientation in magnetic fields. In addition, crucial factors involved in mimicking natural membranes, such as sample hydration, pH and salinity limits, are easy to control in bicelle systems. Bicelles are composed of mixtures of long chain (14–18 carbons) and short chain phospholipids (6–8 carbons) hydrated up to 98% with buffers and may adopt various morphologies depending on lipid composition, temperature and hydration. We have been developing bicelle systems under the form of nano-discs made of lipids with saturated or biphenyl-containing fatty acyl chains. Depending on the lipid nature, these membranous nano-discs may be macroscopically oriented with their normal perpendicular or parallel to the magnetic field, providing a natural ‘molecular goniometer’ for structural and topological studies, especially in the field of NMR. Bicelles can also be spun at the magic angle and lead to the 3D structural determination of molecules in membranes. PMID:19248817

Diller, Anna; Loudet, Cécile; Aussenac, Fabien; Raffard, Gérard; Fournier, Sylvie; Laguerre, Michel; Grélard, Axelle; Opella, Stanley J.; Marassi, Francesca M.; Dufourc, Erick J.

2010-01-01

124

LC-MS with electron ionization of cold molecules in supersonic molecular beams  

NASA Astrophysics Data System (ADS)

A new approach is described for the combination of electron ionization and LC-MS based on sample ionization as vibrationally cold molecules in a supersonic molecular beam (Cold EI). Cold EI of sample compounds in liquid solutions (methanol, acetonitrile, water, etc.) is achieved through spray formation, followed by soft thermal vaporization of the sample particles prior to their supersonic expansion and direct electron ionization of the sample compounds while they are contained in a supersonic molecular beam (SMB). Cold EI mass spectra were demonstrated to combine an enhanced molecular ion and improved mass spectral information (in comparison with standard EI), plus all the library searchable fragments. Cold EI enables the ionization of a broad range of compounds, including the full range of non-polar samples. Four orders of magnitude linear dynamic range is demonstrated and a detection limit of 2 pg was achieved for a 774 amu compound in single ion monitoring mode at m/z = 774. The method and apparatus are under continuous development and we feel that it can excel particularly in the analysis of unknown samples, while enabling fast LC-MS analysis through automated mass spectral deconvolution of coeluting LC peaks. In addition, the same MS system can also serve as an advanced GC-MS with supersonic molecular beams.

Granot, Ori; Amirav, Aviv

2005-06-01

125

The Hedgehog (Hh) family of signaling molecules are key agents in patterning numerous types of tissues. Mutations in Hh  

E-print Network

503 The Hedgehog (Hh) family of signaling molecules are key agents in patterning numerous types of Hh signal transduction. Several new Sonic Hedgehog binding partners have been identified. Cholesterol and palmitic acid modifications of Hh and Sonic hedgehog have been examined in greater detail. Characterization

Perrimon, Norbert

126

Body-fixed relativistic molecular Hamiltonian and its application to nuclear spin-rotation tensor: Linear molecules  

NASA Astrophysics Data System (ADS)

The relativistic molecular Hamiltonian written in the body-fixed frame of reference is the basis for high-precision calculations of spectroscopic parameters involving nuclear vibrations and/or rotations. Such a Hamiltonian that describes electrons fully relativistically and nuclei quasi-relativistically is just developed for semi-rigid nonlinear molecules [Y. Xiao and W. Liu, J. Chem. Phys. 138, 134104 (2013)], 10.1063/1.4797496. Yet, the formulation should somewhat be revised for linear molecules thanks to some unusual features arising from the redundancy of the rotation around the molecular axis. Nonetheless, the resulting isomorphic Hamiltonian is rather similar to that for nonlinear molecules. Consequently, the relativistic formulation of nuclear spin-rotation (NSR) tensor for linear molecules is very much the same as that for nonlinear molecules. So is the relativistic mapping between experimental NSR and NMR.

Xiao, Yunlong; Liu, Wenjian

2013-07-01

127

Native Molecular State of Adeno-Associated Viral Vectors Revealed by Single-Molecule Sequencing  

PubMed Central

Abstract The single-stranded genome of adeno-associated viral (AAV) vectors is one of the key factors leading to slow-rising but long-term transgene expression kinetics. Previous molecular studies have established what is now considered a textbook molecular model of AAV genomes with two copies of inverted tandem repeats at either end. In this study, we profiled hundreds of thousands of individual molecules of AAV vector DNA directly isolated from capsids, using single-molecule sequencing (SMS), which avoids any intermediary steps such as plasmid cloning. The sequence profile at 3? ends of both the regular and oversized vector did show the presence of an inverted terminal repeat (ITR), which provided direct confirmation that AAV vector packaging initiates from its 3? end. Furthermore, the vector 5?-terminus profile showed inconsistent termination for oversized vectors. Such incomplete vectors would not be expected to undergo canonical synthesis of the second strand of their genomic DNA and thus could function only via annealing of complementary strands of DNA. Furthermore, low levels of contaminating plasmid DNA were also detected. SMS may become a valuable tool during the development phase of vectors that are candidates for clinical use and for facilitating/accelerating studies on vector biology. PMID:21875357

Kapranov, Philipp; Chen, Lingxia; Dederich, Debra; Dong, Biao; He, Jie; Steinmann, Kathleen E.; Moore, Andrea R.; Thompson, John F.

2012-01-01

128

First principles investigations of vinazene molecule and molecular crystal: a prospective candidate for organic photovoltaic applications.  

PubMed

Escalating demand for sustainable energy resources, because of the rapid exhaustion of conventional energy resources as well as to maintain the environmental level of carbon dioxide (CO2) to avoid its adverse effect on the climate, has led to the exploitation of photovoltaic technology manifold more than ever. In this regard organic materials have attracted great attention on account of demonstrating their potential to harvest solar energy at an affordable rate for photovoltaic technology. 2-vinyl-4,5-dicyanoimidazole (vinazene) is considered as a suitable material over the fullerenes for photovoltaic applications because of its particular chemical and physical nature. In the present study, DFT approaches are employed to provide an exposition of optoelectronic properties of vinazene molecule and molecular crystal. To gain insight into its properties, different forms of exchange correlation energy functional/potential such as LDA, GGA, BLYP, and BL3YP are used. Calculated electronic structure of vinazene molecule has been displayed via HOMO-LUMO isosurfaces, whereas electronic structure of the vinazene molecular crystal, via electronic band structure, is presented. The calculated electronic and optical properties were analyzed and compared as well. Our results endorse vinazene as a suitable material for organic photovoltaic applications. PMID:25631921

Mohamad, Mazmira; Ahmed, Rashid; Shaari, Amirudin; Goumri-Said, Souraya

2015-02-01

129

The peptide-receptive transition state of MHC-1 molecules: Insight from structure and molecular dynamics  

SciTech Connect

MHC class I (MHC-I) proteins of the adaptive immune system require antigenic peptides for maintenance of mature conformation and immune function via specific recognition by MHC-I-restricted CD8(+) T lymphocytes. New MHC-I molecules in the endoplasmic reticulum are held by chaperones in a peptide-receptive (PR) transition state pending release by tightly binding peptides. In this study, we show, by crystallographic, docking, and molecular dynamics methods, dramatic movement of a hinged unit containing a conserved 3(10) helix that flips from an exposed 'open' position in the PR transition state to a 'closed' position with buried hydrophobic side chains in the peptide-loaded mature molecule. Crystallography of hinged unit residues 46-53 of murine H-2L(d) MHC-I H chain, complexed with mAb 64-3-7, demonstrates solvent exposure of these residues in the PR conformation. Docking and molecular dynamics predict how this segment moves to help form the A and B pockets crucial for the tight peptide binding needed for stability of the mature peptide-loaded conformation, chaperone dissociation, and Ag presentation.

Robinson H.; Mage, M.; Dolan, M.; Wang, R.; Boyd, L.; Revilleza, M.; Natarajan, K.; Myers, N.; Hansen, T.; Margulies, D.

2012-05-01

130

Manipulating the motion of large molecules: Information from the molecular frame  

NASA Astrophysics Data System (ADS)

Large molecules have complex potential-energy surfaces with many local minima. They exhibit multiple stereoisomers, even at the low temperatures (˜1 K) in a molecular beam, with rich intra- and intermolecular dynamics. Over the last years, we have developed methods to manipulate the motion of large, complex molecules and to select their quantum states. We have exploited this state-selectivity, for example, to spatially separate individual structural isomers of complex molecules [1] and to demonstrate unprecedented degrees of laser alignment and mixed-field orientation of these molecules [2]. Such clean, well-defined samples strongly benefit, or simply allow, novel experiments on the dynamics of complex molecules, for instance, femtosecond pump-probe measurements, X-ray or electron diffraction of molecular ensembles (including diffraction-from-within experiments), or tomographic reconstructions of molecular orbitals. These samples could also be very advantageous for metrology applications, such as, for example, matter-wave interferometry or the search for electroweak interactions in chiral molecules. Moreover, they provide an extreme level of control for stereo-dynamically controlled reaction dynamics. We have recently exploited these state-selected and oriented samples to measure photoelectron angular distributions in the molecular frame (MFPADs) from non-resonant femtosecond-laser photoionization [3] and using the X-ray Free-Electron-Laser LCLS. We have also investigated X-ray diffraction imaging and, using ion momentum imaging, the induced radiation damage of these samples using the LCLS. This work was carried out within a collaboration for which J. Küpper, H. Chapman, and D. Rolles are spokespersons. The collaboration consists of CFEL (DESY, MPG, University Hamburg), Fritz-Haber-Institute Berlin, MPI Nuclear Physics Heidelberg, MPG Semi-conductor Lab, Aarhus University, FOM AMOLF Amsterdam, Lund University, MPI Medical Research Heidelberg, TU Berlin, Max Born Institute Berlin, and SLAC Menlo Park, CA, USA. The experiments were carried out using CAMP (designed and built by the MPG-ASG at CFEL) [4] at the LCLS (operated by Stanford University on behalf of the US DOE) [5]. [4pt] [1] Filsinger, Erlekam, von Helden, Küpper, Meijer, Phys. Rev. Lett. 100, 133003 (2008); Filsinger, Küpper, Meijer, Hansen, Maurer, Nielsen, Holmegaard, Stapelfeldt, Angew. Chem. Int. Ed. 48, 6900 (2009)[0pt] [2] Holmegaard, Nielsen, Nevo, Stapelfeldt, Filsinger, Küpper, Meijer, Phys. Rev. Lett. 102, 023001 (2009); Filsinger, Küpper, Meijer, Holmegaard, Nielsen, Nevo, Hansen, Stapelfeldt, J. Chem. Phys. 131, 064309, (2009); Nevo, Holmegaard, Nielsen, Hansen, Stapelfeldt, Filsinger, Meijer, Küpper, Phys. Chem. Chem. Phys. 11, 9912 (2009)[0pt] [3] Holmegaard, Hansen, Kalhøj, Kragh, Stapelfeldt, Filsinger, Küpper, Meijer, Dimitrovski, Abu-samha, Martiny, Madsen, Nature Phys. 6, 428 (2010)[0pt] [4] Strüder et al. Nucl Instrum Meth A 614, 483 (2010)[0pt] [5] Emma et al. Nat Photonics 4, 641 (2010)

Küpper, Jochen

2011-06-01

131

Molecular Motions of Small Molecules in Porous Silica Sol-Gel Glass.  

NASA Astrophysics Data System (ADS)

Monolithic samples of sol-gel glass of pore diameters varing form 10 to 100 A have been produced. The highly porous samples have been impregnated by different fluids and molecular motions of confined molecules have been studied using Raman spectroscopy. Some studies have been extended to silica sol-gel glass of modified surfaces. The prefferential adsorption and translational diffusion have been investigated in mixtures of pyridine with polar and non-polar solvents. It has been confirmed that pyridine can be preferentially adsorbed on silica, and it has been suggested that the process results in a bilayer structure of the interface. Rotational relaxation of carbon disulfide, chloroform, acetonitrile, and sulfur hexafluoride inside pores of diameter a couple of times larger than diameter of molecules has been studied. High temperature and pressure study have been employed for SF_6 measurements. The effect of pore diameters and different surface coverage on rotational diffusion has been discussed. It has been shown that surface interactions, in particular, hydrogen bonding between the imbedded molecules and silanols groups, were responsible for slowing down the rotational relaxations within small pores. The experimental results have been compared with EDJ and FPL theoretical models. Vibrational dephasing, intermolecular energy exchange and intramolecular energy coupling have been investigated in chloroform, acetonitrile, nitromethane, acetone, and methyl iodide. The vibrational modulation times were obtained from the Kubo theoretical function and used to analyze molecular interactions near the silica surface. The Fermi resonance effect has been studied in acetonitrile and the coupling constant has been obtained from the standard quantum mechanics analysis. The non-coincidence effect has been measured in acetone within pores of different surface structure under different concentrations. The Schweizer-Chandler dephasing model and energy exchange model have been tested for methyl iodide. It has been found that the Harris energy exchange model cannot explain the mechanism responsible for the band shapes of any of the modes of methyl iodide adsorbed on silica.

Nikiel, Leszek

1991-05-01

132

Nanomechanical recognition measurements of individual DNA molecules reveal epigenetic methylation patterns  

Microsoft Academic Search

Atomic force microscopy (AFM) is a powerful tool for analysing the shapes of individual molecules and the forces acting on them. AFM-based force spectroscopy provides insights into the structural and energetic dynamics of biomolecules by probing the interactions within individual molecules, or between a surface-bound molecule and a cantilever that carries a complementary binding partner. Here, we show that an

Rong Zhu; Stefan Howorka; Johannes Pröll; Ferry Kienberger; Johannes Preiner; Jan Hesse; Andreas Ebner; Vassili Ph. Pastushenko; Hermann J. Gruber; Peter Hinterdorfer

2010-01-01

133

Collision dynamics of methyl radicals and highly vibrationally excited molecules using crossed molecular beams  

SciTech Connect

The vibrational to translational (V{yields}T) energy transfer in collisions between large highly vibrationally excited polyatomics and rare gases was investigated by time-of-flight techniques. Two different methods, UV excitation followed by intemal conversion and infrared multiphoton excitation (IRMPE), were used to form vibrationally excited molecular beams of hexafluorobenzene and sulfur hexafluoride, respectively. The product translational energy was found to be independent of the vibrational excitation. These results indicate that the probability distribution function for V{yields}T energy transfer is peaked at zero. The collisional relaxation of large polyatomic molecules with rare gases most likely occurs through a rotationally mediated process. Photodissociation of nitrobenzene in a molecular beam was studied at 266 nm. Two primary dissociation channels were identified including simple bond rupture to produce nitrogen dioxide and phenyl radical and isomerization to form nitric oxide and phenoxy radical. The time-of-flight spectra indicate that simple bond rupture and isomerization occurs via two different mechanisms. Secondary dissociation of the phenoxy radicals to carbon monoxide and cyclopentadienyl radicals was observed as well as secondary photodissociation of phenyl radical to give H atom and benzyne. A supersonic methyl radical beam source is developed. The beam source configuration and conditions were optimized for CH{sub 3} production from the thermal decomposition of azomethane. Elastic scattering of methyl radical and neon was used to differentiate between the methyl radicals and the residual azomethane in the molecular beam.

Chu, P.M.Y.

1991-10-01

134

Testosterone Induces Molecular Changes in Dopamine Signaling Pathway Molecules in the Adolescent Male Rat Nigrostriatal Pathway  

PubMed Central

Adolescent males have an increased risk of developing schizophrenia, implicating testosterone in the precipitation of dopamine-related psychopathology. Evidence from adult rodent brain indicates that testosterone can modulate nigrostriatal dopamine. However, studies are required to understand the role testosterone plays in maturation of dopamine pathways during adolescence and to elucidate the molecular mechanism(s) by which testosterone exerts its effects. We hypothesized that molecular indices of dopamine neurotransmission [synthesis (tyrosine hydroxylase), breakdown (catechol-O-methyl transferase; monoamine oxygenase), transport [vesicular monoamine transporter (VMAT), dopamine transporter (DAT)] and receptors (DRD1-D5)] would be changed by testosterone or its metabolites, dihydrotestosterone and 17?-estradiol, in the nigrostriatal pathway of adolescent male rats. We found that testosterone and dihydrotestosterone increased DAT and VMAT mRNAs in the substantia nigra and that testosterone increased DAT protein at the region of the cell bodies, but not in target regions in the striatum. Dopamine receptor D2 mRNA was increased and D3 mRNA was decreased in substantia nigra and/or striatum by androgens. These data suggest that increased testosterone at adolescence may change dopamine responsivity of the nigrostriatal pathway by modulating, at a molecular level, the capacity of neurons to transport and respond to dopamine. Further, dopamine turnover was increased in the dorsal striatum following gonadectomy and this was prevented by testosterone replacement. Gene expression changes in the dopaminergic cell body region may serve to modulate both dendritic dopamine feedback inhibition and reuptake in the dopaminergic somatodendritic field as well as dopamine release and re-uptake dynamics at the presynaptic terminals in the striatum. These testosterone-induced changes of molecular indices of dopamine neurotransmission in males are primarily androgen receptor-driven events as estradiol had minimal effect. We conclude that nigrostriatal responsivity to dopamine may be modulated by testosterone acting via androgen receptors to alter gene expression of molecules involved in dopamine signaling during adolescence. PMID:24618531

Purves-Tyson, Tertia D.; Owens, Samantha J.; Double, Kay L.; Desai, Reena; Handelsman, David J.; Weickert, Cynthia Shannon

2014-01-01

135

Ab initio study of transport properties of an all-carbon molecular switch based on C20 molecule  

NASA Astrophysics Data System (ADS)

Choosing closed-ended armchair (5, 5) single-wall carbon nanotubes (CCNTs) as electrodes, we have investigated the electron transport properties across a carbon molecular junction consisting of a C20 molecule sandwiched between two semi-infinite carbon nanotubes. It is shown that the Landauer conductance of this carbon hybrid system can be tuned within several orders of magnitude not only by varying the tube-C20 distance, but more importantly by changing the orientation of the C20 molecule and rotating the C20 molecule or one of the tubes around the symmetry axis of the system at fixed distances. This fact could make this all-carbon molecular system a possible candidate for a nano-electronic switching device. Moreover, our study also reveals that molecular configuration selection and structural relaxation would play an important role in the design of such devices.

Ouyang, Fang-Ping; Xu, Hui

2007-03-01

136

Distribution of molecular centres in unit cells with respect to packing patterns.  

PubMed

Packing patterns, a new description of the limited number of possible arrangements of molecular building blocks in a unit cell, were assigned to many thousands of structures belonging to the space groups P2(1)/c, P1(-), P2(1)2(1)2(1), P2(1) and C2/c. The position of the molecular centre (in fractional coordinates) in the unit cell for these structures has been surveyed, with respect to the space group and the packing pattern. The results clearly show that the position at which the molecular centre is found in the unit cell is correlated with the packing pattern. The relationships between the orientation of the packing pattern in the unit cell and the symmetry operators of the space group are explored. Popular orientations of packing patterns within the unit cell are given. PMID:15367789

Pidcock, Elna; Motherwell, W D Sam

2004-10-01

137

Molecular dynamics simulation of the homogeneous nucleation of UF6 molecules  

NASA Astrophysics Data System (ADS)

Molecular dynamics simulations of nucleation of UF6 molecules have been performed. We observed two phenomena which demonstrate that the nucleation process occurs in the state far from thermal equilibrium. First, the excited hot clusters were produced and continued to exist during the nucleation process. Second, the relationship between the potential energy and temperature of the clusters depends on the monomer temperature, that is, the potential energy at a temperature decreases with the increase in monomer temperature. In the simulations, various types of cluster configurations were observed: prolate, oblate, sphere-like, and confeito-like. The confeito-like cluster is composed of one core and a few horns, and it was found predominantly in the hotter clusters. As a result, we found that the spectra measured in the supercooled state can be attributed to the excited hot clusters, the configurations of which are confeito-like.

Tanimura, Shinobu; Yasuoka, Kenji

2000-08-01

138

Operation mechanism of rotary molecular motor F1 probed by single-molecule techniques  

NASA Astrophysics Data System (ADS)

F1 is a rotary motor protein. Three catalytic ?-subunits in the stator ?3?3 ring are torque generators, and rotate the rotor ?-subunit by sequential and cooperative conformational changes coupled with adenosine triphosphate (ATP) hydrolysis reaction. F1 shows remarkable performances such as rotation rate faster than 10,000 rpm, high reversibility and efficiency in chemo-mechanical energy conversion. I will introduce basic characteristics of F1 revealed by single-molecule imaging and manipulation techniques based on optical microscopy and high-speed atomic force microscopy. I will also discuss the possible operation mechanism behind the F1, along with structurally-related hexameric ATPases, also mentioning the possibility of generating hybrid molecular motors.

Iino, Ryota

2013-03-01

139

Rotation commensurate echo of asymmetric molecules—Molecular fingerprints in the time domain  

NASA Astrophysics Data System (ADS)

Using the pulses of terahertz free electron laser and ultra-fast Schottky diode detectors, we observed the coherent transients within a free induction decay of gaseous nitrogen dioxide NO2. The laser excited different sub-bands of rotation spectra of NO2 containing about 50-70 lines. The free induction signal continued more than 30 ns and consisted of many echo-like bursts duration about 0.2 ns. Unlike the similar effect observed previously for linear and symmetric top molecules, the sequence of echo bursts is not periodic. The values for delay of individual echo are stable, and the set of these delays can be considered as a "molecular fingerprint" in the time domain.

Chesnokov, E. N.; Kubarev, V. V.; Koshlyakov, P. V.

2014-12-01

140

Nectin family of cell-adhesion molecules: structural and molecular aspects of function and specificity.  

PubMed

Cell-cell adhesive processes are central to the physiology of multicellular organisms. A number of cell surface molecules contribute to cell-cell adhesion, and the dysfunction of adhesive processes underlies numerous developmental defects and inherited diseases. The nectins, a family of four immunoglobulin superfamily members (nectin-1 to -4), interact through their extracellular domains to support cell-cell adhesion. While both homophilic and heterophilic interactions among the nectins are implicated in cell-cell adhesion, cell-based and biochemical studies suggest heterophilic interactions are stronger than homophilic interactions and control a range of physiological processes. In addition to interactions within the nectin family, heterophilic associations with nectin-like molecules, immune receptors, and viral glycoproteins support a wide range of biological functions, including immune modulation, cancer progression, host-pathogen interactions and immune evasion. We review current structural and molecular knowledge of nectin recognition processes, with a focus on the biochemical and biophysical determinants of affinity and selectivity that drive distinct nectin associations. These proteins and interactions are discussed as potential targets for immunotherapy. PMID:25326769

Samanta, Dibyendu; Almo, Steven C

2015-02-01

141

Affinity flow fractionation of cells via transient interactions with asymmetric molecular patterns  

PubMed Central

Flow fractionation of cells using physical fields to achieve lateral displacement finds wide applications, but its extension to surface molecule-specific separation requires labeling. Here we demonstrate affinity flow fractionation (AFF) where weak, short-range interactions with asymmetric molecular patterns laterally displace cells in a continuous, label-free process. We show that AFF can directly draw neutrophils out of a continuously flowing stream of blood with an unprecedented 400,000-fold depletion of red blood cells, with the sorted cells being highly viable, unactivated, and functionally intact. The lack of background erythrocytes enabled the use of AFF for direct enumeration of neutrophils by a downstream detector, which could distinguish the activation state of neutrophils in blood. The compatibility of AFF with capillary microfluidics and its ability to directly separate cells with high purity and minimal sample preparation will facilitate the design of simple and portable devices for point-of-care diagnostics and quick, cost-effective laboratory analysis. PMID:23900203

Bose, Suman; Singh, Rishi; Hanewich-Hollatz, Mikhail; Shen, Chong; Lee, Chia-Hua; Dorfman, David M.; Karp, Jeffrey M.; Karnik, Rohit

2013-01-01

142

Molecular subtypes of breast cancer are associated with characteristic DNA methylation patterns  

Microsoft Academic Search

INTRODUCTION: Five different molecular subtypes of breast cancer have been identified through gene expression profiling. Each subtype has a characteristic expression pattern suggested to partly depend on cellular origin. We aimed to investigate whether the molecular subtypes also display distinct methylation profiles. METHODS: We analysed methylation status of 807 cancer-related genes in 189 fresh frozen primary breast tumours and four

Karolina Holm; Cecilia Hegardt; Johan Staaf; Johan Vallon-Christersson; Göran Jönsson; Håkan Olsson; Åke Borg; Markus Ringnér

2010-01-01

143

Efficient small molecule bulk heterojunction solar cells with high fill factors via pyrene-directed molecular self-assembly.  

PubMed

Efficient organic photovoltaic (OPV) materials are constructed by attaching completely planar, symmetric end-groups to donor-acceptor electroactive small molecules. Appending C2-pyrene as the small molecule end-group to a diketopyrrolopyrrole core leads to materials with a tight, aligned crystal packing and favorable morphology dictated by ?-? interactions, resulting in high power conversion efficiencies and high fill factors. The use of end-groups to direct molecular self-assembly is an effective strategy for designing high-performance small molecule OPV devices. PMID:22021084

Lee, Olivia P; Yiu, Alan T; Beaujuge, Pierre M; Woo, Claire H; Holcombe, Thomas W; Millstone, Jill E; Douglas, Jessica D; Chen, Mark S; Fréchet, Jean M J

2011-12-01

144

Researchers use changes in the patterns of sugar molecules to detect cells before they develop into esophageal cancer:  

Cancer.gov

Scientists working at Britain's Medical Research Council, in collaboration with researchers from New York University, have identified changes in the patterns of sugar molecules that line pre-cancerous cells in the esophagus, a condition called Barrett’s dysplasia, making it much easier to detect and remove these cells before they develop into esophageal cancer. These findings, reported in the journal Nature Medicine, have important implications for patients and may help to monitor their condition and prevent the development of cancer.

145

Danger-associated molecular patterns and inflammatory bowel disease: is there a connection?  

PubMed

The innate immune system is of critical importance for maintaining the local tissue homeostasis in the intestinal mucosa. It must recognize and rapidly respond to microbial antigens and danger signals to provide a first line of host defense. This is primarily accomplished through an array of pattern recognition receptors that are located in distinct (sub)cellular compartments and bind pathogen-associated and danger-associated molecular patterns (PAMPs and DAMPs, respectively). The impact of PAMPs, in particular NOD2/CARD15, in the pathogenesis of Crohn's disease is widely established. The involvement of DAMPs in the pathogenesis of inflammatory bowel disease (IBD), however, is much less recognized. DAMPs (also known as alarmins) represent non-pathogen-derived molecules, such as intracellular proteins released from damaged and stressed cells. Although the ligand(s) for the triggering receptor expressed on myeloid cells (TREM)-1 have not yet been fully identified, circumstantial evidence indicates that DAMPs are the inducers of the TREM-1-mediated, excessive induction of proinflammatory effects, also seen in patients with active IBD. Blocking the interactions between TREM-1 with its ligand(s) by the administration of a TREM-1-derived antagonistic peptide even attenuates the progression of established colonic inflammation. Hence, DAMPs can contribute to, and exacerbate, colonic inflammation in mouse models of IBD, in particular when they trigger innate immune cells of the intestinal lamina propria. DAMPs and PAMPs, however, may also be required for maintaining intestinal epithelial barrier functions as demonstrated by the enhanced susceptibility for colitis development in mice deficient for the NLRP6 or NLRC4 sensors in inflammasomes in intestinal epithelial cells. PMID:23295691

Mueller, Christoph

2012-01-01

146

PDMS-Glass bonding using grafted polymeric adhesive - Alternative process flow for compatibility with patterned biological molecules  

PubMed Central

We report a novel modification of silicone elastomer, polydimethylsiloxane (PDMS) with a polymer graft that allows interfacial bonding between elastomer and glass substrate to be performed without exposure of said substrate to harsh treatment conditions like oxygen plasma. Organic molecules can thus be patterned within microfluidic channels and still remain functional post-bonding. In addition, after polymer grafting the PDMS can be stored in a desiccator for at least 40 days, and activated upon exposure to acidic buffer for bonding. The bonded devices remain fully bonded in excess of 80 psi driving pressure, with no signs of compromise to the bond integrity. Finally, we demonstrate the compatibility of our method with biological molecules using a proof-of-concept DNA sensing device, in which fluorescently-labelled DNA targets are successfully captured by a patterned probe in a device sealed using our method, while the pattern on a plasma-treated device was completely destroyed. Therefore, this method provides a much-needed alternative bonding process for incorporation of biological molecules in microfluidic devices. PMID:22858861

Beh, Cyrus Weijie; Zhou, Weizhuang

2013-01-01

147

Photodissociation of a water molecule in ice: a molecular dynamics study  

NASA Astrophysics Data System (ADS)

UV irradiation of ice may be important for dust grain chemistry in dense clouds through (i) the photolysis of molecules in the icy mantles releasing reactive species that can react with eachother or other species present in the ice, (ii) desorption of atoms and molecules into the gas phase, and (iii) phase transformation of the ice. There have been a number of experiments studying the effects of UV irradiation of water ice. Ghormley and Hochanadel (1971) studied flash photolysis of crystalline hexagonal ice at 263 K and could detect OH radicals in the ice. In a study of different UV doses on the chemical composition of a number of pure ices at 10 K, Gerakines et al. (1996), OH, H2O2, and HO2 were detected after UV irradiation of amorphous ice. In their work on UV iradiation of amorphous D2O ice, Watanabe et al. (2000) found that D2 was efficiently formed upon irradiation of 9.8 eV photons, while Yabushita et al. (2004) detected H atoms desorbing from amorphous ice that had been irradiated by 6.4 eV photons. The amorphization of crystalline cubic ice at 16 K was shown to be quite efficient through Ly-? irradiation (Leto & Baratta 2003). In the work presented here the photodissociation dynamics of a water molecule in crystalline and amorphous pure water ices is studied computationally using classical molecular dynamics (Andersson et al. in press, Andersson et al. in prep). Photodissociation in the first bilayer of crystalline ice leads mainly to H atoms desorbing, while in the third bilayer trapping of H and OH dominates. Results for amorphous ice shows a similar depth dependence for the outcome of photodissociation. The probability of H atom desorption is however somewhat higher for the upper layers of amorphous ice compared to the corresponding layers in crystalline ice. The kinetic energy distribution of the desorbing H atoms is much broader than that for the corresponding gas-phase photodissociation due to loss of energy through collisional encounters with the ice water molecules. H atom desorption from amorphous ice shows a hotter kinetic energy distribution than the one for crystalline ice. The H atoms on average move about 10 Å before becoming trapped, while OH radicals typically move 2 Å, their motion through the ice being more restricted. OH formed from photodisscation at the surface has in some cases however been found to move more than 50 Å over the surface before being readsorbed. In accordance with experiments a blueshift of the absorption spectrum is obtained relative to gas-phase water.

Andersson, Stefan; Kroes, Geert-Jan; van Dishoeck, Ewine F.

148

Large-area molecular patterning with polymer pen lithography.  

PubMed

The challenge of constructing surfaces with nanostructured chemical functionality is central to many areas of biology and biotechnology. This protocol describes the steps required for performing molecular printing using polymer pen lithography (PPL), a cantilever-free scanning probe-based technique that can generate sub-100-nm molecular features in a massively parallel fashion. To illustrate how such molecular printing can be used for a variety of biologically relevant applications, we detail the fabrication of the lithographic apparatus and the deposition of two materials, an alkanethiol and a polymer onto a gold and silicon surface, respectively, and show how the present approach can be used to generate nanostructures composed of proteins and metals. Finally, we describe how PPL enables researchers to easily create combinatorial arrays of nanostructures, a powerful approach for high-throughput screening. A typical protocol for fabricating PPL arrays and printing with the arrays takes 48-72 h to complete, including two overnight waiting steps. PMID:24263094

Eichelsdoerfer, Daniel J; Liao, Xing; Cabezas, Maria D; Morris, William; Radha, Boya; Brown, Keith A; Giam, Louise R; Braunschweig, Adam B; Mirkin, Chad A

2013-12-01

149

Hydro-chemical study of the evolution of interstellar pre-biotic molecules during the collapse of molecular clouds  

NASA Astrophysics Data System (ADS)

One of the stumbling blocks for studying the evolution of interstellar molecules is the lack of adequate knowledge about the rate coefficients of various reactions which take place in the interstellar medium and molecular clouds. Some theoretical models of rate coefficients do exist in the literature for computing abundances of complex pre-biotic molecules. So far these have been used to study the abundances of these molecules in space. However, in order to obtain more accurate final compositions in these media, we have calculated the rate coefficients for the formation of some of the most important interstellar pre-biotic molecules by using quantum chemical theory. We use these rates inside our hydro-chemical model to examine the chemical evolution and final abundances of pre-biotic species during the collapsing phase of a proto-star. We find that a significant amount of various pre-biotic molecules could be produced during the collapse phase of a proto-star. We thoroughly study the formation of these molecules via successive neutral-neutral and radical-radical/radical-molecular reactions. We present the time evolution of the chemical species with an emphasis on how the production of these molecules varies with the depth of a cloud. We compare the formation of adenine in interstellar space using our rate-coefficients and using those obtained from existing theoretical models. Formation routes of the pre-biotic molecules are found to be highly dependent on the abundances of the reactive species and the rate coefficients involved in the reactions. The presence of grains strongly affects the abundances of the gas phase species. We also carry out a comparative study between different pathways available for the synthesis of adenine, alanine, glycine and other molecules considered in our network. Despite the huge abundances of the neutral reactive species, production of adenine is found to be strongly dominated by the radical-radical/radical-molecular reaction pathways. If all the reactions considered here contribute to the production of alanine and glycine, then neutral-neutral and radical-radical/radical-molecular pathways are both found to have a significant part in the production of alanine. Moreover, radical-radical/radical-molecular pathways also play a major role in the production of glycine.

Majumdar, Liton; Das, Ankan; Chakrabarti, Sandip K.; Chakrabarti, Sonali

2012-12-01

150

Molecular dynamics study of structure H clathrate hydrates of methane and large guest molecules  

NASA Astrophysics Data System (ADS)

Methane storage in structure H (sH) clathrate hydrates is attractive due to the relatively higher stability of sH as compared to structure I methane hydrate. The additional stability is gained without losing a significant amount of gas storage density as happens in the case of structure II (sII) methane clathrate. Our previous work has showed that the selection of a specific large molecule guest substance (LMGS) as the sH hydrate former is critical in obtaining the optimum conditions for crystallization kinetics, hydrate stability, and methane content. In this work, molecular dynamics simulations are employed to provide further insight regarding the dependence of methane occupancy on the type of the LMGS and pressure. Moreover, the preference of methane molecules to occupy the small (512) or medium (435663) cages and the minimum cage occupancy required to maintain sH clathrate mechanical stability are examined. We found that thermodynamically, methane occupancy depends on pressure but not on the nature of the LMGS. The experimentally observed differences in methane occupancy for different LMGS may be attributed to the differences in crystallization kinetics and/or the nonequilibrium conditions during the formation. It is also predicted that full methane occupancies in both small and medium clathrate cages are preferred at higher pressures but these cages are not fully occupied at lower pressures. It was found that both small and medium cages are equally favored for occupancy by methane guests and at the same methane content, the system suffers a free energy penalty if only one type of cage is occupied. The simulations confirm the instability of the hydrate when the small and medium cages are empty. Hydrate decomposition was observed when less than 40% of the small and medium cages are occupied.

Susilo, Robin; Alavi, Saman; Ripmeester, John A.; Englezos, Peter

2008-05-01

151

Different molecular patterns in glioblastoma multiforme subtypes upon recurrence  

Microsoft Academic Search

One of the hallmarks of glioblastoma is its inherent tendency to recur. At this point patients with relapsed GBM show a survival\\u000a time of only few months. The molecular basis of the recurrence process in GBM is still poorly understood. The aim of the present\\u000a study was to investigate the genetic profile of relapsed GBM compared to their respective primary

Ramon Martinez; Veit Rohde; Gabriele Schackert

2010-01-01

152

Ion and molecule sensors using molecular recognition in luminescent, conductive polymers. FY 1997 year-end progress report  

SciTech Connect

'The purpose of this project is to use molecular recognition strategies to develop sensor technology based on luminescent, conductive polymers that contain sites for binding specific molecules or ions in the presence of related molecules or ions. Selective binding of a particular molecule or ion of interest to these polymers will result in a large change in their luminescence and/or conductivity, which can be used to both qualitatively and quantitatively sense the presence of the bound molecules or ions. The main thrusts and accomplishments in the first year of this project involve developing polymer syntheses that yield conjugated polymers to which a wide variety of ligands for metal ion binding can be readily incorporated.'

Wasielewski, M.R.

1997-01-01

153

Photoisomerization dynamics of a rhodopsin-based molecule (potential molecular switch) with high quantum yields  

NASA Astrophysics Data System (ADS)

It is worthwhile to explore the detailed reaction dynamics of various candidates for molecular switches, in order to understand, e.g., the differences in quantum yields and switching times. Here we report density-functional-based simulations for the rhodopsin-based molecule 4-[4-methylbenzylidene]-5-p-tolyl-3,4-dihydro-2H-pyrrole (MDP), synthesized by Sampedro et al We find that the photoisomerization quantum yields are remarkably high: 82% for cis-to-trans, and 68% for trans-to-cis. The lifetimes of the S1 excited state in cis-MDP in our calculations are in the range of 900–1800 fs, with a mean value of 1270 fs, while the range of times required for full cis-to-trans isomerization are 1100–2000 fs, with a mean value of 1530 fs. In trans-MDP, the calculated S1 excited state lifetimes are 860–2140 fs, with a mean value of 1330 fs, and with the full trans-to-cis isomerization completed about 200 fs later. In both cases, the dominant reaction mechanism is rotation around the central C=C bond (connected to the pyrroline ring), and de-excitation occurs at an avoided crossing between the ground state and the lowest singlet state, near the midpoint of the rotational pathway. Perhaps remarkably, but apparently because of electrostatic repulsion, the direction of rotation is the same for both reactions.

Jiang, Chen-Wei; Zhang, Xiu-Xing; Fang, Ai-Ping; Li, Hong-Rong; Xie, Rui-Hua; Li, Fu-Li; Allen, Roland E.

2015-02-01

154

Hunting complex differential gene interaction patterns across molecular contexts.  

PubMed

Heterogeneity in genetic networks across different signaling molecular contexts can suggest molecular regulatory mechanisms. Here we describe a comparative chi-square analysis (CP?(2)) method, considerably more flexible and effective than other alternatives, to screen large gene expression data sets for conserved and differential interactions. CP?(2) decomposes interactions across conditions to assess homogeneity and heterogeneity. Theoretically, we prove an asymptotic chi-square null distribution for the interaction heterogeneity statistic. Empirically, on synthetic yeast cell cycle data, CP?(2) achieved much higher statistical power in detecting differential networks than alternative approaches. We applied CP?(2) to Drosophila melanogaster wing gene expression arrays collected under normal conditions, and conditions with overexpressed E2F and Cabut, two transcription factor complexes that promote ectopic cell cycling. The resulting differential networks suggest a mechanism by which E2F and Cabut regulate distinct gene interactions, while still sharing a small core network. Thus, CP?(2) is sensitive in detecting network rewiring, useful in comparing related biological systems. PMID:24482443

Song, Mingzhou; Zhang, Yang; Katzaroff, Alexia J; Edgar, Bruce A; Buttitta, Laura

2014-04-01

155

Patterning of polypyrrole using a fluoropolymer as an adsorption-protecting molecule  

NASA Astrophysics Data System (ADS)

Patterning of the conducting polymer polypyrrole (PPy) was achieved using perfluoropolyether (PFPE) as a mask material. The fluoropolymer PFPE has both hydrophobic and oleophobic properties that allowed the generation of passivated patterns against PPy deposition. We exploited these properties to achieve the selective micropattern deposition of PPy, by simple chemical oxidation in an aqueous solution. Using a microcontact printing method, circle patterns with exposed carboxyl groups were prepared, while other region was protected by PFPE. Chemical oxidation of PPy on the patterned substrate resulted in selective deposition of PPy onto only the carboxylate-terminated regions, with little deposition on the PFPE layer. Cross-sectional analysis of the pattern revealed that the PFPE layer would form a hole-like structure around the carboxylate-terminated surfaces, with PPy deposition only in the holes. The PFPE layer had little influence on surface smoothness, compared to other self-assembled monolayers. These results suggest that PFPE can be used as a protective material for the surface modification and patterning of various materials.

Kwon, Sunil; Ha, Jong-Wook; Noh, Jiwhan; Lee, Sang-Yup

2010-10-01

156

Molecular population dynamics of DNA structures in a bcl-2 promoter sequence is regulated by small molecules and the transcription factor hnRNP LL.  

PubMed

Minute difference in free energy change of unfolding among structures in an oligonucleotide sequence can lead to a complex population equilibrium, which is rather challenging for ensemble techniques to decipher. Herein, we introduce a new method, molecular population dynamics (MPD), to describe the intricate equilibrium among non-B deoxyribonucleic acid (DNA) structures. Using mechanical unfolding in laser tweezers, we identified six DNA species in a cytosine (C)-rich bcl-2 promoter sequence. Population patterns of these species with and without a small molecule (IMC-76 or IMC-48) or the transcription factor hnRNP LL are compared to reveal the MPD of different species. With a pattern recognition algorithm, we found that IMC-48 and hnRNP LL share 80% similarity in stabilizing i-motifs with 60 s incubation. In contrast, IMC-76 demonstrates an opposite behavior, preferring flexible DNA hairpins. With 120-180 s incubation, IMC-48 and hnRNP LL destabilize i-motifs, which has been previously proposed to activate bcl-2 transcriptions. These results provide strong support, from the population equilibrium perspective, that small molecules and hnRNP LL can modulate bcl-2 transcription through interaction with i-motifs. The excellent agreement with biochemical results firmly validates the MPD analyses, which, we expect, can be widely applicable to investigate complex equilibrium of biomacromolecules. PMID:24609386

Cui, Yunxi; Koirala, Deepak; Kang, HyunJin; Dhakal, Soma; Yangyuoru, Philip; Hurley, Laurence H; Mao, Hanbin

2014-05-01

157

Molecular recognition pattern of cytotoxic alkaloid vinblastine with multiple targets.  

