Rapid molecular evolution of human bocavirus revealed by Bayesian coalescent inference.

Science.gov (United States)

Zehender, Gianguglielmo; De Maddalena, Chiara; Canuti, Marta; Zappa, Alessandra; Amendola, Antonella; Lai, Alessia; Galli, Massimo; Tanzi, Elisabetta

2010-03-01

Human bocavirus (HBoV) is a linear single-stranded DNA virus belonging to the Parvoviridae family that has recently been isolated from the upper respiratory tract of children with acute respiratory infection. All of the strains observed so far segregate into two genotypes (1 and 2) with a low level of polymorphism. Given the recent description of the infection and the lack of epidemiological and molecular data, we estimated the virus's rates of molecular evolution and population dynamics. A dataset of forty-nine dated VP2 sequences, including also eight new isolates obtained from pharyngeal swabs of Italian patients with acute respiratory tract infections, was submitted to phylogenetic analysis. The model parameters, evolutionary rates and population dynamics were co-estimated using a Bayesian Markov Chain Monte Carlo approach, and site-specific positive and negative selection was also investigated. Recombination was investigated by seven different methods and one suspected recombinant strain was excluded from further analysis. The estimated mean evolutionary rate of HBoV was 8.6x10(-4)subs/site/year, and that of the 1st+2nd codon positions was more than 15 times less than that of the 3rd codon position. Viral population dynamics analysis revealed that the two known genotypes diverged recently (mean tMRCA: 24 years), and that the epidemic due to HBoV genotype 2 grew exponentially at a rate of 1.01year(-1). Selection analysis of the partial VP2 showed that 8.5% of sites were under significant negative pressure and the absence of positive selection. Our results show that, like other parvoviruses, HBoV is characterised by a rapid evolution. The low level of polymorphism is probably due to a relatively recent divergence between the circulating genotypes and strong purifying selection acting on viral antigens.

The interaction properties of the human Rab GTPase family--comparative analysis reveals determinants of molecular binding selectivity.

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Matthias Stein

Full Text Available Rab GTPases constitute the largest subfamily of the Ras protein superfamily. Rab proteins regulate organelle biogenesis and transport, and display distinct binding preferences for effector and activator proteins, many of which have not been elucidated yet. The underlying molecular recognition motifs, binding partner preferences and selectivities are not well understood.Comparative analysis of the amino acid sequences and the three-dimensional electrostatic and hydrophobic molecular interaction fields of 62 human Rab proteins revealed a wide range of binding properties with large differences between some Rab proteins. This analysis assists the functional annotation of Rab proteins 12, 14, 26, 37 and 41 and provided an explanation for the shared function of Rab3 and 27. Rab7a and 7b have very different electrostatic potentials, indicating that they may bind to different effector proteins and thus, exert different functions. The subfamily V Rab GTPases which are associated with endosome differ subtly in the interaction properties of their switch regions, and this may explain exchange factor specificity and exchange kinetics.We have analysed conservation of sequence and of molecular interaction fields to cluster and annotate the human Rab proteins. The analysis of three dimensional molecular interaction fields provides detailed insight that is not available from a sequence-based approach alone. Based on our results, we predict novel functions for some Rab proteins and provide insights into their divergent functions and the determinants of their binding partner selectivity.

C sub 6 sub 0 fullerene and its molecular complexes under axial and shear deformation

CERN Document Server

Spitsina, N G; Bashkin, I V; Meletov, K P

2002-01-01

We have studied the pristine C sub 6 sub 0 and its molecular complexes with the organic donors bis(ethylenedithio) tetrathiafulvalene (BEDT-TTF or ET) and tetramethyltetraselenafulvalene (TMTSF) by means of ESR and Raman spectroscopy at high pressure. The important changes in the ESR signal of C sub 6 sub 0 were observed under axial pressure combined with shear deformation. It is shown that the treatment at a anisotropic pressure of 4 GPa results in a reduction in the symmetry of the C sub 6 sub 0 molecule and the formation of radicals. Treatment of the molecular complex of (ET) sub 2 centre dot C sub 6 sub 0 at a pressure of approx 4.5 GPa and a temperature of 150 deg. C leads to the formation of C sub 6 sub 0 dimers. The Raman spectra of the molecular complex C sub 6 sub 0 centre dot TMTSF centre dot 2(CS sub 2) were measured in situ at ambient temperature and pressures up to 9.5 GPa. The pressure behaviour of the Raman peaks reveals singularity at 5.0 +- 0.5 GPa related to the softening and splitting of so...