PubMed

Vinblastine (VLB), a cytotoxic alkaloid is used extensively against various cancer types and the crystal structure of its tubulin complex is already known. Multitarget affinity of vinblastine has been investigated and the nature of binding with biological receptors namely, duplex DNA and Human serum albumin (HSA) has been compared to the binding characteristics of its known complex with natural high affinity receptor tubulin using molecular docking and QM-MM calculations. VLB is found to interact with DNA as well as HSA protein, though, with weaker affinity as compared to tubulin. Analysis of various docked complexes revealed that the H-bonds and cation-pi bonds do not have significant contribution to the binding interactions and despite its large size, VLB remains in relaxed conformation and fits in the hydrophobic regions on the receptors. PMID:25241127

Pandya, Prateek; Agarwal, Lokesh Kr; Gupta, Neelima; Pal, Sourav

2014-11-01

158

Onset of Patterns in an Ocillated Granular Layer: Continuum and Molecular Dynamics Simulations  

E-print Network

We study the onset of patterns in vertically oscillated layers of frictionless dissipative particles. Using both numerical solutions of continuum equations to Navier-Stokes order and molecular dynamics (MD) simulations, we find that standing waves form stripe patterns above a critical acceleration of the cell. Changing the frequency of oscillation of the cell changes the wavelength of the resulting pattern; MD and continuum simulations both yield wavelengths in accord with previous experimental results. The value of the critical acceleration for ordered standing waves is approximately 10% higher in molecular dynamics simulations than in the continuum simulations, and the amplitude of the waves differs significantly between the models. The delay in the onset of order in molecular dynamics simulations and the amplitude of noise below this onset are consistent with the presence of fluctuations which are absent in the continuum theory. The strength of the noise obtained by fit to Swift-Hohenberg theory is orders of magnitude larger than the thermal noise in fluid convection experiments, and is comparable to the noise found in experiments with oscillated granular layers and in recent fluid experiments on fluids near the critical point. Good agreement is found between the mean field value of onset from the Swift-Hohenberg fit and the onset in continuum simulations. Patterns are compared in cells oscillated at two different frequencies in MD; the layer with larger wavelength patterns has less noise than the layer with smaller wavelength patterns.

J. Bougie; J. Kreft; J. B. Swift; Harry L. Swinney

2009-09-15

159

Nanoscale patterning of a self-assembled monolayer by modification of the molecule–substrate bond  

PubMed Central

Summary The intercalation of Cu at the interface of a self-assembled monolayer (SAM) and a Au(111)/mica substrate by underpotential deposition (UPD) is studied as a means of high resolution patterning. A SAM of 2-(4'-methylbiphenyl-4-yl)ethanethiol (BP2) prepared in a structural phase that renders the Au substrate completely passive against Cu-UPD, is patterned by modification with the tip of a scanning tunneling microscope. The tip-induced defects act as nucleation sites for Cu-UPD. The lateral diffusion of the metal at the SAM–substrate interface and, thus, the pattern dimensions are controlled by the deposition time. Patterning down to the sub-20 nm range is demonstrated. The difference in strength between the S–Au and S–Cu bond is harnessed to develop the latent Cu-UPD image into a patterned binary SAM. Demonstrated by the exchange of BP2 by adamantanethiol (AdSH) this is accomplished by a sequence of reductive desorption of BP2 in Cu free areas followed by adsorption of AdSH. The appearance of Au adatom islands upon the thiol exchange suggests that the interfacial structures of BP2 and AdSH SAMs are different. PMID:24778947

Shen, Cai

2014-01-01

160

Pattern recognition analysis in complex molecule synthesis and the preparation of iso-Diels–Alder motifs  

PubMed Central

The identification of synthesizable substructural domains within more complex structural targets is of significant value in designing a workable plan of synthesis. We term this process “pattern recognition analysis” (PRA). In this paper we continued to build on the theme of PRA as a potential resource in retrosynthetic blueprints to reach highly challenging targets. The paper operates at two levels. First, there is provided a clear sense of definitions of categories by which patterns are related to hypothetical reaction types. Although the required reaction type may for the moment not exist, we believe that this method of analysis is likely to promote innovation that identifies unmet needs and opportunities to advance the cause of complex target synthesis. In addition, we describe reductions to practice in expanding the menu of achievable patterns. It is likely that the future value of PRA will be associated with its utility in leading the way to new and exploitable chemical innovation. PMID:23784777

Peng, Feng; Grote, Robin E.; Wilson, Rebecca M.; Danishefsky, Samuel J.

2013-01-01

161

Genetic basis of dental agenesis - molecular genetics patterning clinical dentistry  

PubMed Central

Tooth agenesis is one of the most common congenital malformations in humans. Hypodontia can either occur as an isolated condition (non-syndromic hypodontia) or can be associated with a syndrome (syndromic hypodontia), highlighting the heterogeneity of the condition. Though much progress has been made to identify the developmental basis of tooth formation, knowledge of the etiological basis of inherited tooth loss is still lacking. To date, the mutation spectra of non-syndromic form of familial and sporadic tooth agenesis in humans have revealed defects in various such genes that encode transcription factors, MSX1 and PAX9 or genes that code for a protein involved in canonical Wnt signaling (AXIN2), and a transmembrane receptor of fibroblast growth factors (FGFR1). The aim of this paper is to review the current literature on the molecular mechanisms responsible for selective hypodontia in humans and to present a detailed overview of causative genes and syndromes associated with hypodontia. Key words:Tooth agenesis, hypodontia, growth factors, mutations. PMID:24121910

Goswami, Mridula; Chhabra, Anuj

2014-01-01

162

An efficient approach for calculating vibrational wave functions and zero-point vibrational corrections to molecular properties of polyatomic molecules  

NASA Astrophysics Data System (ADS)

We have recently presented a formalism for calculating zero-point vibrational corrections to molecular properties of polyatomic molecules in which the contribution to the zero-point vibrational correction from the anharmonicity of the potential is included in the calculations by performing a perturbation expansion of the vibrational wave function around an effective geometry. In this paper we describe an implementation of this approach, focusing on computational aspects such as the definition of normal coordinates at a nonequilibrium geometry and the use of the Eckart frame in order to obtain accurate nonisotropic molecular properties. The formalism allows for a black-box evaluation of zero-point vibrational corrections, completed in two successive steps, requiring a total of two molecular Hessians, 6K-11 molecular gradients, and 6K-11 property evaluations, K being the number of atoms. We apply the approach to the study of a number of electric and magnetic properties—the dipole and quadrupole moments, the static and frequency-dependent polarizability, the magnetizability, the rotational g tensor and the nuclear shieldings—of the molecules hydrogen fluoride, water, ammonia, and methane. Particular attention is paid to the importance of electron correlation and of the importance of the zero-point vibrational corrections for obtaining accurate estimates of molecular properties for a direct comparison with experiment.

Ruud, Kenneth; Åstrand, Per-Olof; Taylor, Peter R.

2000-02-01

163

A two-color tunable infrared/vacuum ultraviolet spectrometer for high-resolution spectroscopy of molecules in molecular beams  

NASA Astrophysics Data System (ADS)

We describe here the key technical elements of a two-color tunable IR/VUV photoionization TOF mass spectrometer system which allows a wide-range of high-resolution experiments to be performed on a diverse range of cold molecules and clusters in a molecular beam. In particular we highlight the methods we have applied to provide efficient wavelength separation of the VUV radiation from the longer wavelength components used to generate it and discuss a number of systems that we have studied with the instrument which highlight its flexibility for use in the study of molecular spectroscopy.

Woodward, Jonathan R.; Watanabe, Hirokazu; Ishiuchi, Shun-Ichi; Fujii, Masaaki

2012-01-01

164

A two-color tunable infrared/vacuum ultraviolet spectrometer for high-resolution spectroscopy of molecules in molecular beams  

SciTech Connect

We describe here the key technical elements of a two-color tunable IR/VUV photoionization TOF mass spectrometer system which allows a wide-range of high-resolution experiments to be performed on a diverse range of cold molecules and clusters in a molecular beam. In particular we highlight the methods we have applied to provide efficient wavelength separation of the VUV radiation from the longer wavelength components used to generate it and discuss a number of systems that we have studied with the instrument which highlight its flexibility for use in the study of molecular spectroscopy.

Woodward, Jonathan R.; Watanabe, Hirokazu; Ishiuchi, Shun-Ichi; Fujii, Masaaki [Chemical Resources Laboratory, Tokyo Institute of Technology, Yokohama (Japan)

2012-01-15

165

A third-generation density-functional-theory-based method for calculating canonical molecular orbitals of large molecules.  

PubMed

We used grid-free modified Cholesky decomposition (CD) to develop a density-functional-theory (DFT)-based method for calculating the canonical molecular orbitals (CMOs) of large molecules. Our method can be used to calculate standard CMOs, analytically compute exchange-correlation terms, and maximise the capacity of next-generation supercomputers. Cholesky vectors were first analytically downscaled using low-rank pivoted CD and CD with adaptive metric (CDAM). The obtained Cholesky vectors were distributed and stored on each computer node in a parallel computer, and the Coulomb, Fock exchange, and pure exchange-correlation terms were calculated by multiplying the Cholesky vectors without evaluating molecular integrals in self-consistent field iterations. Our method enables DFT and massively distributed memory parallel computers to be used in order to very efficiently calculate the CMOs of large molecules. PMID:24622472

Hirano, Toshiyuki; Sato, Fumitoshi

2014-07-28

166

A molecular symmetry analysis of the electronic states and transition dipole moments for molecules with two torsional degrees of freedom.  

PubMed

We present a molecular symmetry analysis of electronic states and transition dipole moments for molecules which undergo large amplitude intramolecular torsions. The method is based on the correlation between the point group of the molecule at highly symmetric configurations and the molecular symmetry group. As an example, we determine the global irreducible representations of the electronic states and transition dipole moments for the quinodimethane derivative 2-[4-(cyclopenta-2,4-dien-1-ylidene)cyclohexa-2,5-dien-1-ylidene]-2H-1,3-dioxole for which two torsional degrees of freedom can be activated upon photo-excitation and construct the resulting symmetry adapted transition dipole functions. PMID:25681914

Obaid, R; Leibscher, M

2015-02-14

167

Molecular model of biaxial ordering in nematic liquid crystals composed of flat molecules with four mesogenic groups  

NASA Astrophysics Data System (ADS)

Relative stability of uniaxial and biaxial nematic phases is analyzed in a model nematic liquid crystal composed of flat molecules of C2h symmetry with four mesogenic groups rigidly linked to the same center. The generalized effective quadrupole mean-field potential is proposed and its constants are evaluated numerically for the pair intermolecular potential based on Gay-Berne interaction between mesogenic groups. The dependencies of the constants on molecular shape parameters are systematically analyzed. Order parameters of the uniaxial and biaxial nematic phases are evaluated by direct minimization of the free energy at different temperatures. The corresponding phase diagrams are obtained enabling one to study the effects of molecular model parameters on the stability regions of uniaxial and biaxial phases. The results are used to clarify the nature of experimentally observed biaxial ordering in nematic liquid crystals composed of tetrapode molecules with the same symmetry.

Gorkunov, M. V.; Osipov, M. A.; Kocot, A.; Vij, J. K.

2010-06-01

168

H2 Molecular Clusters with Embedded Molecules and Atoms as the Source of the Diffuse Interstellar Bands  

NASA Astrophysics Data System (ADS)

We suggest that the diffuse interstellar bands (DIBs) arise from absorption lines of electronic transitions in molecular clusters primarily composed of a single molecule, atom, or ion ("seed"), embedded in a single-layer shell of H2 molecules. Less abundant variants of the cluster, including two seed molecules and/or a two-layer shell of H2 molecules, may also occur. The lines are broadened, blended, and wavelength-shifted by interactions between the seed and surrounding H2 shell. We refer to these clusters as contaminated H2 clusters (CHCs). We show that CHC spectroscopy matches the diversity of observed DIB spectral profiles and provides good fits to several DIB profiles based on a rotational temperature of 10 K. CHCs arise from ~centimeter-sized, dirty H2 ice balls, called contaminated H2 ice macro-particles (CHIMPs), formed in cold, dense, giant molecular clouds (GMCs), and later released into the interstellar medium (ISM) upon GMC disruption. Attractive interactions, arising from Van der Waals and ion-induced dipole potentials, between the seeds and H2 molecules enable CHIMPs to attain centimeter-sized dimensions. When an ultraviolet (UV) photon is absorbed in the outer layer of a CHIMP, it heats the icy matrix and expels CHCs into the ISM. While CHCs are quickly destroyed by absorbing UV photons, they are replenished by the slowly eroding CHIMPs. Since CHCs require UV photons for their release, they are most abundant at, but not limited to, the edges of UV-opaque molecular clouds, consistent with the observed, preferred location of DIBs. An inherent property of CHCs, which can be characterized as nanometer size, spinning, dipolar dust grains, is that they emit in the radio-frequency region. We also show that the CHCs offer a natural explanation for the anomalous microwave emission feature in the ~10-100 GHz spectral region.

Bernstein, L. S.; Clark, F. O.; Lynch, D. K.

2013-05-01

169

Oxidation-specific epitopes are danger-associated molecular patterns recognized by pattern recognition receptors of innate immunity.  

PubMed

Oxidation reactions are vital parts of metabolism and signal transduction. However, they also produce reactive oxygen species, which damage lipids, proteins and DNA, generating "oxidation-specific" epitopes. In this review, we discuss the hypothesis that such common oxidation-specific epitopes are a major target of innate immunity, recognized by a variety of "pattern recognition receptors" (PRRs). By analogy with microbial "pathogen-associated molecular patterns" (PAMPs), we postulate that host-derived, oxidation-specific epitopes can be considered to represent "danger (or damage)-associated molecular patterns" (DAMPs). We also argue that oxidation-specific epitopes present on apoptotic cells and their cellular debris provided the primary evolutionary pressure for the selection of such PRRs. Furthermore, because many PAMPs on microbes share molecular identity and/or mimicry with oxidation-specific epitopes, such PAMPs provide a strong secondary selecting pressure for the same set of oxidation-specific PRRs as well. Because lipid peroxidation is ubiquitous and a major component of the inflammatory state associated with atherosclerosis, the understanding that oxidation-specific epitopes are DAMPs, and thus the target of multiple arcs of innate immunity, provides novel insights into the pathogenesis of atherosclerosis. As examples, we show that both cellular and soluble PRRs, such as CD36, toll-like receptor-4, natural antibodies, and C-reactive protein recognize common oxidation-specific DAMPs, such as oxidized phospholipids and oxidized cholesteryl esters, and mediate a variety of immune responses, from expression of proinflammatory genes to excessive intracellular lipoprotein accumulation to atheroprotective humoral immunity. These insights may lead to improved understanding of inflammation and atherogenesis and suggest new approaches to diagnosis and therapy. PMID:21252151

Miller, Yury I; Choi, Soo-Ho; Wiesner, Philipp; Fang, Longhou; Harkewicz, Richard; Hartvigsen, Karsten; Boullier, Agnès; Gonen, Ayelet; Diehl, Cody J; Que, Xuchu; Montano, Erica; Shaw, Peter X; Tsimikas, Sotirios; Binder, Christoph J; Witztum, Joseph L

2011-01-21

170

Self-Assembled DNA Nanostructures for Molecular Scale Patterning, Computation and Motors  

E-print Network

Self-Assembled DNA Nanostructures for Molecular Scale Patterning, Computation and Motors John H. Reif Department of Computer Science, Duke University 1 #12;DNA Nanostructures: DNA tiles: composed ACGCTCGT 2 2 1 3 4 1 4 3 DNA TX tile Nanostructures: · 3 double stranded DNA with Holiday junctions

Reif, John H.

171

Self-assembling DNA Nanostructures for Patterned Molecular Assembly Thomas H. LaBeana  

E-print Network

1 Self-assembling DNA Nanostructures for Patterned Molecular Assembly Thomas H. LaBeana , Kurt V-assembly. DNA-nanostructures provide a versatile toolbox with which to organize nanoscale materials. We begin with a discussion of DNA-nanostructures, starting with the self-assembly of various building-blocks known as DNA

Reif, John H.

172

LARGE SCALE EVALUATION OF A PATTERN RECOGNITION/EXPERT SYSTEM FOR MASS SPECTRAL MOLECULAR WEIGHT ESTIMATION  

EPA Science Inventory

A fast, personal-computer based method of estimating molecular weights of organic compounds from low resolution mass I spectra has been thoroughly evaluated. he method is based on a rule-based pattern,recognition/expert system approach which uses empirical linear corrections whic...

173

Video Article Assay for Pathogen-Associated Molecular Pattern (PAMP)-Triggered Immunity (PTI)  

E-print Network

Video Article Assay for Pathogen-Associated Molecular Pattern (PAMP)-Triggered Immunity (PTI or their activity, which leads to effector-triggered immunity (ETI)2. We describe a cell death-based assay for PTI induced by the first infiltration is able to delay or prevent the appearance of cell death due

Pawlowski, Wojtek

174

Patterning a hydrogen-bonded molecular monolayer with a hand-controlled scanning probe microscope  

PubMed Central

Summary One of the paramount goals in nanotechnology is molecular-scale functional design, which includes arranging molecules into complex structures at will. The first steps towards this goal were made through the invention of the scanning probe microscope (SPM), which put single-atom and single-molecule manipulation into practice for the first time. Extending the controlled manipulation to larger molecules is expected to multiply the potential of engineered nanostructures. Here we report an enhancement of the SPM technique that makes the manipulation of large molecular adsorbates much more effective. By using a commercial motion tracking system, we couple the movements of an operator's hand to the sub-angstrom precise positioning of an SPM tip. Literally moving the tip by hand we write a nanoscale structure in a monolayer of large molecules, thereby showing that our method allows for the successful execution of complex manipulation protocols even when the potential energy surface that governs the interaction behaviour of the manipulated nanoscale object(s) is largely unknown. PMID:25383304

Green, Matthew F B; Esat, Taner; Wagner, Christian; Leinen, Philipp; Grötsch, Alexander; Tautz, F Stefan

2014-01-01

175

Molecular analysis of different classes of RNA molecules from formalin-fixed paraffin-embedded autoptic tissues: a pilot study.  

PubMed

For a long time, it has been thought that fresh and frozen tissues are the only possible source of biological material useful to extract nucleic acids suitable for downstream molecular analysis. Recently, for forensic purpose such as personal identification, also fixed tissues have been used to recover DNA molecules, whereas RNA extracted from such material is still considered too degraded for gene expression studies. In the present pilot study, we evaluated the possibility to use forensic formalin-fixed paraffin-embedded (FFPE) samples, collected at autopsy at different postmortem intervals (PMI) from four individuals, to perform advanced molecular analyses. In particular, we performed qualitative and quantitative analyses of total RNAs extracted from different FFPE tissues and put expression profiles in relation with the organ type and the duration of PMI. Different classes of RNA molecular targets were studied by real-time quantitative RT-PCR. We report molecular evidence that small RNAs are the only RNA molecules still detectable in all the FFPE autoptic tissues. In particular, microRNAs (miRNAs) represent a consistent, stable, and well-preserved molecular target detectable even from tissue sources displaying signs of ongoing putrefaction at autopsy. In this pilot study, we show that miRNAs could represent a highly sensitive and potentially useful forensic marker. Amplification of specific miRNAs using paraffin-embedded blocks could facilitate retrospective molecular analysis using specific forensic-archived tissues chosen as most suitable according to PMI, and this approach would address molecular evidence in forensic cases in which fresh or frozen material is no longer available. PMID:25135750

Muciaccia, Barbara; Vico, Carmen; Aromatario, Mariarosaria; Fazi, Francesco; Cecchi, Rossana

2015-01-01

176

The molecular Zeeman effect in diamagnetic molecules and the determination of molecular magnetic moments (g values), magnetic susceptibilities, and molecular quadrupole moments  

Microsoft Academic Search

The experimental and theoretical literature on the molecular Zeeman effect is surveyed. The observation of the linear (H) and quadratic (H ) Zeeman effect leads to a direct determination of the molecular g values, magnetic susceptibility anisotropies and molecular quadrupole moments. The recent results are discussed and the available molecular g values, magnetic susceptibility anisotropies, and molecular quadrupole moments are

W. H. Flygare; R. C. Benson

1971-01-01

177

Pattern recognition receptors--molecular orchestrators of inflammation in inflammatory bowel disease.  

PubMed

Pattern recognition receptors (PRRs) are a family of germline encoded receptors responsible for the detection of "pathogen associated molecular patterns" (PAMPs) or host derived "damage associated molecular patterns" (DAMPs) which induce innate immune signalling to generate a pro-inflammatory profile within the host. Four main classes of PRRs are recognised, Toll-like receptors (TLRs), NOD-like receptors (NLRs), RIG-like receptors (RLRs) and C-type lectin receptors (CLRs). Abnormal activation of PRRs has been implicated in various autoimmune and inflammatory conditions including rheumatoid arthritis and asthma. Recent growing evidence has implicated these PRRs as contributory elements to the pathogenesis of inflammatory bowel disease (IBD) and colitis-associated cancer (CAC). Here, the current literature which implicates PRRs in IBD and CAC is comprehensively reviewed. PMID:23102645

Walsh, David; McCarthy, Joanna; O'Driscoll, Caitriona; Melgar, Silvia

2013-04-01

178

RNA:DNA hybrids are a novel molecular pattern sensed by TLR9  

PubMed Central

The sensing of nucleic acids by receptors of the innate immune system is a key component of antimicrobial immunity. RNA:DNA hybrids, as essential intracellular replication intermediates generated during infection, could therefore represent a class of previously uncharacterised pathogen-associated molecular patterns sensed by pattern recognition receptors. Here we establish that RNA:DNA hybrids containing viral-derived sequences efficiently induce pro-inflammatory cytokine and antiviral type I interferon production in dendritic cells. We demonstrate that MyD88-dependent signalling is essential for this cytokine response and identify TLR9 as a specific sensor of RNA:DNA hybrids. Hybrids therefore represent a novel molecular pattern sensed by the innate immune system and so could play an important role in host response to viruses and the pathogenesis of autoimmune disease. PMID:24514026

Rigby, Rachel E; Webb, Lauren M; Mackenzie, Karen J; Li, Yue; Leitch, Andrea; Reijns, Martin A M; Lundie, Rachel J; Revuelta, Ailsa; Davidson, Donald J; Diebold, Sandra; Modis, Yorgo; MacDonald, Andrew S; Jackson, Andrew P

2014-01-01

179

Peripheral Neural Detection of Danger–Associated and Pathogen–Associated Molecular Patterns  

PubMed Central

Objective: Bidirectional links between the nervous and immune systems modulate inflammation. The cellular mechanisms underlying the detection of danger-associated molecular patterns and pathogen-associated molecular patterns by the nervous system are not well understood. We hypothesized that the carotid body, a tissue of neural crest origin, detect pathogen associated molecular patterns and danger associated molecular patterns via an inflammasome-dependent mechanism similar to that described in immune cells. Design: Randomized, controlled laboratory investigation. Setting: University laboratory. Subjects: C57Bl/6J mice; juvenile Sprague-Dawley rats, primary human neutrophils. Interventions: Rat carotid body chemosensitive cells, and human neutrophils, were treated with TLR agonists to activate inflammasome-dependent pathways. In mice, systemic inflammation was induced by the pathogen associated molecular pattern zymosan (intraperitoneal injection; 500 mg/kg). Isolated carotid body/carotid sinus nerve preparations were used to assess peripheral chemoafferent activity. Ventilation was measured by whole-body plethysmography. Measurements and Main Results: Chemosensitive carotid body glomus cells exhibited toll-like receptor (TLR-2 and TLR-4), NLRP1, and NLRP3 inflammasome immunoreactivities. Zymosan increased NLRP3 inflammasome and interleukin-1? expression in glomus cells (p < 0.01). Human neutrophils demonstrated similar LPS-induced changes in inflammasome expression. Carotid body glomus cells also expressed IL-1 receptor and responded to application of IL-1? with increases in intracellular [Ca2+]. Four hours after injection of zymosan carotid sinus nerve chemoafferent discharge assessed in vitro (i.e., in the absence of acidosis/circulating inflammatory mediators) was increased five-fold (p < 0.001). Accordingly, zymosan-induced systemic inflammation was accompanied by enhanced respiratory activity. Conclusions: In carotid body chemosensitive glomus cells, activation of toll-like receptors increases NLRP3 inflammasome expression, and enhances IL-1? production, which is capable of acting in an autocrine manner to enhance peripheral chemoreceptor drive. PMID:23507714

Kazymov, Vitaly; Marina, Nephtali; Singer, Mervyn; Gourine, Alexander V.

2013-01-01

180

The molecular transport and intercalation of guest molecules into hydrogen-bonded metal-organic frameworks (HMOFs)  

NASA Astrophysics Data System (ADS)

The process of molecular transport and intercalation has been widely studied for many years, resulting in the discovery of molecular frameworks that are capable of hosting guest molecules or ions. Layered and porous metal-organic frameworks (MOFs) have been found to have applications in the field of catalysis, storage, separations, and ion-exchange. More recently, molecular components with peripheral hydrogen-bonding moieties have been used to affect the synthesis of hydrogen-bonded metal-organic frameworks (HMOFs) as an alternative to MOFs, which are interconnected via coordinate-covalent bonds. While MOFs are perhaps stronger materials, HMOFs have the advantage of being easily modifiable and more flexible. Because HMOFs have not been extensively studied for their ability to host molecules, and because their ability to withstand guest loss and guest exchange is essentially unknown, here we report the synthesis and molecular transport properties of both close-packed and porous HMOFs. Layered materials can mimic the behavior of naturally occurring clays, where guest molecules are absorbed and the layer will expand to accommodate the entering guest molecule. We have created a clay mimic composed of a metal pyridine-dicarboxylates and ammonium counterions (a layered HMOF), which is suitable for studying the ability of such materials to absorb guest molecules. We can control the distance of the interlayer region, as well as the chemical nature (hydrophobic or hydrophilic) by varying the organic amine. The metal complex contains axial water ligands that are replaceable, and such ligand exchange has precedence in coordination polymer (MOF) systems, and has been termed "coordinative intercalation". Using the synthesized layered material we examined the process of intercalation, having chosen a variety of guest molecules ranging from alkyl to aryl molecules, each of which have substituents varying in size, shape and electronics. The first set of guest molecules are non-coordinating and are theoretically capable of entering the layer and anchoring freely through the use of non-covalent interactions. The second set of guest molecules contain a pyridine moiety that can exchange with the coordinated water ligand through coordinative-intercalation. The products have been characterized by TGA, DSC, UV-Vis, and powder XRD. Further work was dedicated to examining porous materials, which were created using organic diamines, rather than simple primary amines, as starting materials. The resulting diammonium cations act as pillars, forming open channels. The predefined channel dimensions allow the insertion of specific sized guest molecules. The walls of the channel are close-packed, so that in theory guest molecules can travel in one direction through the solid. Using the synthesized pillared structure we investigated guest inclusion and selectivity through the process of co-crystallization. The stability of the pillared structure in the absence of guests is also reported, as well as the potential for the empty pillared structure to withstand guest re-insertion and removal.

Hogan, Greg Anthony

181

Sialyllactose in Viral Membrane Gangliosides Is a Novel Molecular Recognition Pattern for Mature Dendritic Cell Capture of HIV-1  

PubMed Central

HIV-1 is internalized into mature dendritic cells (mDCs) via an as yet undefined mechanism with subsequent transfer of stored, infectious virus to CD4+ T lymphocytes. Thus, HIV-1 subverts a DC antigen capture mechanism to promote viral spread. Here, we show that gangliosides in the HIV-1 membrane are the key molecules for mDC uptake. HIV-1 virus-like particles and liposomes mimicking the HIV-1 lipid composition were shown to use a common internalization pathway and the same trafficking route within mDCs. Hence, these results demonstrate that gangliosides can act as viral attachment factors, in addition to their well known function as cellular receptors for certain viruses. Furthermore, the sialyllactose molecule present in specific gangliosides was identified as the determinant moiety for mDC HIV-1 uptake. Thus, sialyllactose represents a novel molecular recognition pattern for mDC capture, and may be crucial both for antigen presentation leading to immunity against pathogens and for succumbing to subversion by HIV-1. PMID:22545022

Contreras, F.-Xabier; Rodriguez-Plata, Maria T.; Glass, Bärbel; Erkizia, Itziar; Prado, Julia G.; Casas, Josefina; Fabriàs, Gemma; Kräusslich, Hans-Georg; Martinez-Picado, Javier

2012-01-01

182

Theoretical Study of Donor - Spacer - Acceptor Structure Molecule for Molecular Rectifier  

Microsoft Academic Search

Recently, the molecular electronics has attracted strong attention as a ``post-silicone technology'' to establish a future nanoscale electronic devices. To realize this molecular device, unimolecular rectifiering function is one of the most important constituents in nanotechnology [C. Majumder, H. Mizuseki, and Y. Kawazoe, Molecular Scale Rectifier: Theoretical Study, J. Phys. Chem. A, 105 (2001) 9454-9459.]. In the present study, the

Hiroshi Mizuseki; Niimura Kenji; Rodion Belosludov; Amir Farajian; Yoshiyuki Kawazoe; C. Majumder

2003-01-01

183

A Recombinant Horseshoe Crab Plasma Lectin Recognizes Specific Pathogen-Associated Molecular Patterns of Bacteria through Rhamnose  

PubMed Central

Horseshoe crab is an ancient marine arthropod that, in the absence of a vertebrate-like immune system, relies solely on innate immune responses by defense molecules found in hemolymph plasma and granular hemocytes for host defense. A plasma lectin isolated from the hemolymph of Taiwanese Tachypleus tridentatus recognizes bacteria and lipopolysaccharides (LPSs), yet its structure and mechanism of action remain unclear, largely because of limited availability of horseshoe crabs and the lack of a heterogeneous expression system. In this study, we have successfully expressed and purified a soluble and functional recombinant horseshoe crab plasma lectin (rHPL) in an Escherichia coli system. Interestingly, rHPL bound not only to bacteria and LPSs like the native HPL but also to selective medically important pathogens isolated from clinical specimens, such as Gram-negative Pseudomonas aeruginosa and Klebsiella pneumoniae and Gram-positive Streptococcus pneumoniae serotypes. The binding was demonstrated to occur through a specific molecular interaction with rhamnose in pathogen-associated molecular patterns (PAMPs) on the bacterial surface. Additionally, rHPL inhibited the growth of P. aeruginosa PAO1 in a concentration-dependent manner. The results suggest that a specific protein-glycan interaction between rHPL and rhamnosyl residue may further facilitate development of novel diagnostic and therapeutic strategies for microbial pathogens. PMID:25541995

Ng, Sim-Kun; Huang, Yu-Tsyr; Lee, Yuan-Chuan; Low, Ee-Ling; Chiu, Cheng-Hsun; Chen, Shiu-Ling; Mao, Liang-Chi; Chang, Margaret Dah-Tsyr

2014-01-01

184

A recombinant horseshoe crab plasma lectin recognizes specific pathogen-associated molecular patterns of bacteria through rhamnose.  

PubMed

Horseshoe crab is an ancient marine arthropod that, in the absence of a vertebrate-like immune system, relies solely on innate immune responses by defense molecules found in hemolymph plasma and granular hemocytes for host defense. A plasma lectin isolated from the hemolymph of Taiwanese Tachypleus tridentatus recognizes bacteria and lipopolysaccharides (LPSs), yet its structure and mechanism of action remain unclear, largely because of limited availability of horseshoe crabs and the lack of a heterogeneous expression system. In this study, we have successfully expressed and purified a soluble and functional recombinant horseshoe crab plasma lectin (rHPL) in an Escherichia coli system. Interestingly, rHPL bound not only to bacteria and LPSs like the native HPL but also to selective medically important pathogens isolated from clinical specimens, such as Gram-negative Pseudomonas aeruginosa and Klebsiella pneumoniae and Gram-positive Streptococcus pneumoniae serotypes. The binding was demonstrated to occur through a specific molecular interaction with rhamnose in pathogen-associated molecular patterns (PAMPs) on the bacterial surface. Additionally, rHPL inhibited the growth of P. aeruginosa PAO1 in a concentration-dependent manner. The results suggest that a specific protein-glycan interaction between rHPL and rhamnosyl residue may further facilitate development of novel diagnostic and therapeutic strategies for microbial pathogens. PMID:25541995

Ng, Sim-Kun; Huang, Yu-Tsyr; Lee, Yuan-Chuan; Low, Ee-Ling; Chiu, Cheng-Hsun; Chen, Shiu-Ling; Mao, Liang-Chi; Chang, Margaret Dah-Tsyr

2014-01-01

185

Recognizing molecular patterns by machine learning: an agnostic structural definition of the hydrogen bond  

E-print Network

The concept of chemical bonding can ultimately be seen as a rationalization of the recurring structural patterns observed in molecules and solids. Chemical intuition is nothing but the ability to recognize and predict such patterns, and how they transform into one another. Here we discuss how to use a computer to identify atomic patterns automatically, so as to provide an algorithmic definition of a bond based solely on structural information. We concentrate in particular on hydrogen bonding -- a central concept to our understanding of the physical chemistry of water, biological systems and many technologically important materials. Since the hydrogen bond is a somewhat fuzzy entity that covers a broad range of energies and distances, many different criteria have been proposed and used over the years, based either on sophisticate electronic structure calculations followed by an energy decomposition analysis, or on somewhat arbitrary choices of a range of structural parameters that is deemed to correspond to a ...

Gasparotto, Piero

2014-01-01

186

Large-area ordered Ge-Si compound quantum dot molecules on dot-patterned Si (001) substrates.  

PubMed

We report on the formation of large-area ordered Ge-Si compound quantum dot molecules (CQDMs) in a combination of nanosphere lithography and self-assembly. Truncated-pyramid-like Si dots with {11n} facets are readily formed, which are spatially ordered in a large area with controlled period and size. Each Si dot induces four self-assembled Ge-rich dots at its base edges that can be fourfold symmetric along <110> directions. A model based on surface chemical potential accounts well for these phenomena. Our results disclose the critical effect of surface curvature on the diffusion and the aggregation of Ge adatoms and shed new light on the unique features and the inherent mechanism of self-assembled QDs on patterned substrates. Such a configuration of one Si QD surrounded by fourfold symmetric Ge-rich QDs can be seen as a CQDM with unique features, which will have potential applications in novel devices. PMID:25078348

Lei, Hui; Zhou, Tong; Wang, Shuguang; Fan, Yongliang; Zhong, Zhenyang

2014-08-29

187

Imaging molecular structure through femtosecond photoelectron diffraction on aligned and oriented gas-phase molecules.  

PubMed

This paper gives an account of our progress towards performing femtosecond time-resolved photoelectron diffraction on gas-phase molecules in a pump-probe setup combining optical lasers and an X-ray free-electron laser. We present results of two experiments aimed at measuring photoelectron angular distributions of laser-aligned 1-ethynyl-4-fluorobenzene (C8H5F) and dissociating, laser-aligned 1,4-dibromobenzene (C6H4Br2) molecules and discuss them in the larger context of photoelectron diffraction on gas-phase molecules. We also show how the strong nanosecond laser pulse used for adiabatically laser-aligning the molecules influences the measured electron and ion spectra and angular distributions, and discuss how this may affect the outcome of future time-resolved photoelectron diffraction experiments. PMID:25290160

Boll, Rebecca; Rouzée, Arnaud; Adolph, Marcus; Anielski, Denis; Aquila, Andrew; Bari, Sadia; Bomme, Cédric; Bostedt, Christoph; Bozek, John D; Chapman, Henry N; Christensen, Lauge; Coffee, Ryan; Coppola, Niccola; De, Sankar; Decleva, Piero; Epp, Sascha W; Erk, Benjamin; Filsinger, Frank; Foucar, Lutz; Gorkhover, Tais; Gumprecht, Lars; Hömke, André; Holmegaard, Lotte; Johnsson, Per; Kienitz, Jens S; Kierspel, Thomas; Krasniqi, Faton; Kühnel, Kai-Uwe; Maurer, Jochen; Messerschmidt, Marc; Moshammer, Robert; Müller, Nele L M; Rudek, Benedikt; Savelyev, Evgeny; Schlichting, Ilme; Schmidt, Carlo; Scholz, Frank; Schorb, Sebastian; Schulz, Joachim; Seltmann, Jörn; Stener, Mauro; Stern, Stephan; Techert, Simone; Thøgersen, Jan; Trippel, Sebastian; Viefhaus, Jens; Vrakking, Marc; Stapelfeldt, Henrik; Küpper, Jochen; Ullrich, Joachim; Rudenko, Artem; Rolles, Daniel

2014-01-01

188

Molecular tunneling ionization of the carbonyl sulfide molecule by double-frequency phase-controlled laser fields  

NASA Astrophysics Data System (ADS)

We have investigated the orientation-selective molecular tunneling ionization of carbonyl sulfide (OCS) molecules induced by linearly polarized double-frequency phase-controlled laser fields consisting of a fundamental and a second-harmonic light with a pulse duration of 130 fs and an intensity of 5 × 1013 W/cm2. We performed simultaneous measurements using gas mixtures of OCS and carbon monoxide to calibrate the relative phase difference of the phase-controlled fields and to verify the mechanism of the tunnel ionization. It is demonstrated that there is a definite correlation between the orientation of ionized molecules and the structure of the highest occupied molecular orbital. We have discussed the experimental results by means of the weak field asymptotic theory. In addition, we have analyzed the quantum dynamics of photoelectrons in simultaneous ion-electron detection. The experimental results can be explained by a two-step model including the interaction with the parent ion. The recollision process plays a minor role for determining the preferable directions of polar molecules in the tunneling ionization at the experimental laser intensity used.

Ohmura, Hideki; Saito, Naoaki; Morishita, Toru

2014-01-01

189

Movies of molecular motions and reactions: the single-molecule, real-time transmission electron microscope imaging technique.  

PubMed

"The truth is, the Science of Nature has been already too long made only a work of the Brain and the Fancy: It is now high time that it should return to the plainness and soundness of Observations on material and obvious things," proudly declared Robert Hooke in his highly successful picture book of microscopic and telescopic images, "Micrographia" in 1665. Hooke's statement has remained true in chemistry, where a considerable work of the brain and the fancy is still necessary. Single-molecule, real-time transmission electron microscope (SMRT-TEM) imaging at an atomic resolution now allows us to learn about molecules simply by watching movies of them. Like any dream come true, the new analytical technique challenged the old common sense of the communities, and offers new research opportunities that are unavailable by conventional methods. With its capacity to visualize the motions and the reactions of individual molecules and molecular clusters, the SMRT-TEM technique will become an indispensable tool in molecular science and the engineering of natural and synthetic substances, as well as in science education. PMID:23280645

Nakamura, Eiichi

2013-01-01

190

Effect of an improved molecular potential on strong-field tunneling ionization of molecules  

SciTech Connect

We study the effect of one-electron model potentials on the tunneling ionization rates of molecules in strong fields. By including electron correlation using the modified Leeuwen-Baerends (LB {alpha}) model, the binding energies of outer shells of molecules are significantly improved. However, we show that the tunneling ionization rates from the LB {alpha} do not differ much from the earlier calculations [Phys. Rev. A 81, 033423 (2010)], in which the local correlation potential was neglected.

Zhao Songfeng; Jin Cheng [J. R. Macdonald Laboratory, Physics Department, Kansas State University, Manhattan, Kansas 66506-2604 (United States); College of Physics and Electronic Engineering, Northwest Normal University, Lanzhou, Gansu 730070 (China); Le, Anh-Thu; Lin, C. D. [J. R. Macdonald Laboratory, Physics Department, Kansas State University, Manhattan, Kansas 66506-2604 (United States)

2010-09-15

191

Effect of solution viscosity on generating long DNA nanostrands array via patterned molecular combing  

NASA Astrophysics Data System (ADS)

In this study, we have investigated the effect of solution viscosity on generating the aligned and long DNA nanostrands array via modified molecular combing/soft lithography technique (or patterned molecular combing). By using the solution with higher viscosity, a low peeling-off speed can be applied to generate the long DNA nanostrands and the thornlike structures can be eliminated effectively. The DNA nanostrands array can also be generated by utilizing the polydimethylsiloxane stamp having microwells with larger diameter; however, variation of the lengths of the DNA nanostrands becomes greater as the solution viscosity and the size of microwells increase.

Cheng, Jun-Jie; Chang, Yuan-Hsin; Huang, Wan-Yu; Juang, Yi-Je

2009-06-01

192

Extended molecular Ornstein-Zernike integral equation for fully anisotropic solute molecules: formulation in a rectangular coordinate system.  

PubMed

An extended molecular Ornstein-Zernike (XMOZ) integral equation is formulated to calculate the spatial distribution of solvent around a solute of arbitrary shape and solid surfaces. The conventional MOZ theory employs spherical harmonic expansion technique to treat the molecular orientation of components of solution. Although the MOZ formalism is fully exact analytically, the truncation of the spherical harmonic expansion requires at a finite order for numerical calculation and causes the significant error for complex molecules. The XMOZ integral equation is the natural extension of the conventional MOZ theory to a rectangular coordinate system, which is free from the truncation of spherical harmonic expansion with respect to solute orientation. In order to show its applicability, we applied the XMOZ theory to several systems using the hypernetted-chain (HNC) and Kovalenko-Hirata approximations. The quality of results obtained within our theory is discussed by comparison with values from the conventional MOZ theory, molecular dynamics simulation, and three-dimensional reference interaction site model theory. The spatial distributions of water around the complex of non-charged sphere and dumbbell were calculated. Using this system, the approximation level of the XMOZ and other methods are discussed. To assess our theory, we also computed the excess chemical potentials for three realistic molecules (water, methane, and alanine dipeptide). We obtained the qualitatively reasonable results by using the XMOZ/HNC theory. The XMOZ theory covers a wide variety of applications in solution chemistry as a useful tool to calculate solvation thermodynamics. PMID:24006986

Ishizuka, Ryosuke; Yoshida, Norio

2013-08-28

193

Extended molecular Ornstein-Zernike integral equation for fully anisotropic solute molecules: Formulation in a rectangular coordinate system  

NASA Astrophysics Data System (ADS)

An extended molecular Ornstein-Zernike (XMOZ) integral equation is formulated to calculate the spatial distribution of solvent around a solute of arbitrary shape and solid surfaces. The conventional MOZ theory employs spherical harmonic expansion technique to treat the molecular orientation of components of solution. Although the MOZ formalism is fully exact analytically, the truncation of the spherical harmonic expansion requires at a finite order for numerical calculation and causes the significant error for complex molecules. The XMOZ integral equation is the natural extension of the conventional MOZ theory to a rectangular coordinate system, which is free from the truncation of spherical harmonic expansion with respect to solute orientation. In order to show its applicability, we applied the XMOZ theory to several systems using the hypernetted-chain (HNC) and Kovalenko-Hirata approximations. The quality of results obtained within our theory is discussed by comparison with values from the conventional MOZ theory, molecular dynamics simulation, and three-dimensional reference interaction site model theory. The spatial distributions of water around the complex of non-charged sphere and dumbbell were calculated. Using this system, the approximation level of the XMOZ and other methods are discussed. To assess our theory, we also computed the excess chemical potentials for three realistic molecules (water, methane, and alanine dipeptide). We obtained the qualitatively reasonable results by using the XMOZ/HNC theory. The XMOZ theory covers a wide variety of applications in solution chemistry as a useful tool to calculate solvation thermodynamics.

Ishizuka, Ryosuke; Yoshida, Norio

2013-08-01

194

Toward Molecular Mechanism of Xenon Anesthesia: A Link to Studies of Xenon Complexes with Small Aromatic Molecules.  

PubMed

The present study illustrates the steps toward understanding molecular mechanism of xenon anesthesia by focusing on a link to the structures and spectra of intermolecular complexes of xenon with small aromatic molecules. A primary cause of xenon anesthesia is attributed to inhibition of N-methyl-d-aspartate (NMDA) receptors by an unknown mechanism. Following the results of quantum mechanics/molecular mechanics (QM/MM) and molecular dynamics (MD) calculations we report plausible xenon action sites in the ligand binding domain of the NMDA receptor, which are due to interaction of xenon atoms with aromatic amino-acid residues. We rely in these calculations on computational protocols adjusted in combined experimental and theoretical studies of intermolecular complexes of xenon with phenol. Successful reproduction of vibrational shifts in molecular species upon complexation with xenon measured in low-temperature matrices allowed us to select a proper functional form in density functional theory (DFT) approach for use in QM subsystems, as well as to calibrate force field parameters for MD simulations. The results of molecular modeling show that xenon atoms can compete with agonists for a place in the corresponding protein cavity, thus indicating their active role in anesthetic action. PMID:25285819

Andrijchenko, Natalya N; Ermilov, Alexander Yu; Khriachtchev, Leonid; Räsänen, Markku; Nemukhin, Alexander V

2014-10-15

195

Molecular-orbital decomposition of the ionization continuum for a diatomic molecule by angle-and energy-resolved photoelectron spectroscopy.  

E-print Network

the NO A 2 0 state to each partial wave in the ionization continuum that yields the NO X 1 0 ion, provideMolecular-orbital decomposition of the ionization continuum for a diatomic molecule by angle distributions PADs from the direct photoionization of a diatomic molecule in which both the ionizing state

Zare, Richard N.

196

Host-guest interactions in the confined geometries formed from molecular aggregates of push-pull molecules.  

PubMed

We have considered push-pull molecules, aminonitroacetylene and aminonitrodiacetylene (O2N-(C?C)n-NH2; n = 1 and 2) as the basic units to design a series of molecular aggregates containing favorable hydrogen bonding interactions. Linear, closed, and stacked geometries of dimers, trimers, tetramers, and pentamers formed from these molecules are found to have very good stabilization energies due to the strong hydrogen bonding abilities of the terminal -NO2 and -NH2 groups. The closed hydrogen-bonded assemblies can act as supramolecular hosts for accommodating some molecules and ions as guests. We have been able to find substantial host-guest interaction energies for the complexes of the hydrogen-bonded closed assemblies with some highly reactive molecules like hexahydro-1,3,5-trinitro-s-triazine (RDX), octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX), pentafluoroethane (R-125), and difluoromethane (R-32). Further investigations on the interaction of the ions Li(+), Na(+), K(+), Mg(2+), Ca(2+), Al(3+), F(-), Cl(-), and Br(-) with the monomers as well as the oligomers reveal the formation of strong ion-? complexes, unlike the conventional weak ion-? complexes found in similar acetylenic systems without the end groups. This opens up the possibility of tuning the nature of ionic interactions in ?-systems by varying the terminal groups. PMID:23772692

K, Rohini; Swathi, R S

2013-07-18

197

Oligogalacturonides: plant damage-associated molecular patterns and regulators of growth and development  

PubMed Central

Oligogalacturonides (OGs) are oligomers of alpha-1,4-linked galacturonosyl residues released from plant cell walls upon partial degradation of homogalacturonan. OGs are able to elicit defense responses, including accumulation of reactive oxygen species and pathogenesis-related proteins, and protect plants against pathogen infections. Recent studies demonstrated that OGs are perceived by wall-associated kinases and share signaling components with microbe-associated molecular patterns. For this reason OGs are now considered true damage-associated molecular patterns that activate the plant innate immunity and may also be involved in the activation of responses to mechanical wounding. Furthermore, OGs appear to modulate developmental processes, likely through their ability to antagonize auxin responses. Here we review our current knowledge on the role and mode of action of this class of oligosaccharides in plant defense and development. PMID:23493833

Ferrari, Simone; Savatin, Daniel V.; Sicilia, Francesca; Gramegna, Giovanna; Cervone, Felice; Lorenzo, Giulia De

2013-01-01

198

Calculating Structures and Free Energies of Complex Molecules:  Combining Molecular Mechanics and Continuum Models  

Microsoft Academic Search

A historical perspective on the application of molecular dynamics (MD) to biological macromolecules is presented. Recent develop- ments combining state-of-the-art force fields with continuum solvation calculations have allowed us to reach the fourth era of MD applications in which one can often derive both accurate structure and accurate relative free energies from molecular dynam- ics trajectories. We illustrate such applications

Peter A. Kollman; Irina Massova; Carolina Reyes; Bernd Kuhn; Shuanghong Huo; Lillian Chong; Matthew Lee; Taisung Lee; Yong Duan; Wei Wang; Oreola Donini; Piotr Cieplak; Jaysharee Srinivasan; David A. Case; Thomas E. Cheatham

2000-01-01

199

Walking Molecules   

E-print Network

Inspired by the motor protein kinesin, an ambitious and unprecedented mimic is proposed – a synthetic molecular motor that can walk. This thesis aims to explain the basic principles which define such walking molecules, ...

Symes, Mark D

2009-01-01

200

Design and development of a field-deployable single-molecule detector (SMD) for the analysis of molecular markers†  

PubMed Central

Single-molecule detection (SMD) has demonstrated some attractive benefits for many types of biomolecular analyses including enhanced processing speed by eliminating processing steps, elimination of ensemble averaging and single-molecule sensitivity. However, it's wide spread use has been hampered by the complex instrumentation required for its implementation when using fluorescence as the readout modality. We report herein a simple and compact fluorescence single-molecule instrument that is straightforward to operate and consisted of fiber optics directly coupled to a microfluidic device. The integrated fiber optics served as waveguides to deliver the laser excitation light to the sample and collecting the resulting emission, simplifying the optical requirements associated with traditional SMD instruments by eliminating the need for optical alignment and simplification of the optical train. Additionally, the use of a vertical cavity surface emitting laser and a single photon avalanche diode serving as the excitation source and photon transducer, respectively, as well as a field programmable gate array (FPGA) integrated into the processing electronics assisted in reducing the instrument footprint. This small footprint SMD platform was tested using fluorescent microspheres and single AlexaFluor 660 molecules to determine the optimal operating parameters and system performance. As a demonstration of the utility of this instrument for biomolecular analyses, molecular beacons (MBs) were designed to probe bacterial cells for the gene encoding Gram-positive species. The ability to monitor biomarkers using this simple and portable instrument will have a number of important applications, such as strain-specific detection of pathogenic bacteria or the molecular diagnosis of diseases requiring rapid turn-around-times directly at the point-of-use. PMID:22005669

Emory, Jason M.; Peng, Zhiyong; Young, Brandon; Hupert, Mateusz L.; Rousselet, Arnold; Patterson, Donald; Ellison, Brad; Soper, Steven A.

2012-01-01

201

What can be learned about molecular reorientation from single molecule polarization microscopy?  

NASA Astrophysics Data System (ADS)

We have developed a general approach for the calculation of the single molecule polarization correlation function C(t ), which delivers a correlation of the emission dichroisms at time 0 and t. The approach is model independent and valid for general asymmetric top molecules. The key dynamic quantities of our analysis are the even-rank orientational correlation functions, the weighted sum of which yields C(t ). We have demonstrated that the use of nonorthogonal schemes for the detection of the single molecule polarization responses makes it possible to manipulate the weighting coefficients in the expansion of C(t ). Thus valuable information about the orientational correlation functions of the rank higher than the second can be extracted from C(t ).

Gelin, M. F.; Kosov, D. S.

2006-08-01

202

Molecular locks and keys: the role of small molecules in phytohormone research  

PubMed Central

Plant adaptation, growth and development rely on the integration of many environmental and endogenous signals that collectively determine the overall plant phenotypic plasticity. Plant signaling molecules, also known as phytohormones, are fundamental to this process. These molecules act at low concentrations and regulate multiple aspects of plant fitness and development via complex signaling networks. By its nature, phytohormone research lies at the interface between chemistry and biology. Classically, the scientific community has always used synthetic phytohormones and analogs to study hormone functions and responses. However, recent advances in synthetic and combinational chemistry, have allowed a new field, plant chemical biology, to emerge and this has provided a powerful tool with which to study phytohormone function. Plant chemical biology is helping to address some of the most enduring questions in phytohormone research such as: Are there still undiscovered plant hormones? How can we identify novel signaling molecules? How can plants activate specific hormone responses in a tissue-specific manner? How can we modulate hormone responses in one developmental context without inducing detrimental effects on other processes? The chemical genomics approaches rely on the identification of small molecules modulating different biological processes and have recently identified active forms of plant hormones and molecules regulating many aspects of hormone synthesis, transport and response. We envision that the field of chemical genomics will continue to provide novel molecules able to elucidate specific aspects of hormone-mediated mechanisms. In addition, compounds blocking specific responses could uncover how complex biological responses are regulated. As we gain information about such compounds we can design small alterations to the chemical structure to further alter specificity, enhance affinity or modulate the activity of these compounds. PMID:25566283

Fonseca, Sandra; Rosado, Abel; Vaughan-Hirsch, John; Bishopp, Anthony; Chini, Andrea

2014-01-01

203

Direct observation of molecularly-aligned molecules in the second physisorbed layer-CO/Ag(110)  

SciTech Connect

We report the direct observation of oriented second-layer physisorbed molecules on a single crystal surface by electron stimulated desorption. Experiments and simulations show that the orientation of the second-layer physisorbed CO molecules on Ag(110) is the result of both electrostatic and dispersion forces from the underlying chemisorbed CO and Ag atoms. At 25 K, the physisorbed C-O bond is tilted and azimuthally oriented with the C-O bond axis inclined in an azimuthal plane at 45° to the principal Ag( 110) azimuthal crystallographic directions. The O atom in CO is directed outward, giving an O+ beam at 43° to the normal.

Lee, J.-G. (Chevron Science Center, Pittsburgh, PA); Hong, S.-H. (Chevron Science Center, Pittsburgh, PA); Ahner, J. (Chevron Science Center, Pittsburgh, PA); Zhao, X. (Univ. of Pittsburgh, PA); Chen, L.; Johnson, J.K.; Yates, J.T., Jr. (Chevron Science Center, Pittsburgh, PA)

2006-01-25

204

Absolute Single-Molecule Entropies from Quasi-Harmonic Analysis of Microsecond Molecular Dynamics: Correction Terms and Convergence Properties  

PubMed Central

The convergence properties of the absolute single-molecule configurational entropy and the correction terms used to estimate it are investigated using microsecond molecular dynamics simulation of a peptide test system and an improved methodology. The results are compared with previous applications for systems of diverse chemical nature. It is shown that (i) the effect of anharmonicity is small, (ii) the effect of pairwise correlation is typically large, and (iii) the latter affects to a larger extent the entropy estimate of thermodynamic states characterized by a higher motional correlation. The causes of such deviations from a quasi-harmonic behavior are explained. This improved approach provides entropies also for molecular systems undergoing conformational transitions and characterized by highly frustrated energy surfaces, thus not limited to systems sampling a single quasi-harmonic basin. Overall, this study emphasizes the need for extensive phase-space sampling in order to obtain a reliable estimation of entropic contributions. PMID:20011626

2009-01-01

205

Small molecule inhibitors of histone arginine methyltransferases: homology modeling, molecular docking, binding mode analysis, and biological evaluations.  

PubMed

The screening of the inhibition capabilities of dye-like small molecules from a focused library against both human PRMT1 and Aspergillus nidulans RmtA is reported as well as molecular modeling studies (homology modeling, molecular docking, and 3-D QSAR) of the catalytic domain of the PRMT1 fungal homologue RmtA. The good correlation between computational and biological results makes RmtA a reliable tool for screening arginine methyltransferase inhibitors. In addition, the binding mode analyses of tested derivatives reveal the crucial role of two regions, the pocket formed by Ile12, His13, Met16, and Thr49 and the SAM cisteinic binding site subsite. These regions should be taken into account in the design of novel PRMT inhibitors. PMID:17323938

Ragno, Rino; Simeoni, Silvia; Castellano, Sabrina; Vicidomini, Caterina; Mai, Antonello; Caroli, Antonella; Tramontano, Anna; Bonaccini, Claudia; Trojer, Patrick; Bauer, Ingo; Brosch, Gerald; Sbardella, Gianluca

2007-03-22

206

'Molecules and monkeys': George Gaylord Simpson and the challenge of molecular evolution.  

PubMed

In this paper, I analyze George Gaylord Simpson's response to the molecularization of evolutionary biology from his unique perspective as a paleontologist. I do so by exploring his views on early attempts to reconstruct phylogenetic relationships among primates using molecular data. Particular attention is paid to Simpson's role in the evolutionary synthesis of the 1930s and 1940s, as well as his concerns about the rise of molecular biology as a powerful discipline and world-view in the 1960s. I argue that Simpson's belief in the supremacy of natural selection as the primary driving force of evolution, as well as his view that biology was a historical science that seeks ultimate causes and highlights contingency, prevented him from acknowledging that the study of molecular evolution was an inherently valuable part of the life sciences. PMID:15045833

Aronson, Jay D

2002-01-01

207

Quasi- and inelastic neutron scattering to investigate the molecular dynamics of discotic molecules in the bulk  

NASA Astrophysics Data System (ADS)

In- and quasielastic neutron scattering is employed to investigate both the vibrational density of states and the molecular dynamics of two homologous discotic liquid crystals (DLC) with different length of the alkyl side chain based on a triphenylene derivate. For both compounds characteristic low frequency excess contributions to the vibrational density of states are found. Therefore it is concluded that these liquid crystals show a glass-like behaviour. Elastic scans further show that in these materials a rich molecular dynamics takes place.

Krause, Christina; Zorn, Reiner; Frick, Bernhard; Schönhals, Andreas

2015-01-01

208

Conductance of Alkanedithiol Single-Molecule Junctions: A Molecular Dynamics Study  

Microsoft Academic Search

We study the formation and conductance of alkanedithiol molecular wire junctions using density- functional based molecular dynamics and non-equilibrium Green's function techniques. The stretch- ing of the junction involves straightening of the wire, migration of thiol end-groups on the Au contact surfaces and pulling out of Au atoms. The low-bias conductance traces show clear plateaux which magnitude is found to

Magnus Paulsson; Casper Krag; Thomas Frederiksen; Mads Brandbyge

2009-01-01

209

Tonal Interface to MacroMolecules (TIMMol): A Textual and Tonal Tool for Molecular Visualization  

ERIC Educational Resources Information Center

We developed the three-dimensional visualization software, Tonal Interface to MacroMolecules or TIMMol, for studying atomic coordinates of protein structures. Key features include audio tones indicating x, y, z location, identification of the cursor location in one-dimensional and three-dimensional space, textual output that can be easily linked…

Cordes, Timothy J.; Carlson, C. Britt; Forest, Katrina T.

2008-01-01

210

Influence of molecular size, polarity and charge on the retention of organic molecules by nanofiltration  

Microsoft Academic Search

Because of the growing interest in nanofiltration for industrial use, a better insight in the retention mechanisms in nanofiltration is needed, which will make it possible to understand membrane performances for specific applications. In this paper, the retention of a series of organic molecules by four nanofiltration membranes was studied. The membranes that were used are NF70 (Dow\\/FilmTec), NTR 7450

B. Van der Bruggen; J. Schaep; D. Wilms; C. Vandecasteele

1999-01-01

211

Molecular structures of gas-phase polyatomic molecules determined by spectroscopic methods  

Microsoft Academic Search

Spectroscopic data related to the structures of polyatomic molecules in the gas phase have been reviewed, critically evaluated, and compiled. All reported bond distances and angles have been classified as equilibrium (re), average (rz), substitution (rs), or effective (ro) parameters, and have been given a quality rating which is a measure of the parameter uncertainty. The surveyed literature includes work

Marlin D. Harmony; Victor W. Laurie; Robert L. Kuczkowski; R. H. Schwendeman; D. A. Ramsay; Frank J. Lovas; Walter J. Lafferty; Arthur G. Maki

1979-01-01

212

The nociceptin receptor (NOPR) and its interaction with clinically important agonist molecules: a membrane molecular dynamics simulation study.  

PubMed

The nociceptin receptor (NOPR) is an orphan G protein-coupled receptor that contains seven transmembrane helices. NOPR has a distinct mechanism of activation, though it shares a significant homology with other opioid receptors. Previously there have been reports on homology modeling of NOPR and also molecular dynamics simulation studies for a short period. Recently the crystal structure of NOPR was reported. In this study, we analyzed the time dependent behavior of NOPR docked with clinically important agonist molecules such as NOP (natural agonist) peptide and compound 10 (SCH-221510 derivative) using molecular dynamics simulations (MDS) for 100 ns. Molecular dynamics simulations of NOPR-agonist complexes allowed us to refine the system and to also identify stable structures with better binding modes. Structure activity relationships (SAR) for SCH221510 derivatives were investigated and reasons for the activities of these derivatives were determined. Our molecular dynamics trajectory analysis of NOPR-peptide and NOPR-compound 10 complexes found residues to be crucial for binding. Mutagenesis studies on the residues identified from our analysis could prove useful. Our results could also provide useful information in the structure-based drug design of novel and potent agonists targeting NOPR. PMID:25259728

Kothandan, Gugan; Gadhe, Changdev G; Balupuri, Anand; Ganapathy, Jagadeesan; Cho, Seung Joo

2014-12-01

213

Resonance enhanced multiphoton and single-photon ionization of molecules and molecular fragments. Final report, May 1993--April 1997  

SciTech Connect

Resonance enhanced multiphoton ionization (REMPI) utilizes pulsed laser radiation to prepare a molecule in an excited state via absorption of one or more photons and to subsequently ionize that level before it decays. A remarkable feature of REMPI is that the very narrow bandwidth of laser radiation makes it possible to select a specific rotational level in the initial (ground) state and to prepare the excited state of interest in a single rotational level. Thus, by suitable choice of the excitation step, it is possible to selectively ionize a species that may be present. The key objective of the effort is to carry out quantitative studies of REMPI of molecules and molecular fragments, as well as of single-photon ionization of these species by coherent VUV radiation, in order to provide a robust description of significant spectral features of interest in related experiments and needed insight into the underlying dynamics of these spectra. A major focus of the effort is joint theoretical and experimental studies of these ion rotational distributions which are being widely studied by the zero-kinetic-energy (ZEKE) technique. This technique, which is based on the detection of photoelectrons resulting from pulsed-field ionization of very high Rydberg states lying just below an ion threshold, makes it possible to obtain cation distributions with subwavenumber resolution. The unprecedented resolution of this ZEKE technique is opening up entirely new vistas in studies of photoionization dynamics, ion spectroscopy, and state-selected ion-molecule reactions. Emerging applications built on the ultra-high resolution of this technique include its use for accurate determination of thermochemically important ionization energies, for characterization of ion rovibrational level structure of large organic molecules, of elemental clusters, and of weakly bound molecular complexes, for probing reactive fragments, and for pump-probe photoelectron studies of wavepacket dynamics. This surge of experimental activity in ultra-high resolution studies of molecular photoelectron spectra continues to raise new theoretical challenges and has provided the stimulus for several of the collaborations with experimental groups in North America and Europe.

McKoy, V.

1998-09-01

214

Modeling Stochastic Kinetics of Molecular Machines at Multiple Levels: From Molecules to Modules  

PubMed Central

A molecular machine is either a single macromolecule or a macromolecular complex. In spite of the striking superficial similarities between these natural nanomachines and their man-made macroscopic counterparts, there are crucial differences. Molecular machines in a living cell operate stochastically in an isothermal environment far from thermodynamic equilibrium. In this mini-review we present a catalog of the molecular machines and an inventory of the essential toolbox for theoretically modeling these machines. The tool kits include 1), nonequilibrium statistical-physics techniques for modeling machines and machine-driven processes; and 2), statistical-inference methods for reverse engineering a functional machine from the empirical data. The cell is often likened to a microfactory in which the machineries are organized in modular fashion; each module consists of strongly coupled multiple machines, but different modules interact weakly with each other. This microfactory has its own automated supply chain and delivery system. Buoyed by the success achieved in modeling individual molecular machines, we advocate integration of these models in the near future to develop models of functional modules. A system-level description of the cell from the perspective of molecular machinery (the mechanome) is likely to emerge from further integrations that we envisage here. PMID:23746505

Chowdhury, Debashish

2013-01-01

215

The signature molecular descriptor. 2. Enumerating molecules from their extended valence sequences.  

PubMed

We present a new algorithm that enumerates molecular structures matching a predefined extended valence sequence or signature. The algorithm can construct molecular structures composed of about 50 non-hydrogen atoms in CPU seconds time scale. The algorithm is run to produce all molecular structures matching the binding affinities (IC(50)) of some HIV-1 protease inhibitors. The algorithm is also used to compute the degeneracy, or the number of molecular structures, corresponding to a given signature. Signature degeneracy is systematically studied for varying signature heights on four molecular series, alkanes, alcohols, fullerene-type structures, and peptides. Signature degeneracy is compared with similar results obtained with popular topological indices (TIs). As a general rule, we find that signature degeneracy decreases as the signature height increases. We also find that alkanes, alcohols, and fullerene-type structures comprising n non-hydrogen atoms are uniquely characterized by signatures of height n/4, while peptides up to 4000 amino acids can be singled out with signatures of heights as small as 2 and 3. PMID:12767130

Faulon, Jean-Loup; Churchwell, Carla J; Visco, Donald P

2003-01-01

216

Crossed molecular beams study of O({sup 1}D) reactions with H{sub 2} molecules  

SciTech Connect

Reaction dynamics of O({sup 1}D) atoms with H{sub 2} molecules was reinvestigated using the crossed molecular beams technique with pulsed beams. The O({sup 1}D) beam was generated by photodissociating O{sub 3} molecules at 248 nm. Time-of-flight spectra and the laboratory angular distribution of the OH products were measured. The derived OH product center-of-mass flux-velocity contour diagram shows more backward scattered intensity with respect to the O({sup 1}D) beam. In contrast to previous studies which show that the insertion mechanism is the dominant process, our results indicate that the contribution from the collinear approach of the O({sup 1}D) atom to the H{sub 2} molecule on the first excited state potential energy surface is significant and the energy barrier for the collinear approach is therefore minimal. Despite the increased time resolution in this experiment, no vibrational structure in the OH product time-of-flight spectra was resolved. This is in agreement with LIF studies, which have shown that the rotational distributions of the OH products in all vibrational states are broad and highly inverted.

Miau, T.T.

1995-05-01

217

Lubrication by physisorbed molecules in equilibrium with vapor at ambient condition: effects of molecular structure and substrate chemistry.  

PubMed

The effects of physisorbed organic vapor molecules on friction and wear were studied for various materials with different surface chemistries (metals, ceramics, glasses, carbons, polymers) and adsorbed species with distinct functional groups (short linear-chain, branched, and fluorinated alcohols with alkyl chain lengths up to five carbons as well as acetone and n-decane). Friction test results of stainless steel under equilibrium vapor adsorption conditions indicated that the longer chain length of the adsorbed alcohols results in lower friction and that n-pentanol gives the lowest friction and wear among the molecules investigated. The adsorption isotherm measurements revealed that the functional groups of the adsorbed molecules appear to play important roles in lubrication. Friction coefficients that ranged from 0.02 to 0.9 for the various materials in dry and humid environments converged to ?0.15 for the inorganic solid materials tested in n-pentanol. These findings indicate that the molecular lubrication by the physisorbed species dominates the tribological behaviors of the inorganic solid materials, regardless of bulk mechanical properties. Tribotests using polymeric materials did not show the same lubricating effects for n-pentanol vapor. The failure of n-pentanol to lubricate polymeric materials may be due to vapor ingress into the polymer and the absence of an adsorbed surface layer. PMID:24827583

Barthel, Anthony J; Kim, Seong H

2014-06-10

218

Development of small molecule non-peptide formyl peptide receptor (FPR) ligands and molecular modeling of their recognition.  

PubMed

Formyl peptide receptors (FPRs) are G protein-coupled receptors (GPCRs) expressed on a variety of cell types. These receptors play an important role in the regulation of inflammatory reactions and sensing cellular damage. They have also been implicated in the pathogenesis of various diseases, including neurodegenerative diseases, cataract formation, and atherogenesis. Thus, FPR ligands, both agonists and antagonists, may represent novel therapeutics for modulating host defense and innate immunity. A variety of molecules have been identified as receptor subtype-selective and mixed FPR agonists with potential therapeutic value during last decade. This review describes our efforts along with recent advances in the identification, optimization, biological evaluation, and structure-activity relationship (SAR) analysis of small molecule non-peptide FPR agonists and antagonists, including chiral molecules. Questions regarding the interaction at the molecular level of benzimidazoles, pyrazolones, pyridazin-3(2H)-ones, N-phenylureas and other derivatives with FPR1 and FPR2 are discussed. Application of computational models for virtual screening and design of FPR ligands is also considered. PMID:24350845

Schepetkin, I A; Khlebnikov, A I; Giovannoni, M P; Kirpotina, L N; Cilibrizzi, A; Quinn, M T

2014-01-01

219

Recognizing molecular patterns by machine learning: An agnostic structural definition of the hydrogen bond  

NASA Astrophysics Data System (ADS)

The concept of chemical bonding can ultimately be seen as a rationalization of the recurring structural patterns observed in molecules and solids. Chemical intuition is nothing but the ability to recognize and predict such patterns, and how they transform into one another. Here, we discuss how to use a computer to identify atomic patterns automatically, so as to provide an algorithmic definition of a bond based solely on structural information. We concentrate in particular on hydrogen bonding - a central concept to our understanding of the physical chemistry of water, biological systems, and many technologically important materials. Since the hydrogen bond is a somewhat fuzzy entity that covers a broad range of energies and distances, many different criteria have been proposed and used over the years, based either on sophisticate electronic structure calculations followed by an energy decomposition analysis, or on somewhat arbitrary choices of a range of structural parameters that is deemed to correspond to a hydrogen-bonded configuration. We introduce here a definition that is univocal, unbiased, and adaptive, based on our machine-learning analysis of an atomistic simulation. The strategy we propose could be easily adapted to similar scenarios, where one has to recognize or classify structural patterns in a material or chemical compound.

Gasparotto, Piero; Ceriotti, Michele

2014-11-01

220

Recognizing molecular patterns by machine learning: an agnostic structural definition of the hydrogen bond.  

PubMed

The concept of chemical bonding can ultimately be seen as a rationalization of the recurring structural patterns observed in molecules and solids. Chemical intuition is nothing but the ability to recognize and predict such patterns, and how they transform into one another. Here, we discuss how to use a computer to identify atomic patterns automatically, so as to provide an algorithmic definition of a bond based solely on structural information. We concentrate in particular on hydrogen bonding--a central concept to our understanding of the physical chemistry of water, biological systems, and many technologically important materials. Since the hydrogen bond is a somewhat fuzzy entity that covers a broad range of energies and distances, many different criteria have been proposed and used over the years, based either on sophisticate electronic structure calculations followed by an energy decomposition analysis, or on somewhat arbitrary choices of a range of structural parameters that is deemed to correspond to a hydrogen-bonded configuration. We introduce here a definition that is univocal, unbiased, and adaptive, based on our machine-learning analysis of an atomistic simulation. The strategy we propose could be easily adapted to similar scenarios, where one has to recognize or classify structural patterns in a material or chemical compound. PMID:25381505

Gasparotto, Piero; Ceriotti, Michele

2014-11-01

221

Molecular patterns of X chromosome-linked color vision genes among 134 menof European ancestry  

SciTech Connect

The authors used Southern blot hybridization to study X chromosome-linked color vision genes encoding the apoproteins of red and green visual pigments in 134 unselected Caucasian men. One hundred and thirteen individuals (84.3%) had a normal arrangement of their color vision pigment genes. All had one red pigment gene; the number of green pigment genes ranged from one to five with a mode of two. The frequency of molecular genotypes indicative of normal color vision (84.3%) was significantly lower than had been observed in previous studies of color vision phenotypes. Color vision defects can be due to deletions of red or green pigment genes or due to formation of hybrid genes comprising portions of both red and green pigment genes. Characteristic anomalous patterns were seen in 15 (11.2%) individuals: 7 (5.2%) had patterns characteristic of deuteranomaly, 2 (1.5%) had patterns characteristic of deuteranopia, and 6 (4.5%) had protan patterns. Previously undescribed hybrid gene patterns consisting of both green and red pigment gene fragments in addition to normal red and green genes were observed in another 6 individuals (4.5%). Thus, DNA testing detected anomalous color vision pigment genes at a higher frequency than expected from phenotypic color vision tests.

Drummond-Borg, M.; Deeb, S.S.; Motulsky, A.G. (Univ. of Washington, Seattle (USA))

1989-02-01

222

Fundamental molecular mechanism for the cellular uptake of guanidinium-rich molecules.  

PubMed

Guanidinium-rich molecules, such as cell-penetrating peptides, efficiently enter living cells in a non-endocytic energy-independent manner and transport a wide range of cargos, including drugs and biomarkers. The mechanism by which these highly cationic molecules efficiently cross the hydrophobic barrier imposed by the plasma membrane remains a fundamental open question. Here, a combination of computational results and in vitro and live-cell experimental evidence reveals an efficient energy-independent translocation mechanism for arginine-rich molecules. This mechanism unveils the essential role of guanidinium groups and two universal cell components: fatty acids and the cell membrane pH gradient. Deprotonated fatty acids in contact with the cell exterior interact with guanidinium groups, leading to a transient membrane channel that facilitates the transport of arginine-rich peptides toward the cell interior. On the cytosolic side, the fatty acids become protonated, releasing the peptides and resealing the channel. This fundamental mechanism appears to be universal across cells from different species and kingdoms. PMID:25405895

Herce, Henry D; Garcia, Angel E; Cardoso, M Cristina

2014-12-17

223

Viewing Dynamic Assembly of Molecular Complexes by Multi-Wavelength Single-Molecule Fluorescence  

PubMed Central

Complexes of macromolecules that transiently self-assemble, perform a particular function, and then dissociate are a recurring theme in biology. Such systems often have a large number of possible assembly/disassembly intermediates and complex, highly branched reaction pathways. Measuring the single-step kinetic parameters in these reactions would help to identify the functionally significant pathways. We have therefore constructed a novel single-molecule fluorescence microscope capable of efficiently detecting the colocalization of multiple components in a macromolecular complex when each component is labeled using a different color fluorescent dye. In this through-objective excitation, total internal reflection instrument, the dichroic mirror conventionally used to spectrally segregate the excitation and emission pathways was replaced with small broadband mirrors. This design spatially segregates the excitation and emission pathways and thereby permits efficient collection of the spectral range of emitted fluorescence when three or more dyes are used. In a test experiment with surface-immobilized single-stranded DNA molecules, we directly monitored the time course of a hybridization reaction with three different oligonucleotides, each labeled with a different color dye. The experiment reveals which of the possible reaction intermediates were traversed by each immobilized molecule, measures the hybridization rate constants for each oligonucleotide, and characterizes kinetic interdependences of the reaction steps. PMID:16698779

Friedman, Larry J.; Chung, Johnson; Gelles, Jeff

2006-01-01

224

Molecular bioelectricity: how endogenous voltage potentials control cell behavior and instruct pattern regulation in vivo.  

PubMed

In addition to biochemical gradients and transcriptional networks, cell behavior is regulated by endogenous bioelectrical cues originating in the activity of ion channels and pumps, operating in a wide variety of cell types. Instructive signals mediated by changes in resting potential control proliferation, differentiation, cell shape, and apoptosis of stem, progenitor, and somatic cells. Of importance, however, cells are regulated not only by their own Vmem but also by the Vmem of their neighbors, forming networks via electrical synapses known as gap junctions. Spatiotemporal changes in Vmem distribution among nonneural somatic tissues regulate pattern formation and serve as signals that trigger limb regeneration, induce eye formation, set polarity of whole-body anatomical axes, and orchestrate craniofacial patterning. New tools for tracking and functionally altering Vmem gradients in vivo have identified novel roles for bioelectrical signaling and revealed the molecular pathways by which Vmem changes are transduced into cascades of downstream gene expression. Because channels and gap junctions are gated posttranslationally, bioelectrical networks have their own characteristic dynamics that do not reduce to molecular profiling of channel expression (although they couple functionally to transcriptional networks). The recent data provide an exciting opportunity to crack the bioelectric code, and learn to program cellular activity at the level of organs, not only cell types. The understanding of how patterning information is encoded in bioelectrical networks, which may require concepts from computational neuroscience, will have transformative implications for embryogenesis, regeneration, cancer, and synthetic bioengineering. PMID:25425556

Levin, Michael

2014-12-01

225

Molecular bioelectricity: how endogenous voltage potentials control cell behavior and instruct pattern regulation in vivo  

PubMed Central

In addition to biochemical gradients and transcriptional networks, cell behavior is regulated by endogenous bioelectrical cues originating in the activity of ion channels and pumps, operating in a wide variety of cell types. Instructive signals mediated by changes in resting potential control proliferation, differentiation, cell shape, and apoptosis of stem, progenitor, and somatic cells. Of importance, however, cells are regulated not only by their own Vmem but also by the Vmem of their neighbors, forming networks via electrical synapses known as gap junctions. Spatiotemporal changes in Vmem distribution among nonneural somatic tissues regulate pattern formation and serve as signals that trigger limb regeneration, induce eye formation, set polarity of whole-body anatomical axes, and orchestrate craniofacial patterning. New tools for tracking and functionally altering Vmem gradients in vivo have identified novel roles for bioelectrical signaling and revealed the molecular pathways by which Vmem changes are transduced into cascades of downstream gene expression. Because channels and gap junctions are gated posttranslationally, bioelectrical networks have their own characteristic dynamics that do not reduce to molecular profiling of channel expression (although they couple functionally to transcriptional networks). The recent data provide an exciting opportunity to crack the bioelectric code, and learn to program cellular activity at the level of organs, not only cell types. The understanding of how patterning information is encoded in bioelectrical networks, which may require concepts from computational neuroscience, will have transformative implications for embryogenesis, regeneration, cancer, and synthetic bioengineering. PMID:25425556

Levin, Michael

2014-01-01

226

Liquid crystal polymer networks: preparation, properties, and applications of films with patterned molecular alignment.  

PubMed

Monolithically ordered liquid crystal polymer networks are formed by the photoinitiated polymerization of multifunctional liquid crystal monomers. This paper describes the relevant principles and methods, the basic structure-property relationships in terms of mesogenic properties of the monomers, and the mechanical and optical properties of the polymers. Strategies are discussed to control the molecular orientation by various means and in all three dimensions. The versatility of the process is demonstrated by two examples of films with a patterned molecular order. It is shown that patterned retarders can be made by a two-step polymerization process which is successfully employed in a transflective display principle. A transflective display is a liquid crystal display that operates in both a reflective mode using ambient light and a transmissive mode with light coming from a backlight system. Furthermore, a method is discussed to create a patterned film in a single polymerization process. This film has alternating planar chiral nematic areas next to perpendicularly oriented (so-called homeotropic) areas. When applied as a coating to a substrate, the film changes its surface texture. During exposure to UV light, it switches from a flat to a corrugated state. PMID:24707811

Liu, Danqing; Broer, Dirk J

2014-11-18

227

Synergistic effect of high and low molecular weight molecules in the foamability and foam stability of sparkling wines.  

PubMed

The foam of sparkling wines is a key parameter of their quality. However, the compounds that are directly involved in foam formation and stabilization are not yet completely established. In this work, seven sparkling wines were produced in Bairrada appellation (Portugal) under different conditions and their foaming properties evaluated using a Mosalux-based device. Fractionation of the sparkling wines into four independent fractions, (1) high molecular weight material, with molecular weight higher than 12 kDa (HMW), (2) hydrophilic material with molecular weigh between 1 and 12 kDa (AqIMW), (3) hydrophobic material with molecular weigh between 1 and 12 kDa (MeIMW), and (4) hydrophobic material with a molecular weight lower than 1 kDa (MeLMW), allowed the observation that the wines presenting the lower foam stability were those that presented lower amounts of the MeLMW fraction. The fraction that presented the best foam stability was HMW. When HMW is combined with MeLMW fraction, the foam stability largely increased. This increase was even larger, approaching the foam stability of the sparkling wine, when HMW was combined with the less hydrophobic subfraction of MeLMW (fraction 3). Electrospray tandem mass spectrometry (ESI-MS/MS) of fraction 3 allowed the assignment of polyethylene glycol oligomers (n = 5-11) and diethylene glycol 8-hydroxytridecanoate glyceryl acetate. To observe if these molecules occur in sparkling wine foam, the MeLMW was recovered directly from the sparkling wine foam and was also analyzed by ESI-MS/MS. The presence of monoacylglycerols of palmitic and stearic acids, as well as four glycerylethylene glycol fatty acid derivatives, was observed. These surface active compounds are preferentially partitioned by the sparkling wine foam rather than the liquid phase, allowing the inference of their role as key components in the promotion and stabilization of sparkling wine foam. PMID:21375299

Coelho, Elisabete; Reis, Ana; Domingues, M Rosário M; Rocha, Sílvia M; Coimbra, Manuel A

2011-04-13

228

Meet the Molecules in Chocolate: Informal Opportunities for Building Thematic Molecular Models with Children  

ERIC Educational Resources Information Center

We describe the development and use of a molecular model building activity with a chocolate theme, suitable for a public presentation of chemistry through interaction with visitors to science festivals and museums, and as a special classroom activity during science weeks, and so forth. (Contains 3 figures.)

Amey, Jennifer R.; Fletcher, Matthew D.; Fletcher, Rachael V.; Jones, Alison; Roberts, Erica W.; Roberts, Ieuan O.

2008-01-01

229

Friction and energy dissipation mechanisms in adsorbed molecules and molecularly thin films  

Microsoft Academic Search

This review provides an overview of recent advances that have been achieved in understanding the basic physics of friction and energy dissipation in molecularly thin adsorbed films and the associated impact on friction at microscopic and macroscopic length scales. Topics covered include a historical overview of the fundamental understanding of macroscopic friction, theoretical treatments of phononic and electronic energy dissipation

Jacqueline Krim

2012-01-01

230

Proton Donor/acceptor Propensities of Ammonia: Rotational Studies of its Molecular Complexes with Organic Molecules  

NASA Astrophysics Data System (ADS)

We studied the rotational spectra of the adducts of ammonia with several organic molecules, namely tert-butanol, glycidol, ethyl alcohol, anisol and 1,4-difluorobenzene. The adducts with glycidol and ethanol have been observed for both conformers of the substrate molecule. Based on the rotational and ^{14}N quadrupole coupling constants of the various complexes, we found a considerably different behaviour of ammonia, with respect to water, in its proton donor/acceptor double role. In the interaction with the three alcohol molecules, NH_{3} acts as a proton acceptor and the OH groups as a proton donor. However, in the case of glycidol-NH_{3}, a secundary N-H\\cdotsO interaction occurrs between ammonia and the ether oxygen. This interaction generates a sizable V_{3} barrier to the internal rotation of the NH_{3} moiety, while NH_{3} undergoes a free rotation in tert-butanol-NH_{3} and in ethanol-NH_{3}. As to the anisole-NH_{3} and 1,4-difluorobenzene-NH_{3} complexes, the NH_{3} group explicits its double proton donor/acceptor role, although through two weak (C_{Me}-H\\cdotsN and N-H\\cdots?) H-bonds. There is, however, an important difference between the two complexes, because in the first one NH_{3} lies out of the aromatic plane, while in the second one it is in the plane of the aromatic ring. B. M. Giuliano, M. C. Castrovilli, A. Maris, S. Melandri, W. Caminati and E. A. Cohen, Chem.Phys.Lett., 2008, 463, 330 B. M. Giuliano, S. Melandri, A. Maris, L. B. Favero and W. Caminati, Angew.Chem.Int.Ed., 2009, 48, 1102

Giuliano, Barbara M.; Maris, Assimo; Melandri, Sonia; Favero, Laura B.; Evangelisti, Luca; Caminati, Walther

2009-06-01

231

The plant hormone auxin has been implicated in vascular development, but the molecular details of patterned vascular  

E-print Network

406 The plant hormone auxin has been implicated in vascular development, but the molecular details of patterned vascular differentiation have remained elusive. Research in the past year has identified new genes that control vascular patterning, and auxin transport and perception. New experimental strategies have been

Mattsson, Jim

232

Molecular basis of natural variation and environmental control of trichome patterning  

PubMed Central

Trichomes are differentiated epidermal cells on above ground organs of nearly all land plants. They play important protective roles as structural defenses upon biotic attacks such as herbivory, oviposition and fungal infections, and against abiotic stressors such as drought, heat, freezing, excess of light, and UV radiation. The pattern and density of trichomes is highly variable within natural population suggesting tradeoffs between traits positively affecting fitness such as resistance and the costs of trichome production. The spatial distribution of trichomes is regulated through a combination of endogenous developmental programs and external signals. This review summarizes the current understanding on the molecular basis of the natural variation and the role of phytohormones and environmental stimuli on trichome patterning. PMID:25071803

Hauser, Marie-Theres

2014-01-01

233

Intramolecular vibrations and noise effects on pattern formation in a molecular helix.  

PubMed

Modulational instability in a biexciton molecular chain is addressed. We show that the model can be reduced to a set of three coupled equations: two nonlinear Schrödinger equations and a Boussinesq equation. The linear stability analysis of continuous wave solutions of the coupled systems is performed and the growth rate of instability is found numerically. Simulations of the full discrete systems reveal some behaviors of modulational instability, since wave patterns are observed for the excitons and the phonon spectrum. We also take the effect of thermal fluctuations into account and we numerically study both the stability and the instability of the plane waves under 300 K. The plane wave is found to be stable under modulation, but displays a gradual increase of the wave amplitudes. Under modulation, the same behaviors are observed and wave patterns are found to resist thermal fluctuations, which is in agreement with earlier research on localized structure stability under thermal noise. PMID:21878712

Fouda, H P Ekobena; Tabi, C B; Mohamadou, A; Kofané, T C

2011-09-21

234

Structures of pattern recognition receptors reveal molecular mechanisms of autoinhibition, ligand recognition and oligomerization  

PubMed Central

Pattern recognition receptors (PRRs) are essential sentinels for pathogens or tissue damage and integral components of the innate immune system. Recent structural studies have provided unprecedented insights into the molecular mechanisms of ligand recognition and signal transduction by several PRR families at distinct subcellular compartments. Here we highlight some of the recent discoveries and summarize the common themes that are emerging from these exciting studies. Better mechanistic understanding of the structure and function of the PRRs will improve future prospects of therapeutic targeting of these important innate immune receptors. PMID:24419035

Xiao, T. Sam

2013-01-01

235

Identification of DNA adduct formation of small molecules by molecular descriptors and machine learning methods  

Microsoft Academic Search

In this study, we developed new computational DNA adduct prediction models by using significantly more diverse training data-set of 217 DNA adducts and 1024 non-DNA adducts, and applying five machine learning methods which include support vector machine (SVM), k-nearest neighbour, artificial neural networks, logistic regression and continuous kernel discrimination. The molecular descriptors used for DNA adduct prediction were selected from

Hanbing Rao; Xianyin Zeng; Yanying Wang; Hua He; Feng Zhu; Zerong Li; Yuzong Chen

2011-01-01

236

Identification of DNA adduct formation of small molecules by molecular descriptors and machine learning methods  

Microsoft Academic Search

In this study, we developed new computational DNA adduct prediction models by using significantly more diverse training data-set of 217 DNA adducts and 1024 non-DNA adducts, and applying five machine learning methods which include support vector machine (SVM), k-nearest neighbour, artificial neural networks, logistic regression and continuous kernel discrimination. The molecular descriptors used for DNA adduct prediction were selected from

Hanbing Rao; Xianyin Zeng; Yanying Wang; Hua He; Feng Zhu; Zerong Li; Yuzong Chen

2012-01-01

237

Low Energy Positron Interactions with Biological Molecules  

NASA Astrophysics Data System (ADS)

There is some experimental evidence that positrons can produce distinctive molecular fragmentation patterns. It is known that tuning the incident positron energy to near resonance with molecule vibrations can strongly enhance the positron annihilation probability for a molecule. This suggests that fragmentation induced by slow positrons may provide valuable complementary information to existing techniques for identification and study of proteins. In order to study this concept, we are developing a general quantum method for reliably calculating the density distribution for positrons bound to large biological molecules using NEO/GAMESS. We find that the outer molecular orbitals as well as the higher p orbitals on the O atoms contribute heavily to the total annihilation rate. Using the basis sets and approximations we have tested to predict where annihilation occurs can ultimately help us understand the resulting fragmentation patterns of larger biological molecules.