Lung eQTLs to help reveal the molecular underpinnings of asthma.

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Ke Hao

Full Text Available Genome-wide association studies (GWAS have identified loci reproducibly associated with pulmonary diseases; however, the molecular mechanism underlying these associations are largely unknown. The objectives of this study were to discover genetic variants affecting gene expression in human lung tissue, to refine susceptibility loci for asthma identified in GWAS studies, and to use the genetics of gene expression and network analyses to find key molecular drivers of asthma. We performed a genome-wide search for expression quantitative trait loci (eQTL in 1,111 human lung samples. The lung eQTL dataset was then used to inform asthma genetic studies reported in the literature. The top ranked lung eQTLs were integrated with the GWAS on asthma reported by the GABRIEL consortium to generate a Bayesian gene expression network for discovery of novel molecular pathways underpinning asthma. We detected 17,178 cis- and 593 trans- lung eQTLs, which can be used to explore the functional consequences of loci associated with lung diseases and traits. Some strong eQTLs are also asthma susceptibility loci. For example, rs3859192 on chr17q21 is robustly associated with the mRNA levels of GSDMA (P = 3.55 × 10(-151. The genetic-gene expression network identified the SOCS3 pathway as one of the key drivers of asthma. The eQTLs and gene networks identified in this study are powerful tools for elucidating the causal mechanisms underlying pulmonary disease. This data resource offers much-needed support to pinpoint the causal genes and characterize the molecular function of gene variants associated with lung diseases.

Electron-vibrational transitions under molecular ions collisions with slow electrons

International Nuclear Information System (INIS)

Andreev, E.A.

1993-01-01

A concept of a multichannel quantum defect is considered and basic theoretic ratios of inelastic collisional processes with the participation of molecular positive ions and slow electrons playing an important role both in atmospheric and laboratory plasma, are presented. The problem of scattering channel number limitation with the provision of S-matrix unique character is considered. Different models of electron rotation-vibrational connection under collision of two-atom molecular ions with slow electrons are analysed. Taking N 2 + as an example, a high efficiency of transitions between different electron states of a molecular ion is shown. 73 refs., 9 figs., 1 tab

Revealing Atomic-Level Mechanisms of Protein Allostery with Molecular Dynamics Simulations.

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Samuel Hertig

2016-06-01

Full Text Available Molecular dynamics (MD simulations have become a powerful and popular method for the study of protein allostery, the widespread phenomenon in which a stimulus at one site on a protein influences the properties of another site on the protein. By capturing the motions of a protein's constituent atoms, simulations can enable the discovery of allosteric binding sites and the determination of the mechanistic basis for allostery. These results can provide a foundation for applications including rational drug design and protein engineering. Here, we provide an introduction to the investigation of protein allostery using molecular dynamics simulation. We emphasize the importance of designing simulations that include appropriate perturbations to the molecular system, such as the addition or removal of ligands or the application of mechanical force. We also demonstrate how the bidirectional nature of allostery-the fact that the two sites involved influence one another in a symmetrical manner-can facilitate such investigations. Through a series of case studies, we illustrate how these concepts have been used to reveal the structural basis for allostery in several proteins and protein complexes of biological and pharmaceutical interest.

Molecular mechanisms underlying the emergence of bacterial pathogens: an ecological perspective.

Science.gov (United States)

Bartoli, Claudia; Roux, Fabrice; Lamichhane, Jay Ram

2016-02-01

The rapid emergence of new bacterial diseases negatively affects both human health and agricultural productivity. Although the molecular mechanisms underlying these disease emergences are shared between human- and plant-pathogenic bacteria, not much effort has been made to date to understand disease emergences caused by plant-pathogenic bacteria. In particular, there is a paucity of information in the literature on the role of environmental habitats in which plant-pathogenic bacteria evolve and on the stress factors to which these microbes are unceasingly exposed. In this microreview, we focus on three molecular mechanisms underlying pathogenicity in bacteria, namely mutations, genomic rearrangements and the acquisition of new DNA sequences through horizontal gene transfer (HGT). We briefly discuss the role of these mechanisms in bacterial disease emergence and elucidate how the environment can influence the occurrence and regulation of these molecular mechanisms by directly impacting disease emergence. The understanding of such molecular evolutionary mechanisms and their environmental drivers will represent an important step towards predicting bacterial disease emergence and developing sustainable management strategies for crops. © 2015 BSPP AND JOHN WILEY & SONS LTD.