Wanniarachchi, Indika; Morgan, Caroline; Schlegel, Bernhard; Kedziora, Gary; Burgrraf, Larry; Pak, Michael; Hammes-Schiffer, Sharon

2012-10-01

238

Molecular basis for small molecule inhibition of g protein-coupled receptor kinases.  

PubMed

Small molecules that inhibit the protein kinase A, G, and C (AGC) family of serine/threonine kinases can exert profound effects on cell homeostasis and thereby regulate fundamental processes such as heart rate, blood pressure, and metabolism, but there is not yet a clinically approved drug in the United States selective for a member of this family. One subfamily of AGC kinases, the G protein-coupled receptor (GPCR) kinases (GRKs), initiates the desensitization of active GPCRs. Of these, GRK2 has been directly implicated in the progression of heart failure. Thus, there is great interest in the identification of GRK2-specific chemical probes that can be further developed into therapeutics. Herein, we compare crystal structures of small molecule inhibitors in complex with GRK2 to those of highly selective compounds in complex with Rho-associated coiled-coil containing kinase 1 (ROCK1), a closely related AGC kinase. This analysis suggests that reduced hydrogen-bond formation with the hinge of the kinase domain, occupation of the hydrophobic subsite, and, consequently, higher buried surface area are key drivers of potency and selectivity among GRK inhibitors. PMID:24984143

Homan, Kristoff T; Tesmer, John J G

2015-01-16

239

Major histocompatibility complex class IIA and IIB genes of Nile tilapia Oreochromis niloticus: genomic structure, molecular polymorphism and expression patterns.  

PubMed

Major histocompatibility complex (MHC) is a large genomic region characterized by extremely high polymorphism, and it plays an important role in the immune response of vertebrates. In the present study, we isolated MHC class II genes from Nile tilapia in order to investigate the immune mechanism in tilapia and develop better strategies for disease prevention. Moreover, we cloned the full-length cDNA sequences of MHC IIA and IIB from Nile tilapia by the RACE approach. In addition, the genomic structure, molecular polymorphism and expression patterns of MHC II genes in Nile tilapia were also examined. Compared with that of other teleosts, Nile tilapia MHC class IIA contained four exons and three introns. The deduced amino acid sequence of the MHC IIA molecule shared 25.4-64.5% similarity with those of other teleosts and mammals. Six exons and five introns were identified from Nile tilapia MHC IIB, and the deduced amino acid sequence shared 26.9-74.7% similarity with those of other teleosts and mammals. All the characteristic features of MHC class II chain structure could be identified in the deduced sequences of MHC IIA and IIB molecules, including the leader peptide, ?1/?1 and ?2/?2 domains, connecting peptide and transmembrane and cytoplasmic regions, as well as conserved cysteines and N-glycosylation site. A total of 12 MHC IIA alleles were identified from six individuals. Four alleles originating from a single individual suggested that at least four MHC IIA loci existed. Moreover, 10 MHC IIB alleles were identified, among which four were detected in a single individual, suggesting that at least four MHC IIB loci existed. The expression of MHC IIA and IIB at the mRNA level in 10 types of normal tissues was determined using quantitative real-time PCR analysis. The highest expression level was detected in stomach and gill, whereas the lowest expression was detected in muscle and brain. Furthermore, MHC IIA and IIB were probably two candidate immune molecules involved in the resistance against streptococcosis, because their expression was significantly up-regulated in gill, kidney, intestine and spleen after the intraperitoneal injection of Streptococcus agalactiae. PMID:23261509

Pang, Ji-cai; Gao, Feng-ying; Lu, Mai-xin; Ye, Xing; Zhu, Hua-ping; Ke, Xiao-li

2013-02-01

240

Molecular modeling of crystal morphology of ginsenoside compound K solvates and its crystal habit modification by solvent molecules  

NASA Astrophysics Data System (ADS)

The crystal growth morphology of ginsenoside compound K solvates was predicted by molecular modeling, and the solvent effect on crystal habits was considered to obtain a more accurate predicted result. The single crystal structures of two solvates of ginsenoside compound K (acetone-water solvate, monohydrate) were obtained by single crystal X-ray diffraction. On the basis of single crystal data, the crystal habits of the solvates were predicted by Bravais-Friedel-Donnay-Harker (BFDH) model and Attachment Energy (AE) model. From the image of scanning electron microscopy (SEM), it was shown that the AE model fits much better than the BFDH model. In addition, considering the interaction energy between solvent molecules and crystal faces (Eint), the AE model was modified. With the modification of AE model, the predicted crystal habits were in good agreement with our experimental results.

Gu, Huike; Li, Runyan; Sun, Yajuan; Li, Shaohua; Dong, Weibing; Gong, Junbo

2013-06-01

241

Molecular Collision Cross Section of the CHF3 Molecule Due to Higher Order Interactions  

NASA Astrophysics Data System (ADS)

The foreign-gas broadening parameters for fluoroform molecules interacting with spherical (He, Ne, Ar, Kr, Xe, CH4, CCl4) perturbers have been measured. The results are pressure broadening coefficients (in kHz/Pa) for J=1?0 transition of CHF3: Cw(He)=23.8±0.4, Cw(Ne)=16.4±0.5, Cw(Ar)=18.5±0.4, Cw(Kr)=19.7±0.6, Cw(Xe)=21.7±0.5, Cw(CH4)=26.3±0.7, Cw(CCl4)=34.7±0.7. Experimental linewidth parameters are interpreted using Anderson-Tsao-Curnutte as well as Murphy-Boggs theories for the mixed - interactions case. The first-order London dispersion forces, induction forces and exchange forces were taken into account.

Gierszal, S.; Galica, J.; Mi?-Ku?mi?ska, E.

242

Theoretical study of the alkyl derivative C 37H 50N 4O 4 molecule for use as a stable molecular rectifier: geometric and electronic structures  

Microsoft Academic Search

The realization of a molecular device with a unimolecular rectifying function is one of the most important requirements in nanotechnology. In the present study, the geometric and electronic structure of the alkyl derivative molecule C37H50N4O4 has been investigated theoretically using ab initio quantum mechanical calculations. This molecule has a donor–spacer–acceptor structure, and is a leading candidate for the creation of

Hiroshi Mizuseki; Kenji Niimura; Chiranjib Majumder; Yoshiyuki Kawazoe

2003-01-01

243

Photodissociation and recombination of F2 molecule in Ar54 cluster: Nonadiabatic molecular dynamics simulations  

NASA Astrophysics Data System (ADS)

Photodissociation and recombination of an F2 molecule embedded in an Ar cluster is investigated. The electronic states involved are described by the valence bond approach for the F(2P)+F(2P) interaction, with spin-orbit coupling included and the anisotropic interactions between F and Ar atoms described by the diatomics-in-molecules (DIM) approach. The potential energy surfaces for 36 electronic states and the nonadiabatic couplings between them are constructed in this basis. The surface hopping method is used for dynamical simulations. The main results are: (i) Spin nonconserving transitions play a crucial role both in the dissociation and in the recombination dynamics. (ii) The ratio between the population of the triplet states and the population of the singlet states reaches the statistical equilibrium value of 3:1 60 fs after the photoexcitation, but the population of specific singlet and triplet states remains nonstatistical for at least 1.5 ps. (iii) Recombination on the only bound excited state (3?u) becomes significant within 100 fs and builds up to 40% of the trajectories within 1 ps after excitation of the cluster with 4.6 eV. This is in accord with recent experiments on ClF/Ar solid, where strong emission from this state was found. (iv) 3% of recombination on the ground 1?g state is found as well. (v) For excitation energy of 4.6 eV, the dissociation can be direct or delayed. In delayed dissociation the F photofragments hit the Ar cage more than once before escaping the cage. (vi) For excitation energy of 6.53 eV the yield of dissociation was found to be 100%, and the dissociation is direct only.

Niv, M. Y.; Bargheer, M.; Gerber, R. B.

2000-10-01

244

On the functions associated with the Burrau approximation for the hydrogen molecular ion and analogous molecules  

Microsoft Academic Search

The Schro¨dinger equation for the Burrau-like molecular species (A-B)ZA+ZB?1 is (?h&slash;2\\/2me) ?2 &psgr; + [?ZAe2\\/rA?ZBe2\\/rB +ZAZBe2\\/RAB]&psgr; = E&psgr;. After separation using prolate spheroidal coordinates, the mathematical analysis of this equation can be reduced to the investigation of the ordinary differential equation (d\\/dx) { (1?x2)[dP (x)\\/dx]} + {[?m2\\/(1?x2)] + 2??x + ?2x2 + ?} P (x) =0, where m is an

Paul Caylor McKinney

1977-01-01

245

On the functions associated with the Burrau approximation for the hydrogen molecular ion and analogous molecules  

Microsoft Academic Search

The Schrödinger equation for the Burrau-like molecular species (A-B)ZA+ZB-1 is (-ℏ2\\/2me) ?2 psi + [-ZAe2\\/rA-ZBe2\\/rB +ZAZBe2\\/RAB]psi = Epsi. After separation using prolate spheroidal coordinates, the mathematical analysis of this equation can be reduced to the investigation of the ordinary differential equation (d\\/dx) { (1-x2)[dP (x)\\/dx]} + {[-m2\\/(1-x2)] + 2alphabetax + alpha2x2 + sigma} P (x) =0, where m is an

Paul Caylor McKinney

1977-01-01

246

Evaluation of 99mTc-peptide-ZHER2:342 Affibody® molecule for in vivo molecular imaging  

PubMed Central

Objective: The aim of this study was to develop an improved method for labelling ZHER2:342 with Technetium-99m (99mTc) using Gly-(d) Ala-Gly-Gly as a chelator and to evaluate the feasibility of its use for visualization of HER2 expression in vivo. Methods: The Affibody® molecule ZHER2:342 was synthesized by Fmoc/tBu solid phase synthesis. The chelator, Gly-(d) Ala-Gly-Gly, was introduced by manual synthesis as the N-terminal extensions of ZHER2:342. ZHER2:342 was labelled with 99mTc. The labelling efficiency, radiochemical purity and in vitro stability of the labelled molecular probe were analysed by reversed-phase high performance liquid chromatography. Biodistribution and molecular imaging using 99mTc-peptide-ZHER2:342 were performed. Results: The molecular probe was successfully synthesized and labelled with 99mTc with the labelling efficiency of 98.10?±?1.73% (n?=?5). The radiolabelled molecular probe remained highly stable in vitro. The molecular imaging showed high uptake in HER2-expressing SKOV-3 xenografts, whereas the MDA-MB-231 xenografts with low HER2 expression were not clearly imaged at any time after the injection of 99mTc-peptide-ZHER2:342. The predominant clearance pathway for 99mTc-peptide-ZHER2:342 was through the kidneys. Conculsion: 99mTc-peptide-ZHER2:342 using Gly-(d) Ala-Gly-Gly as a chelator is a promising tracer agent with favourable biodistribution and imaging properties that may be developed as a radiopharmaceutical for the detection of HER2-positive malignant tumours. Advances in knowledge: The 99mTc-peptide-ZHER2:342 molecular probe is a promising tracer agent, and the results in this study provide a foundation for future development of protocols for earlier visual detection of cancer in the clinical setting. PMID:24273251

Zhang, J-M; Zhao, X-M; Ren, X-C; Wang, N; Han, J-Y; Jia, L-Z

2014-01-01

247

Gate-induced switching and negative differential resistance in a single-molecule transistor: emergence of fixed and shifting states with molecular length.  

PubMed

The quantum transport of a gated polythiophene nanodevice is analyzed using density functional theory and nonequilibrium Green's function approach. For this typical molecular field effect transistor, we prove the existence of two main features of electronic components, i.e., negative differential resistance and good switching. Ab initio based explanations of these features are provided by distinguishing fixed and shifting conducting states, which are shown to arise from the interface and functional molecule, respectively. The results show that proper functional molecules can be used in conjunction with metallic electrodes to achieve basic electronics functionality at molecular length scales. PMID:17640145

Farajian, A A; Belosludov, R V; Mizuseki, H; Kawazoe, Y; Hashizume, T; Yakobson, B I

2007-07-14

248

On the functions associated with the Burrau approximation for the hydrogen molecular ion and analogous molecules  

Microsoft Academic Search

The Schroedinger equation for the Burrau-like molecular species (A-B)\\/sub Z\\/A\\/sup +\\/\\/sub Z\\/B⁻¹ is (-h²\\/2m\\/sub e\\/) del² psi + (-Z\\/sub A\\/e²\\/r\\/sub A\\/-Z\\/sub B\\/e²\\/r\\/sub B\\/ +Z\\/sub A\\/Z\\/sub B\\/e²\\/R\\/sub A\\/\\/sub B\\/)psi = Epsi. After separation using prolate spheroidal coordinates, the mathematical analysis of this equation can be reduced to the investigation of the ordinary differential equation (d\\/dx) ) (1-x²)(dP (x)\\/dx)) + )(-m²\\/(1-x²)) +

Paul Caylor McKinney

1977-01-01

249

Molecular dynamics of DNA quadruplex molecules containing inosine, 6-thioguanine and 6-thiopurine.  

PubMed Central

The ability of the four-stranded guanine (G)-DNA motif to incorporate nonstandard guanine analogue bases 6-oxopurine (inosine, I), 6-thioguanine (tG), and 6-thiopurine (tI) has been investigated using large-scale molecular dynamics simulations. The simulations suggest that a G-DNA stem can incorporate inosines without any marked effect on its structure and dynamics. The all-inosine quadruplex stem d(IIII)(4) shows identical dynamical properties as d(GGGG)(4) on the nanosecond time scale, with both molecular assemblies being stabilized by monovalent cations residing in the channel of the stem. However, simulations carried out in the absence of these cations show dramatic differences in the behavior of d(GGGG)(4) and d(IIII)(4). Whereas vacant d(GGGG)(4) shows large fluctuations but does not disintegrate, vacant d(IIII)(4) is completely disrupted within the first nanosecond. This is a consequence of the lack of the H-bonds involving the N2 amino group that is not present in inosine. This indicates that formation of the inosine quadruplex could involve entirely different intermediate structures than formation of the guanosine quadruplex, and early association of cations in this process appears to be inevitable. In the simulations, the incorporation of 6-thioguanine and 6-thiopurine sharply destabilizes four-stranded G-DNA structures, in close agreement with experimental data. The main reason is the size of the thiogroup leading to considerable steric conflicts and expelling the cations out of the channel of the quadruplex stem. The G-DNA stem can accommodate a single thioguanine base with minor perturbations. Incorporation of a thioguanine quartet layer is associated with a large destabilization of the G-DNA stem whereas the all-thioguanine quadruplex immediately collapses. PMID:11159416

Stefl, R; Spacková, N; Berger, I; Koca, J; Sponer, J

2001-01-01

250

Synthesis and molecular recognition studies on small-molecule inhibitors for thioredoxin reductase.  

PubMed

Thioredoxin reductase (TrxR), which is overexpressed in many aggressive cancers, plays a crucial role in redox balance and antioxidant function, including defense of oxidative stress, control of cell proliferation, and regulation of cell apoptosis. Deactivation of TrxR can destroy the homeostasis of the cancer cells, inducing elevation of reactive oxygen species (ROS) levels and the oxidation of enzymatic substrates. Here, we synthesized and identified a new gold(I) small molecule (D9) that possesses two strong electron-donating moieties, i.e., 4-methylphenyl alkynyl and thionyldiphenyl phosphine, exhibiting an enhanced p-? conjunction effect. The resulting compound shows the increased soft Lewis acids and the stability of gold(I). And we demonstrated that D9 could efficiently and specifically inhibit the activity of TrxR in vitro and in vivo, and it could effectively avoid the ligand exchange with albumin that was one of the most abundant proteins in blood. We believe that these comprehensive studies on the relationship between the structure and performance will provide inspiring information on the precise synthesis and design of new compounds for targeting TrxR. PMID:25249032

Zhang, Di; Xu, Zhonghe; Yuan, Jia; Zhao, Ying-Xi; Qiao, Zeng-Ying; Gao, Yu-Juan; Yu, Guang-Ao; Li, Jingyuan; Wang, Hao

2014-10-01

251

Molecular Clock Regulates Daily ?1-2-Fucosylation of the Neural Cell Adhesion Molecule (NCAM) within Mouse Secondary Olfactory Neurons.  

PubMed

The circadian clock regulates various behavioral and physiological rhythms in mammals. Circadian changes in olfactory functions such as neuronal firing in the olfactory bulb (OB) and olfactory sensitivity have recently been identified, although the underlying molecular mechanisms remain unknown. We analyzed the temporal profiles of glycan structures in the mouse OB using a high-density microarray that includes 96 lectins, because glycoconjugates play important roles in the nervous system such as neurite outgrowth and synaptogenesis. Sixteen lectin signals significantly fluctuated in the OB, and the intensity of all three that had high affinity for ?1-2-fucose (?1-2Fuc) glycan in the microarray was higher during the nighttime. Histochemical analysis revealed that ?1-2Fuc glycan is located in a diurnal manner in the lateral olfactory tract that comprises axon bundles of secondary olfactory neurons. The amount of ?1-2Fuc glycan associated with the major target glycoprotein neural cell adhesion molecule (NCAM) varied in a diurnal fashion, although the mRNA and protein expression of Ncam1 did not. The mRNA and protein expression of Fut1, a ?1-2-specific fucosyltransferase gene, was diurnal in the OB. Daily fluctuation of the ?1-2Fuc glycan was obviously damped in homozygous Clock mutant mice with disrupted diurnal Fut1 expression, suggesting that the molecular clock governs rhythmic ?1-2-fucosylation in secondary olfactory neurons. These findings suggest the possibility that the molecular clock is involved in the diurnal regulation of olfaction via ?1-2-fucosylation in the olfactory system. PMID:25384980

Kondoh, Daisuke; Tateno, Hiroaki; Hirabayashi, Jun; Yasumoto, Yuki; Nakao, Reiko; Oishi, Katsutaka

2014-12-26

252

From a single molecule to a membrane of structured ionic polymers: A molecular dynamic simulation study  

NASA Astrophysics Data System (ADS)

The association of an A-B-C-B-A co-polymer with an ionizable center and a bulky end block has been investigated using molecular dynamic simulations. The center block consists of a randomly sulfonated polystyrene connected to a flexible poly (ethylene-r-propylene) bridge and end caped with poly (t-butyl styrene). Tailoring the nature of individual segments within a block co-polymer is a potential design tool to form membranes with desired properties. The association mode and the dynamics of the segments control the overall characteristics. The membranes with three sulfonation level for the center block were made by evaporating a common solvent for all blocks. The local structure including size and distribution of the ionic blocks and the continuity of the styrene phase as well as long range correlations were identified at 300 and 500K. The initial membrane structure is affected by the structure in solution. Studies on changes that take place above the glass transition temperature for each of the blocks will also be presented.

Aryal, Dipak; Perahia, Dvora; Grest, Gary S.

2012-02-01

253

A Molecular Dynamics Study on the Confinement of Carbon Dioxide Molecules in Carbon Nanotubes  

NASA Astrophysics Data System (ADS)

The influence of atmospheric carbon dioxide (CO2) concentration on global warming is considered as one of the primary environmental issues of the past two decades. The main source of CO2 emission is human activity, such as the use of fossil fuels in transportation and industrial plants. Following the release of Kyoto Protocol in 1997, effective ways of controlling CO2 emissions received much attention. As a result, various materials such as activated carbon, zeolites, and carbon nanotubes (CNTs) were investigated for their CO2 adsorbing properties. CNTs were reported to have CO2 adsorption capability twice that of activated carbon, hence they received the most attention. In the current study, single walled carbon nanotubes (SWNTs) were used as one dimensional nanoporous materials and their CO2 adsorption capacity was analyzed with Molecular Dynamics simulations. Results indicated that SWNTs are excellent CO2 adsorbers and their effectiveness increase at low CO2 concentrations. In addition, we showed that by varying temperature, CO2 can be removed from the SWNTs, providing a simple method to reuse SWNTs.

Lazor, Meagan; Rende, Deniz; Baysal, Nihat; Ozisik, Rahmi

2012-02-01

254

Phases, line tension and pattern formation in molecularly thin films at the air-water interface  

NASA Astrophysics Data System (ADS)

A Langmuir film, which is a molecularly thin insoluble film on a liquid substrate, is one practical realization of a quasi-two dimensional matter. The major advantages of this system for the study of phase separation and phase co-existence are (a) it allows accurate control of the components and molecular area of the film and (b) it can be studied by various methods that require very flat films. Phase separation in molecularly thin films plays an important role in a range of systems from biomembranes to biosensors. For example, phase-separated lipid nano-domains in biomembranes are thought to play crucial roles in membrane function. I use Brewster Angel Microscopy (BAM) coupled with Fluorescence Microscopy (FM) and static Light Scattering Microscopy (LSM) to image phases and patterns within Langmuir films. The three microscopic techniques --- BAM, FM and LSM --- are complimentary to each other, providing distinct sets of information. They allow direct comparison with literature results in lipid systems. I have quantitatively validated the use of detailed hydrodynamic simulations to determine line tension in monolayers. Line tension decreases as temperature rises. This decrease gives us information on the entropy associated with the line, and thus about line structure. I carefully consider the thermodynamics of line energy and entropy to make this connection. In the longer run, LSM will be exploited to give us further information about line structure. I have also extended the technique by testing it on domains within the curved surface of a bilayer vesicle. I also note that in the same way that the presence of surface-active agents, known as surfactants, affects surface energy, the addiction of line active agents alters the inter-phase line energy. Thus my results set to stage to systematically study the influence of line active agents ---'linactants' --- on the inter-phase line energy. Hierarchal self-assembled chiral patterns were observed as a function of temperature. I found that the appearance of these domains could be explained with a simple uniaxial optical axis in the underlying structure, which is the first critical step to understanding the origin of these patterns.

Mandal, Pritam

255

Novel Strategy for Biofilm Inhibition by Using Small Molecules Targeting Molecular Chaperone DnaK.  

PubMed

Biofilms are complex communities of microorganisms that attach to surfaces and are embedded in a self-produced extracellular matrix. Since these cells acquire increased tolerance against antimicrobial agents and host immune systems, biofilm-associated infectious diseases tend to become chronic. We show here that the molecular chaperone DnaK is important for biofilm formation and that chemical inhibition of DnaK cellular functions is effective in preventing biofilm development. Genetic, microbial, and microscopic analyses revealed that deletion of the dnaK gene markedly reduced the production of the extracellular functional amyloid curli, which contributes to the robustness of Escherichia coli biofilms. We tested the ability of DnaK inhibitors myricetin (Myr), telmisartan, pancuronium bromide, and zafirlukast to prevent biofilm formation of E. coli. Only Myr, a flavonol widely distributed in plants, inhibited biofilm formation in a concentration-dependent manner (50% inhibitory concentration [IC50] = 46.2 ?M); however, it did not affect growth. Transmission electron microscopy demonstrated that Myr inhibited the production of curli. Phenotypic analyses of thermosensitivity, cell division, intracellular level of RNA polymerase sigma factor RpoH, and vulnerability to vancomycin revealed that Myr altered the phenotype of E. coli wild-type cells to make them resemble those of the isogenic dnaK deletion mutant, indicating that Myr inhibits cellular functions of DnaK. These findings provide insights into the significance of DnaK in curli-dependent biofilm formation and indicate that DnaK is an ideal target for antibiofilm drugs. PMID:25403660

Arita-Morioka, Ken-Ichi; Yamanaka, Kunitoshi; Mizunoe, Yoshimitsu; Ogura, Teru; Sugimoto, Shinya

2015-01-01

256

Tridimensional model structure and patterns of molecular evolution of Pepino mosaic virus TGBp3 protein  

PubMed Central

Background Pepino mosaic virus (PepMV) is considered one of the most dangerous pathogens infecting tomatoes worldwide. The virus is highly diverse and four distinct genotypes, as well as inter-strain recombinants, have already been described. The isolates display a wide range on symptoms on infected plant species, ranging from mild mosaic to severe necrosis. However, little is known about the mechanisms and pattern of PepMV molecular evolution and about the role of individual proteins in host-pathogen interactions. Methods The nucleotide sequences of the triple gene block 3 (TGB3) from PepMV isolates varying in symptomatology and geographic origin have been analyzed. The modes and patterns of molecular evolution of the TGBp3 protein were investigated by evaluating the selective constraints to which particular amino acid residues have been subjected during the course of diversification. The tridimensional structure of TGBp3 protein has been modeled de novo using the Rosetta algorithm. The correlation between symptoms development and location of specific amino acids residues was analyzed. Results The results have shown that TGBp3 has been evolving mainly under the action of purifying selection operating on several amino acid sites, thus highlighting its functional role during PepMV infection. Interestingly, amino acid 67, which has been previously shown to be a necrosis determinant, was found to be under positive selection. Conclusions Identification of diverse selection events in TGB3p3 will help unraveling its biological functions and is essential to an understanding of the evolutionary constraints exerted on the Potexvirus genome. The estimated tridimensional structure of TGBp3 will serve as a platform for further sequence, structural and function analysis and will stimulate new experimental advances. PMID:21702943

2011-01-01

257

Properties and Reactivity Patterns of AsP3: An Experimental and Computational Study of Group 15 Elemental Molecules  

E-print Network

Facile synthetic access to the isolable, thermally robust AsP3 molecule has allowed for a thorough study of its physical properties and reaction chemistry with a variety of transition-metal and organic fragments. The ...

Cossairt, Brandi M.

258

The Relation between Recombination Rate and Patterns of Molecular Evolution and Variation in Drosophila melanogaster  

PubMed Central

Genetic recombination associated with sexual reproduction increases the efficiency of natural selection by reducing the strength of Hill–Robertson interference. Such interference can be caused either by selective sweeps of positively selected alleles or by background selection (BGS) against deleterious mutations. Its consequences can be studied by comparing patterns of molecular evolution and variation in genomic regions with different rates of crossing over. We carried out a comprehensive study of the benefits of recombination in Drosophila melanogaster, both by contrasting five independent genomic regions that lack crossing over with the rest of the genome and by comparing regions with different rates of crossing over, using data on DNA sequence polymorphisms from an African population that is geographically close to the putatively ancestral population for the species, and on sequence divergence from a related species. We observed reductions in sequence diversity in noncrossover (NC) regions that are inconsistent with the effects of hard selective sweeps in the absence of recombination. Overall, the observed patterns suggest that the recombination rate experienced by a gene is positively related to an increase in the efficiency of both positive and purifying selection. The results are consistent with a BGS model with interference among selected sites in NC regions, and joint effects of BGS, selective sweeps, and a past population expansion on variability in regions of the genome that experience crossing over. In such crossover regions, the X chromosome exhibits a higher rate of adaptive protein sequence evolution than the autosomes, implying a Faster-X effect. PMID:24489114

Campos, José L.; Halligan, Daniel L.; Haddrill, Penelope R.; Charlesworth, Brian

2014-01-01

259

Molecular dynamics of single-particle impacts predicts phase diagrams for large scale pattern formation.  

PubMed

Energetic particle irradiation can cause surface ultra-smoothening, self-organized nanoscale pattern formation or degradation of the structural integrity of nuclear reactor components. A fundamental understanding of the mechanisms governing the selection among these outcomes has been elusive. Here we predict the mechanism governing the transition from pattern formation to flatness using only parameter-free molecular dynamics simulations of single-ion impacts as input into a multiscale analysis, obtaining good agreement with experiment. Our results overturn the paradigm attributing these phenomena to the removal of target atoms via sputter erosion: the mechanism dominating both stability and instability is the impact-induced redistribution of target atoms that are not sputtered away, with erosive effects being essentially irrelevant. We discuss the potential implications for the formation of a mysterious nanoscale topography, leading to surface degradation, of tungsten plasma-facing fusion reactor walls. Consideration of impact-induced redistribution processes may lead to a new design criterion for stability under irradiation. PMID:21505432

Norris, Scott A; Samela, Juha; Bukonte, Laura; Backman, Marie; Djurabekova, Flyura; Nordlund, Kai; Madi, Charbel S; Brenner, Michael P; Aziz, Michael J

2011-01-01

260

Morphologic and molecular evaluation of Chlamydia trachomatis growth in human endocervix reveals distinct growth patterns  

PubMed Central

In vitro models of Chlamydia trachomatis growth have long been studied to predict growth in vivo. Alternative or persistent growth modes in vitro have been shown to occur under the influence of numerous stressors but have not been studied in vivo. Here, we report the development of methods for sampling human infections from the endocervix in a manner that permits a multifaceted analysis of the bacteria, host and the endocervical environment. Our approach permits evaluating total bacterial load, transcriptional patterns, morphology by immunofluorescence and electron microscopy, and levels of cytokines and nutrients in the infection microenvironment. By applying this approach to two pilot patients with disparate infections, we have determined that their contrasting growth patterns correlate with strikingly distinct transcriptional biomarkers, and are associated with differences in local levels of IFN?. Our multifaceted approach will be useful to dissect infections in the human host and be useful in identifying patients at risk for chronic disease. Importantly, the molecular and morphological analyses described here indicate that persistent growth forms can be isolated from the human endocervix when the infection microenvironment resembles the in vitro model of IFN?-induced persistence. PMID:24959423

Lewis, Maria E.; Belland, Robert J.; AbdelRahman, Yasser M.; Beatty, Wandy L.; Aiyar, Ashok A.; Zea, Arnold H.; Greene, Sheila J.; Marrero, Luis; Buckner, Lyndsey R.; Tate, David J.; McGowin, Chris L.; Kozlowski, Pamela A.; O'Brien, Michelle; Lillis, Rebecca A.; Martin, David H.; Quayle, Alison J.

2014-01-01

261

Pathogen Associated Molecular Pattern (PAMP)-Triggered Immunity Is Compromised under C-Limited Growth.  

PubMed

In the interaction between plants and pathogens, carbon (C) resources provide energy and C skeletons to maintain, among many functions, the plant immune system. However, variations in C availability on pathogen associated molecular pattern (PAMP) triggered immunity (PTI) have not been systematically examined. Here, three types of starch mutants with enhanced susceptibility to Pseudomonas syringae pv. tomato DC3000 hrcC were examined for PTI. In a dark period-dependent manner, the mutants showed compromised induction of a PTI marker, and callose accumulation in response to the bacterial PAMP flagellin, flg22. In combination with weakened PTI responses in wild type by inhibition of the TCA cycle, the experiments determined the necessity of C-derived energy in establishing PTI. Global gene expression analyses identified flg22 responsive genes displaying C supply-dependent patterns. Nutrient recycling-related genes were regulated similarly by C-limitation and flg22, indicating re-arrangements of expression programs to redirect resources that establish or strengthen PTI. Ethylene and NAC transcription factors appear to play roles in these processes. Under C-limitation, PTI appears compromised based on suppression of genes required for continued biosynthetic capacity and defenses through flg22. Our results provide a foundation for the intuitive perception of the interplay between plant nutrition status and pathogen defense. PMID:25387755

Park, Hyeong Cheol; Lee, Shinyoung; Park, Bokyung; Choi, Wonkyun; Kim, Chanmin; Lee, Sanghun; Chung, Woo Sik; Lee, Sang Yeol; Sabir, Jamal; Bressan, Ray A; Bohnert, Hans J; Mengiste, Tesfaye; Yun, Dae-Jin

2015-01-31

262

Molecular insights into the origin of the Hox-TALE patterning system  

PubMed Central

Despite tremendous body form diversity in nature, bilaterian animals share common sets of developmental genes that display conserved expression patterns in the embryo. Among them are the Hox genes, which define different identities along the anterior–posterior axis. Hox proteins exert their function by interaction with TALE transcription factors. Hox and TALE members are also present in some but not all non-bilaterian phyla, raising the question of how Hox–TALE interactions evolved to provide positional information. By using proteins from unicellular and multicellular lineages, we showed that these networks emerged from an ancestral generic motif present in Hox and other related protein families. Interestingly, Hox-TALE networks experienced additional and extensive molecular innovations that were likely crucial for differentiating Hox functions along body plans. Together our results highlight how homeobox gene families evolved during eukaryote evolution to eventually constitute a major patterning system in Eumetazoans. DOI: http://dx.doi.org/10.7554/eLife.01939.001 PMID:24642410

Hudry, Bruno; Thomas-Chollier, Morgane; Volovik, Yael; Duffraisse, Marilyne; Dard, Amélie; Frank, Dale; Technau, Ulrich; Merabet, Samir

2014-01-01

263

Pathogen Associated Molecular Pattern (PAMP)-Triggered Immunity Is Compromised under C-Limited Growth  

PubMed Central

In the interaction between plants and pathogens, carbon (C) resources provide energy and C skeletons to maintain, among many functions, the plant immune system. However, variations in C availability on pathogen associated molecular pattern (PAMP) triggered immunity (PTI) have not been systematically examined. Here, three types of starch mutants with enhanced susceptibility to Pseudomonas syringae pv. tomato DC3000 hrcC were examined for PTI. In a dark period-dependent manner, the mutants showed compromised induction of a PTI marker, and callose accumulation in response to the bacterial PAMP flagellin, flg22. In combination with weakened PTI responses in wild type by inhibition of the TCA cycle, the experiments determined the necessity of C-derived energy in establishing PTI. Global gene expression analyses identified flg22 responsive genes displaying C supply-dependent patterns. Nutrient recycling-related genes were regulated similarly by C-limitation and flg22, indicating re-arrangements of expression programs to redirect resources that establish or strengthen PTI. Ethylene and NAC transcription factors appear to play roles in these processes. Under C-limitation, PTI appears compromised based on suppression of genes required for continued biosynthetic capacity and defenses through flg22. Our results provide a foundation for the intuitive perception of the interplay between plant nutrition status and pathogen defense. PMID:25387755

Park, Hyeong Cheol; Lee, Shinyoung; Park, Bokyung; Choi, Wonkyun; Kim, Chanmin; Lee, Sanghun; Chung, Woo Sik; Lee, Sang Yeol; Sabir, Jamal; Bressan, Ray A.; Bohnert, Hans J.; Mengiste, Tesfaye; Yun, Dae-Jin

2015-01-01

264

Molecular fingerprinting of lacustrian cyanobacterial communities: regional patterns in summer diversity.  

PubMed

The assessment of lacustrian water quality is necessary to comply with environmental regulations. At the regional scale, difficulties reside in the selection of representative lakes. Given the risks towards water quality associated with phytoplankton blooms, a mesoscale survey was carried out in Irish lakes to identify patterns in the distribution and diversity of planktonic cyanobacteria. A stratified sampling strategy was carried out via geographic information systems (GIS) analysis of river catchment attributes due to the range of hydrogeomorphological features and the high number of lakes within the study area. 16S rRNA gene denaturing gradient gel electrophoresis analysis showed variation between the cyanobacterial communities sampled, with lower occurrence of cyanobacteria in August concomitant to increased wind and precipitation regimes. Multivariate analysis delineated three ecoregions based on land cover typology and revealed significant patterns in the distribution of cyanobacterial diversity. A majority of filamentous cyanobacteria genotypes occurred in larger lakes contained river catchments with substantial forest cover. In contrast, higher diversity of spherical cyanobacteria genotypes was observed in lakes of lesser trophic state. In the context of aquatic resource management, the combined use of GIS-based sampling strategy and molecular methods offers promising prospects for assessing microbial community structure at varying scales of space and time. PMID:23802655

Touzet, Nicolas; McCarthy, David; Fleming, Gerard T A

2013-12-01

265

Analysis of molecular expression patterns and integration with other knowledge bases using probabilistic Bayesian network models  

SciTech Connect

How can molecular expression experiments be interpreted with greater than ten to the fourth measurements per chip? How can one get the most quantitative information possible from the experimental data with good confidence? These are important questions whose solutions require an interdisciplinary combination of molecular and cellular biology, computer science, statistics, and complex systems analysis. The explosion of data from microarray techniques present the problem of interpreting the experiments. The availability of large-scale knowledge bases provide the opportunity to maximize the information extracted from these experiments. We have developed new methods of discovering biological function, metabolic pathways, and regulatory networks from these data and knowledge bases. These techniques are applicable to analyses for biomedical engineering, clinical, and fundamental cell and molecular biology studies. Our approach uses probabilistic, computational methods that give quantitative interpretations of data in a biological context. We have selected Bayesian statistical models with graphical network representations as a framework for our methods. As a first step, we use a nave Bayesian classifier to identify statistically significant patterns in gene expression data. We have developed methods which allow us to (a) characterize which genes or experiments distinguish each class from the others, (b) cross-index the resulting classes with other databases to assess biological meaning of the classes, and (c) display a gross overview of cellular dynamics. We have developed a number of visualization tools to convey the results. We report here our methods of classification and our first attempts at integrating the data and other knowledge bases together with new visualization tools. We demonstrate the utility of these methods and tools by analysis of a series of yeast cDNA microarray data and to a set of cancerous/normal sample data from colon cancer patients. We discuss extending our methods to inferring biological pathways and networks using more complex dynamic Bayesian networks.

Moler, Edward J.; Mian, I.S.

2000-03-01

266

A pillared-layer coordination polymer with a rotatable pillar acting as a molecular gate for guest molecules.  

PubMed

The design of pore properties utilizing flexible motifs and functional groups is of importance to obtain porous coordination polymers with desirable functions. We have prepared a 3D pillared-layer coordination polymer, {[Cd(2)(pzdc)(2)L(H(2)O)(2)].5(H(2)O).(CH(3)CH(2)OH)}(n) (1, H(2)pzdc = 2,3-pyrazinedicarboxylic acid; L = 2,5-bis(2-hydroxyethoxy)-1,4-bis(4-pyridyl)benzene) showing (i) a rotatable pillar bearing ethylene glycol side chains acting as a molecular gate with locking/unlocking interactions triggered by guest inclusion between the side chains, (ii) framework flexibility with slippage of the layers, and (iii) coordinatively unsaturated metal centers as guest accessible sites through the removal of the water coligands. The framework clearly shows reversible single-crystal-to-single-crystal transformations in response to the removal and rebinding of guest molecules, the observation of these processes has provided fundamental clues to the understanding of the sorption profiles. The X-ray structures indicate that the 3D host framework is retained during the transformations, involving mainly rotation of the pillars and slippage of the layers. The structure of dried form 2, [Cd(2)(pzdc)(2)L](n), has no void volume and no water coligands. Interestingly, the adsorption isotherm of water for 2 at 298 K exhibits three distinct steps coinciding with the framework functions. Compound 2 favors the uptake of CO(2) (195 K) over N(2) (77 K) and O(2) (77 K). Above all, we report on a molecular gate with a rotational module exhibiting a locking/unlocking system which accounts for gate-opening type sorption profiles. PMID:19681608

Seo, Joobeom; Matsuda, Ryotaro; Sakamoto, Hirotoshi; Bonneau, Charlotte; Kitagawa, Susumu

2009-09-01

267

A coarse-grained method based on the analysis of short molecular dynamics trajectories for the simulation of non-Markovian dynamics of molecules adsorbed in microporous materials  

NASA Astrophysics Data System (ADS)

We developed a coarse-grained model suitable for the study of adsorbed molecules in microporous materials. A partition of the space available to the motion of adsorbed molecules was carried out, which allows to formulate the dynamics in terms of jumps between discrete regions. The probabilities of observing given pairs of successive jumps were calculated from Molecular Dynamics (MD) simulations, performed on small systems, and used to drive the motion of molecules in a lattice-gas model. Dynamics is thus reformulated in terms of event-space dynamics and this allows to treat the system despite its inherent non markovity. Despite the assumptions enforced in the algorithm, results show that it can be applied to various spherical molecules adsorbed in the all-silica zeolite ITQ-29, establishing a suitable direct bridge between MD simulation results and coarse-grained models.

Pintus, Alberto M.; Gabrieli, Andrea; Pazzona, Federico G.; Demontis, Pierfranco; Suffritti, Giuseppe B.

2014-08-01

268

Molecular characterization and expression patterns of myogenin in compensatory growth of Megalobrama amblycephala.  

PubMed

Myogenin (myog) is a muscle-specific basic helix-loop-helix (bHLH) transcription factor that plays an essential role in regulating skeletal muscle development and growth. To investigate molecular characterization of myog and the effect of starvation/refeeding on the gene expression, we isolated the myog cDNA sequence and analyzed the expression patterns using quantitative real-time polymerase chain reaction in Megalobrama amblycephala. Sequence analysis indicated that M. amblycephala myog shared an analogous structure with the highly conserved His/Cys-rich, bHLH and C-terminal helix III domains with other vertebrates. Sequence alignment and phylogenetic tree showed that M. amblycephala myog had the highest identity with the homologues of Ctenopharyngodon idella and Cyprinus carpio. Spatio-temporal expression patterns revealed that myog mRNA levels at the segmentation period and 12 h post-hatching (hph) were significantly higher than at other development stages (P<0.05). Furthermore, the highest myog expression level was predominantly observed in white muscle compared with the other types of muscle. Fish body weight continuously decreased during 21-day starvation and then significantly increased after 7days of refeeding and reached the similar level to the control at 21days of refeeding, indicating that the pattern of complete compensatory growth possibly occurred in M. amblycephala; meanwhile, the relative somatic growth rate after refeeding was also dramatically higher than the control group. In addition, the myog expression decreased during 21days of starvation and then exhibited a strong rebound effect after 7days of refeeding and subsequently declined gradually to the control level by 21days of refeeding. PMID:24440962

Zhu, Kecheng; Chen, Liping; Zhao, Jinkun; Wang, Huijuan; Wang, Weimin; Li, Zhong; Wang, Huanling

2014-04-01

269

Recurrence patterns across medulloblastoma subgroups: an integrated clinical and molecular analysis  

PubMed Central

Background Recurrent medulloblastoma is a daunting therapeutic challenge as it is almost universally fatal. Recent studies confirmed that medulloblastoma comprises four distinct subgroups. We sought to delineate subgroup specific differences in medulloblastoma recurrence patterns. Methods We retrospectively identified a discovery cohort of all recurrent medulloblastomas at the Hospital for Sick Children between 1994-2012, and performed molecular subgrouping on FFPE tissues using a nanoString-based assay. The anatomical site of recurrence (local tumour bed or leptomeningeal metastasis), time to recurrence and survival post-recurrence were determined in a subgroup specific fashion. Subgroup specific recurrence patterns were confirmed in two independent, non-overlapping FFPE validation cohorts. Where possible molecular subgrouping was performed on tissue obtained from both the initial surgery and at recurrence. Results A screening cohort of 30 recurrent medulloblastomas was assembled; nine with local recurrences, and 21 metastatic. When re-analysed in a subgroup specific manner, local recurrences were more frequent in SHH tumours (8/9, 88%) and metastatic recurrences were more common in Group 3 and 4 (17/20 [85%] with one WNT, p=0.0014, local vs metastatic recurrence, SHH vs Group 3 vs Group 4). The subgroup specific location of recurrence was confirmed in a multicenter validation cohort (p=0·0013 for local vs metastatic recurrence SHH vs Group 3 vs Group 4, n=77), and a second independent validation cohort comprising 96 recurrences (p<0·0001 for local vs metastatic recurrence SHH vs Group 3 vs Group 4, n=96). Treatment with craniospinal irradiation at diagnosis was not significantly associated with the anatomical pattern of recurrence. Survival post recurrence was significantly longer in Group 4 patients (p=0·013) as confirmed in a multicenter validation cohort (p=0·0075). Strikingly, subgroup affiliation remained stable at recurrence in all 34 cases with available matched primary and recurrent pairs. Conclusions Medulloblastoma does not switch subgroup at the time of recurrence further highlighting the stability of the four principle medulloblastoma subgroups. Significant differences in the location and timing of recurrence across medulloblastoma subgroups were observed which have potential treatment ramifications. Specifically, intensified local (posterior fossa) therapy should be tested in the initial treatment of SHH patients. Refinement of therapy for Groups 3 and 4 should focus on the metastatic compartment, as it is the near universal cause of patient deaths. PMID:24140199

Ramaswamy, Vijay; Remke, Marc; Bouffet, Eric; Faria, Claudia C.; Perreault, Sebastien; Cho, Yoon-Jae; Shih, David J.; Luu, Betty; Dubuc, Adrian M.; Northcott, Paul A.; Schüller, Ulrich; Gururangan, Sridharan; McLendon, Roger; Bigner, Darell; Fouladi, Maryam; Ligon, Keith L.; Pomeroy, Scott L.; Dunn, Sandra; Triscott, Joanna; Jabado, Nada; Fontebasso, Adam; Jones, David T. W.; Kool, Marcel; Karajannis, Matthias A.; Gardner, Sharon L.; Zagzag, David; Nunes, Sofia; Pimentel, José; Mora, Jaume; Lipp, Eric; Walter, Andrew W.; Ryzhova, Marina; Zheludkova, Olga; Kumirova, Ella; Alshami, Jad; Croul, Sidney E.; Rutka, James T.; Hawkins, Cynthia; Tabori, Uri; Codispoti, Kari-Elise T.; Packer, Roger J.; Pfister, Stefan M.; Korshunov, Andrey; Taylor, Michael D.

2014-01-01

270

Molecular dynamics simulations of the homogeneous nucleation of UF6 and SF6 molecules: Effects of the intramolecular vibrational relaxations on the nucleation rates  

NASA Astrophysics Data System (ADS)

The effects of flexibility in the homogeneous nucleation processes of UF6 and SF6 molecules from vapor phase were investigated by classical molecular dynamics (MD) simulations. We performed MD simulations using a flexible-molecule model and compared the results with those obtained from a rigid-molecule model. We took into account the flexibility of molecules in MD simulations by a harmonic intramolecular potential. We found that the nucleation rate in the flexible model of the UF6 molecule was about twice as large as that in the rigid model of UF6. This acceleration in nucleation rate was attributed to the flow of the condensation heat into the intramolecular vibrations. On the other hand, the nucleation rates in rigid and flexible models of SF6 were almost the same because the flow of the condensation heat into the intramolecular vibrations in the flexible model of SF6 was negligibly small. In order to confirm the reliability of the classical intramolecular vibrational model in the present work, we estimated the intramolecular vibrational relaxation times of the flexible UF6 and the flexible SF6 molecules in the gas phase using the same MD simulation technique as used for the nucleations. The intramolecular vibrational relaxation times obtained from the MD simulations were in good agreement with those from the experimental data in cases of both UF6 and SF6 molecules.

Tanimura, Shinobu; Yasuoka, Kenji; Ebisuzaki, Toshikazu

1998-09-01

271

Molecular dynamics simulation of the homogeneous nucleation of UF6 molecules: Configurations and infrared spectra of the excited hot clusters  

NASA Astrophysics Data System (ADS)

The temperature, potential energy, and configurations of the clusters produced in the homogeneous nucleation of UF6 molecules from the supercooled (supersaturated) vapor phase were determined by classical molecular dynamics (MD) simulations. We observed two phenomena which demonstrate that the nucleation process occurs in the state far from thermal equilibrium. First, the excited hot clusters, the temperature of which is much higher than that of the monomer, were produced and continued to exist during the nucleation process. Second, the relationship between the potential energy and temperature of the clusters depends on the monomer temperature, that is, the potential energy at a temperature decreases with the increase in monomer temperature. In the simulations, various types of cluster configurations were observed: prolate, oblate, spherelike, and confeitolike. The confeitolike cluster is composed of one core and a few horns, and it was found predominantly in the hotter clusters. The infrared spectra of the UF6 clusters were calculated using a dipole-dipole and dipole-induced dipole interaction model and compared with those measured in a supercooled state by Tanimura et al. [J. Chem. Phys. 107, 7096 (1997)]. As a result, we found that the spectra measured in the supercooled state can be attributed to the excited hot clusters, the configuration of which are confeitolike.

Tanimura, Shinobu; Yasuoka, Kenji; Ebisuzaki, Toshikazu

2000-02-01

272

Theoretical study of quantum molecular reaction dynamics and of the effects of intense laser radiation on a diatomic molecule  

SciTech Connect

Within the very broad field of molecular dynamics, we have concentrated on two simple yet important systems. The systems are simple enough so that they are adequately described with a single Born-Oppenheimer potential energy surface and that the dynamics can be calculated accurately. They are important because they give insight into solving more complicated systems. First we discuss H + H/sub 2/ reactive scattering. We present an exact formalism for atom-diatom reactive scattering which avoids the problem of finding a coordinate system appropriate for both reactants and products. We present computational results for collinear H + H/sub 2/ reactive scattering which agree very well with previous calculations. We also present a coupled channel distorted wave Born approximation for atom-diatom reactive scattering which we show is a first order approximation to our exact formalism. We present coupled channel DWBA results for three dimensional H + H/sub 2/ reactive scattering. The second system is an isolated HF molecule in an intense laser field. Using classical trajectories and quantum dynamics, we look at energy absorbed and transition probabilities as a function of the laser pulse time and also averaged over the pulse time. Calculations are performed for both rotating and nonrotating HF. We examine one and two photon absorption about the fundamental frequency, multiphoton absorption, and overtone absorption. 127 references, 31 figures, 12 tables.

Dardi, P.S.

1984-11-01

273

Molecular profiling of experimental endometriosis identified gene expression patterns in common with human disease  

PubMed Central

OBJECTIVE To validate a rat model of endometriosis using cDNA microarrays by identifying common gene expression patterns beween experimental and natural disease. DESIGN Autotransplantation rat model. SETTING Medical school department. ANIMALS Female Sprague-Dawley rats. INTERVENTIONS Endometriosis was surgically-induced by suturing uterine horn implants next to the small intestine’s mesentery. Control rats received sutures with no implants. After 60 days, endometriotic implants and uterine horn were obtained. MAIN OUTCOME MEASURES Gene expression levels determined by cDNA microarrays and QRT-PCR. METHODS Cy5-labeled cDNA was synthesized from total RNA obtained from endometriotic implants. Cy3-labeled cDNA was synthesized using uterine RNA from a control rat. Gene expression levels were analyzed after hybridizing experimental and control labeled cDNA to PIQOR™ Toxicology Rat Microarrays (Miltenyi Biotec) containing 1,252 known genes. Cy5/Cy3 ratios were determined and genes with >2-fold higher or <0.5-fold lower expression levels were selected. Microarray results were validated by QRT-PCR. RESULTS We observed differential expression of genes previously shown to be upregulated in patients, including growth factors, inflammatory cytokines/receptors, tumor invasion/metastasis factors, adhesion molecules, and anti-apoptotic factors. CONCLUSIONS This study presents evidence in support of using this rat model to study the natural history of endometriosis and test novel therapeutics for this incurable disease. PMID:17478174

Flores, Idhaliz; Rivera, Elizabeth; Ruiz, Lynnette A.; Santiago, Olga I.; Vernon, Michael W.; Appleyard, Caroline B.

2007-01-01

274

Surface-aligned ion-molecule reaction on the surface of a molecular crystal CD3+ + CD3I --> C2D5+ + DI.  

PubMed

An ion-molecule reaction has been observed from a condensed molecular crystal of CD(3)I using the time-of-flight electron-stimulated desorption ion angular distribution technique. The CD(3)I multilayer is produced by growth on an ordered substrate. The reaction occurs between CD(3)(+) ions produced by electron-stimulated desorption and neighbor CD(3)I molecules in the topmost layer of the molecular crystal of CD(3)I, forming product C(2)D(5)(+) ions whose desorption dynamics have been measured. The normal momentum of the product ion is close to that of the reactant ion, suggesting that the reaction is dominated by a two-body collision, i.e., the momentum of the reactant CD(3)(+) ion governs the momentum of the product C(2)D(5)(+) ion. The ion-molecule reaction is of high cross section since the C(2)D(5)(+) yield is comparable to the CD(3)(+) yield. It is found that the yield and directionality of the emission of the C(2)D(5)(+) product ion is governed by the molecular order that is characteristic of the molecular crystal of CD(3)I. Destroying or modifying this order by using a spacer layer of H(2)O diminishes the C(2)D(5)(+) product ion yield relative to the reactant CD(3)(+) yield and broadens the ion emission directions. PMID:15469305

Lee, Jae-Gook; Yates, John T

2004-10-13

275

Methanol and ethanol modulate responses to danger- and microbe-associated molecular patterns.  

PubMed

Methanol is a byproduct of cell wall modification, released through the action of pectin methylesterases (PMEs), which demethylesterify cell wall pectins. Plant PMEs play not only a role in developmental processes but also in responses to herbivory and infection by fungal or bacterial pathogens. Molecular mechanisms that explain how methanol affects plant defenses are poorly understood. Here we show that exogenously supplied methanol alone has weak effects on defense signaling in three dicot species, however, it profoundly alters signaling responses to danger- and microbe-associated molecular patterns (DAMPs, MAMPs) such as the alarm hormone systemin, the bacterial flagellum-derived flg22 peptide, and the fungal cell wall-derived oligosaccharide chitosan. In the presence of methanol the kinetics and amplitudes of DAMP/MAMP-induced MAP kinase (MAPK) activity and oxidative burst are altered in tobacco and tomato suspension-cultured cells, in Arabidopsis seedlings and tomato leaf tissue. As a possible consequence of altered DAMP/MAMP signaling, methanol suppressed the expression of the defense genes PR-1 and PI-1 in tomato. In cell cultures of the grass tall fescue (Festuca arundinacea, Poaceae, Monocots), methanol alone activates MAPKs and increases chitosan-induced MAPK activity, and in the darnel grass Lolium temulentum (Poaceae), it alters wound-induced MAPK signaling. We propose that methanol can be recognized by plants as a sign of the damaged self. In dicots, methanol functions as a DAMP-like alarm signal with little elicitor activity on its own, whereas it appears to function as an elicitor-active DAMP in monocot grasses. Ethanol had been implicated in plant stress responses, although the source of ethanol in plants is not well established. We found that it has a similar effect as methanol on responses to MAMPs and DAMPs. PMID:25360141

Hann, Claire T; Bequette, Carlton J; Dombrowski, James E; Stratmann, Johannes W

2014-01-01

276

Methanol and ethanol modulate responses to danger- and microbe-associated molecular patterns  

PubMed Central

Methanol is a byproduct of cell wall modification, released through the action of pectin methylesterases (PMEs), which demethylesterify cell wall pectins. Plant PMEs play not only a role in developmental processes but also in responses to herbivory and infection by fungal or bacterial pathogens. Molecular mechanisms that explain how methanol affects plant defenses are poorly understood. Here we show that exogenously supplied methanol alone has weak effects on defense signaling in three dicot species, however, it profoundly alters signaling responses to danger- and microbe-associated molecular patterns (DAMPs, MAMPs) such as the alarm hormone systemin, the bacterial flagellum-derived flg22 peptide, and the fungal cell wall-derived oligosaccharide chitosan. In the presence of methanol the kinetics and amplitudes of DAMP/MAMP-induced MAP kinase (MAPK) activity and oxidative burst are altered in tobacco and tomato suspension-cultured cells, in Arabidopsis seedlings and tomato leaf tissue. As a possible consequence of altered DAMP/MAMP signaling, methanol suppressed the expression of the defense genes PR-1 and PI-1 in tomato. In cell cultures of the grass tall fescue (Festuca arundinacea, Poaceae, Monocots), methanol alone activates MAPKs and increases chitosan-induced MAPK activity, and in the darnel grass Lolium temulentum (Poaceae), it alters wound-induced MAPK signaling. We propose that methanol can be recognized by plants as a sign of the damaged self. In dicots, methanol functions as a DAMP-like alarm signal with little elicitor activity on its own, whereas it appears to function as an elicitor-active DAMP in monocot grasses. Ethanol had been implicated in plant stress responses, although the source of ethanol in plants is not well established. We found that it has a similar effect as methanol on responses to MAMPs and DAMPs. PMID:25360141

Hann, Claire T.; Bequette, Carlton J.; Dombrowski, James E.; Stratmann, Johannes W.

2014-01-01

277

Diverse redox-active molecules bearing O-, S-, or Se-terminated tethers for attachment to silicon in studies of molecular information storage.  

PubMed

A molecular approach to information storage employs redox-active molecules tethered to an electroactive surface. Attachment of the molecules to electroactive surfaces requires control over the nature of the tether (linker and surface attachment group). We have synthesized a collection of redox-active molecules bearing different linkers and surface anchor groups in free or protected form (hydroxy, mercapto, S-acetylthio, and Se-acetylseleno) for attachment to surfaces such as silicon, germanium, and gold. The molecules exhibit a number of cationic oxidation states, including one (ferrocene), two [zinc(II)porphyrin], three [cobalt(II)porphyrin], or four (lanthanide triple-decker sandwich compound). Electrochemical studies of monolayers of a variety of the redox-active molecules attached to Si(100) electrodes indicate that molecules exhibit a regular mode of attachment (via a Si-X bond, X = O, S, or Se), relatively homogeneous surface organization, and robust reversible electrochemical behavior. The acetyl protecting group undergoes cleavage during the surface deposition process, enabling attachment to silicon via thio or seleno groups without handling free thiols or selenols. PMID:14986994

Balakumar, Arumugham; Lysenko, Andrey B; Carcel, Carole; Malinovskii, Vladimir L; Gryko, Daniel T; Schweikart, Karl-Heinz; Loewe, Robert S; Yasseri, Amir A; Liu, Zhiming; Bocian, David F; Lindsey, Jonathan S

2004-03-01

278

Complex temporal patterns in molecular dynamics: A direct measure of the phase-space exploration by the trajectory at macroscopic time scales  

E-print Network

Complex temporal patterns in molecular dynamics: A direct measure of the phase-space exploration how the trajectory explores the phase space and independent from the particular molecular signal used in liquids form complex patterns in the phase space. Because of the system's high dimensionality defined

Nerukh, Dmitry

279

Oxaliplatin induces different cellular and molecular chemoresistance patterns in colorectal cancer cell lines of identical origins  

PubMed Central

Background Cancer cells frequently adopt cellular and molecular alterations and acquire resistance to cytostatic drugs. Chemotherapy with oxaliplatin is among the leading treatments for colorectal cancer with a response rate of 50%, inducing intrastrand cross-links on the DNA. Despite of this drug’s efficiency, resistance develops in nearly all metastatic patients. Chemoresistance being of crucial importance for the drug’s clinical efficiency this study aimed to contribute to the identification and description of some cellular and molecular alterations induced by prolonged oxaliplatin therapy. Resistance to oxaliplatin was induced in Colo320 (Colo320R) and HT-29 (HT-29R) colorectal adenocarcinoma cell lines by exposing the cells to increasing concentrations of the drug. Alterations in morphology, cytotoxicity, DNA cross-links formation and gene expression profiles were assessed in the parental and resistant variants with microscopy, MTT, alkaline comet and pangenomic microarray assays, respectively. Results Morphology analysis revealed epithelial-to-mesenchymal transition in the resistant vs parental cells suggesting alterations of the cells’ adhesion complexes, through which they acquire increased invasiveness and adherence. Cytotoxicity measurements demonstrated resistance to oxaliplatin in both cell lines; Colo320 being more sensitive than HT-29 to this drug (P?molecular chemoresistance patterns induced by prolonged treatment with oxaliplatin in cell lines with identical origins (colorectal adenocarcinomas). PMID:23865481

2013-01-01

280

Adapting SAFT-? perturbation theory to site-based molecular dynamics simulation. III. Molecules with partial charges at bulk phases, confined geometries and interfaces  

NASA Astrophysics Data System (ADS)

In Paper I [A. F. Ghobadi and J. R. Elliott, J. Chem. Phys. 139(23), 234104 (2013)], we showed that how a third-order Weeks-Chandler-Anderson (WCA) Thermodynamic Perturbation Theory and molecular simulation can be integrated to characterize the repulsive and dispersive contributions to the Helmholtz free energy for realistic molecular conformations. To this end, we focused on n-alkanes to develop a theory for fused and soft chains. In Paper II [A. F. Ghobadi and J. R. Elliott, J. Chem. Phys. 141(2), 024708 (2014)], we adapted the classical Density Functional Theory and studied the microstructure of the realistic molecular fluids in confined geometries and vapor-liquid interfaces. We demonstrated that a detailed consistency between molecular simulation and theory can be achieved for both bulk and inhomogeneous phases. In this paper, we extend the methodology to molecules with partial charges such as carbon dioxide, water, 1-alkanols, nitriles, and ethers. We show that the electrostatic interactions can be captured via an effective association potential in the framework of Statistical Associating Fluid Theory (SAFT). Implementation of the resulting association contribution in assessing the properties of these molecules at confined geometries and interfaces presents satisfactory agreement with molecular simulation and experimental data. For example, the predicted surface tension deviates less than 4% comparing to full potential simulations. Also, the theory, referred to as SAFT-? WCA, is able to reproduce the specific orientation of hydrophilic head and hydrophobic tail of 1-alkanols at the vapor-liquid interface of water.

Ghobadi, Ahmadreza F.; Elliott, J. Richard

2014-09-01

281

Molecular characterization and functional analysis of a complement C3 molecule in the orange-spotted grouper (Epinephelus coioides).  

PubMed

Complement component C3 is a key molecule in the complement system whose activation is essential for all the important functions performed by this system. In this study, we examined a temperature-subtracted library from the orange-spotted grouper (Epinephelus coioides), and identified a sequence with high similarity to other complement C3 proteins. Rapid amplification of the cDNA ends (RACE) yielded the full open reading frame of this protein, and subsequent analysis indicated that the Ec-C3 (E. coioides-C3) gene encodes a protein of 1657 amino acid residues with a molecular mass of 184.56 kDa. The deduced amino acid sequence showed that Ec-C3 has conserved residues and domains known to be critical for C3 function. RT-PCR assays showed that under normal physiological conditions Ec-C3 mRNA is most strongly expressed in the liver, but relatively high levels were also found in many other tissues, including intestine, muscles, gills, hemocytes, heart, spleen, head, kidney and brain. Further analysis of Ec-C3 gene expression in liver tissue by quantitative real-time PCR demonstrated that Ec-C3 transcript levels increased when the fish were exposed to both pH and temperature stress, but the time when its expression level peaked differed under these stresses. The results show that Ec-C3 mRNA expression in the orange-spotted grouper is influenced by pH and temperature stress and that Ec-C3 may play an important role in antioxidation mechanisms. PMID:22005515

Qi, Zeng-Hua; Liu, Yu-Feng; Wang, Wei-Na; Wu, Xin; Xin, Yu; Lu, Yi-Fei; Wang, An-Li

2011-12-01

282

Simulation of single DNA molecule stretching and immobilization in a de-wetting two-phase flow over micropillar-patterned surface  

PubMed Central

We investigate single DNA stretching dynamics in a de-wetting flow over micropillars using Brownian dynamics simulation. The Brownian dynamics simulation is coupled with transient flow field computation through a numerical particle tracking algorithm. The droplet formation on the top of the micropillar during the de-wetting process creates a flow pattern that allows DNA to stretch across the micropillars. It is found that DNA nanowire forms if DNA molecules could extend across the stagnation point inside the connecting water filament before its breakup. It also shows that DNA locates closer to the top wall of the micropillar has higher chance to enter the flow pattern of droplet formation and thus has higher chance to be stretched across the micropillars. Our simulation tool has the potential to become a design tool for DNA manipulation in complex biomicrofluidic devices. PMID:24404023

Liao, Wei-Ching; Hu, Xin; Wang, Weixiong; James Lee, L.

2013-01-01

283

Overview of single-molecule methods including high-force, force-fluorescence, and dual-trap studies for probing molecular and cellular machinery  

NASA Astrophysics Data System (ADS)

High force optical trapping, including double trap geometry and simultaneous visualization with single molecule fluorescence imaging enables a wide range of measurement capabilities applicable for probing molecular and cellular machinery. A series of single molecule measurement methods will be presented. Force-fluorescence microscopy enables visualizing amyloid fibers while physically probing their structures including direct unfolding and rupture of fibers with a high force optical trap. Force spectroscopy is employed to probe the strength of single peptide aptamer bonds. A dual-trap geometry allows for direct tracking of unfolding and translocation machinery of the biological motor ClpXP. Force fluorescence microscopy directly visualizes T-cell activation. Automation and flexibility in our instruments coupled with advances in physical assay design strategies are leveraged to access a broad set of molecular and cellular measurement targets.

Lang, Matthew

2011-03-01

284

[Different patterns of molecular evolution of influenza A viruses in avian and human population].  

PubMed

Patterns of molecular evolution of the influenza virus proteins and genes are discussed. The subsets of all viral genes corresponding to statistically significant clusters on dendrogram were shown to fall into two distinct groups. The first group was characterized by the presence of an exact linear relationship between the year of the strain isolation and the evolutionary distance. The subsets of human influenza virus genes belong to this group. A method for eliminating the "frozen" strains from the subsets and for calculating the evolutionary rates without construction of phylogenetic trees has been elaborated. The substitution rates calculated according to this technique agreed with the data obtained previously. A linear relationship was not observed in the second group. This group was predominantly composed of avian influenza virus genes. The lack of linear correlation pointed to the cocirculation of a large amount of different influenza virus genomic segments in the avian population. An approach for an examination of the role of intragenic recombination in the development of the antigenic subtypes of hemagglutinin is suggested. Our results suggest that recombination did not play a considerable role in this process, and that all modern subtypes of this protein were probably formed before the introduction of the influenza viruses into the human population. These findings are consistent with the hypothesis that influenza viruses penetrated into human population from their pools in avian populations. PMID:9749330

Makarova, K S; Wulf YuI; Tereza, E P; Ratner, V A

1998-07-01

285

Formation of Ga droplets on patterned GaAs (100) by molecular beam epitaxy  

PubMed Central

In this paper, the formation of Ga droplets on photo-lithographically patterned GaAs (100) and the control of the size and density of Ga droplets by droplet epitaxy using molecular beam epitaxy are demonstrated. In extension of our previous result from the journal Physical Status Solidi A, volume 209 in 2012, the sharp contrast of the size and density of Ga droplets is clearly observed by high-resolution scanning electron microscope, atomic force microscope, and energy dispersive X-ray spectrometry. Also, additional monolayer (ML) coverage is added to strength the result. The density of droplets is an order of magnitude higher on the trench area (etched area), while the size of droplets is much larger on the strip top area (un-etched area). A systematic variation of ML coverage results in an establishment of the control of size and density of Ga droplets. The cross-sectional line profile analysis and root mean square roughness analysis show that the trench area (etched area) is?approximately?six times rougher. The atomic surface roughness is suggested to be the main cause of the sharp contrast of the size and density of Ga droplets and is discussed in terms of surface diffusion. PMID:23033893

2012-01-01

286

Two-dimensional molecular patterning by surface-enhanced Zn-porphyrin coordination.  

PubMed

In this contribution, we show how zinc-5,10,15,20-meso-tetradodecylporphyrins (Zn-TDPs) self-assemble into stable organized arrays on the surface of graphite, thus positioning their metal center at regular distances from each other, creating a molecular pattern, while retaining the possibility to coordinate additional ligands. We also demonstrate that Zn-TDPs coordinated to 3-nitropyridine display a higher tendency to be adsorbed at the surface of highly oriented pyrolytic graphite (HOPG) than noncoordinated ones. In order to investigate the two-dimensional (2D) self-assembly of coordinated Zn-TDPs, solutions with different relative concentrations of 3-nitropyridine and Zn-TDP were prepared and deposited on the surface of HOPG. STM measurements at the liquid-solid interface reveal that the ratio of coordinated Zn-TDPs over noncoordinated Zn-TDPs is higher at the n-tetradecane/HOPG interface than in n-tetradecane solution. This enhanced binding of the axial ligand at the liquid/solid interface is likely related to the fact that physisorbed Zn-TDPs are better binding sites for nitropyridines. PMID:19341279

Visser, Johan; Katsonis, Nathalie; Vicario, Javier; Feringa, Ben L

2009-05-19

287

Innate Immune Responses Activated in Arabidopsis Roots by Microbe-Associated Molecular Patterns[W][OA  

PubMed Central

Despite the fact that roots are the organs most subject to microbial interactions, very little is known about the response of roots to microbe-associated molecular patterns (MAMPs). By monitoring transcriptional activation of ?-glucuronidase reporters and MAMP-elicited callose deposition, we show that three MAMPs, the flagellar peptide Flg22, peptidoglycan, and chitin, trigger a strong tissue-specific response in Arabidopsis thaliana roots, either at the elongation zone for Flg22 and peptidoglycan or in the mature parts of the roots for chitin. Ethylene signaling, the 4-methoxy-indole-3-ylmethylglucosinolate biosynthetic pathway, and the PEN2 myrosinase, but not salicylic acid or jasmonic acid signaling, play major roles in this MAMP response. We also show that Flg22 induces the cytochrome P450 CYP71A12-dependent exudation of the phytoalexin camalexin by Arabidopsis roots. The phytotoxin coronatine, an Ile-jasmonic acid mimic produced by Pseudomonas syringae pathovars, suppresses MAMP-activated responses in the roots. This suppression requires the E3 ubiquitin ligase COI1 as well as the transcription factor JIN1/MYC2 but does not rely on salicylic acid–jasmonic acid antagonism. These experiments demonstrate the presence of highly orchestrated and tissue-specific MAMP responses in roots and potential pathogen-encoded mechanisms to block these MAMP-elicited signaling pathways. PMID:20348432

Millet, Yves A.; Danna, Cristian H.; Clay, Nicole K.; Songnuan, Wisuwat; Simon, Matthew D.; Werck-Reichhart, Danièle; Ausubel, Frederick M.

2010-01-01

288

Strontium mono-chloride - A new molecule for the determination of chlorine using high-resolution graphite furnace molecular absorption spectrometry and direct solid sample analysis  

NASA Astrophysics Data System (ADS)

A new method has been developed for the determination of chlorine in biological reference materials using high-resolution continuum source graphite furnace molecular absorption spectrometry (HR-CS GF MAS) of the strontium mono-chloride (SrCl) molecule and direct solid sample analysis. The use of the SrCl molecule for high-temperature MAS was not described up to now in the literature. Preliminary time-dependent density functional theory calculations of the SrCl structure were carried out in order to obtain reasonable estimates of the absorption spectrum of the target molecule. The calculations, which were carried out at BHandHLyp/def2-QZVP level of theory, proved a very accurate and inexpensive way to get information about the spectrum of the SrCl molecule, which enabled us to perform the Cl determination with good sensitivity and specificity. The molecular absorption of the SrCl molecule has been measured using the wavelength at 635.862 nm, and zirconium and palladium have been evaluated as the chemical modifiers in order to increase the sensitivity of the gaseous SrCl molecule generated in the graphite furnace. The pyrolysis and vaporization temperatures were 600 °C and 2300 °C, respectively. Accuracy and precision of the method have been evaluated using biological certified reference materials of both animal and plant origins, showing good agreement with the informed and certified values. Limit of detection and characteristic mass were 1.0 and 2.2 ng, respectively. The results found using HR-CS GF MAS were in agreement (95% confidence level) compared to those obtained by electrothermal vaporization-inductively coupled plasma mass spectrometry.

Pereira, Éderson R.; Welz, Bernhard; Lopez, Alfredo H. D.; de Gois, Jefferson S.; Caramori, Giovanni F.; Borges, Daniel L. G.; Carasek, Eduardo; de Andrade, Jailson B.

2014-12-01

289

A quantum chemical study from a molecular transport perspective: ionization and electron attachment energies for species often used to fabricate single-molecule junctions.  

PubMed

The accurate determination of the lowest electron attachment (EA) and ionization (IP) energies for molecules embedded in molecular junctions is important for correctly estimating, for example, the magnitude of the currents (I) or the biases (V) where an I-V curve exhibits significant non-Ohmic behavior. Benchmark calculations for the lowest electron attachment and ionization energies of several typical molecules utilized to fabricate single-molecule junctions characterized by n-type conduction (4,4'-bipyridine, 1,4-dicyanobenzene and 4,4'-dicyano-1,1'-biphenyl) and p-type conduction (benzenedithiol, biphenyldithiol, hexanemonothiol and hexanedithiol) based on the EOM-CCSD (equation-of-motion coupled-cluster singles and doubles) state-of-the-art method of quantum chemistry are presented. They indicate significant differences from the results obtained within current approaches to molecular transport. The present study emphasizes that, in addition to a reliable quantum chemical method, basis sets much better than the ubiquitous double-zeta set employed for transport calculations are needed. The latter is a particularly critical issue for correctly determining EAs, which is impossible without including sufficient diffuse basis functions. The spatial distribution of the dominant molecular orbitals (MOs) is another important issue, on which the present study draws attention, because it sensitively affects the MO energy shifts ? due to image charges formed in electrodes. The present results cannot substantiate the common assumption of a point-like MO midway between electrodes, which substantially affects the actual ?-values. PMID:25270244

Bâldea, Ioan

2014-01-01

290

Spectroscopic and Theoretical Study on the Structures and Dynamics of Functional Molecules - Towards AN Understanding of the Molecular Recognition for Encapsulation Complexes  

NASA Astrophysics Data System (ADS)

Functional molecules, such as crown ethers and calixarenes, can act as hosts for encapsulating guest species through non-covalent interactions. Applications of crown ethers and calixarenes as molecular receptors, metal cation extraction agents, fluoro-ionophores and phase transfer catalytic media have been previously reported in a number of studies in the literature. One of the important aspects of these host/guest molecular assemblies is their selectivity in the encapsulation of guest species. Two important factors that control this selectivity are: (1) the size and the flexibility of the host cavity and (2) the properties of solvent molecules. Molecular complexes formed in supersonic jets provide ideal systems for the selective study of the conformational preference and micro-solvated effects under solvent-controlled conditions. This talk will review our spectroscopic and theoretical studies of the structures of dibenzo-18-crown-6-ether (DB18C6), benzo-18-crown-6-ether (B18C6), calix[4]arene (C4A) and their complexes with guest molecules. We apply laser-induced fluorescence (LIF), resonance enhanced two-photon ionization (R2PI) and UV-UV hole-burning (HB) spectroscopy for obtaining electronic spectra and IR-UV doubleresonance and IR photodissociation (IRPD) spectroscopy for the IR spectra. The electronic and IR spectra are compared with the corresponding results obtained by DFT calculations and high-level first principles electronic structure calculations [MP2 and CCSD(T)]. Based on these joint studies we can elucidate the nature of interactions that control the encapsulation of a guest molecular species as well as how the host can adjust its conformation to accommodate a specific guest, leading to the molecular recognition.

Ebata, Takayuki; Kusaka, Ryoji; Inokuchi, Yoshiya; Xantheas, Sotiris S.

2011-06-01

291

Molecules between the Stars.  

ERIC Educational Resources Information Center

Provides a listing of molecules discovered to date in the vast interstellar clouds of dust and gas. Emphasizes the recent discoveries of organic molecules. Discusses molecular spectral lines, MASERs (microwave amplification by stimulated emission of radiation), molecular clouds, and star birth. (TW)

Verschuur, Gerrit L.

1987-01-01

292

Second-Harmonic-Generation Microscopy Using Excitation Beam with Controlled Polarization Pattern to Determine Three-Dimensional Molecular Orientation  

NASA Astrophysics Data System (ADS)

We have developed a second-harmonic-generation (SHG) microscope using an excitation beam with a controlled polarization pattern in order to detect three-dimensional molecular orientation. The electric field at the focus is controlled three-dimensionally by modifying the polarization distribution with a parallel-aligned nematic-liquid-crystal spatial-light-modulator without any mechanical moving parts. We demonstrated that the SHG signal from an Achilles tendon, sliced so that collagen fibers were aligned parallel to the optical axis, excited by a radially polarized beam was higher than those excited by linearly polarized beams. The possibility of determinating three-dimensional molecular orientation was thus shown.

Yoshiki, Keisuke; Hashimoto, Mamoru; Araki, Tsutomu

2005-08-01

293

Moving Molecules!  

NSDL National Science Digital Library

In this activity about molecular diffusion (located on page 2 of the PDF), learners will make predictions and move molecules of iodine through a seemingly solid plastic sandwich bag. The process of diffusion will be visually indicated by a color change when the iodine reacts with starch inside the bag. Information in the resource explains how this activity relates to nanoparticles and research. Related to linked video, DragonflyTV Nano: Nanosilver.

Twin Cities Public Television, Inc.

2008-01-01

294

The molecular yo-yo method: Live jump detection improves throughput of single-molecule force spectroscopy for out-of-equilibrium transitions  

NASA Astrophysics Data System (ADS)

By monitoring multiple molecular transitions, force-clamp, and trap-position-clamp methods have led to precise determinations of the free energies and free energy landscapes for molecular states populated in equilibrium at the same or similar forces. Here, we present a powerful new elaboration of the force-clamp and force-jump methods, applicable to transitions far from equilibrium. Specifically, we have implemented a live jump detection and force-clamp algorithm that intelligently adjusts and maintains the force on a single molecule in response to the measured state of that molecule. We are able to collect hundreds of individual molecular transitions at different forces, many times faster than previously, permitting us to accurately determine force-dependent lifetime distributions and reaction rates. Application of our method to unwinding and rewinding the nucleosome inner turn, using optical tweezers reveals experimental lifetime distributions that comprise a statistically meaningful number of transitions, and that are accurately single exponential. These measurements significantly reduce the error in the previously measured rates, and demonstrate the existence of a single, dominant free energy barrier at each force studied. A key benefit of the molecular yo-yo method for nucleosomes is that it reduces as far as possible the time spent in the tangentially bound state, which minimizes the loss of nucleosomes by dissociation.

Mack, A. H.; Schlingman, D. J.; Kamenetska, M.; Collins, R.; Regan, L.; Mochrie, S. G. J.

2013-08-01

295

Microbe associated molecular patterns from rhizosphere bacteria trigger germination and Papaver somniferum metabolism under greenhouse conditions.  

PubMed

Ten PGPR from different backgrounds were assayed on Papaver somniferum var. Madrigal to evaluate their potential as biotic elicitors to increase alkaloid content under the rationale that some microbe associated molecular patterns (MAMPs) are able to trigger plant metabolism. First, the 10 strains and their culture media at two different concentrations were tested for their ability to trigger seed germination. Then, the best three strains were tested for their ability to increase seedling growth and alkaloid levels under greenhouse conditions. Only three strains and their culture media enhanced germination. Then, germination enhancing capacity of these best three strains, N5.18 Stenotrophomonas maltophilia, Aur9 Chryseobacterium balustinum and N21.4 Pseudomonas fluorescens was evaluated in soil. Finally, the three strains were applied on seedlings at two time points, by soil drench or by foliar spray. Photosynthesis was measured, plant height was recorded, capsules were weighted and alkaloids analyzed by HPLC. Only N5.18 delivered by foliar spray significantly increased plant height coupled to an increase in total alkaloids and a significant increase in opium poppy straw dry weight; these increases were supported by a better photosynthetic efficiency. The relative contents of morphine, thebaine, codeine and oripavine were affected by this treatment causing a significant increase in morphine coupled to a decrease in thebaine, demonstrating the effectivity of MAMPs from N5.18 in this plant species. Considering the increase in capsule biomass and alkaloids together with the acceleration of germination, strain N5.18 appears as a good candidate to elicit plant metabolism and consequently, to increase productivity of Papaver somniferum. PMID:24296249

Bonilla, A; Sarria, A L F; Algar, E; Muñoz Ledesma, F J; Ramos Solano, B; Fernandes, J B; Gutierrez Mañero, F J

2014-01-01

296

MCL and Mincle: C-Type Lectin Receptors That Sense Damaged Self and Pathogen-Associated Molecular Patterns  

PubMed Central

Macrophage C-type lectin (MCL) and macrophage inducible C-type lectin (Mincle) comprise part of an extensive repertoire of pattern recognition receptors with the ability to sense damage-associated and pathogen-associated molecular patterns. In this review, we cover the discovery and molecular characterization of these C-type lectin receptors, and highlight recent advances in the understanding of their roles in orchestrating the response of the immune system to bacterial and fungal infection, and damaged self. We also discuss the identification and structure–activity relationships of activating ligands, particularly trehalose dimycolate and related mycobacterial glycolipids, which have significant potential in the development of TH1/TH17 vaccination strategies. PMID:25002863

Richardson, Mark B.; Williams, Spencer J.

2014-01-01

297

Heparin coated cardiopulmonary bypass circuits selectively deplete the pattern recognition molecule Ficolin-2 of the lectin complement pathway in vivo.  

PubMed

The complement system can be activated via the lectin pathway by the recognition molecules mannose-binding lectin (MBL) and the ficolins. Ficolin-2 exhibits binding against a broad range of ligands including biomaterials in vitro and low Ficolin-2 levels are associated with increased risk of infections. Thus, we investigated the biocompatibility of the recognition molecules of the lectin pathway in two different types of cardiopulmonary bypass circuits. Blood were drawn at five time points before, during and post-operatively from 30 patients undergoing elective cardiac surgery. Patients were randomized in two groups using different coatings of cardiopulmonary bypass circuits, Phisio® (phosporylcholine polymer coating) and Bioline® (albumin-heparin coating). Concentrations of MBL, Ficolin-1, -2 and -3 and soluble C3a and terminal complement complex (TCC) in plasma samples were measured. Ficolin-3 mediated complement activation potential was evaluated with C4, C3 and TCC as output. There was no significant difference between the two circuit materials regarding MBL, Ficolin-1 and -3. In the Bioline® group the Ficolin-2 levels significantly decreased after initiation of surgery (P<0.0001) and remained reduced throughout the sampling period. This was not seen for Phisio® coated circuits. Ficolin-3 mediated complement activation potential was significantly reduced in both groups after start of operation (P<0.0001), whereas soluble C3a and TCC in the samples were increased (P<0.0001). Ficolin-2 was depleted from plasma during cardiac surgery when using heparin coated bypass circuits and did not reach base line level 24 hours post-operation. These findings may have implications for the postoperative susceptibility to infections in patients undergoing extracorporeal circulation procedures. PMID:25174443

Hein, Estrid; Munthe-Fog, Lea; Thiara, Amrit Singh; Fiane, Arnt E; Mollnes, Tom Eirik; Garred, Peter

2014-09-01

298

Hybrid diatomics-in-molecules-based quantum mechanical\\/molecular mechanical approach applied to the modeling of structures and spectra of mixed molecular clusters Arn(HCl)m and Arn(HF)m  

Microsoft Academic Search

A new hybrid QM\\/DIM approach aimed at describing equilibrium structures and spectroscopic properties of medium size mixed molecular clusters is developed. This methodology is applied to vibrational spectra of hydrogen chloride and hydrogen fluoride clusters with up to four monomer molecules embedded in argon shells Arn(H(Cl\\/F))m (n=1-62, m=1-4). The hydrogen halide complexes (QM part) are treated at the MP2\\/aug-cc-pVTZ level,

A. V. Bochenkova; M. A. Suhm; A. A. Granovsky; A. V. Nemukhin

2004-01-01

299

Repression of Sucrose/Ultraviolet B Light-Induced Flavonoid Accumulation in Microbe-Associated Molecular Pattern-Triggered Immunity in Arabidopsis1[W  

PubMed Central

Recognition of microbe-associated molecular patterns (MAMPs) leads to the generation of MAMP-triggered immunity (MTI), which restricts the invasion and propagation of potentially infectious microbes. It has been described that the perception of different bacterial and fungal MAMPs causes the repression of flavonoid induction upon light stress or sucrose application. However, the functional significance of this MTI-associated signaling output remains unknown. In Arabidopsis (Arabidopsis thaliana), FLAGELLIN-SENSING2 (FLS2) and EF-TU RECEPTOR act as the pattern recognition receptors for the bacterial MAMP epitopes flg22 (of flagellin) and elf18 (of elongation factor [EF]-Tu), respectively. Here, we reveal that reactive oxygen species spiking and callose deposition are dispensable for the repression of flavonoid accumulation by both pattern recognition receptors. Importantly, FLS2-triggered activation of PATHOGENESIS-RELATED (PR) genes and bacterial basal defenses are enhanced in transparent testa4 plants that are devoid of flavonoids, providing evidence for a functional contribution of flavonoid repression to MTI. Moreover, we identify nine small molecules, of which eight are structurally unrelated, that derepress flavonoid accumulation in the presence of flg22. These compounds allowed us to dissect the FLS2 pathway. Remarkably, one of the identified compounds uncouples flavonoid repression and PR gene activation from the activation of reactive oxygen species, mitogen-activated protein kinases, and callose deposition, corroborating a close link between the former two outputs. Together, our data imply a model in which MAMP-induced repression of flavonoid accumulation serves a role in removing the inherent inhibitory action of flavonoids on an MTI signaling branch. PMID:22080602

Serrano, Mario; Kanehara, Kazue; Torres, Martha; Yamada, Kohji; Tintor, Nico; Kombrink, Erich; Schulze-Lefert, Paul; Saijo, Yusuke

2012-01-01

300

Reconstruction of the Electron Density of Molecules with Single-Axis Alignment  

SciTech Connect

Diffraction from the individual molecules of a molecular beam, aligned parallel to a single axis by a strong electric field or other means, has been proposed as a means of structure determination of individual molecules. As in fiber diffraction, all the information extractable is contained in a diffraction pattern from incidence of the diffracting beam normal to the molecular alignment axis. We present two methods of structure solution for this case. One is based on the iterative projection algorithms for phase retrieval applied to the coefficients of the cylindrical harmonic expansion of the molecular electron density. Another is the holographic approach utilizing presence of the strongly scattering reference atom for a specific molecule.