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

Energy Technology Data Exchange (ETDEWEB)

Prates, Luciana Louzada [Department of Animal and Poultry Science, College of Agriculture and Bioresources, University of Saskatchewan, Saskatoon, Saskatchewan, Canada; Yu, Peiqiang [Department of Animal and Poultry Science, College of Agriculture and Bioresources, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

2017-05-16

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

Sequence analysis of serum albumins reveals the molecular evolution of ligand recognition properties.

Science.gov (United States)

Fanali, Gabriella; Ascenzi, Paolo; Bernardi, Giorgio; Fasano, Mauro

2012-01-01

Serum albumin (SA) is a circulating protein providing a depot and carrier for many endogenous and exogenous compounds. At least seven major binding sites have been identified by structural and functional investigations mainly in human SA. SA is conserved in vertebrates, with at least 49 entries in protein sequence databases. The multiple sequence analysis of this set of entries leads to the definition of a cladistic tree for the molecular evolution of SA orthologs in vertebrates, thus showing the clustering of the considered species, with lamprey SAs (Lethenteron japonicum and Petromyzon marinus) in a separate outgroup. Sequence analysis aimed at searching conserved domains revealed that most SA sequences are made up by three repeated domains (about 600 residues), as extensively characterized for human SA. On the contrary, lamprey SAs are giant proteins (about 1400 residues) comprising seven repeated domains. The phylogenetic analysis of the SA family reveals a stringent correlation with the taxonomic classification of the species available in sequence databases. A focused inspection of the sequences of ligand binding sites in SA revealed that in all sites most residues involved in ligand binding are conserved, although the versatility towards different ligands could be peculiar of higher organisms. Moreover, the analysis of molecular links between the different sites suggests that allosteric modulation mechanisms could be restricted to higher vertebrates.

Multiple roles of integrin-linked kinase in epidermal development, maturation and pigmentation revealed by molecular profiling.

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David Judah

Full Text Available Integrin-linked kinase (ILK is an important scaffold protein that mediates a variety of cellular responses to integrin stimulation by extracellular matrix proteins. Mice with epidermis-restricted inactivation of the Ilk gene exhibit pleiotropic phenotypic defects, including impaired hair follicle morphogenesis, reduced epidermal adhesion to the basement membrane, compromised epidermal integrity, as well as wasting and failure to thrive leading to perinatal death. To better understand the underlying molecular mechanisms that cause such a broad range of alterations, we investigated the impact of Ilk gene inactivation on the epidermis transcriptome. Microarray analysis showed over 700 differentially regulated mRNAs encoding proteins involved in multiple aspects of epidermal function, including keratinocyte differentiation and barrier formation, inflammation, regeneration after injury, and fundamental epidermal developmental pathways. These studies also revealed potential effects on genes not previously implicated in ILK functions, including those important for melanocyte and melanoblast development and function, regulation of cytoskeletal dynamics, and homeobox genes. This study shows that ILK is a critical regulator of multiple aspects of epidermal function and homeostasis, and reveals the previously unreported involvement of ILK not only in epidermal differentiation and barrier formation, but also in melanocyte genesis and function.

Multiple roles of integrin-linked kinase in epidermal development, maturation and pigmentation revealed by molecular profiling.

Science.gov (United States)