Starodub, Dmitri

2011-08-12

301

Engineering crystals of dendritic molecules  

PubMed Central

A detailed single-crystal X-ray study of conformationally flexible sulfonimide-based dendritic molecules with systematically varied molecular architectures was undertaken. Thirteen crystal structures reported in this work include 9 structures of the second-generation dendritic sulfonimides decorated with different aryl groups, 2 compounds bearing branches of both second and first generation, and 2 representatives of the first generation. Analysis of the packing patterns of 9 compounds bearing second-generation branches shows that despite their lack of strong directive functional groups there is a repeatedly reproduced intermolecular interaction mode consisting in an anchor-type packing of complementary second-generation branches of neighbouring molecules. The observed interaction tolerates a wide range of substituents in meta- and para-positions of the peripheral arylsulfonyl rings. Quantum chemical calculations of the molecule-molecule interaction energies agree at the qualitative level with the packing preferences found in the crystalline state. The calculations can therefore be used as a tool to rationalize and predict molecular structures with commensurate and non-commensurate branches for programming of different packing modes in crystal. PMID:19549870

Lukin, Oleg; Schubert, Dirk; Müller, Claudia M.; Schweizer, W. Bernd; Gramlich, Volker; Schneider, Julian; Dolgonos, Grygoriy; Shivanyuk, Alexander

2009-01-01

302

Theoretical study of donor–spacer–acceptor structure molecule for use as stable molecular rectifier: geometric and electronic structures  

Microsoft Academic Search

Recently, molecular electronics has attracted much attention as a ‘post-silicon technology’ for future nanoscale electronic devices. One of the most important elements in molecular electronic devices is the realization of a unimolecular rectifier. In the present study, the geometric and electronic structure of the TTF-derivative (donor)–sigma-bond–TCNQ-derivative (acceptor), a leading candidate for a molecular rectifying device has been investigated theoretically using

H. Mizuseki; N. Igarashi; C. Majumder; R. V. Belosludov; A. A. Farajian; Y. Kawazoe

2003-01-01

303

Two different molecular species of pig calpastatin. Structural and functional relationship between 107 kDa and 68 kDa molecules.  

PubMed Central

Calpastatin, the inhibitor protein acting specifically on calpain (EC 3.4.22.17; Ca2+-dependent cysteine proteinase), is known to be widely distributed in mammalian and avian cells. Two different molecular species of calpastatin were isolated and purified to homogeneity from pig heart muscle and from pig erythrocytes, and shown to be of 107 kDa and 68 kDa respectively on SDS/polyacrylamide-gel electrophoresis. Both calpastatins had very similar amino acid compositions when expressed as mol per cent of the residues, differed by only 0.1 pH unit in their isoelectric points, and showed immunological cross-reactivity. One molecule of the 107 kDa species could bind approx. 8 calpain molecules, whereas the 68 kDa inhibitor could bind approx. 5 calpain molecules. These findings suggest similar protein structures of the 107 kDa and 68 kDa calpastatins, each being composed of extended multidomains, with unit inhibitor domains aligned along the polypeptide chain of the molecule. The present study does not conclude, however, whether or not the 68 kDa calpastatin found in erythrocytes is a derived product from the 107 kDa species, which is present as such in heart muscle. Images Fig. 1. Fig. 4. PMID:3755595

Takano, E; Kitahara, A; Sasaki, T; Kannagi, R; Murachi, T

1986-01-01

304

Combined Quantum Mechanics/Molecular Mechanics (QM/MM) Simulations for Protein-Ligand Complexes: Free Energies of Binding of Water Molecules in Influenza Neuraminidase.  

PubMed

The applicability of combined quantum mechanics/molecular mechanics (QM/MM) methods for the calculation of absolute binding free energies of conserved water molecules in protein/ligand complexes is demonstrated. Here, we apply QM/MM Monte Carlo simulations to investigate binding of water molecules to influenza neuraminidase. We investigate five different complexes, including those with the drugs oseltamivir and peramivir. We investigate water molecules in two different environments, one more hydrophobic and one hydrophilic. We calculate the free-energy change for perturbation of a QM to MM representation of the bound water molecule. The calculations are performed at the BLYP/aVDZ (QM) and TIP4P (MM) levels of theory, which we have previously demonstrated to be consistent with one another for QM/MM modeling. The results show that the QM to MM perturbation is significant in both environments (greater than 1 kcal mol(-1)) and larger in the more hydrophilic site. Comparison with the same perturbation in bulk water shows that this makes a contribution to binding. The results quantify how electronic polarization differences in different environments affect binding affinity and also demonstrate that extensive, converged QM/MM free-energy simulations, with good levels of QM theory, are now practical for protein/ligand complexes. PMID:25340313

Woods, Christopher J; Shaw, Katherine E; Mulholland, Adrian J

2014-11-01

305

Molecular evolution of rbcL in three gymnosperm families: identifying adaptive and coevolutionary patterns  

PubMed Central

Background The chloroplast-localized ribulose-1, 5-biphosphate carboxylase/oxygenase (Rubisco), the primary enzyme responsible for autotrophy, is instrumental in the continual adaptation of plants to variations in the concentrations of CO2. The large subunit (LSU) of Rubisco is encoded by the chloroplast rbcL gene. Although adaptive processes have been previously identified at this gene, characterizing the relationships between the mutational dynamics at the protein level may yield clues on the biological meaning of such adaptive processes. The role of such coevolutionary dynamics in the continual fine-tuning of RbcL remains obscure. Results We used the timescale and phylogenetic analyses to investigate and search for processes of adaptive evolution in rbcL gene in three gymnosperm families, namely Podocarpaceae, Taxaceae and Cephalotaxaceae. To understand the relationships between regions identified as having evolved under adaptive evolution, we performed coevolutionary analyses using the software CAPS. Importantly, adaptive processes were identified at amino acid sites located on the contact regions among the Rubisco subunits and on the interface between Rubisco and its activase. Adaptive amino acid replacements at these regions may have optimized the holoenzyme activity. This hypothesis was pinpointed by evidence originated from our analysis of coevolution that supported the correlated evolution between Rubisco and its activase. Interestingly, the correlated adaptive processes between both these proteins have paralleled the geological variation history of the concentration of atmospheric CO2. Conclusions The gene rbcL has experienced bursts of adaptations in response to the changing concentration of CO2 in the atmosphere. These adaptations have emerged as a result of a continuous dynamic of mutations, many of which may have involved innovation of functional Rubisco features. Analysis of the protein structure and the functional implications of such mutations put forward the conclusion that this evolutionary scenario has been possible through a complex interplay between adaptive mutations, often structurally destabilizing, and compensatory mutations. Our results unearth patterns of evolution that have likely optimized the Rubisco activity and uncover mutational dynamics useful in the molecular engineering of enzymatic activities. Reviewers This article was reviewed by Prof. Christian Blouin (nominated by Dr W Ford Doolittle), Dr Endre Barta (nominated by Dr Sandor Pongor), and Dr Nicolas Galtier. PMID:21639885

2011-01-01

306

Small molecule chemokine mimetics suggest a molecular basis for the observation that CXCL10 and CXCL11 are allosteric ligands of CXCR3  

PubMed Central

BACKGROUND AND PURPOSE The chemokine receptor CXCR3 directs migration of T-cells in response to the ligands CXCL9/Mig, CXCL10/IP-10 and CXCL11/I-TAC. Both ligands and receptors are implicated in the pathogenesis of inflammatory disorders, including atherosclerosis and rheumatoid arthritis. Here, we describe the molecular mechanism by which two synthetic small molecule agonists activate CXCR3. EXPERIMENTAL APPROACH As both small molecules are basic, we hypothesized that they formed electrostatic interactions with acidic residues within CXCR3. Nine point mutants of CXCR3 were generated in which an acidic residue was mutated to its amide counterpart. Following transient expression, the ability of the constructs to bind and signal in response to natural and synthetic ligands was examined. KEY RESULTS The CXCR3 mutants D112N, D195N and E196Q were efficiently expressed and responsive in chemotaxis assays to CXCL11 but not to CXCL10 or to either of the synthetic agonists, confirmed with radioligand binding assays. Molecular modelling of both CXCL10 and CXCR3 suggests that the small molecule agonists mimic a region of the ‘30s loop’ (residues 30–40 of CXCL10) which interacts with the intrahelical CXCR3 residue D112, leading to receptor activation. D195 and E196 are located in the second extracellular loop and form putative intramolecular salt bridges required for a CXCR3 conformation that recognizes CXCL10. In contrast, CXCL11 recognition by CXCR3 is largely independent of these residues. CONCLUSION AND IMPLICATIONS We provide here a molecular basis for the observation that CXCL10 and CXCL11 are allosteric ligands of CXCR3. Such findings may have implications for the design of CXCR3 antagonists. LINKED ARTICLE This article is commented on by O'Boyle, pp. 895–897 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476-5381.2011.01759.x PMID:21895630

Nedjai, Belinda; Li, Hubert; Stroke, Ilana L; Wise, Emma L; Webb, Maria L; Merritt, J Robert; Henderson, Ian; Klon, Anthony E; Cole, Andrew G; Horuk, Richard; Vaidehi, Nagarajan; Pease, James E

2012-01-01

307

Molecular characterization of Thai Salmonella enterica serotype typhimurium and serotype 4,5,12:i:- reveals distinct genetic deletion patterns.  

PubMed

Abstract In order to better understand the relationship between Salmonella serotypes Typhimurium and its monophasic variant 4,5,12:i:- found in Thailand, a total of 138 isolates from various sources were characterized using different molecular subtyping methods (i.e., pulsed-field gel electrophoresis [PFGE] and polymerase chain reaction [PCR]) and antibiotic resistance (AbR) patterns. PFGE revealed 52 distinct band patterns among these isolates, 3 of which were shared between the two serotypes. PCR characterization of genomic deletion patterns reveals that Thai S. 4,5,12:i:- isolates contain a distinct deletion pattern in the fljAB region, which can be used as a specific genetic marker for primary identification of S. 4,5,12:i:- sources. AbR study shows that, among 50 representative serotype-confirmed strains, 48.28% (14/29) of Salmonella Typhimurium and 90.48% (19/21) of 4,5,12:i:- isolates are multidrug-resistant Salmonella as they are resistant to at least 3 antimicrobial categories. The AmpST pattern for resistance to ampicillin, streptomycin, and tetracycline was found in high proportions of Salmonella Typhimurium (10 of 29) and S. 4,5,12:i:- (15 of 21) isolates. PMID:24906076

Huoy, Laingshun; Pornruangwong, Srirat; Pulsrikarn, Chaiwat; Chaturongakul, Soraya

2014-08-01

308

Hydration properties of ligands and drugs in protein binding sites: tightly-bound, bridging water molecules and their effects and consequences on molecular design strategies.  

PubMed

Some water molecules in binding sites are important for intermolecular interactions and stability. The way binding site explicit water molecules are dealt with affects the diversity and nature of designed ligand chemical structures and properties. The strategies commonly employed frequently assume that a gain in binding affinity will be achieved by their targeting or neglect. However, in the present work, 2332 high-resolution X-ray crystal structures of hydrated and nonhydrated, drug and nondrug compounds in biomolecular complexes with reported Ki or Kd show that compounds that use tightly bound, bridging water molecules are as potent as those that do not. The distribution of their energies, physicochemical properties, and ligand efficiency indices were compared for statistical significance, and the results were confirmed using 2000 permutation runs. Ligand cases were also split into agonists and antagonists, and crystal structure pairs with differing tightly bound water molecules were also compared. In addition, agonists and antagonists that use tightly bound water bridges are smaller, less lipophilic, and less planar; have deeper ligand efficiency indices; and in general, possess better physicochemical properties for further development. Therefore, tightly bound, bridging water molecules may in some cases be replaced and targeted as a strategy, though sometimes keeping them as bridges may be better from a pharmacodynamic perspective. The results suggest general indications on tightly hydrated and nontightly hydrated compounds in binding sites and practical considerations to adopt a strategy in drug and molecular design when faced with this special type of water molecules. There are also benefits of lower log P and better developability for tightly hydrated compounds, while stronger potency is not always required or beneficial. The hydrated binding site may be one of the many structure conformations available to the receptor, and different ligands will have a different ability to select either hydrated or nonhydrated receptor binding site conformations. Compounds may thus be designed, and if a tightly bound, bridging water molecule is observed in the binding site, attempts to replace it should only be made if the subsequent ligand modification would improve also its ligand efficiency, enthalpy, specificity, and pharmacokinetic properties. If the modification does succeed in replacing the tightly bound, bridging water molecule, it will have at least achieved benefits for ligand optimization and development independently of either positive or negative change in binding affinity outcome. PMID:23662606

García-Sosa, Alfonso T

2013-06-24

309

A molecular toggle after exocytosis sequesters the presynaptic syntaxin1a molecules involved in prior vesicle fusion.  

PubMed

Neuronal synapses are among the most scrutinized of cellular systems, serving as a model for all membrane trafficking studies. Despite this, synaptic biology has proven difficult to interrogate directly in situ due to the small size and dynamic nature of central synapses and the molecules within them. Here we determine the spatial and temporal interaction status of presynaptic proteins, imaging large cohorts of single molecules inside active synapses. Measuring rapid interaction dynamics during synaptic depolarization identified the small number of syntaxin1a and munc18-1 protein molecules required to support synaptic vesicle exocytosis. After vesicle fusion and subsequent SNARE complex disassembly, a prompt switch in syntaxin1a and munc18-1-binding mode, regulated by charge alteration on the syntaxin1a N-terminal, sequesters monomeric syntaxin1a from other disassembled fusion complex components, preventing ectopic SNARE complex formation, readying the synapse for subsequent rounds of neurotransmission. PMID:25517944

Kavanagh, Deirdre M; Smyth, Annya M; Martin, Kirsty J; Dun, Alison; Brown, Euan R; Gordon, Sarah; Smillie, Karen J; Chamberlain, Luke H; Wilson, Rhodri S; Yang, Lei; Lu, Weiping; Cousin, Michael A; Rickman, Colin; Duncan, Rory R

2014-01-01

310

Molecular recognition of PTCDI-C8 molecules on the Si(1 1 0)-(16 × 2) surface  

NASA Astrophysics Data System (ADS)

Mechanisms of PTCDI-C8 adsorption and thin films growth on Si(1 1 0)-(16 × 2) have been studied using a combination of X-ray photoelectron spectroscopy, scanning tunneling microscopy, and density functional theory. Oxygen atoms of the PTCDI-C8 molecule interact with the substrate increasing substantially the adsorption energy. Adsorbed molecules do not form long-range ordered structures on the surface but local chain-like arrangements. A good agreement between the calculated isosurfaces of electronic charge density and the scanning tunneling microscopy images of the filled electron states of clean and adsorbate-covered surfaces allows to recognize the PTCDI-C8 molecules adsorbed on Si(1 1 0)-(16 × 2).

Lament, Katarzyna; Kami?ski, Wojciech; Mazur, Piotr; Zuber, Stefan; Ciszewski, Antoni

2014-06-01

311

A molecular toggle after exocytosis sequesters the presynaptic syntaxin1a molecules involved in prior vesicle fusion  

PubMed Central

Neuronal synapses are among the most scrutinized of cellular systems, serving as a model for all membrane trafficking studies. Despite this, synaptic biology has proven difficult to interrogate directly in situ due to the small size and dynamic nature of central synapses and the molecules within them. Here we determine the spatial and temporal interaction status of presynaptic proteins, imaging large cohorts of single molecules inside active synapses. Measuring rapid interaction dynamics during synaptic depolarization identified the small number of syntaxin1a and munc18-1 protein molecules required to support synaptic vesicle exocytosis. After vesicle fusion and subsequent SNARE complex disassembly, a prompt switch in syntaxin1a and munc18-1-binding mode, regulated by charge alteration on the syntaxin1a N-terminal, sequesters monomeric syntaxin1a from other disassembled fusion complex components, preventing ectopic SNARE complex formation, readying the synapse for subsequent rounds of neurotransmission. PMID:25517944

Kavanagh, Deirdre M.; Smyth, Annya M.; Martin, Kirsty J.; Dun, Alison; Brown, Euan R.; Gordon, Sarah; Smillie, Karen J.; Chamberlain, Luke H.; Wilson, Rhodri S.; Yang, Lei; Lu, Weiping; Cousin, Michael A.; Rickman, Colin; Duncan, Rory R.

2014-01-01

312

Effect of a Low Molecular Weight Heparin Molecule, Dalteparin, on Cellular Apoptosis and Inflammatory Process in an Incisional Wound-Healing Model  

Microsoft Academic Search

Purpose  In this study we aimed to test the effect of a low molecular weight heparin molecule, namely dalteparin, on the inflammation\\u000a and cellular apoptosis in an incisional wound-healing model in rats.\\u000a \\u000a \\u000a \\u000a Methods  Eighteen male Sprague–Dawley rats were randomly assigned to three groups (n = 6 for each group). Two full-thickness skin incisions were made over cervical and lumbar regions of all

Ali Civelek; Koray Ak; Ozlem Kurtkaya; Atike Tekeli; Selim Isbir; Erol Nargileci; Sinan Arsan; Aydin Sav

2007-01-01

313

A new molecular logic for BMP-mediated dorsoventral patterning, in the leech Helobdella  

PubMed Central

Summary BMP signaling is broadly implicated in dorsoventral (DV) patterning of bilaterally symmetric animals [1–3], and its role in axial patterning apparently predates the birth of Bilateria [4–7]. In fly and vertebrate embryos, BMPs and their antagonists (primarily Sog/chordin) diffuse and interact to generate signaling gradients that pattern fields of cells [8–10]. Work in other species reveals diversity in essential facets of this ancient patterning process, however. Here, we report that BMP signaling patterns the DV axis of segmental ectoderm in the leech Helobdella, a clitellate annelid (Super-phylum Lophotrochozoa) featuring stereotyped developmental cell lineages; but the detailed mechanisms of DV patterning in Helobdella differ markedly from fly and vertebrates. In Helobdella, BMP2/4s are expressed broadly, rather than in dorsal territory, while a dorsally expressed BMP5-8 specifies dorsal fate by short-range signaling. A BMP antagonist, gremlin, is up-regulated by BMP5-8 in dorsolateral territory, rather than ventral, and yet the BMP-antagonizing activity of gremlin is required for normal ventral cell fates. Gremlin promotes ventral fates without disrupting dorsal fates by selectively inhibiting BMP2/4s, not BMP5-8. Thus, DV patterning in the development of the leech revealed unexpected evolutionary plasticity of the ‘conserved’ BMP patterning system, presumably reflecting its adaptation to different modes of embryogenesis. PMID:21782437

Kuo, Dian-Han; Weisblat, David A.

2011-01-01

314

Mask pattern transferred transient grating technique for molecular-dynamics study in solutions  

E-print Network

transferred transient grating (MPT-TG) technique by using metal grating films. Transient thermal grating is generated by an ultraviolet light pattern transfer to nitrobenzene in 2-propanol solution by an optical interference pattern generated by two crossing pump beams. As parameters, sev- eral properties

Okamoto, Koichi

315

The Pattern of Secreted Molecules During the Co-Inoculation of Alfalfa Plants With Sinorhizobium meliloti and Delftia sp. strain JD2: An Interaction That Improves Plant Yield.  

PubMed

Delftia sp. strain JD2 is a plant-growth-promoting bacterium that enhances legume nodulation and growth, acting as nodule-assisting bacterium during the co-inoculation of plants with rhizobial strains. In this work, we evaluate how the co-inoculation of alfalfa with Sinorhizobium meliloti U143 and JD2 increases plant yield under greenhouse conditions and we analyze the pattern of secreted bioactive compounds which may be involved in the microbe-plant communication. The chemical composition of extracellular cultures (EC) produced in hydroponic conditions (collected 4, 7, and 14 days after bacterial treatment) were characterized using different chromatographic and elucidation techniques. In addition, we assessed the effect that plant irrigation with cell-free EC, produced during co-inoculation experiments, would have on plant yield. Results showed increased alfalfa shoot and root matter, suggesting that U143-JD2 co-inoculation might be a beneficial agricultural practice. The pattern of secreted secondary metabolites among treatments showed important differences. Qualitative and quantitative changes in phenolic compounds (including flavonoids), organic acids, and volatile compounds were detected during the early microbe-plant interaction, suggesting that the production of some molecules positively affects the microbe-plant association. Finally, the irrigation of co-inoculated plants with cell-free EC under greenhouse conditions increased plant yield over agronomic expectations. This effect might be attributed to the bioactive secondary metabolites incorporated during the irrigation. PMID:25353366

Morel, M A; Cagide, C; Minteguiaga, M A; Dardanelli, M S; Castro-Sowinski, S

2015-02-01

316

Molecular eigenstate spectroscopy: Application to the intramolecular dynamics of some polyatomic molecules in the 3000 to 7000 cm{sup {minus}1} region  

SciTech Connect

Intramolecular vibrational redistribution (IVR) appears to be a universal property of polyatomic molecules in energy regions where the vibrational density of states is greater than about 5 to 30 states per cm{sup {minus}1}. Interest in IVR stems from its central importance to the spectroscopy, photochemistry, and reaction kinetics of these molecules. A bright state, {var_phi}{sub s}, which may be a C-H stretching vibration, carries the oscillator strength from the ground state. This bright state may mix with bath rotational-vibrational levels to form a clump of molecular eigenstates, each of which carries a portion of the oscillator strength from the ground state. In this work the authors explicitly resolve transitions to each of these molecular eigenstates. Detailed information about the nature of IVR is contained in the frequencies and intensities of the observed discrete transitions. The primary goal of this research is to probe the coupling mechanisms by which IVR takes place. The most fundamental distinction to be made is between anharmonic coupling which is independent of molecular rotation and rotationally-mediated coupling. The authors are also interested in the rate at which IVR takes place. Measurements are strictly in the frequency domain but information is obtained about the decay of the zero order state, {var_phi}{sub s}, which could be prepared in a hypothetical experiment as a coherent excitation of the clump of molecular eigenstates. As the coherent superposition dephases, the energy would flow from the initially prepared mode into nearby overtones and combinations of lower frequency vibrational modes. The decay of the initially prepared mode is related to a pure sequence infrared absorption spectrum by a Fourier transform.

Perry, D.S. [Univ. of Akron, OH (United States)

1993-12-01

317

Blood transfusion products contain mitochondrial DNA damage-associated molecular patterns: a potential effector of transfusion-related acute lung injury  

PubMed Central

Background Transfusion-related acute lung injury (TRALI) is the most frequent and severe complication in patients receiving multiple blood transfusions. Current pathogenic concepts hold that proinflammatory mediators present in transfused blood products are responsible for the initiation of TRALI, but the identity of the critical effector molecules is yet to be determined. We hypothesize that mtDNA damage-associated molecular patterns (DAMPs) are present in blood transfusion products, which may be important in the initiation of TRALI. Methods: DNA was extracted from consecutive samples of packed red blood cells, fresh frozen plasma (FFP), and platelets procured from the local blood bank. Quantitative realtime polymerase chain reaction was used to quantify ? 200 bp sequences from the COX1, ND1, ND6, and D-loop regions of the mitochondrial genome. Results A range of mtDNA DAMPs were detected in all blood components measured, with FFP displaying the largest variation. Conclusions We conclude that mtDNA DAMPs are present in packed red blood cells, FFP, and platelets. These observations provide proof of the concept that mtDNA DAMPs may be mediators of TRALI. Further studies are needed to test this hypothesis and to determine the origin of mtDNA DAMPs in transfused blood. PMID:25039013

Lee, Yann-Leei; King, Madelyn B.; Gonzalez, Richard P.; Brevard, Sidney B.; Frotan, M. Amin; Gillespie, Mark N.; Simmons, Jon D.

2015-01-01

318

Molecular Shot Noise, Burst Size Distribution, and Single-Molecule Detection in Fluid Flow: Effects of Multiple Occupancy  

E-print Network

M888, Los Alamos National Laboratory, Los Alamos, New Mexico 87545 ReceiVed: March 5, 1997; In Final of single fluorescent molecules in liquids at room temperature has made big advances.1-15 The possible of a given width. The common way of processing this measured raw data is to first apply a digital filter

Enderlein, Jörg

319

Molecular mechanisms of regeneration initiation and dorsal-ventral patterning in planarians  

E-print Network

Regeneration is widespread among animals, yet very little is known about the molecular mechanisms that govern regenerative processes. Planarians have emerged in recent years as a powerful model for studying regeneration ...

Gaviño, Michael A. (Michael Alexander)

2013-01-01

320

Potent New Small-Molecule Inhibitor of Botulinum Neurotoxin Serotype A Endopeptidase Developed by Synthesis-Based Computer-Aided Molecular Design  

PubMed Central

Botulinum neurotoxin serotype A (BoNTA) causes a life-threatening neuroparalytic disease known as botulism. Current treatment for post exposure of BoNTA uses antibodies that are effective in neutralizing the extracellular toxin to prevent further intoxication but generally cannot rescue already intoxicated neurons. Effective small-molecule inhibitors of BoNTA endopeptidase (BoNTAe) are desirable because such inhibitors potentially can neutralize the intracellular BoNTA and offer complementary treatment for botulism. Previously we reported a serotype-selective, small-molecule BoNTAe inhibitor with a Kiapp value of 3.8±0.8 µM. This inhibitor was developed by lead identification using virtual screening followed by computer-aided optimization of a lead with an IC50 value of 100 µM. However, it was difficult to further improve the lead from micromolar to even high nanomolar potency due to the unusually large enzyme-substrate interface of BoNTAe. The enzyme-substrate interface area of 4,840 Å2 for BoNTAe is about four times larger than the typical protein-protein interface area of 750–1,500 Å2. Inhibitors must carry several functional groups to block the unusually large interface of BoNTAe, and syntheses of such inhibitors are therefore time-consuming and expensive. Herein we report the development of a serotype-selective, small-molecule, and competitive inhibitor of BoNTAe with a Ki value of 760±170 nM using synthesis-based computer-aided molecular design (SBCAMD). This new approach accounts the practicality and efficiency of inhibitor synthesis in addition to binding affinity and selectivity. We also report a three-dimensional model of BoNTAe in complex with the new inhibitor and the dynamics of the complex predicted by multiple molecular dynamics simulations, and discuss further structural optimization to achieve better in vivo efficacy in neutralizing BoNTA than those of our early micromolar leads. This work provides new insight into structural modification of known small-molecule BoNTAe inhibitors. It also demonstrates that SBCAMD is capable of improving potency of an inhibitor lead by nearly one order of magnitude, even for BoNTAe as one of the most challenging protein targets. The results are insightful for developing effective small-molecule inhibitors of protein targets with large active sites. PMID:19901994

Pang, Yuan-Ping; Vummenthala, Anuradha; Mishra, Rajesh K.; Park, Jewn Giew; Wang, Shaohua; Davis, Jon; Millard, Charles B.; Schmidt, James J.

2009-01-01

321

AMBER, a package of computer programs for applying molecular mechanics, normal mode analysis, molecular dynamics and free energy calculations to simulate the structural and energetic properties of molecules  

Microsoft Academic Search

We describe the development, current features, and some directions for future development of the AMBER package of computer programs. This package has evolved from a program that was constructed to do Assisted Model Building and Energy Refinement to a group of programs embodying a number of the powerful tools of modern computational chemistry-molecular dynamics and free energy calculations.

David A. Pearlman; David A. Case; James W. Caldwell; Wilson S. Ross; Thomas E. Cheatham; Steve Debolt; David Ferguson; George Seibel; Peter Kollman

1995-01-01

322

Molecular dynamics simulation study of the ejection and transport of polymer molecules in matrix-assisted pulsed laser evaporation  

E-print Network

-assisted pulsed laser evaporation Elodie Leveugle and Leonid V. Zhigileia Department of Materials Science the regime where molecular ejection is limited to matrix evaporation from the surface up to more than twice of the simulations are related to experimental observations obtained in matrix-assisted pulsed laser evaporation

Zhigilei, Leonid V.

323

Polyatomic Molecules under Intense Femtosecond Laser Irradiation.  

PubMed

Interaction of intense laser pulses with atoms and molecules is at the forefront of atomic, molecular, and optical physics. It is the gateway to powerful new tools that include above threshold ionization, high harmonic generation, electron diffraction, molecular tomography, and attosecond pulse generation. Intense laser pulses are ideal for probing and manipulating chemical bonding. Though the behavior of atoms in strong fields has been well studied, molecules under intense fields are not as well understood and current models have failed in certain important aspects. Molecules, as opposed to atoms, present confounding possibilities of nuclear and electronic motion upon excitation. The dynamics and fragmentation patterns in response to the laser field are structure sensitive; therefore, a molecule cannot simply be treated as a "bag of atoms" during field induced ionization. In this article we present a set of experiments and theoretical calculations exploring the behavior of a large collection of aryl alkyl ketones when irradiated with intense femtosecond pulses. Specifically, we consider to what extent molecules retain their molecular identity and properties under strong laser fields. Using time-of-flight mass spectrometry in conjunction with pump-probe techniques we study the dynamical behavior of these molecules, monitoring ion yield modulation caused by intramolecular motions post ionization. The set of molecules studied is further divided into smaller sets, sorted by type and position of functional groups. The pump-probe time-delay scans show that among positional isomers the variations in relative energies, which amount to only a few hundred millielectronvolts, influence the dynamical behavior of the molecules despite their having experienced such high fields (V/Å). High level ab initio quantum chemical calculations were performed to predict molecular dynamics along with single and multiphoton resonances in the neutral and ionic states. We propose the following model of strong-field ionization and subsequent fragmentation for polyatomic molecules: Single electron ionization occurs on a suboptical cycle time scale, and the electron carries away essentially all of the energy, leaving behind little internal energy in the cation. Subsequent fragmentation of the cation takes place as a result of further photon absorption modulated by one- and two-photon resonances, which provide sufficient energy to overcome the dissociation energy. The proposed hypothesis implies the loss of a photoelectron at a rate that is faster than intramolecular vibrational relaxation and is consistent with the observation of nonergodic photofragmentation of polyatomic molecules as well as experimental results from many other research groups on different molecules and with different pulse durations and wavelengths. PMID:25314590

Konar, Arkaprabha; Shu, Yinan; Lozovoy, Vadim V; Jackson, James E; Levine, Benjamin G; Dantus, Marcos

2014-12-11

324

Speckle Patterns with Atomic and Molecular de Broglie Waves Forest S. Patton,1  

E-print Network

into a 2 m diameter nozzle [15]. Gaseous He or H2 at variable stag- nation temperature T0 and pressure P0 developed a nozzle source that delivers a continuous beam of atomic helium or molecular hydrogen having expands freely through the nozzle into vacuum. Using a small nozzle diameter and high P0 will produce

Kevan, Stephen D.

325

R.E.D. Server: a web service for deriving RESP and ESP charges and building force field libraries for new molecules and molecular fragments  

PubMed Central

R.E.D. Server is a unique, open web service, designed to derive non-polarizable RESP and ESP charges and to build force field libraries for new molecules/molecular fragments. It provides to computational biologists the means to derive rigorously molecular electrostatic potential-based charges embedded in force field libraries that are ready to be used in force field development, charge validation and molecular dynamics simulations. R.E.D. Server interfaces quantum mechanics programs, the RESP program and the latest version of the R.E.D. tools. A two step approach has been developed. The first one consists of preparing P2N file(s) to rigorously define key elements such as atom names, topology and chemical equivalencing needed when building a force field library. Then, P2N files are used to derive RESP or ESP charges embedded in force field libraries in the Tripos mol2 format. In complex cases an entire set of force field libraries or force field topology database is generated. Other features developed in R.E.D. Server include help services, a demonstration, tutorials, frequently asked questions, Jmol-based tools useful to construct PDB input files and parse R.E.D. Server outputs as well as a graphical queuing system allowing any user to check the status of R.E.D. Server jobs. PMID:21609950

Vanquelef, Enguerran; Simon, Sabrina; Marquant, Gaelle; Garcia, Elodie; Klimerak, Geoffroy; Delepine, Jean Charles; Cieplak, Piotr; Dupradeau, François-Yves

2011-01-01

326

R.E.D. Server: a web service for deriving RESP and ESP charges and building force field libraries for new molecules and molecular fragments.  

PubMed

R.E.D. Server is a unique, open web service, designed to derive non-polarizable RESP and ESP charges and to build force field libraries for new molecules/molecular fragments. It provides to computational biologists the means to derive rigorously molecular electrostatic potential-based charges embedded in force field libraries that are ready to be used in force field development, charge validation and molecular dynamics simulations. R.E.D. Server interfaces quantum mechanics programs, the RESP program and the latest version of the R.E.D. tools. A two step approach has been developed. The first one consists of preparing P2N file(s) to rigorously define key elements such as atom names, topology and chemical equivalencing needed when building a force field library. Then, P2N files are used to derive RESP or ESP charges embedded in force field libraries in the Tripos mol2 format. In complex cases an entire set of force field libraries or force field topology database is generated. Other features developed in R.E.D. Server include help services, a demonstration, tutorials, frequently asked questions, Jmol-based tools useful to construct PDB input files and parse R.E.D. Server outputs as well as a graphical queuing system allowing any user to check the status of R.E.D. Server jobs. PMID:21609950

Vanquelef, Enguerran; Simon, Sabrina; Marquant, Gaelle; Garcia, Elodie; Klimerak, Geoffroy; Delepine, Jean Charles; Cieplak, Piotr; Dupradeau, François-Yves

2011-07-01

327

DISPERSAL PATTERN OF BLACK-BILLED MAGPIES (PICA HUDSONIA) MEASURED BY MOLECULAR GENETIC (RAPD) ANALYSIS  

Microsoft Academic Search

Black-billed Magpies (Pica hudsonia) are a relatively sedentary corvid, with greater dispersal of females than males. To genetically confirm that dispersal pattern, 29 reproductively active adults were captured over two years and were scored for primer-spe- cific random amplified polymorphic DNA (RAPD) bands (53 polymorphic bands in 1996 and 104 in 1997). In both years, we captured more previously banded

XIAO-HONG WANGAND; Charles H. Trost

2001-01-01

328

Learning the local molecular pattern of Alzheimer's disease by non-negative matrix factorization  

Microsoft Academic Search

Gene microarray technology is an effective tool to monitor simultaneous activity of multiple cellular pathways from thousands of genes in a single chip. Many clustering methods have been developed to identify groups of genes or experimental conditions that exhibit similar expression patterns from gene expression data, such as hierarchical clustering, k-means, and self-organizing maps (SOM). The limitations of these clustering

Wei Kong; Xiaoyang Mou; Qiao Li; Yipeng Song

2010-01-01

329

InAs/GaAs nanostructures grown on patterned Si(001) by molecular beam epitaxy.  

PubMed

The potential benefit from the combination of the optoelectronic and electronic functionality of III-V semiconductors with silicon technology is one of the most desired outcomes to date. Here we have systematically investigated the optical properties of InAs quantum structure embedded in GaAs grown on patterned sub-micron and nanosize holes on Si(001). III-V material tends to accumulate in the patterned sub-micron holes and a material depletion region is observed around holes when GaAs/InAs/GaAs is deposited directly on patterned Si(001). By use of a 60 nm SiO(2) layer and patterning sub-micron and nanosize holes through the oxide layer to the substrate, we demonstrate that high optical quality InAs nanostructures, both quantum dots and quantum wells, formed by a two-monolayer InAs layer embedded in GaAs can be epitaxially grown on Si(001). We also report the power-dependent and temperature-dependent photoluminescence spectra of these structures. The results show that hole diameter (sub-micron versus nanosize) has a strong effect on the structural and optical properties of GaAs/InAs/GaAs nanostructures. PMID:21832784

He, Jun; Yadavalli, Kameshwar; Zhao, Zuoming; Li, Ning; Hao, Zhibiao; Wang, Kang L; Jacob, Ajey P

2008-11-12

330

Patterns of inheritance with RAPD molecular markers reveal novel types of polymorphism in the honey bee  

Microsoft Academic Search

The polymerase chain reaction (PCR) was used to generate random amplified polymorphic DNA (RAPD) from honey bee DNA samples in order to follow the patterns of inheritance of RAPD markers in a haplodiploid insect. The genomic DNA samples from two parental bees, a haploid drone and a diploid queen, were screened for polymorphism with 68 different tennucleotide primers of random

Greg J. Hunt; Robert E. Page

1992-01-01

331

Monolayer patterning using ketone dipoles.  

PubMed

The self-assembly of multi-component monolayers with designed patterns requires molecular recognition among components. Dipolar interactions have been found to influence morphologies of self-assembled monolayers and can affect molecular recognition functions. Ketone groups have large dipole moments (2.6 D) and are easily incorporated into molecules. The potential of ketone groups for dipolar patterning has been evaluated through synthesis of two 1,5-disubstituted anthracenes bearing mono-ketone side chains, STM characterization of monolayers self-assembled from their single and two component solutions and molecular mechanics simulations to determine their self-assembly energetics. The results reveal that (i) anthracenes bearing self-repulsive mono-ketone side chains assemble in an atypical monolayer morphology that establishes dipolar attraction, instead of repulsion, between ketones in adjacent side chains; (ii) pairs of anthracene molecules whose self-repulsive ketone side chains are dipolar complementary spontaneously assemble compositionally patterned monolayers, in which the two components segregate into neighboring, single component columns, driven by side chain dipolar interactions; (iii) compositionally patterned monolayers also assemble from dipolar complementary anthracene pairs that employ different dipolar groups (ketones or CF2 groups) in their side chains; (iv) the ketone group, with its larger dipole moment and size, provides comparable driving force for patterned monolayer formation to that of the smaller dipole, and smaller size, CF2 group. PMID:23632754

Kim, Min Kyoung; Xue, Yi; Pašková, Tereza; Zimmt, Matthew B

2013-08-14

332

Surface expression patterns of negative regulatory molecules identify determinants of virus-specific CD8+ T-cell exhaustion in HIV infection  

PubMed Central

A highly complex network of coinhibitory and costimulatory receptors regulates the outcome of virus-specific CD8+ T-cell responses. Here, we report on the expression patterns of multiple inhibitory receptors on HIV-specific, cytomegalovirus-specific, and bulk CD8+ T-cell memory populations. In contrast to cytomegalovirus-specific CD8+ T cells, the majority of HIV-specific CD8+ T cells exhibited an immature phenotype and expressed Programmed Death-1, CD160 and 2B4 but not lymphocyte activation gene-3. Notably, before antiretroviral therapy, simultaneous expression of these negative regulators correlated strongly with both HIV load and impaired cytokine production. Suppression of HIV replication by antiretroviral therapy was associated with reduced surface expression of inhibitory molecules on HIV-specific CD8+ T cells. Furthermore, in vitro manipulation of Programmed Death-1 and 2B4 inhibitory pathways increased the proliferative capacity of HIV-specific CD8+ T cells. Thus, multiple coinhibitory receptors can affect the development of HIV-specific CD8+ T-cell responses and, by extension, represent potential targets for new immune-based interventions in HIV-infected persons. PMID:21398582

Yamamoto, Takuya; Price, David A.; Casazza, Joseph P.; Ferrari, Guido; Nason, Martha; Chattopadhyay, Pratip K.; Roederer, Mario; Gostick, Emma; Katsikis, Peter D.; Douek, Daniel C.; Haubrich, Richard; Petrovas, Constantinos

2011-01-01

333

Pattern Transformation with DNA Circuits  

PubMed Central

Readily programmable chemical networks are important tools as the scope of chemistry expands from individual molecules to larger molecular systems. While many complex systems have been constructed using conventional organic and inorganic chemistry, the programmability of biological molecules such as nucleic acids allows for precise, high-throughput, and automated design, as well as simple, rapid, and robust implementation. Here we show that systematic and quantitative control over the diffusivity and reactivity of DNA molecules yields highly programmable chemical reaction networks (CRNs) that execute at the macroscale. In particular, we design and implement non-enzymatic DNA circuits capable of performing pattern transformation algorithms such as edge detection. We also show that it is possible to fine-tune and multiplex such circuits. We believe these strategies will provide programmable platforms for prototyping CRNs, for discovering bottom-up construction principles, and for generating patterns in materials. PMID:24256862

Chirieleison, Steven M.; Allen, Peter B.; Simpson, Zack B.; Ellington, Andrew D.; Chen, Xi

2014-01-01

334

Pores in Bilayer Membranes of Amphiphilic Molecules: Coarse-Grained Molecular Dynamics Simulations Compared with Simple Mesoscopic Models  

E-print Network

We investigate pores in fluid membranes by molecular dynamics simulations of an amphiphile-solvent mixture, using a molecular coarse-grained model. The amphiphilic membranes self-assemble into a lamellar stack of amphiphilic bilayers separated by solvent layers. We focus on the particular case of tension less membranes, in which pores spontaneously appear because of thermal fluctuations. Their spatial distribution is similar to that of a random set of repulsive hard discs. The size and shape distribution of individual pores can be described satisfactorily by a simple mesoscopic model, which accounts only for a pore independent core energy and a line tension penalty at the pore edges. In particular, the pores are not circular: their shapes are fractal and have the same characteristics as those of two dimensional ring polymers. Finally, we study the size-fluctuation dynamics of the pores, and compare the time evolution of their contour length to a random walk in a linear potential.

Claire Loison; Michel Mareschal; Friederike Schmid

2005-01-05

335

Non-linear optical properties of molecules in heterogeneous environments: a quadratic density functional/molecular mechanics response theory.  

PubMed

We generalize a density functional theory/molecular mechanics approach for heterogeneous environments with an implementation of quadratic response theory. The updated methodology allows us to address a variety of non-linear optical, magnetic and mixed properties of molecular species in complex environments, such as combined metallic, solvent and confined organic environments. Illustrating calculations of para-nitroaniline on gold surfaces and in solution reveals a number of aspects that come into play when analyzing second harmonic generation of such systems--such as surface charge flow, coupled surface-solvent dynamics and induced geometric and electronic structure effects of the adsorbate. Some ramifications of the methodology for applied studies are discussed. PMID:24695833

Rinkevicius, Zilvinas; Li, Xin; Sandberg, Jaime A R; Ågren, Hans

2014-05-21

336

Viral Pathogen-Associated Molecular Patterns Regulate Blood-Brain Barrier Integrity via Competing Innate Cytokine Signals  

PubMed Central

ABSTRACT Pattern recognition receptor (PRR) detection of pathogen-associated molecular patterns (PAMPs), such as viral RNA, drives innate immune responses against West Nile virus (WNV), an emerging neurotropic pathogen. Here we demonstrate that WNV PAMPs orchestrate endothelial responses to WNV via competing innate immune cytokine signals at the blood-brain barrier (BBB), a multicellular interface with highly specialized brain endothelial cells that normally prevents pathogen entry. While Th1 cytokines increase the permeability of endothelial barriers, type I interferon (IFN) promoted and stabilized BBB function. Induction of innate cytokines by pattern recognition pathways directly regulated BBB permeability and tight junction formation via balanced activation of the small GTPases Rac1 and RhoA, which in turn regulated the transendothelial trafficking of WNV. In vivo, mice with attenuated type I IFN signaling or IFN induction (Ifnar?/? Irf7?/?) exhibited enhanced BBB permeability and tight junction dysregulation after WNV infection. Together, these data provide new insight into host-pathogen interactions at the BBB during neurotropic viral infection. PMID:25161189

Daniels, Brian P.; Holman, David W.; Cruz-Orengo, Lillian; Jujjavarapu, Harsha; Durrant, Douglas M.