Judah, David; Rudkouskaya, Alena; Wilson, Ryan; Carter, David E; Dagnino, Lina

2012-01-01

Integrin-linked kinase (ILK) is an important scaffold protein that mediates a variety of cellular responses to integrin stimulation by extracellular matrix proteins. Mice with epidermis-restricted inactivation of the Ilk gene exhibit pleiotropic phenotypic defects, including impaired hair follicle morphogenesis, reduced epidermal adhesion to the basement membrane, compromised epidermal integrity, as well as wasting and failure to thrive leading to perinatal death. To better understand the underlying molecular mechanisms that cause such a broad range of alterations, we investigated the impact of Ilk gene inactivation on the epidermis transcriptome. Microarray analysis showed over 700 differentially regulated mRNAs encoding proteins involved in multiple aspects of epidermal function, including keratinocyte differentiation and barrier formation, inflammation, regeneration after injury, and fundamental epidermal developmental pathways. These studies also revealed potential effects on genes not previously implicated in ILK functions, including those important for melanocyte and melanoblast development and function, regulation of cytoskeletal dynamics, and homeobox genes. This study shows that ILK is a critical regulator of multiple aspects of epidermal function and homeostasis, and reveals the previously unreported involvement of ILK not only in epidermal differentiation and barrier formation, but also in melanocyte genesis and function.

STRUCTURED MOLECULAR GAS REVEALS GALACTIC SPIRAL ARMS

Energy Technology Data Exchange (ETDEWEB)

Sawada, Tsuyoshi [Joint ALMA Office, Alonso de Cordova 3107, Vitacura, Santiago 763-0355 (Chile); Hasegawa, Tetsuo [NAOJ Chile Observatory, Joaquin Montero 3000 Oficina 702, Vitacura, Santiago 763-0409 (Chile); Koda, Jin, E-mail: sawada.tsuyoshi@nao.ac.jp [Department of Physics and Astronomy, Stony Brook University, Stony Brook, NY 11794-3800 (United States)

2012-11-01

We explore the development of structures in molecular gas in the Milky Way by applying the analysis of the brightness distribution function and the brightness distribution index (BDI) in the archival data from the Boston University-Five College Radio Astronomy Observatory {sup 13}CO J = 1-0 Galactic Ring Survey. The BDI measures the fractional contribution of spatially confined bright molecular emission over faint emission extended over large areas. This relative quantity is largely independent of the amount of molecular gas and of any conventional, pre-conceived structures, such as cores, clumps, or giant molecular clouds. The structured molecular gas traced by higher BDI is located continuously along the spiral arms in the Milky Way in the longitude-velocity diagram. This clearly indicates that molecular gas changes its structure as it flows through the spiral arms. Although the high-BDI gas generally coincides with H II regions, there is also some high-BDI gas with no/little signature of ongoing star formation. These results support a possible evolutionary sequence in which unstructured, diffuse gas transforms itself into a structured state on encountering the spiral arms, followed by star formation and an eventual return to the unstructured state after the spiral arm passage.

The Molecular Architecture of Cell Adhesion: Dynamic Remodeling Revealed by Videonanoscopy

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Arnauld eSergé

2016-05-01

Full Text Available The plasma membrane delimits the cell, which is the basic unit of living organisms, and is also a privileged site for cell communication with the environment. Cell adhesion can occur through cell-cell and cell-matrix contacts. Adhesion proteins such as integrins and cadherins also constitute receptors for inside-out and outside-in signaling within proteolipidic platforms. Adhesion molecule targeting and stabilization relies on specific features such as preferential segregation by the sub-membrane cytoskeleton meshwork and within membrane proteolipidic microdomains. This review presents an overview of the recent insights brought by the latest developments in microscopy, to unravel the molecular remodeling occurring at cell contacts. The dynamic aspect of cell adhesion was recently highlighted by super-resolution videomicroscopy, also named videonanoscopy. By circumventing the diffraction limit of light, nanoscopy has allowed the monitoring of molecular localization and behavior at the single-molecule level, on fixed and living cells. Accessing molecular-resolution details such as quantitatively monitoring components entering and leaving cell contacts by lateral diffusion and reversible association has revealed an unexpected plasticity. Adhesion structures can be highly specialized, such as focal adhesion in motile cells, as well as immune and neuronal synapses. Spatiotemporal reorganization of adhesion molecules, receptors and adaptors directly relates to structure/function modulation. Assembly of these supramolecular complexes is continuously balanced by dynamic events, remodeling adhesions on various timescales, notably by molecular conformation switches, lateral diffusion within the membrane and endo/exocytosis. Pathological alterations in cell adhesion are involved in cancer evolution, through cancer stem cell interaction with stromal niches, growth, extravasation and metastasis.

Thermal buckling behavior of defective CNTs under pre-load: A molecular dynamics study.