2014-01-01

337

Isolation and Molecular Characterization of Biofouling Bacteria and Profiling of Quorum Sensing Signal Molecules from Membrane Bioreactor Activated Sludge  

PubMed Central

The formation of biofilm in a membrane bioreactor depends on the production of various signaling molecules like N-acyl homoserine lactones (AHLs). In the present study, a total of 200 bacterial strains were isolated from membrane bioreactor activated sludge and screened for AHLs production using two biosensor systems, Chromobacterium violaceum CV026 and Agrobacterium tumefaciens A136. A correlation between AHLs production and biofilm formation has been made among screened AHLs producing strains. The 16S rRNA gene sequence analysis revealed the dominance of Aeromonas and Enterobacter sp. in AHLs production; however few a species of Serratia, Leclercia, Pseudomonas, Klebsiella, Raoultella and Citrobacter were also identified. The chromatographic characterization of sludge extract showed the presence of a broad range of quorum sensing signal molecules. Further identification of sludge AHLs by thin layer chromatography bioassay and high performance liquid chromatography confirms the presence of C4-HSL, C6-HSL, C8-HSL, 3-oxo-C8-HSL, C10-HSL, C12-HSL, 3-oxo-C12-HSL and C14-HSL. The occurrence of AHLs in sludge extract and dominance of Aeromonas and Enterobacter sp. in activated sludge suggests the key role of these bacterial strains in AHLs production and thereby membrane fouling. PMID:24499972

Lade, Harshad; Paul, Diby; Kweon, Ji Hyang

2014-01-01

338

Statistical analysis of metal-molecule contacts in alkyl molecular junctions: sulfur versus selenium end-group.  

PubMed

We fabricated a large number of microscale via-hole structure molecular devices (2240 devices) using octane-Se [CH3(CH2)7Se] self assembled monolayers (SAMs) and compared their charge transport properties with those of octane-S [CH3(CH2)7S] SAMs molecular devices in terms of current density, resistance, and tunneling decay coefficient. The device yield of the "working" octane-Se molecular devices was found to be approximately 1.7% (38/2240), which was similar to the yield of approximately 1.1% (50/4480) for octane-S devices. Our statistical analysis revealed that for octane-Se devices the tunneling current was slightly smaller and the low-bias resistance and decay coefficient were slightly larger than those for octane-S devices. The standard deviations of these transport parameters of octane-Se devices were found to be broader than those for octane-S devices due to irregularity of the binding sites of octane-Se on Au electrode surface. PMID:19908717

Yoo, Hana; Choi, Jungseok; Wang, Gunuk; Kim, Tae-Wook; Noh, Jaegeun; Lee, Takhee

2009-12-01

339

Gene expression patterns unveil a new level of molecular heterogeneity in colorectal cancer  

PubMed Central

The recognition that colorectal cancer (CRC) is a heterogeneous disease in terms of clinical behaviour and response to therapy translates into an urgent need for robust molecular disease subclassifiers that can explain this heterogeneity beyond current parameters (MSI, KRAS, BRAF). Attempts to fill this gap are emerging. The Cancer Genome Atlas (TGCA) reported two main CRC groups, based on the incidence and spectrum of mutated genes, and another paper reported an EMT expression signature defined subgroup. We performed a prior free analysis of CRC heterogeneity on 1113 CRC gene expression profiles and confronted our findings to established molecular determinants and clinical, histopathological and survival data. Unsupervised clustering based on gene modules allowed us to distinguish at least five different gene expression CRC subtypes, which we call surface crypt-like, lower crypt-like, CIMP-H-like, mesenchymal and mixed. A gene set enrichment analysis combined with literature search of gene module members identified distinct biological motifs in different subtypes. The subtypes, which were not derived based on outcome, nonetheless showed differences in prognosis. Known gene copy number variations and mutations in key cancer-associated genes differed between subtypes, but the subtypes provided molecular information beyond that contained in these variables. Morphological features significantly differed between subtypes. The objective existence of the subtypes and their clinical and molecular characteristics were validated in an independent set of 720 CRC expression profiles. Our subtypes provide a novel perspective on the heterogeneity of CRC. The proposed subtypes should be further explored retrospectively on existing clinical trial datasets and, when sufficiently robust, be prospectively assessed for clinical relevance in terms of prognosis and treatment response predictive capacity. Original microarray data were uploaded to the ArrayExpress database (http://www.ebi.ac.uk/arrayexpress/) under Accession Nos E-MTAB-990 and E-MTAB-1026. PMID:23836465

Budinska, Eva; Popovici, Vlad; Tejpar, Sabine; D'Ario, Giovanni; Lapique, Nicolas; Sikora, Katarzyna Otylia; Di Narzo, Antonio Fabio; Yan, Pu; Hodgson, John Graeme; Weinrich, Scott; Bosman, Fred; Roth, Arnaud; Delorenzi, Mauro

2013-01-01

340

Molecular Universe  

NSDL National Science Digital Library

This fantastic resource for college-level students of chemistry provides abundant images and explanatory text on molecules and molecular systems. The site's main provider is Richard Catlow, Director of the Davy Faraday Research Laboratory at the Royal Institution of Great Britain. Molecular Universe presents a collection of lessons, arranged into categories such as Building in Three Dimensions, Boundaries and Barriers, and The Molecules of Life. The sleek color illustrations demonstrate everything from diamond structure to a DNA molecule. Highlights of the site include a detailed look at protein folding, how molecules taste, and molecules and computers. Both students and professors should journey to the Molecular Universe.

Catlow, C. R. A. (Charles Richard Arthur), 1947-

2000-01-01

341

Heterogeneity of molecular resistance patterns in antimony-resistant field isolates of Leishmania species from the western Mediterranean area.  

PubMed

Antimonials remain the first-line treatment for the various manifestations of leishmaniasis in most areas where the disease is endemic, and increasing cases of therapeutic failure associated with parasite resistance have been reported. In this study, we assessed the molecular status of 47 clinical isolates of Leishmania causing visceral and cutaneous leishmaniasis from Algeria, Tunisia, and southern France. In total, we examined 14 genes that have been shown to exhibit significant variations in DNA amplification, mRNA levels, or protein expression with respect to resistance to antimonials. The gene status of each clinical isolate was assessed via qPCR and qRT-PCR. We then compared the molecular pattern against the phenotype determined via an in vitro sensitivity test of the clinical isolates against meglumine antimoniate, which is considered the reference technique. Our results demonstrate significant DNA amplification and/or RNA overexpression in 56% of the clinical isolates with the resistant phenotype. All clinical isolates that exhibited significant overexpression of at least 2 genes displayed a resistant phenotype. Among the 14 genes investigated, 10 genes displayed either significant amplification or overexpression in at least 1 clinical isolate; these genes are involved in several metabolic pathways. Moreover, various gene associations were observed depending on the clinical isolates, supporting the multifactorial nature of Leishmania resistance. Molecular resistance features were found in the 3 Leishmania species investigated (Leishmania infantum, Leishmania major, and Leishmania killicki). To our knowledge, this is the first report of the involvement of molecular resistance genes in field isolates of Leishmania major and Leishmania killicki with the resistance phenotype. PMID:24913173

Jeddi, Fakhri; Mary, Charles; Aoun, Karim; Harrat, Zoubir; Bouratbine, Aïda; Faraut, Françoise; Benikhlef, Rezika; Pomares, Christelle; Pratlong, Francine; Marty, Pierre; Piarroux, Renaud

2014-08-01

342

Computational mass spectrometry for small molecules  

PubMed Central

The identification of small molecules from mass spectrometry (MS) data remains a major challenge in the interpretation of MS data. This review covers the computational aspects of identifying small molecules, from the identification of a compound searching a reference spectral library, to the structural elucidation of unknowns. In detail, we describe the basic principles and pitfalls of searching mass spectral reference libraries. Determining the molecular formula of the compound can serve as a basis for subsequent structural elucidation; consequently, we cover different methods for molecular formula identification, focussing on isotope pattern analysis. We then discuss automated methods to deal with mass spectra of compounds that are not present in spectral libraries, and provide an insight into de novo analysis of fragmentation spectra using fragmentation trees. In addition, this review shortly covers the reconstruction of metabolic networks using MS data. Finally, we list available software for different steps of the analysis pipeline. PMID:23453222

2013-01-01

343

Molecular dynamics simulations of self-assembly and nanotube formation by amphiphilic molecules in aqueous solution: a coarse-grain approach  

NASA Astrophysics Data System (ADS)

Self-assembly of a nanotube forming molecule, hexa-peri-hexabenzocoronene (hbc), in aqueous solution is studied using a coarse-grain (CG) force-field in molecular dynamics (MD) simulations. The simulations yield details of the pre-aggregation regime, which is generally inaccessible to experimental studies. The simulations also provide insights into the self-assembly mechanism, revealing how the aggregates formed in the initial stages of self-assembly grow in size to form a columnar structure. At later stages self-organization results in the formation of a twisted ribbon-like structure that remains stable for the duration of the simulation. This twisted ribbon-like structure is probably an intermediate in the formation of a nanotubular object.

Srinivas, Goundla; Klein, Michael L.

2007-05-01

344

Perturbation theory of the electron correlation effects for atomic and molecular properties. VI. Complete active space (CAS) SCF and MBPT calculations of electric properties of the FH molecule  

NASA Astrophysics Data System (ADS)

A comparative study of the applicability of the CAS SCF and different fourth-order MBPT methods for the calculation of molecular electric properties is performed. The accuracy of the CAS SCF results for the dipole moment and dipole polarizability tensor of the FH molecule is governed and limited by the size of the active orbital subspace, while the complete fourth-order MBPT results seem to suffer from the truncation of the correlation perturbation series. Relatively large fourth-order correlation corrections to the calculated properties, arising from single and triple substitutions, have been found and indicate the importance of a careful treatment of all substitutions contributing in the given order of the MBPT expansion.

Diercksen, Geerd H. F.; Kellö, Vladimir; Roos, Björn O.; Sadlej, Andrzej J.

1983-05-01

345

Virtual screening of natural inhibitors to the predicted HBx protein structure of Hepatitis B Virus using molecular docking for identification of potential lead molecules for liver cancer  

PubMed Central

The HBx protein in Hepatitis B Virus (HBV) is a potential target for anti-liver cancer molecules. Therefore, it is of interest to screen known natural compounds against the HBx protein using molecular docking. However, the structure of HBx is not yet known. Therefore, the predicted structure of HBx using threading in LOMET was used for docking against plant derived natural compounds (curcumin, oleanolic acid, resveratrol, bilobetin, luteoline, ellagic acid, betulinic acid and rutin) by Molegro Virtual Docker. The screening identified rutin with binding energy of -161.65 Kcal/mol. Thus, twenty derivatives of rutin were further designed and screened against HBx. These in silico experiments identified compounds rutin01 (-163.16 Kcal/mol) and rutin08 (- 165.76 Kcal/mol) for further consideration and downstream validation. PMID:25187683

Pathak, Rajesh Kumar; Baunthiyal, Mamta; Taj, Gohar; Kumar, Anil

2014-01-01

346

Theoretical study on the molecular structure and vibrational properties, NBO and HOMO-LUMO analysis of the POX3 (X = F, Cl, Br, I) series of molecules  

NASA Astrophysics Data System (ADS)

The fourth member of the series of compounds of the type POX3 with X = I was synthesized and characterized by infrared spectroscopy. The geometrical parameters and vibrational properties of POX3 (X = F, Cl, Br, I) molecules were investigated theoretically by means DFT and ab initio methods. Available geometrical and vibrational data were used together with theoretical calculations in order to obtain a set of scaled force constants. The observed trends in geometrical parameters are analyzed and compared with those obtained in a previous work for the VOX3 (X = F, Cl, Br, I) series of compounds. NBO analysis was performed in order to know the hyper-conjugative interactions that favor one structure over another. The molecular properties such as ionization potential, electron affinity, electronegativity, chemical potential, chemical hardness, softness and global electrophilicity index have been deduced from HOMO-LUMO analysis.

Galván, Jorge E.; Gil, Diego M.; Lanús, Hernán E.; Altabef, Aida Ben

2015-02-01

347

Molecular characterization of Chilli leaf curl virus and satellite molecules associated with leaf curl disease of Amaranthus spp.  

PubMed

Amaranthus, collectively known as amaranth, is an annual or short-lived perennial plant used as leafy vegetables, cereals and for ornamental purposes in many countries including India. During 2011, leaf samples of Amaranthus plants displaying leaf curling, leaf distortion, leaf crinkling and yellow leaf margins were collected from Banswara district, Rajasthan in India. Full-length clones of a monopartite begomovirus, a betasatellite and an alphasatellite were characterized. The complete nucleotide sequence of the isolated begomovirus features as a typical 'Old World' begomovirus with the highest nucleotide per cent identity with Chilli leaf curl virus and hence, considered as an isolate of Chilli leaf curl virus. The complete nucleotide sequences of betasatellite and alphasatellite possess maximum nucleotide identity with Tomato yellow leaf curl Thailand betasatellite and Chilli leaf curl alphasatellite, respectively. This is the first report of the association of chilli-infecting begomovirus and satellite molecules infecting a new host, Amaranthus, causing leaf curl disease. PMID:24368759

George, B; Kumar, R Vinoth; Chakraborty, S

2014-04-01

348

Identification and molecular characterization of a complement C3 molecule in a lophotrochozoan, the Hawaiian bobtail squid Euprymna scolopes  

PubMed Central

Examination of the EST database of the light organ of the Hawaiian bobtail squid Euprymna scolopes revealed a sequence with similarity to complement C3. RACE yielded the full open reading frame of this protein. Analysis of the resultant sequence revealed that Es-C3 (E. scolopes-C3) has conserved residues and domains known to be critical for C3 function. The gene encoding C3 was expressed in all tissues tested, indicating that its expression is widely distributed throughout the animal’s body. Immunocytochemistry using an antibody against Es-C3 revealed that the protein is produced principally in the apical surfaces of epithelial cells. The finding of the gene encoding C3 in this mollusk extends the occurrence of this molecule to the lophotrochozoans, demonstrating that complement genes occur in all major branches of the animal kingdom. PMID:18765250

Castillo, Maria G.; Goodson, Michael S.; McFall-Ngai, Margaret

2008-01-01

349

A theoretical and experimental study on the molecular and electronic structures of artemisinin and related drug molecules  

NASA Astrophysics Data System (ADS)

The equilibrium structures of artemisinin and a selection of its derivatives (potent antimalarial drugs) have been studied with the density functional theory ansatz B3LYP. Of the five rings of the artemisinin framework, it is only the pyranose ring B that exhibits a marked conformational flexibility, especially on addition of a pendant side chain at C-10. For the derivatives, the ? isomer with the axial substituent group is found to be energetically more stable than the ? isomer with the equatorial group. The assignment of the vibrational fundamentals has been supported by calculations on related model molecules and a normal coordinate analysis. This allows for a reliable characterization of the normal modes, mainly involving the peroxide linkage, in the claimed fingerprint region of 1,2,4-trioxanes. The electronic structures have also been studied by measuring and calculating significant features of the NMR, photoelectron and electron transmission spectra. In particular, a representative set of NMR chemical shifts and nuclear spin-spin coupling constants, obtained with DFT formalisms, compares favourably with experiment and fits expectation in terms of stereoelectronic effects of the vicinal oxygen lone pairs. Based on ab initio outer valence Green's function calculations, a consistent interpretation of the uppermost bands in the photoelectron spectra of artemisinin and derivatives has been advanced. The top ionization energies reflect a complex interaction of the various oxygen lone pair orbitals. Electron transmission spectroscopy is applied for the first time to compounds containing the peroxide bond and elucidates the empty level electronic structure of artemisinin and derivatives in the 0-6 eV energy range, with the support of MO calculations and comparison with the spectra of reference molecules. Electron attachment to the lowest-lying empty ?? MO, mainly localized on the O-O bridge, occurs at an energy (1.7 eV) exceptionally low for compounds not containing third-row or heavier elements.

Galasso, V.; Kova?, B.; Modelli, A.

2007-06-01

350

Coupling between side chain interactions and binding pocket flexibility in HLA-B*44:02 molecules investigated by molecular dynamics simulations.  

PubMed

MHC class I molecules present antigenic peptides to cytotoxic T-cells at the cell surface. Peptide loading of class I molecules in the endoplasmatic reticulum can involve interaction with the tapasin chaperone protein. The human class I allotype HLA-B*44:02 with an Asp at position 116 at the floor of the F pocket (which binds the peptide C-terminal residues) depends on tapasin for efficient peptide loading. However, HLA-B*44:05 (identical to B*44:02 except for tyrosine 116) can efficiently load peptides in the absence of tapasin. Both allotypes adopt very similar structures in the presence of the same peptide. Molecular dynamics simulations indicate a significantly higher conformational flexibility of the F pocket in the absence of a peptide for B*44:02 compared to B*44:05. Free energy simulations to open the F pocket indicate a molecular side chain switch mechanism that underlies the global opening motion. This side chain switch involves the rearrangement of salt bridges and hydrogen bonding of the basic arginine 97 with three acidic aspartate residues 114, 116 and 156 near the F pocket. A replica exchange simulation to specifically accelerate side chain motions demonstrates that the same side chain rearrangements induce global opening motions of the F pocket. In case of B*44:05 the free energy barrier for F pocket opening was significantly higher compared to B*44:02 and no associated side chain rearrangement was observed. Such coupling of local side chain rearrangements with global conformational changes might be the basis for allosteric changes in other class I allotypes as well as for allosteric changes in other proteins. PMID:25146482

Ostermeir, Katja; Springer, Sebastian; Zacharias, Martin

2015-02-01

351

Experimental and theoretical investigation of the molecular structure, conformational stability, hyperpolarizability, electrostatic potential, thermodynamic properties and NMR spectra of pharmaceutical important molecule: 4'-methylpropiophenone.  

PubMed

Combined experimental and theoretical studies have been performed on the structure and vibrational spectra (IR and Raman spectra) of 4'-methylpropiophenone (MPP). The FT-IR and FT-Raman spectra of 4'-methylpropiophenone (MPP) have been recorded in the region 4000-400 cm(-1) and 3500-100 cm(-1), respectively. The harmonic vibrational frequencies were calculated and the scaled values have been compared with experimental FT-IR and FT-Raman spectra. A detailed interpretation of the infrared and Raman spectra of MPP are also reported based on total energy distribution (TED). The observed and the calculated frequencies are found to be in good agreement. The (1)H and (13)C NMR chemical shifts have been calculated by Gauge-Independent Atomic Orbital (GIAO) method with B3LYP/6-311++G(d,p). The natural bond orbital (NBO), natural hybrid orbital (NHO) analysis and electronic properties, such as HOMO and LUMO energies, were performed by DFT approach. The calculated HOMO and LUMO energies show that charge transfer occurs within molecule. The first order hyperpolarizability (?0) of the novel molecular system and related properties (?tot, ?0 and ??) of MPP are calculated using DFT/6-311++G(d,p) method on the finite-field approach. The Mulliken charges, the values of electric dipole moment (?) of the molecule were computed using DFT calculations. The thermodynamic functions of the title compound were also performed at the above method and basis set. PMID:24657464

Karunakaran, V; Balachandran, V

2014-07-15

352

Effects of nitrogen monoxide and carbon monoxide on molecular and cellular iron metabolism: mirror-image effector molecules that target iron.  

PubMed Central

Many effector functions of nitrogen monoxide (NO) and carbon monoxide (CO) are mediated through their high-affinity for iron (Fe). In this review, the roles of NO and CO are examined in terms of their effects on the molecular and cellular mechanisms involved in Fe metabolism. Both NO and CO avidly form complexes with a plethora of Fe-containing molecules. The generation of NO and CO is mediated by the nitric oxide synthase and haem oxygenase (HO) families of enzymes respectively. The effects of NO on Fe metabolism have been well characterized, whereas knowledge of the effects of CO remains within its infancy. In terms of the role of NO in Fe metabolism, one of the best characterized interactions includes its effect on the iron regulatory proteins. These molecules are mRNA-binding proteins that control the expression of the transferrin receptor 1 and ferritin, molecules that are involved in Fe uptake and storage respectively. Apart from this, activated macrophages impart their cytotoxic activity by generating NO, which results in marked Fe mobilization from tumour-cell targets. This deprives the cell of the Fe that is required for DNA synthesis and energy production. Considering that HO degrades haem, resulting in the release of CO, Fe(II) and biliverdin, it is suggested that a CO-Fe complex will form. This may account for the rapid Fe mobilization observed from macrophages after haemoglobin catabolism. Intriguingly, overexpression of HO results in cellular Fe mobilization, suggesting that CO has a similar effect to NO on Fe trafficking. Preliminary evidence suggests that, like NO, CO plays important roles in Fe metabolism. PMID:12423201

Watts, Ralph N; Ponka, Prem; Richardson, Des R

2003-01-01

353

Porous organic molecules  

NASA Astrophysics Data System (ADS)

Most synthetic materials that show molecular-scale porosity consist of one-, two- or three-dimensional networks. Porous metal-organic frameworks in particular have attracted a lot of recent attention. By contrast, discrete molecules tend to pack efficiently in the solid state, leaving as little empty space as possible, which leads to non-porous materials. This Perspective discusses recent developments with discrete organic molecules that are porous in the solid state. Such molecules, which may be either crystalline or amorphous, can be categorized as either intrinsically porous (containing permanent covalent cavities) or extrinsically porous (inefficiently packed). We focus on the possible advantages of organic molecules over inorganic or hybrid systems in terms of molecular solubility, choice of components and functionalities, and structural mobility and responsiveness in non-covalent extended solids. We also highlight the potential for 'undiscovered' porous systems among the large number of cage-like organic molecules that are already known.

Holst, James R.; Trewin, Abbie; Cooper, Andrew I.

2010-11-01

354

Optical characterization of GaAs pyramid microstructures formed by molecular beam epitaxial regrowth on pre-patterned substrates  

SciTech Connect

Arrays of GaAs pyramids with square (001) bases of length 1{endash}5 {mu}m have been fabricated by molecular beam epitaxy regrowth on pre-patterned GaAs (001) substrates. The optical properties of the pyramid faces have been studied by microreflection and microtransmission imaging measurements with light ({lambda}=900{endash}1000nm) incident through the pyramid base. Digitized charge coupled device images indicate that total internal reflection occurs at the {l_brace}110{r_brace} pyramid facets and that their reflectivities are greater than 80%, provided overgrowth of the facets does not occur. These properties suggest that such structures may be suitable as the top mirror in novel micron-scale vertical microcavity devices. {copyright} 2001 American Institute of Physics.

Pritchard, R. E.; Oulton, R. F.; Stavrinou, P. N.; Parry, G.; Williams, R. S.; Ashwin, M. J.; Neave, J. H.; Jones, T. S.

2001-07-01

355

Co-complexes of MASP-1 and MASP-2 associated with the soluble pattern-recognition molecules drive lectin pathway activation in a manner inhibitable by MAp44.  

PubMed

The lectin pathway of complement is an integral component of innate immunity. It is activated upon binding of mannan-binding lectin (MBL) or ficolins (H-, L-, and M-ficolin) to suitable ligand patterns on microorganisms. MBL and ficolins are polydisperse homo-oligomeric molecules, found in complexes with MBL-associated serine proteases (MASP-1, -2, and -3) and MBL-associated proteins (MAp19 and MAp44). This scenario is far more complex than the well-defined activation complex of the classical pathway, C1qC1r(2)C1s(2), and the composition of the activating complexes of the lectin pathway is ill defined. We and other investigators recently demonstrated that both MASP-1 and MASP-2 are crucial to lectin pathway activation. MASP-1 transactivates MASP-2 and, although MASP-1 also cleaves C2, MASP-2 cleaves both C4 and C2, allowing formation of the C3 convertase, C4bC2a. Juxtaposition of MASP-1 and MASP-2 during activation must be required for transactivation. We previously presented a possible scenario, which parallels that of the classical pathway, in which MASP-1 and MASP-2 are found together in the same MBL or ficolin complex. In this study, we demonstrate that, although MASPs do not directly form heterodimers, the addition of MBL or ficolins allows the formation of MASP-1-MASP-2 co-complexes. We find that such co-complexes have a functional role in activating complement and are present in serum at varying levels, impacting on the degree of complement activation. This raises the novel possibility that MAp44 may inhibit complement, not simply by brute force displacement of MASP-2 from MBL or ficolins, but by disruption of co-complexes, hence impairing transactivation. We present support for this contention. PMID:23785123

Degn, Søren E; Jensen, Lisbeth; Olszowski, Tomasz; Jensenius, Jens C; Thiel, Steffen

2013-08-01

356

Biological and Molecular Effects of Small Molecule Kinase Inhibitors on Low-Passage Human Colorectal Cancer Cell Lines  

PubMed Central

Low-passage cancer cell lines are versatile tools to study tumor cell biology. Here, we have employed four such cell lines, established from primary tumors of colorectal cancer (CRC) patients, to evaluate effects of the small molecule kinase inhibitors (SMI) vemurafenib, trametinib, perifosine, and regorafenib in an in vitro setting. The mutant BRAF (V600E/V600K) inhibitor vemurafenib, but also the MEK1/2 inhibitor trametinib efficiently inhibited DNA synthesis, signaling through ERK1/2 and expression of genes downstream of ERK1/2 in BRAF mutant cells only. In case of the AKT inhibitor perifosine, three cell lines showed a high or intermediate responsiveness to the drug while one cell line was resistant. The multikinase inhibitor regorafenib inhibited proliferation of all CRC lines with similar efficiency and independent of the presence or absence of KRAS, BRAF, PIK3CA, and TP53 mutations. Regorafenib action was associated with broad-range inhibitory effects at the level of gene expression but not with a general inhibition of AKT or MEK/ERK signaling. In vemurafenib-sensitive cells, the antiproliferative effect of vemurafenib was enhanced by the other SMI. Together, our results provide insights into the determinants of SMI efficiencies in CRC cells and encourage the further use of low-passage CRC cell lines as preclinical models. PMID:25309914

Lange, Falko; Franz, Benjamin; Maletzki, Claudia; Linnebacher, Michael; Hühns, Maja; Jaster, Robert

2014-01-01

357

Spatial arrangement of molecules in homomolecular Z' = 2 structures.  

PubMed

The Box Model of crystal packing describes unit cells in terms of a limited number of arrangements of molecular building blocks. An analysis of Z' < or = 1 structures has shown that cell dimensions are related to molecular dimensions in a systematic way and that the spatial arrangement of molecules in crystal structures is very similar, irrespective of Z or space group. In this paper it is shown that the spatial arrangement of molecules in Z' = 2 structures are, within the context of the Box Model, very similar to that found for Z' < or = 1 structures. The absence of crystallographic symmetry does not appear to affect correlations between molecular dimensions and cell dimensions, or between the packing patterns and the positions of molecules in the unit cell, established from the analysis of Z' < or = 1 structures. The preference shown by Z' = 2 structures for low surface-area packing patterns and the observation that strong energetic interactions are most often found between the large faces of the independent molecules reaffirms the importance of molecular shape in crystal packing. PMID:16552161

Pidcock, Elna

2006-04-01

358

Molecular inversion probes reveal patterns of 9p21 deletion and copy number aberrations in childhood leukemia  

PubMed Central

Childhood leukemia, which accounts for > 30% of newly diagnosed childhood malignancies, is one of the leading causes of death for children with cancer. Genome-wide studies using microarray chips to identify copy number changes in human cancer are becoming more common. In this pilot study, 45 pediatric leukemia samples were analyzed for gene copy aberrations using novel molecular inversion probe (MIP) technology. Acute leukemia subtypes included precursor B-cell acute lymphoblastic leukemia (ALL) (n = 23), precursor T-cell ALL (n = 6), and acute myeloid leukemia (n = 14). The MIP analysis identified 69 regions of recurring copy number changes, of which 41 have not been identified with other DNA microarray platforms. Copy number gains and losses were validated in 98% of clinical karyotypes and 100% of fluorescence in situ hybridization studies available. We report unique patterns of copy number loss in samples with 9p21.3 (CDKN2A) deletion in the precursor B-cell ALL patients, compared with the precursor T-cell ALL patients. MIPs represent an attractive technology for identifying novel copy number aberrations, validating previously reported copy number changes, and translating molecular findings into clinically relevant targets for further investigation. PMID:19602459

Schiffman, Joshua D.; Wang, Yuker; McPherson, Lisa A.; Welch, Katrina; Zhang, Nancy; Davis, Ronald; Lacayo, Norman J.; Dahl, Gary V.; Faham, Malek; Ford, James M.; Ji, Hanlee P.

2009-01-01

359

Symmetry breaking in nanostructure development of carbogenic molecular sieves: Effects of morphological pattern formation on oxygen and nitrogen transport  

SciTech Connect

A comprehensive study has been undertaken to establish the primary factors that control transport of oxygen and nitrogen in polymer-derived carbogenic molecular sieves (CMS). Characterization of the nanostructure of CMS derived from poly(furfuryl alcohol) (PFA) indicates that significant physical and chemical reorganization occurs as a function of synthesis temperature. Spectroscopic measurements show a drastic decrease in oxygen and hydrogen functionality with increasing pyrolysis temperature. Structural reorganization and elimination of these heteroatoms lead to a measurable increase in the unpaired electron density in these materials. High-resolution transmission electron microscopy and powder neutron diffraction are used to probe the corresponding changes in the physical structural features in the CMS. These indicate that as the pyrolysis temperature is increased, the structure of the CMS transforms from one that is disordered and therefore highly symmetric to one that is more ordered on a length scale of 15 {Angstrom} and hence less symmetric. This structural transformation process, one of symmetry breaking and pattern formation, if often observed in other nonlinear dissipative systems, but not in solids. Symmetry breaking provides the driving force for these high-temperature reorganizations, but unlike most dissipative systems, these less-symmetric structures remain frozen in place when energy is no longer applied. The impact of these nanostructural reorganizations on the molecular sieving character of the CMS is studied in terms of the physical separation of oxygen and nitrogen. 40 refs., 14 figs., 3 tabs.

Kane, M.S.; Goellner, J.F.; Foley, H.C. [Univ. of Delaware, Newark, DE (United States)] [and others] [Univ. of Delaware, Newark, DE (United States); and others

1996-08-01

360

Molecular Detection of Hematozoa Infections in Tundra Swans Relative to Migration Patterns and Ecological Conditions at Breeding Grounds  

PubMed Central

Tundra swans (Cygnus columbianus) are broadly distributed in North America, use a wide variety of habitats, and exhibit diverse migration strategies. We investigated patterns of hematozoa infection in three populations of tundra swans that breed in Alaska using satellite tracking to infer host movement and molecular techniques to assess the prevalence and genetic diversity of parasites. We evaluated whether migratory patterns and environmental conditions at breeding areas explain the prevalence of blood parasites in migratory birds by contrasting the fit of competing models formulated in an occupancy modeling framework and calculating the detection probability of the top model using Akaike Information Criterion (AIC). We described genetic diversity of blood parasites in each population of swans by calculating the number of unique parasite haplotypes observed. Blood parasite infection was significantly different between populations of Alaska tundra swans, with the highest estimated prevalence occurring among birds occupying breeding areas with lower mean daily wind speeds and higher daily summer temperatures. Models including covariates of wind speed and temperature during summer months at breeding grounds better predicted hematozoa prevalence than those that included annual migration distance or duration. Genetic diversity of blood parasites in populations of tundra swans appeared to be relative to hematozoa prevalence. Our results suggest ecological conditions at breeding grounds may explain differences of hematozoa infection among populations of tundra swans that breed in Alaska. PMID:23049862

Ramey, Andrew M.; Ely, Craig R.; Schmutz, Joel A.; Pearce, John M.; Heard, Darryl J.

2012-01-01

361

Molecular recognition of AT-DNA sequences by the induced CD pattern of dibenzotetraaza[14]annulene (DBTAA)–adenine derivatives  

PubMed Central

Summary An investigation of the interactions of two novel and several known DBTAA–adenine conjugates with double-stranded DNA and RNA has revealed the DNA/RNA groove as the dominant binding site, which is in contrast to the majority of previously studied DBTAA analogues (DNA/RNA intercalators). Only DBTAA–propyladenine conjugates revealed the molecular recognition of AT-DNA by an ICD band pattern > 300 nm, whereas significant ICD bands did not appear for other ds-DNA/RNA. A structure–activity relation for the studied series of compounds showed that the essential structural features for the ICD recognition are a) the presence of DNA-binding appendages (adenine side chain and positively charged side chain) on both DBTAA side chains, and b) the presence of a short propyl linker, which does not support intramolecular aromatic stacking between DBTAA and adenine. The observed AT-DNA-ICD pattern differs from previously reported ss-DNA (poly dT) ICD recognition by a strong negative ICD band at 350 nm, which allows for the dynamic differentiation between ss-DNA (poly dT) and coupled ds-AT-DNA. PMID:25246976

Stojkovi?, Marijana Radi?; Škugor, Marko; Dudek, ?ukasz; Grolik, Jaros?aw; Eilmes, Julita

2014-01-01

362

Molecular adaptation in flowering and symbiotic recognition pathways: insights from patterns of polymorphism in the legume Medicago truncatula  

PubMed Central

Background We studied patterns of molecular adaptation in the wild Mediterranean legume Medicago truncatula. We focused on two phenotypic traits that are not functionally linked: flowering time and perception of symbiotic microbes. Phenology is an important fitness component, especially for annual plants, and many instances of molecular adaptation have been reported for genes involved in flowering pathways. While perception of symbiotic microbes is also integral to adaptation in many plant species, very few reports of molecular adaptation exist for symbiotic genes. Here we used data from 57 individuals and 53 gene fragments to quantify the overall strength of both positive and purifying selection in M. truncatula and asked if footprints of positive selection can be detected at key genes of rhizobia recognition pathways. Results We examined nucleotide variation among 57 accessions from natural populations in 53 gene fragments: 5 genes involved in nitrogen-fixing bacteria recognition, 11 genes involved in flowering, and 37 genes used as control loci. We detected 1757 polymorphic sites yielding an average nucleotide diversity (pi) of 0.003 per site. Non-synonymous variation is under sizable purifying selection with 90% of amino-acid changing mutations being strongly selected against. Accessions were structured in two groups consistent with geographical origins. Each of these two groups harboured an excess of rare alleles, relative to expectations of a constant-sized population, suggesting recent population expansion. Using coalescent simulations and an approximate Bayesian computation framework we detected several instances of genes departing from selective neutrality within each group and showed that the polymorphism of two nodulation and four flowering genes has probably been shaped by recent positive selection. Conclusion We quantify the intensity of purifying selection in the M. truncatula genome and show that putative footprints of natural selection can be detected at different time scales in both flowering and symbiotic pathways. PMID:21806823

2011-01-01

363

Molecular characterization, phylogenetic relationships, and developmental expression patterns of prion genes in zebrafish (Danio rerio).  

PubMed

Prion diseases are characterized by the accumulation of a pathogenic misfolded form of a prion protein (PrP) encoded by the Prnp gene in humans. In the present study in zebrafish, two transcripts and the corresponding genes encoding prion proteins, PrP1 and PrP2, related to human PrP have been characterized with a relatively divergent deduced amino acid sequence, but a well preserved overall organization of structural prion protein motifs. Whole-mount in situ hybridization analysis performed during embryonic and larval development showed a high level of PrP1 mRNA spatially restricted to the anterior floor-plate of the central nervous system and in ganglia. Transcripts of prp2 were detected in embryonic cells from the mid-blastula transition to the end of the segmentation period. From 24 h postfertilization up to larval stages, prp2 transcripts were localized in distinct anatomical structures, including a major expression in the brain, eye, kidney, lateral line neuromasts, liver, heart, pectoral fins and posterior intestine. The observed differential developmental expression patterns of the two long PrP forms, prp1 and prp2, and the short PrP form prp3, a more divergent prion-related gene previously identified in zebrafish, should contribute to understanding of the phylogenetic and functional relationships of duplicated prion gene forms in the fish genome. Together, the complex history of prion-related genes, reflected in the deduced structural features, conserved amino acid sequence and repeat motifs of the corresponding proteins, and the presence of differential developmental expression patterns suggest possible acquisition or loss of prion protein functions during vertebrate evolution. PMID:15654888

Cotto, Emmanuelle; André, Michèle; Forgue, Jean; Fleury, Hervé J; Babin, Patrick J

2005-01-01

364

Damage-associated molecular patterns stimulate IL-33 expression in nasal polyp epithelial cells  

PubMed Central

OBJECTIVES Chronic rhinosinusitis with nasal polyps (CRSwNP) is a disorder characterized by eosinophilic inflammation and local Th2 cytokine production. Innate lymphoid cells that elaborate Th2 cytokines have recently been characterized within nasal polyps. These cells can be activated by the epithelial cell-derived cytokine IL-33. The objective of this study is to determine whether two molecules associated with tissue damage (HMGB-1 and ATP) elicit expression of IL-33 in sinonasal epithelial cells (SNEC) derived from recalcitrant CRSwNP patients. METHODS Ethmoid tissue was obtained from 8 recalcitrant CRSwNP and 9 control subjects during ESS. Tissue was prepared for immunohistochemistry and for SNEC air-liquid interface culture. After exposure to either HMGB1 or ATP in vitro, SNEC were processed for mRNA extraction and immunocytochemistry. IL33 levels were determined by real-time PCR and by immunochemical staining with anti-IL-33 antibody. RESULTS Intranuclear IL-33 is normally expressed in basal epithelial cells, but is present in more apical cells and outside the nucleus in CRSwNP. Exposure of SNEC to HMGB-1 or ATP resulted in a statistically significant increase in IL-33 mRNA expression in SNEC derived from recalcitrant CRSwNP patients. This increase was reflected at the protein level by immunochemical staining of IL-33. CONCLUSIONS Tissue damage is a non-specific trigger of epithelial IL-33 production in treatment-recalcitrant polyps, which may be responsible for perpetuating eosinophilic inflammation in CRSwNP. This common pathway may help explain why multiple environmental and infectious agents have been implicated in association with CRSwNP exacerbation. PMID:24574111

Paris, Gina; Pozharskaya, Tatyana; Asempa, Tomefa; Lane, Andrew P.

2013-01-01

365

Relationships between molecular mobility, fibrillogenesis of collagen molecules, and the inflammatory response: an experimental study in vitro and in vivo.  

PubMed

This study was designed to investigate the in vitro adsorption and fibrillogenesis of collagen on a surface with dynamic properties and to investigate how this surface affected the inflammatory response in vivo. Investigation of collagen-surface interactions is directly related to the control of wound healing where collagen adsorption, fibrillization, deposition, and maturation occur. ABA-type block copolymers, composed of polyrotaxane (which possesses ?-cyclodextrin threaded along poly(ethylene glycol)) and hydrophobic terminal segments, were used to prepare mobile surfaces with representative dynamic properties. Analyses using a quartz crystal microbalance with dissipation monitoring (QCM-D) indicated that increasing the mobility of the polymer on the surface led to the formation of a soft collagen layer. The collagens in this layer had rearranged, leading to the formation of thicker collagen fibrils by lateral aggregation. When a surface with a high molecular mobility was subcutaneously implanted into rats, collagen rearrangement occurred leading to suppression of macrophage recruitment at the interface and the formation of a fibrotic capsule around the implant. These results suggest that surface mobility on an implant is an important parameter for normal wound healing. PMID:25112908

Nam, Kwangwoo; Seo, Ji-Hun; Kimura, Tsuyoshi; Yui, Nobuhiko; Kishida, Akio

2014-11-01

366

Development of a membrane-less dynamic field gradient focusing device for the separation of low-molecular-weight molecules.  

PubMed

Dynamic field gradient focusing uses an electric field gradient generated by controlling the voltage profile of an electrode array to separate and concentrate charged analytes according to their individual electrophoretic mobilities. This study describes a new instrument in which the electrodes have been placed within the separation channel. The major challenge faced with this device is that when applied voltages to the electrodes are larger than the redox potential of water, electrolysis will occur, producing hydrogen ions (H+) plus oxygen gas on the anodes and hydroxide (OH(-)) plus hydrogen gas on the cathodes. The resulting gas bubbles and pH excursions can cause problems with system performance and reproducibility. An on-column, degassing system that can remove gas bubbles "on-the-fly" is described. In addition, the use of a high capacity, low-conductivity buffer to address the problem of the pH shift that occurs due to the production of H+ on the anodes is illustrated. Finally, the successful separation of three, low-molecular-weight dyes (amaranth, bromophenol blue and methyl red) is described. PMID:20191553

Burke, Jeffrey M; Smith, Colin D; Ivory, Cornelius F

2010-03-01

367

FTIR and molecular mechanics studies of H-bonds in aliphatic polyurethane and polyamide-66 model molecules  

NASA Astrophysics Data System (ADS)

Model aliphatic polyurethane (APU) hard segment based on 1,6-hexamethylene diisocyanate (HDI) and 1,4-butanediol (BDO) were prepared. FTIR and molecular mechanics (MM) simulation were used to conduct the systematic studies on APU and polyamide-66 (PA-66) whose sole difference lies in the alkoxyl oxygen. It was found that the introduction of the alkoxyl not only increases the conformations in APU, makes it a possible H-bond acceptor, but also weakens the H-bond between NH and O dbnd C in APU. There are two conformers stably existed in APU with lowest energy, leading to eight H-bond complexes based on NH as donor and (1) O dbnd C as acceptor, and another two complexes based on (2) alkoxyl O and (3) urethane N as acceptors, whereas there is only one stable conformer in PA-66, leading to one H-bond complex. One predominant H-bond complex has been found in APU with probability of about 95%. The simulated results are consistent with the ?NH and ?C dbnd O band shifting in FTIR.

Wang, Guoqing; Zhang, Chunxia; Guo, Xiaohe; Ren, Zhiyong

2008-02-01

368

FTIR and molecular mechanics studies of H-bonds in aliphatic polyurethane and polyamide-66 model molecules.  

PubMed

Model aliphatic polyurethane (APU) hard segment based on 1,6-hexamethylene diisocyanate (HDI) and 1,4-butanediol (BDO) were prepared. FTIR and molecular mechanics (MM) simulation were used to conduct the systematic studies on APU and polyamide-66 (PA-66) whose sole difference lies in the alkoxyl oxygen. It was found that the introduction of the alkoxyl not only increases the conformations in APU, makes it a possible H-bond acceptor, but also weakens the H-bond between NH and O=C in APU. There are two conformers stably existed in APU with lowest energy, leading to eight H-bond complexes based on NH as donor and (1) O=C as acceptor, and another two complexes based on (2) alkoxyl O and (3) urethane N as acceptors, whereas there is only one stable conformer in PA-66, leading to one H-bond complex. One predominant H-bond complex has been found in APU with probability of about 95%. The simulated results are consistent with the nuNH and nuC=O band shifting in FTIR. PMID:17590387

Wang, Guoqing; Zhang, Chunxia; Guo, Xiaohe; Ren, Zhiyong

2008-02-01

369

STAT3 Expression, Molecular Features, Inflammation Patterns and Prognosis in a Database of 724 Colorectal Cancers  

PubMed Central

Purpose STAT3 (signal transducer and activator of transcription 3) is a transcription factor that is constitutively activated in some cancers. STAT3 appears to play crucial roles in cell proliferation and survival, angiogenesis, tumor-promoting inflammation and suppression of anti-tumor host immune response in the tumor microenvironment. Although the STAT3 signaling pathway is a potential drug target, clinical, pathologic, molecular or prognostic features of STAT3-activated colorectal cancer remain uncertain. Experimental Design Utilizing a database of 724 colon and rectal cancer cases, we evaluated phosphorylated STAT3 (p-STAT3) expression by immunohistochemistry. Cox proportional hazards model was used to compute mortality hazard ratio (HR), adjusting for clinical, pathologic and molecular features, including microsatellite instability (MSI), the CpG island methylator phenotype (CIMP), LINE-1 methylation, 18q loss of heterozygosity, TP53 (p53), CTNNB1 (?-catenin), JC virus T-antigen, and KRAS, BRAF, and PIK3CA mutations. Results Among the 724 tumors, 131 (18%) showed high-level p-STAT3 expression (p-STAT3-high), 244 (34%) showed low-level expression (p-STAT3-low), and the remaining 349 (48%) were negative for p-STAT3. p-STAT3 overexpression was associated with significantly higher colorectal cancer-specific mortality [log-rank p=0.0020; univariate HR (p-STAT3-high vs. p-STAT3-negative) 1.85, 95% confidence interval (CI) 1.30–2.63, Ptrend =0.0005; multivariate HR, 1.61, 95% CI 1.11–2.34, Ptrend =0.015). p-STAT3 expression was positively associated with peritumoral lymphocytic reaction (multivariate odds ratio 3.23; 95% CI, 1.89–5.53; p<0.0001). p-STAT3 expression was not associated with MSI, CIMP, or LINE-1 hypomethylation. Conclusions STAT3 activation in colorectal cancer is associated with adverse clinical outcome, supporting its potential roles as a prognostic biomarker and a chemoprevention and/or therapeutic target. PMID:21310826

Morikawa, Teppei; Baba, Yoshifumi; Yamauchi, Mai; Kuchiba, Aya; Nosho, Katsuhiko; Shima, Kaori; Tanaka, Noriko; Huttenhower, Curtis; Frank, David A.; Fuchs, Charles S.; Ogino, Shuji

2010-01-01

370

Toll-like receptor 9-mediated protection of enterovirus 71 infection in mice is due to the release of danger-associated molecular patterns.  

PubMed

Enterovirus 71 (EV71), a positive-stranded RNA virus, is the major cause of hand, foot, and mouth disease (HFMD) with severe neurological symptoms. Antiviral type I interferon (alpha/beta interferon [IFN-?/?]) responses initiated from innate receptor signaling are inhibited by EV71-encoded proteases. It is less well understood whether EV71-induced apoptosis provides a signal to activate type I interferon responses as a host defensive mechanism. In this report, we found that EV71 alone cannot activate Toll-like receptor 9 (TLR9) signaling, but supernatant from EV71-infected cells is capable of activating TLR9. We hypothesized that TLR9-activating signaling from plasmacytoid dendritic cells (pDCs) may contribute to host defense mechanisms. To test our hypothesis, Flt3 ligand-cultured DCs (Flt3L-DCs) from both wild-type (WT) and TLR9 knockout (TLR9KO) mice were infected with EV71. More viral particles were produced in TLR9KO mice than by WT mice. In contrast, alpha interferon (IFN-?), monocyte chemotactic protein 1 (MCP-1), tumor necrosis factor-alpha (TNF-?), IFN-?, interleukin 6 (IL-6), and IL-10 levels were increased in Flt3L-DCs from WT mice infected with EV71 compared with TLR9KO mice. Seven-day-old TLR9KO mice infected with a non-mouse-adapted EV71 strain developed neurological lesion-related symptoms, including hind-limb paralysis, slowness, ataxia, and lethargy, but WT mice did not present with these symptoms. Lung, brain, small intestine, forelimb, and hind-limb tissues collected from TLR9KO mice exhibited significantly higher viral loads than equivalent tissues collected from WT mice. Histopathologic damage was observed in brain, small intestine, forelimb, and hind-limb tissues collected from TLR9KO mice infected with EV71. Our findings demonstrate that TLR9 is an important host defense molecule during EV71 infection. Importance: The host innate immune system is equipped with pattern recognition receptors (PRRs), which are useful for defending the host against invading pathogens. During enterovirus 71 (EV71) infection, the innate immune system is activated by pathogen-associated molecular patterns (PAMPs), which include viral RNA or DNA, and these PAMPs are recognized by PRRs. Toll-like receptor 3 (TLR3) and TLR7/8 recognize viral nucleic acids, and TLR9 senses unmethylated CpG DNA or pathogen-derived DNA. These PRRs stimulate the production of type I interferons (IFNs) to counteract viral infection, and they are the major source of antiviral alpha interferon (IFN-?) production in pDCs, which can produce 200- to 1,000-fold more IFN-? than any other immune cell type. In addition to PAMPs, danger-associated molecular patterns (DAMPs) are known to be potent activators of innate immune signaling, including TLR9. We found that EV71 induces cellular apoptosis, resulting in tissue damage; the endogenous DNA from dead cells may activate the innate immune system through TLR9. Therefore, our study provides new insights into EV71-induced apoptosis, which stimulates TLR9 in EV71-associated infections. PMID:25078697

Hsiao, Hung-Bo; Chou, Ai-Hsiang; Lin, Su-I; Chen, I-Hua; Lien, Shu-Pei; Liu, Chia-Chyi; Chong, Pele; Liu, Shih-Jen

2014-10-01

371

Detection of clinical-stage specific molecular Toxoplasma gondii gene patterns in patients with toxoplasmic lymphadenitis.  

PubMed

Three cases of symptomatic toxoplasmic lymphadenitis, together with a serologic profile of recent infection, are described, for which quantitative real-time PCR (LightCycler PCR) targeting different parasite genes was designed, in order to quantify Toxoplasma gondii DNA in acute and follow-up blood specimens. Similar parasite gene kinetics and DNA concentrations were observed in the patients studied. However, the profile of each target gene investigated was different. While the level of B1 DNA remained elevated for the entire time of observation, irrespective of clinical and serologic resolution, the SAG-1 gene was detected at the end of acute symptomatic disease, overlapping with a strong anti-T. gondii IgA antibody response, and persisting for over 3 months after infection and clinical recovery. With respect to the two bradyzoite genes investigated (SAG-4 and MAG-1), levels peaked during the symptomatic phase, but did not fall until 2 or 3 months of follow up. The real-time PCR assay with new alternative targets to the B1 gene may have potential for monitoring the clinical outcome of disease and for providing molecular information regarding the actual state of infection. PMID:16687598

Contini, Carlo; Giuliodori, Margherita; Cultrera, Rosario; Seraceni, Silva

2006-06-01

372

Molecular and structural patterns of bone regeneration in surgically created defects containing bone substitutes.  

PubMed

Several biomaterials have been introduced for bone augmentation. However, information is lacking about the mechanisms of bone regeneration and/or integration of these materials in the recipient bone. This study aimed to determine the molecular and structural events in bone defects after augmentation with synthetic tetrapod-shaped calcium phosphate (Tetrabone; TetraB) compared with natural deproteinized bovine bone (DBB). Defects were created in the epiphyses of rat femurs and filled with TetraB or DBB or left empty (Sham). After 3, 6, 14 and 28 d, samples were harvested for histology, histomorphometry, ultrastructure and gene expression analyses. At 3 d, higher expressions of bone formation (ALP and OC) and remodeling (CatK) genes were detected in TetraB compared with DBB and Sham. Downregulation of bone remodeling genes (TRAP and CatK) was detected in DBB as compared to Sham after 14 d. Histomorphometry at 6 and 14 d demonstrated greater bone contact with the granules in TetraB. At 28 d, a larger bone area per defect was found in TetraB. The present experiments show that a synthetic substitute, consisting of ?-tricalcium and octacalcium phosphates, induces early osteogenic and osteoclastic activities and promotes bone formation in trabecular bone defects. PMID:24439408

Elgali, Ibrahim; Igawa, Kazuyo; Palmquist, Anders; Lennerås, Maria; Xia, Wei; Choi, Sungjin; Chung, Ung-Il; Omar, Omar; Thomsen, Peter

2014-03-01

373

Prevalence, antibiotic resistance patterns and molecular characterization of Escherichia coli from Austrian sandpits.  

PubMed

The aim was to determine the prevalence of E. coli and coliform bacteria in playground sand of all public children's sandpits in Graz (n = 45), Austria, and to assess the frequency of antimicrobial resistance in E. coli. Molecular characterization included the discrimination of O-serotypes and H-antigens and the determination of virulence and resistance genes, using a microarray technology. E. coli isolates were tested for susceptibility to a set of antibiotics by VITEK2 system and disk diffusion method. In total, 22 (49%) and 44 (98%) sandpits were positive for E. coli and coliform bacteria. Median concentrations of E. coli and coliform bacteria in the sand samples were: 2.6 × 10(4) CFU/100 g and 3.0 × 10(5) CFU/100 g. Resistance rates were: ampicillin, 12.5%; piperacillin, 10.4%; amoxicillin/clavulanic acid, 9.4%; cotrimoxazole, 6.3%; tetracycline, 6.3%; piperacillin/tazobactam, 5.2%. No ESBL- or carbapenemase-producing isolates were found. The most prevalent serogroups were O15, O6 and O4. Isolates harbored 0 up to 16 different virulence genes. PMID:25089889

Badura, Alexandra; Luxner, Josefa; Feierl, Gebhard; Reinthaler, Franz F; Zarfel, Gernot; Galler, Herbert; Pregartner, Gudrun; Riedl, Regina; Grisold, Andrea J

2014-11-01

374

Molecular determinants mediating gating of Transient Receptor Potential Canonical (TRPC) channels by stromal interaction molecule 1 (STIM1).  

PubMed

Transient receptor potential canonical (TRPC) channels mediate a critical part of the receptor-evoked Ca(2+) influx. TRPCs are gated open by the endoplasmic reticulum Ca(2+) sensor STIM1. Here we asked which stromal interaction molecule 1 (STIM1) and TRPC domains mediate the interaction between them and how this interaction is used to open the channels. We report that the STIM1 Orai1-activating region domain of STIM1 interacts with the TRPC channel coiled coil domains (CCDs) and that this interaction is essential for opening the channels by STIM1. Thus, disruption of the N-terminal (NT) CCDs by triple mutations eliminated TRPC surface localization and reduced binding of STIM1 to TRPC1 and TRPC5 while increasing binding to TRPC3 and TRPC6. Single mutations in TRPC1 NT or C-terminal (CT) CCDs reduced interaction and activation of TRPC1 by STIM1. Remarkably, single mutations in the TRPC3 NT CCD enhanced interaction and regulation by STIM1. Disruption in the TRPC3 CT CCD eliminated regulation by STIM1 and the enhanced interaction caused by NT CCD mutations. The NT CCD mutations converted TRPC3 from a TRPC1-dependent to a TRPC1-independent, STIM1-regulated channel. TRPC1 reduced the FRET between BFP-TRPC3 and TRPC3-YFP and between CFP-TRPC3-YFP upon stimulation. Accordingly, knockdown of TRPC1 made TRPC3 STIM1-independent. STIM1 dependence of TRPC3 was reconstituted by the TRPC1 CT CCD alone. Knockout of Trpc1 and Trpc3 similarly inhibited Ca(2+) influx, and inhibition of Trpc3 had no further effect on Ca(2+) influx in Trpc1(-/-) cells. Cell stimulation enhanced the formation of Trpc1-Stim1-Trpc3 complexes. These findings support a model in which the TRPC3 NT and CT CCDs interact to shield the CT CCD from interaction with STIM1. The TRPC1 CT CCD dissociates this interaction to allow the STIM1 Orai1-activating region within STIM1 access to the TRPC3 CT CCD and regulation of TRPC3 by STIM1. These studies provide evidence that the TRPC channel CCDs participate in channel gating. PMID:24464579

Lee, Kyu Pil; Choi, Seok; Hong, Jeong Hee; Ahuja, Malini; Graham, Sarabeth; Ma, Rong; So, Insuk; Shin, Dong Min; Muallem, Shmuel; Yuan, Joseph P

2014-03-01

375

Patterns of molecular variation in a species-wide germplasm set of Brassica napus.  

PubMed

Rapeseed (Brassica napus L.) is the leading European oilseed crop serving as source for edible oil and renewable energy. The objectives of our study were to (i) examine the population structure of a large and diverse set of B. napus inbred lines, (ii) investigate patterns of genetic diversity within and among different germplasm types, (iii) compare the two genomes of B. napus with regard to genetic diversity, and (iv) assess the extent of linkage disequilibrium (LD) between simple sequence repeat (SSR) markers. Our study was based on 509 B. napus inbred lines genotyped with 89 genome-specific SSR primer combinations. Both a principal coordinate analysis and software STRUCTURE revealed that winter types, spring types, and swedes were assigned to three major clusters. The genetic diversity of winter oilseed rape was lower than the diversity found in other germplasm types. Within winter oilseed rape types, a decay of genetic diversity with more recent release dates and reduced levels of erucic acid and glucosinolates was observed. The percentage of linked SSR loci pairs in significant (r (2) > Q (95 unlinked loci pairs)) LD was 6.29% for the entire germplasm set. Furthermore, LD decayed rapidly with distance, which will allow a relatively high mapping resolution in genome-wide association studies using our germplasm set, but, on the other hand, will require a high number of markers. PMID:21847624

Bus, Anja; Körber, Niklas; Snowdon, Rod J; Stich, Benjamin

2011-12-01

376

Molecular characterization and different expression patterns of the FABP gene family during goat skeletal muscle development.  

PubMed

The FABP (adipocyte fatty acid-binding protein) genes play an important role in intracellular fatty acid transport and considered to be candidate genes for fatness traits in domestic animal. In this study, we cloned the cDNA sequences of goat FABP family genes and their expression patterns were detected by semi-quantitative RT-PCR and quantitative real time RT-PCR. Expression analysis showed that goat FABP1 gene was predominantly expressed in liver, kidney and large intestine. While FABP4 was widely expressed in many tissues with a high expression level was observed in the fat, skeletal muscle, stomach and lung. Notably, FABP2 gene was expressed specifically in small intestine. Moreover, goat FABP3 was expressed at 60 day with the highest level, then significantly (p < 0.01) decreased at the 90 day. No significant expression differences were observed in longissimus dorsi muscles among 3 day, 30 day and 60 day. Goat FABP4 was expressed at 3 day with the lowest level, then significantly (p < 0.01) increased to a peak at the 60 day. In addition, a significant relationship between FABP3 mRNA expression levels and intramuscular fat (IMF) content was observed. These results suggest that the FABP3 and FABP4 may be important genes for meat quality and provides useful information for further studies on their roles in skeletal muscle IMF deposit. PMID:25245957

Wang, Linjie; Li, Li; Jiang, Jing; Wang, Yan; Zhong, Tao; Chen, Yu; Wang, Yong; Zhang, Hongping

2015-01-01

377

Molecular Characterization of Three Gonadotropin Subunits and Their Expression Patterns during Ovarian Maturation in Cynoglossus semilaevis.  

PubMed

The endocrine regulation of reproduction in a multiple spawning flatfish with an ovary of asynchronous development remains largely unknown. The objectives of this study were to monitor changes in mRNA expression patterns of three gonadotropin hormone (GTH) subunits (FSH?, LH? and CG?) and plasma GTH levels during ovarian maturation of half-smooth tongue sole Cynoglossus semilaevis. Cloning and sequence analysis revealed that the cDNAs of FSH?, LH? and CG? were 541, 670 and 685 bp in length, and encode for peptides of 130, 158 and 127 amino acids, respectively. The number of cysteine residues and potential N-linked glycosylation sites of the flatfish GTHs were conserved among teleosts. However, the primary structure of GTHs in Pleuronectiformes appeared to be highly divergent. The FSH? transcriptional level in the pituitary remained high during the vitellogenic stage while plasma levels of FSH peaked and oocyte development was stimulated. The LH? expression in the pituitary and ovary reached the maximum level during oocyte maturation stages when the plasma levels of LH peaked. The brain GTHs were expressed at the different ovarian stages. These results suggested that FSH and LH may simultaneously regulate ovarian development and maturation through the brain-pituitary-ovary axis endocrine system in tongue sole. PMID:25633101

Shi, Bao; Liu, Xuezhou; Xu, Yongjiang; Wang, Shanshan

2015-01-01

378

Molecular dynamics in the isothermal-isobaric ensemble: the requirement of a "shell" molecule. III. Discontinuous potentials.  

PubMed

Based on the approach of Gruhn and Monson [Phys. Rev. E 63, 061106 (2001)], we present a new method for deriving the collisions dynamics for particles that interact via discontinuous potentials. By invoking the conservation of the extended Hamiltonian, we generate molecular dynamics (MD) algorithms for simulating the hard-sphere and square-well fluids within the isothermal-isobaric (NpT) ensemble. Consistent with the recent rigorous reformulation of the NpT ensemble partition function, the equations of motion impose a constant external pressure via the introduction of a shell particle of known mass [M. J. Uline and D. S. Corti, J. Chem. Phys. 123, 164101 (2005); 123, 164102 (2005)], which serves to define uniquely the volume of the system. The particles are also connected to a temperature reservoir through the use of a chain of Nose-Hoover thermostats, the properties of which are not affected by a hard-sphere or square-well collision. By using the Liouville operator formalism and the Trotter expansion theorem to integrate the equations of motion, the update of the thermostat variables can be decoupled from the update of the positions of the particles and the momentum changes upon a collision. Hence, once the appropriate collision dynamics for the isobaric-isenthalpic (NpH) equations of motion is known, the adaptation of the algorithm to the NpT ensemble is straightforward. Results of MD simulations for the pure component square-well fluid are presented and serve to validate our algorithm. Finally, since the mass of the shell particle is known, the system itself, and not a piston of arbitrary mass, controls the time scales for internal pressure and volume fluctuations. We therefore consider the influence of the shell particle algorithm on the dynamics of the square-well fluid. PMID:18624470

Uline, Mark J; Corti, David S

2008-07-01

379

Alveolar Macrophages Infected with Ames or Sterne Strain of Bacillus anthracis Elicit Differential Molecular Expression Patterns  

PubMed Central

Alveolar macrophages (AMs) phagocytose Bacillus anthracis following inhalation and induce the production of pro-inflammatory cytokines and chemokines to mediate the activation of innate immunity. Ames, the virulent strain of B. anthracis, contains two plasmids that encode the antiphagocytic poly-?-d-glutamic acid capsule and the lethal toxin. The attenuated Sterne strain of B. anthracis, which lacks the plasmid encoding capsule, is widely adapted as a vaccine strain. Although differences in the outcome of infection with the two strains may have originated from the presence or absence of an anti-phagocytic capsule, the disease pathogenesis following infection will be manifested via the host responses, which is not well understood. To gain understanding of the host responses at cellular level, a microarray analysis was performed using primary rhesus macaque AMs infected with either Ames or Sterne spores. Notably, 528 human orthologs were identified to be differentially expressed in AMs infected with either strain of the B. anthracis. Meta-analyses revealed genes differentially expressed in response to B. anthracis infection were also induced upon infections with multiple pathogens such as Francisella Novicida or Staphylococcus aureus. This suggests the existence of a common molecular signature in response to pathogen infections. Importantly, the microarray and protein expression data for certain cytokines, chemokines and host factors provide further insights on how cellular processes such as innate immune sensing pathways, anti-apoptosis versus apoptosis may be differentially modulated in response to the virulent or vaccine strain of B. anthracis. The reported differences may account for the marked difference in pathogenicity between these two strains. PMID:24516547

Lane, Douglas; Kenny, Tara; Ojeda, Jenifer F.; Zhong, Yang; Che, Jianwei; Zhou, Yingyao; Ribot, Wilson; Kota, Krishna P.; Bavari, Sina; Panchal, Rekha G.

2014-01-01

380

Molecular Evidence of the Toxic Effects of Diatom Diets on Gene Expression Patterns in Copepods  

PubMed Central

Background Diatoms are dominant photosynthetic organisms in the world's oceans and are considered essential in the transfer of energy through marine food chains. However, these unicellular plants at times produce secondary metabolites such as polyunsaturated aldehydes and other products deriving from the oxidation of fatty acids that are collectively termed oxylipins. These cytotoxic compounds are responsible for growth inhibition and teratogenic activity, potentially sabotaging future generations of grazers by inducing poor recruitment in marine organisms such as crustacean copepods. Principal Findings Here we show that two days of feeding on a strong oxylipin-producing diatom (Skeletonema marinoi) is sufficient to inhibit a series of genes involved in aldehyde detoxification, apoptosis, cytoskeleton structure and stress response in the copepod Calanus helgolandicus. Of the 18 transcripts analyzed by RT-qPCR at least 50% were strongly down-regulated (aldehyde dehydrogenase 9, 8 and 6, cellular apoptosis susceptibility and inhibitor of apoptosis IAP proteins, heat shock protein 40, alpha- and beta-tubulins) compared to animals fed on a weak oxylipin-producing diet (Chaetoceros socialis) which showed no changes in gene expression profiles. Conclusions Our results provide molecular evidence of the toxic effects of strong oxylipin-producing diatoms on grazers, showing that primary defense systems that should be activated to protect copepods against toxic algae can be inhibited. On the other hand other classical detoxification genes (glutathione S-transferase, superoxide dismutase, catalase, cytochrome P450) were not affected possibly due to short exposure times. Given the importance of diatom blooms in nutrient-rich aquatic environments these results offer a plausible explanation for the inefficient use of a potentially valuable food resource, the spring diatom bloom, by some copepod species. PMID:22046381

Lauritano, Chiara; Borra, Marco; Carotenuto, Ylenia; Biffali, Elio; Miralto, Antonio; Procaccini, Gabriele; Ianora, Adrianna

2011-01-01

381

Effect of carbapenem consumption patterns on the molecular epidemiology and carbapenem resistance of Acinetobacter baumannii.  

PubMed

This study investigated the molecular epidemiology of Acinetobacter baumannii in the University of Debrecen in relation to antibiotic consumption. Overall and ward-specific antibiotic consumption was measured by the number of defined daily doses (DDD) per 100 bed-days between 2002 and 2012. Consumption was analysed against the number of A. baumannii positive patients per 100 bed-days, number of isolates per positive sample, and proportion of carbapenem resistant A. baumannii, using time-series analysis. Altogether 160 A. baumannii isolates from different wards were collected and analysed. Carbapenemase genes bla(OXA-23-like), bla(OXA-24-like), bla(OXA-48-like), bla(OXA-51-like), bla(OXA-58-like) and integrons were sought by PCR. Relatedness of isolates was assessed by PFGE. Prevalence and carbapenem resistance of A. baumannii were statistically associated with carbapenem consumption. Prevalence data followed carbapenem usage with three quarterly lags (r?=?0.51-0.53, P<0.001), and meropenem and ertapenem, but not imipenem usage, affected prevalence. Colistin usage, in turn, lagged behind prevalence with one lag (r?=?0.68-0.70, P<0.001). Six clusters were identified; the neurology ward with the lowest carbapenem consumption was associated with the carbapenem-susceptible cluster, as well as with the carbapenem-susceptible isolates in the cluster with variable susceptibility. Wards with high carbapenem usage almost exclusively harboured isolates from carbapenem-resistant clusters. All clusters were dominated by isolates of one or two wards, but most wards were represented in multiple clusters. Increases in prevalence and carbapenem resistance of A. baumannii were associated with usage of meropenem and ertapenem but not of imipenem, which led to the spread of multiple clones in the University. PMID:25261064

Mózes, Julianna; Ebrahimi, Fatemeh; Gorácz, Orsolya; Miszti, Cecília; Kardos, Gábor

2014-12-01

382

Two Metallothionein Genes in Oxya chinensis: Molecular Characteristics, Expression Patterns and Roles in Heavy Metal Stress  

PubMed Central

Metallothioneins (MTs) are small, cysteine-rich, heavy metal-binding proteins involved in metal homeostasis and detoxification in living organisms. In the present study, we cloned two MT genes (OcMT1 and OcMT2) from Oxya chinensis, analyzed the expression patterns of the OcMT transcripts in different tissues and at varying developmental stages using real-time quantitative PCR (RT-qPCR), evaluated the functions of these two MTs using RNAi and recombinant proteins in an E. coli expression system. The full-length cDNAs of OcMT1 and OcMT2 encoded 40 and 64 amino acid residues, respectively. We found Cys-Cys, Cys-X-Cys and Cys-X-Y-Z-Cys motifs in OcMT1 and OcMT2. These motifs might serve as primary chelating sites, as in other organisms. These characteristics suggest that OcMT1 and OcMT2 may be involved in heavy metal detoxification by capturing the metals. Two OcMT were expressed at all developmental stages, and the highest levels were found in the eggs. Both transcripts were expressed in all eleven tissues examined, with the highest levels observed in the brain and optic lobes, followed by the fat body. The expression of OcMT2 was also relatively high in the ovaries. The functions of OcMT1 and OcMT2 were explored using RNA interference (RNAi) and different concentrations and treatment times for the three heavy metals. Our results indicated that mortality increased significantly from 8.5% to 16.7%, and this increase was both time- and dose-dependent. To evaluate the abilities of these two MT proteins to confer heavy metal tolerance to E. coli, the bacterial cells were transformed with pET-28a plasmids containing the OcMT genes. The optical densities of both the MT-expressing and control cells decreased with increasing concentrations of CdCl2. Nevertheless, the survival rates of the MT-overexpressing cells were higher than those of the controls. Our results suggest that these two genes play important roles in heavy metal detoxification in O. chinensis. PMID:25391131

Liu, Yaoming; Wu, Haihua; Kou, Lihua; Liu, Xiaojian; Zhang, Jianzhen; Guo, Yaping; Ma, Enbo

2014-01-01

383

Molecule Shapes  

NSDL National Science Digital Library

Explore molecule shapes by building molecules in 3D! How does molecule shape change with different numbers of bonds and electron pairs? Find out by adding single, double or triple bonds and lone pairs to the central atom. Then, compare the model to real molecules!

Simulations, Phet I.; Moore, Emily; Olson, Jonathan; Lancaster, Kelly; Chamberlain, Julia; Perkins, Kathy

2011-10-10

384

Molecular Menagerie  

NSDL National Science Digital Library

In this activity, learners use molecular model kits to construct familiar molecules like lactose, caffeine, and Aspirin. This activity helps learners understand how scientists use models to study molecules as well as how advances in 3-D graphics have made the use of computer models much easier. This activity guide includes chemical formulas and 3-D structural diagrams of various natural and artificial molecules. Note: the cost of molecular model kits is included in the estimated cost of materials.

Howard Hughes Medical Institute

2002-01-01

385

Molecular Properties by Quantum Monte Carlo: An Investigation on the Role of the Wave Function Ansatz and the Basis Set in the Water Molecule  

PubMed Central

Quantum Monte Carlo methods are accurate and promising many body techniques for electronic structure calculations which, in the last years, are encountering a growing interest thanks to their favorable scaling with the system size and their efficient parallelization, particularly suited for the modern high performance computing facilities. The ansatz of the wave function and its variational flexibility are crucial points for both the accurate description of molecular properties and the capabilities of the method to tackle large systems. In this paper, we extensively analyze, using different variational ansatzes, several properties of the water molecule, namely, the total energy, the dipole and quadrupole momenta, the ionization and atomization energies, the equilibrium configuration, and the harmonic and fundamental frequencies of vibration. The investigation mainly focuses on variational Monte Carlo calculations, although several lattice regularized diffusion Monte Carlo calculations are also reported. Through a systematic study, we provide a useful guide to the choice of the wave function, the pseudopotential, and the basis set for QMC calculations. We also introduce a new method for the computation of forces with finite variance on open systems and a new strategy for the definition of the atomic orbitals involved in the Jastrow-Antisymmetrised Geminal power wave function, in order to drastically reduce the number of variational parameters. This scheme significantly improves the efficiency of QMC energy minimization in case of large basis sets. PMID:24526929

Zen, Andrea; Luo, Ye; Sorella, Sandro; Guidoni, Leonardo

2014-01-01

386

Molecular properties by Quantum Monte Carlo: an investigation on the role of the wave function ansatz and the basis set in the water molecule  

E-print Network

Quantum Monte Carlo methods are accurate and promising many body techniques for electronic structure calculations which, in the last years, are encountering a growing interest thanks to their favorable scaling with the system size and their efficient parallelization, particularly suited for the modern high performance computing facilities. The ansatz of the wave function and its variational flexibility are crucial points for both the accurate description of molecular properties and the capabilities of the method to tackle large systems. In this paper, we extensively analyze, using different variational ansatzes, several properties of the water molecule, namely: the total energy, the dipole and quadrupole momenta, the ionization and atomization energies, the equilibrium configuration, and the harmonic and fundamental frequencies of vibration. The investigation mainly focuses on variational Monte Carlo calculations, although several lattice regularized diffusion Monte Carlo calculations are also reported. Through a systematic study, we provide a useful guide to the choice of the wave function, the pseudo potential, and the basis set for QMC calculations. We also introduce a new strategy for the definition of the atomic orbitals involved in the Jastrow - Antisymmetrised Geminal power wave function, in order to drastically reduce the number of variational parameters. This scheme significantly improves the efficiency of QMC energy minimization in case of large basis sets.

Andrea Zen; Ye Luo; Sandro Sorella; Leonardo Guidoni

2013-09-02

387

Damage-associated molecular patterns (DAMPs) in preterm labor with intact membranes and preterm PROM: a study of the alarmin HMGB1  

PubMed Central

Objective Preterm parturition is a syndrome caused by multiple etiologies. Although intra-amniotic infection is causally linked with intrauterine inflammation and the onset of preterm labor, other patients have preterm labor in the absence of demonstrable infection. It is now clear that inflammation may be elicited by activation of the Damage-Associated Molecular Patterns (DAMPs), which include pathogen-associated molecular patterns (PAMPs) as well as “alarmins” (endogenous molecules that signal tissue and cellular damage). A prototypic alarmin is high-mobility group box-1 (HMGB1) protein, capable of inducing inflammation and tissue repair when it reaches the extracellular environment. HMGB1 is a late-mediator of sepsis, and blockade of HMGB1 activity reduces mortality in an animal model of endotoxemia, even if administered late during the course of the disorder. The objectives of this study were to: 1) determine whether intra-amniotic infection/inflammation (IAI) is associated with changes in amniotic fluid concentrations of HMGB1; and 2) localize immunoreactivity of HMGB1 in the fetal membranes and umbilical cord of patients with chorioamnionitis. Methods Amniotic fluid samples were collected from the following groups: 1) preterm labor with intact membranes (PTL) with (n=42) and without IAI (n=84); and 2) preterm prelabor rupture of membranes (PROM) with (n=38) and without IAI (n=35). IAI was defined as either a positive amniotic fluid culture or amniotic fluid concentration of interleukin-6 (IL-6) ?2.6 ng/mL. HMGB1 concentrations in amniotic fluid were determined by ELISA. Immunofluorescence staining for HMGB1 was performed in the fetal membranes and umbilical cord of pregnancies with acute chorioamnionitis. Results Amniotic fluid HMGB1 concentrations were higher in patients with IAI than in those without IAI in both the PTL and preterm PROM groups (PTL IAI: median 3.1 ng/mL vs. without IAI; median 0.98 ng/mL; p<0.001; and preterm PROM with IAI median 7.3 ng/mL vs. without IAI median 2.6 ng/mL; p=0.002); patients with preterm PROM without IAI had a higher median amniotic fluid HMGB1 concentration than those with PTL and intact membranes without IAI (p<0.001); and HMGB1 was immunolocalized to amnion epithelial cells and stromal cells in the Wharton’s jelly (prominent in the nuclei and cytoplasm). Myofibroblasts and macrophages of the chorioamniotic connective tissue layer and infiltrating neutrophils showed diffuse cytoplasmic HMGB1 immunoreactivity. Conclusions Intra-amniotic infection/inflammation is associated with elevated amniotic fluid HMGB1 concentrations regardless of membrane status; preterm PROM was associated with a higher amniotic fluid HMGB1 concentration than PTL with intact membranes, suggesting that rupture of membranes is associated with an elevation of alarmins; immunoreactive HMGB1 was localized to amnion epithelial cells, Wharton’s jelly and cells involved in the innate immune response; and we propose that HMGB1 released from stress or injured cells into amniotic fluid may be responsible, in part, for intra-amniotic inflammation due to non-microbial insults. PMID:21958433

Romero, Roberto; Chaiworapongsa, Tinnakorn; Savasan, Zeynep Alpay; Xu, Yi; Hussein, Youssef; Dong, Zhong; Kusanovic, Juan Pedro; Kim, Chong Jai; Hassan, Sonia S

2012-01-01

388

Molecular evolution of psbA gene in ferns: unraveling selective pressure and co-evolutionary pattern  

PubMed Central

Background The photosynthetic oxygen-evolving photo system II (PS II) produces almost the entire oxygen in the atmosphere. This unique biochemical system comprises a functional core complex that is encoded by psbA and other genes. Unraveling the evolutionary dynamics of this gene is of particular interest owing to its direct role in oxygen production. psbA underwent gene duplication in leptosporangiates, in which both copies have been preserved since. Because gene duplication is often followed by the non-fictionalization of one of the copies and its subsequent erosion, preservation of both psbA copies pinpoint functional or regulatory specialization events. The aim of this study was to investigate the molecular evolution of psbA among fern lineages. Results We sequenced psbA , which encodes D1 protein in the core complex of PSII, in 20 species representing 8 orders of extant ferns; then we searched for selection and convolution signatures in psbA across the 11 fern orders. Collectively, our results indicate that: (1) selective constraints among D1 protein relaxed after the duplication in 4 leptosporangiate orders; (2) a handful positively selected codons were detected within species of single copy psbA, but none in duplicated ones; (3) a few sites among D1 protein were involved in co-evolution process which may intimate significant functional/structural communications between them. Conclusions The strong competition between ferns and angiosperms for light may have been the main cause for a continuous fixation of adaptive amino acid changes in psbA , in particular after its duplication. Alternatively, a single psbA copy may have undergone bursts of adaptive changes at the molecular level to overcome angiosperms competition. The strong signature of positive Darwinian selection in a major part of D1 protein is testament to this. At the same time, species own two psbA copies hardly have positive selection signals among the D1 protein coding sequences. In this study, eleven co-evolving sites have been detected via different molecules, which may be more important than others. PMID:22899792

2012-01-01

389

Characterization of the molecular features and expression patterns of two serine proteases in Hermetia illucens (Diptera: Stratiomyidae) larvae.  

PubMed

To investigate the molecular scavenging capabilities of the larvae of Hermetia illucens, two serine proteases (SPs) were cloned and characterized. Multiple sequence alignments and phylogenetic tree analysis of the deduced amino acid sequences of Hi-SP1 and Hi-SP2 were suggested that Hi-SP1 may be a chymotrypsin- and Hi-SP2 may be a trypsin-like protease. Hi-SP1 and Hi-SP2 3-D homology models revealed that a catalytic triad, three disulfide bonds, and a substrate-binding pocket were highly conserved, as would be expected of a SP. E. coli expressed Hi-SP1 and Hi-SP2 showed chymotrypsin or trypsin activities, respectively. Hi-SP2 mRNAs were consistently expressed during larval development. In contrast, the expression of Hi-SP1 mRNA fluctuated between feeding and molting stages and disappeared at the pupal stages. These expression pattern differences suggest that Hi-SP1 may be a larval specific chymotrypsin-like protease involved with food digestion, while Hi-SP2 may be a trypsin-like protease with diverse functions at different stages. PMID:21699751

Kim, Wontae; Bae, Sungwoo; Kim, Ayoung; Park, Kwanho; Lee, Sangbeom; Choi, Youngcheol; Han, Sangmi; Park, Younghan; Koh, Youngho

2011-06-01

390

The Microgeographical Patterns of Morphological and Molecular Variation of a Mixed Ploidy Population in the Species Complex Actinidia chinensis  

PubMed Central

Polyploidy and hybridization are thought to have significant impacts on both the evolution and diversification of the genus Actinidia, but the structure and patterns of morphology and molecular diversity relating to ploidy variation of wild Actinidia plants remain much less understood. Here, we examine the distribution of morphological variation and ploidy levels along geographic and environmental variables of a large mixed-ploidy population of the A. chinensis species complex. We then characterize the extent of both genetic and epigenetic diversity and differentiation exhibited between individuals of different ploidy levels. Our results showed that while there are three ploidy levels in this population, hexaploids were constituted the majority (70.3%). Individuals with different ploidy levels were microgeographically structured in relation to elevation and extent of niche disturbance. The morphological characters examined revealed clear difference between diploids and hexaploids, however tetraploids exhibited intermediate forms. Both genetic and epigenetic diversity were high but the differentiation among cytotypes was weak, suggesting extensive gene flow and/or shared ancestral variation occurred in this population even across ploidy levels. Epigenetic variation was clearly correlated with changes in altitudes, a trend of continuous genetic variation and gradual increase of epigenomic heterogeneities of individuals was also observed. Our results show that complex interactions between the locally microgeographical environment, ploidy and gene flow impact A. chinensis genetic and epigenetic variation. We posit that an increase in ploidy does not broaden the species habitat range, but rather permits A. chinensis adaptation to specific niches. PMID:25658107

Liu, Yifei; Li, Dawei; Yan, Ling; Huang, Hongwen

2015-01-01

391

Phase-Transfer Energetics of Small-Molecule Alcohols Across the Water-Hexane Interface: Molecular Dynamics Simulation Using Charge Equilibration Models  

PubMed Central

We study the water-hexane interface using molecular dynamics (MD) and polarizable charge equilibration (CHEQ) force fields. Bulk densities for TIP4P-FQ water and hexane, 1.0086±0.0002 g/cm3 and 0.6378±0.0001 g/cm3, demonstrate excellent agreement with experiment. Interfacial width and interfacial tension are consistent with previously reported values. The in-plane component of the dielectric permittivity (??) for water is shown to decrease from 81.7±0.04 to unity, transitioning longitudinally from bulk water to bulk hexane. ?? for hexane reaches a maximum in the interface, but this term represents only a small contribution to the total dielectric constant (as expected for a non-polar species). Structurally, net orientations of the molecules arise in the interfacial region such that hexane lies slightly parallel to the interface and water reorients to maximize hydrogen bonding. Interfacial potentials due to contributions of the water and hexane are calculated to be -567.9±0.13mV and 198.7±0.01mV, respectively, giving rise to a total potential in agreement with the range of values reported from previous simulations of similar systems. Potentials of mean force (PMF) calculated for methanol, ethanol, and 1-propanol for the transfer from water to hexane indicate an interfacial free energy minimum, corresponding to the amphiphilic nature of the molecules. The magnitudes of transfer free energies were further characterized from the solvation free energies of alcohols in water and hexane using thermodynamic integration. This analysis shows that solvation free energies for alcohols in hexane are 0.2-0.3 kcal/mol too unfavorable, whereas solvation of alcohols in water is approximately 1 kcal/mol too favorable. For the pure hexane-water interfacial simulations, we observe a monotonic decrease of the water dipole moment to near-vacuum values. This suggests that the electrostatic component of the desolvation free energy is not as severe for polarizable models than for fixed-charge force fields. The implications of such behavior pertain to the modeling of polar and charged solutes in lipidic environments. PMID:21414823

Bauer, Brad A.; Zhong, Yang; Meninger, David J.; Davis, Joseph E.; Patel, Sandeep

2010-01-01

392

Calculation of total cross sections for charge exchange in molecular collisions  

NASA Technical Reports Server (NTRS)

Areas of investigation summarized include nitrogen ion-nitrogen molecule collisions; molecular collisions with surfaces; molecular identification from analysis of cracking patterns of selected gases; computer modelling of a quadrupole mass spectrometer; study of space charge in a quadrupole; transmission of the 127 deg cylindrical electrostatic analyzer; and mass spectrometer data deconvolution.

Ioup, J.

1979-01-01

393

Molecular fountain.  

SciTech Connect

A molecular fountain directs slowly moving molecules against gravity to further slow them to translational energies that they can be trapped and studied. If the molecules are initially slow enough they will return some time later to the position from which they were launched. Because this round trip time can be on the order of a second a single molecule can be observed for times sufficient to perform Hz level spectroscopy. The goal of this LDRD proposal was to construct a novel Molecular Fountain apparatus capable of producing dilute samples of molecules at near zero temperatures in well-defined user-selectable, quantum states. The slowly moving molecules used in this research are produced by the previously developed Kinematic Cooling technique, which uses a crossed atomic and molecular beam apparatus to generate single rotational level molecular samples moving slowly in the laboratory reference frame. The Kinematic Cooling technique produces cold molecules from a supersonic molecular beam via single collisions with a supersonic atomic beam. A single collision of an atom with a molecule occurring at the correct energy and relative velocity can cause a small fraction of the molecules to move very slowly vertically against gravity in the laboratory. These slowly moving molecules are captured by an electrostatic hexapole guiding field that both orients and focuses the molecules. The molecules are focused into the ionization region of a time-of-flight mass spectrometer and are ionized by laser radiation. The new molecular fountain apparatus was built utilizing a new design for molecular beam apparatus that has allowed us to miniaturize the apparatus. This new design minimizes the volumes and surface area of the machine allowing smaller pumps to maintain the necessary background pressures needed for these experiments.

Strecker, Kevin E.; Chandler, David W.

2009-09-01

394

Molecular visualization of polymer thin films by atomic force microscopy: Towards patterning and replication of soft nanostructures for nanomaterial design and construction  

NASA Astrophysics Data System (ADS)

The creation of materials with sub-100 nm functional architectures is a challenge in nanotechnology. Two ways to create nanostructures are: (i) self-assembly of small molecules into supramolecular structures; and (ii) design of shape-persistent macromolecules. Molecular brushes are ideal candidates as one can control size, shape, interior structure, and surface composition through interactions between multiple branches with heterogeneous chemical composition. Accurate characterization of molecular dimensions and morphology is vital for understanding structure-property relations of mesoscopic molecules and their assemblies. This particularly concerns macromolecules that are small (10-100 nm), flexible, polydisperse, and heterogeneous. Individual molecules and supramolecular assemblies of different heteropolymer brushes were studied. Architectures investigated include brushes with crystalline ends, hetero-grafted brushes, and in detail, brushes with diblock side chains of crystalline poly(epsilon-caprolactone) and amorphous poly(n-butyl acrylate) (PCL-b-PBA). PCL-b-PBA brushes were characterized by AFM, DSC, POM, and X-ray scattering. Single molecules demonstrated unique herringbone morphologies consisting of PCL extended-chain crystallites emanating from backbones and amorphous coronas of PBA chains. Macroscopic samples demonstrated an ability to maintain molecular alignment upon constrained crystallization of PCL. Aligned microphase separated cylinders transformed slowly into oriented lamellae through break-out crystallization of PCL, leading to fused PCL cores. Folded PCL chains formed lamellae parallel to the backbone, i.e. PCL chains oriented perpendicular to the backbone. The diblock side chain composition allowed for accurate control of the number of folds within PCL cores. In addition to PCL-b-PBA brushes, molecular imaging was applied to quantitative characterization of their assemblies as well as branched macromolecules and gradient brushes. However, molecular imaging must be improved in terms of sample preparation so accurate dimensions of soft, nm-sized objects can be determined by contact techniques like AFM. Spherical and cylindrical poly(styrene)-b-poly(isoprene) micelles adsorbed on low surface energy substrates were used as model masters for PFPE-based soft lithography. Masters, molds, and replicas of the micelles were characterized by AFM to verify the fidelity of the lithographic technique in application to soft and weakly-adhering nanoparticles. A threshold surface energy was determined for spherical micelle lift-off from substrates. Above the threshold, molding and replication of the micelles were accomplished at the expense of particle deformation. Below the threshold, particle transfer between substrates is possible.

Yu-Su, Sherryl Yao

395