Science.gov (United States)

Mehralian, Fahimeh; Tadi Beni, Yaghoub; Kiani, Yaser

2017-05-01

Current study is concentrated on the extraordinary properties of defective carbon nanotubes (CNTs). The role of vacancy defects in thermal buckling response of precompressed CNTs is explored via molecular dynamics (MD) simulations. Defective CNTs are initially compressed at a certain ratio of their critical buckling strain and then undergo a uniform temperature rise. Comprehensive study is implemented on both armchair and zigzag CNTs with different vacancy defects including monovacancy, symmetric bivacancy and asymmetric bivacancy. The results reveal that defects have a pronounced impact on the buckling behavior of CNTs; interestingly, defective CNTs under compressive pre-load show higher resistance to thermal buckling than pristine ones. In the following, the buckling response of defective CNTs is shown to be dependent on the vacancy defects, location of defects and chirality. Copyright © 2017 Elsevier Inc. All rights reserved.

Molecular investigations on grain filling rate under terminal heat ...

African Journals Online (AJOL)

Grain yield under post anthesis high temperature stress is largely influenced by grain filling rate (GFR). To investigate molecular basis of this trait, a set of 111 recombinant inbred lines (RILs) derived from Raj 4014, a heat sensitive genotype and WH 730, heat tolerant cultivar was phenotyped during 2009-2010 and ...

Atomistic simulations of highly conductive molecular transport junctions under realistic conditions

KAUST Repository

French, William R.; Iacovella, Christopher R.; Rungger, Ivan; Souza, Amaury Melo; Sanvito, Stefano; Cummings, Peter T.

2013-01-01

We report state-of-the-art atomistic simulations combined with high-fidelity conductance calculations to probe structure-conductance relationships in Au-benzenedithiolate (BDT)-Au junctions under elongation. Our results demonstrate that large increases in conductance are associated with the formation of monatomic chains (MACs) of Au atoms directly connected to BDT. An analysis of the electronic structure of the simulated junctions reveals that enhancement in the s-like states in Au MACs causes the increases in conductance. Other structures also result in increased conductance but are too short-lived to be detected in experiment, while MACs remain stable for long simulation times. Examinations of thermally evolved junctions with and without MACs show negligible overlap between conductance histograms, indicating that the increase in conductance is related to this unique structural change and not thermal fluctuation. These results, which provide an excellent explanation for a recently observed anomalous experimental result [Bruot et al., Nat. Nanotechnol., 2012, 7, 35-40], should aid in the development of mechanically responsive molecular electronic devices. © 2013 The Royal Society of Chemistry.

Communication: High pressure specific heat spectroscopy reveals simple relaxation behavior of glass forming molecular liquid

DEFF Research Database (Denmark)

Roed, Lisa Anita; Niss, Kristine; Jakobsen, Bo

2015-01-01

The frequency dependent specific heat has been measured under pressure for the molecular glass forming liquid 5-polyphenyl-4-ether in the viscous regime close to the glass transition. The temperature and pressure dependences of the characteristic time scale associated with the specific heat...... is compared to the equivalent time scale from dielectric spectroscopy performed under identical conditions. It is shown that the ratio between the two time scales is independent of both temperature and pressure. This observation is non-trivial and demonstrates the existence of specially simple molecular...... liquids in which different physical relaxation processes are both as function of temperature and pressure/density governed by the same underlying “inner clock.” Furthermore, the results are discussed in terms of the recent conjecture that van der Waals liquids, like the measuredliquid, comply...

Molecular determinants of juvenile hormone action as revealed by 3D QSAR analysis in Drosophila.

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Denisa Liszeková

Full Text Available BACKGROUND: Postembryonic development, including metamorphosis, of many animals is under control of hormones. In Drosophila and other insects these developmental transitions are regulated by the coordinate action of two principal hormones, the steroid ecdysone and the sesquiterpenoid juvenile hormone (JH. While the mode of ecdysone action is relatively well understood, the molecular mode of JH action remains elusive. METHODOLOGY/PRINCIPAL FINDINGS: To gain more insights into the molecular mechanism of JH action, we have tested the biological activity of 86 structurally diverse JH agonists in Drosophila melanogaster. The results were evaluated using 3D QSAR analyses involving CoMFA and CoMSIA procedures. Using this approach we have generated both computer-aided and species-specific pharmacophore fingerprints of JH and its agonists, which revealed that the most active compounds must possess an electronegative atom (oxygen or nitrogen at both ends of the molecule. When either of these electronegative atoms are replaced by carbon or the distance between them is shorter than 11.5 A or longer than 13.5 A, their biological activity is dramatically decreased. The presence of an electron-deficient moiety in the middle of the JH agonist is also essential for high activity. CONCLUSIONS/SIGNIFICANCE: The information from 3D QSAR provides guidelines and mechanistic scope for identification of steric and electrostatic properties as well as donor and acceptor hydrogen-bonding that are important features of the ligand-binding cavity of a JH target protein. In order to refine the pharmacophore analysis and evaluate the outcomes of the CoMFA and CoMSIA study we used pseudoreceptor modeling software PrGen to generate a putative binding site surrogate that is composed of eight amino acid residues corresponding to the defined molecular interactions.

HERSCHEL OBSERVATIONS REVEAL ANOMALOUS MOLECULAR ABUNDANCES TOWARD THE GALACTIC CENTER

Energy Technology Data Exchange (ETDEWEB)

Sonnentrucker, P. [Space Telescope Science Institute, Baltimore, MD 21218 (United States); Neufeld, D. A.; Indriolo, N. [Physics and Astronomy Department, Johns Hopkins University, Baltimore, MD 21218 (United States); Gerin, M.; De Luca, M. [LERMA-LRA, UMR 8112 du CNRS, Observatoire de Paris, Ecole Normale Superieure, UPMC and UCP, 24 rue Lhomond, F-75231, Paris Cedex 05 (France); Lis, D. C. [Astronomy Department, California Institute of Technology, Pasadena, CA 91125 (United States); Goicoechea, J. R., E-mail: sonnentr@stsci.edu [Centro de Astrobiologia, CSIC/INTA, E-28850, Madrid (Spain)

2013-01-20

We report the Herschel detections of hydrogen fluoride (HF) and para-water (p-H{sub 2}O) in gas intercepting the sight lines to two well-studied molecular clouds in the vicinity of the Sgr A complex: G-0.02-0.07 (the {sup +}50 km s{sup -1} cloud{sup )} and G-0.13-0.08 (the {sup +}20 km s{sup -1} cloud{sup )}. Toward both sight lines, HF and water absorption components are detected over a wide range of velocities covering {approx}250 km s{sup -1}. For all velocity components with V{sub LSR} > -85 km s{sup -1}, we find that the HF and water abundances are consistent with those measured toward other sight lines probing the Galactic disk gas. The velocity components with V{sub LSR} {<=} -85 km s{sup -1}, which are known to trace gas residing within {approx}200 pc of the Galactic center, however, exhibit water vapor abundances with respect to HF at least a factor three higher than those found in the Galactic disk gas. Comparison with CH data indicates that our observations are consistent with a picture where HF and a fraction of the H{sub 2}O absorption arise in diffuse molecular clouds showing Galactic disk-like abundances while the bulk of the water absorption arises in warmer (T {>=} 400 K) diffuse molecular gas for V{sub LSR} {<=} -85 km s{sup -1}. This diffuse Interstellar Medium (ISM) phase has also been recently revealed through observations of CO, HF, H{sup +}{sub 3}, and H{sub 3}O{sup +} absorption toward other sight lines probing the Galactic center inner region.

The thermodynamics of molecular cloud fragmentation : Star formation under non-Milky Way conditions

NARCIS (Netherlands)

Hocuk, S.; Spaans, M.

Context. Properties of candidate stars, forming out of molecular clouds, depend on the ambient conditions of the parent cloud. We present a series of 2D and 3D simulations of fragmentation of molecular clouds in starburst regions, as well as of clouds under conditions in dwarf galaxies, leading to

Molecular basis of structural make-up of feeds in relation to nutrient absorption in ruminants, revealed with advanced molecular spectroscopy: A review on techniques and models

Energy Technology Data Exchange (ETDEWEB)

Rahman, Md. Mostafizar [Department of Animal and Poultry Science, University of Saskatchewan, Saskatoon, Saskatchewan, Canada; Yu, Peiqiang [Department of Animal and Poultry Science, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

2017-01-31

Progress in ruminant feed research is no more feasible only based on wet chemical analysis, which is merely able to provide information on chemical composition of feeds regardless of their digestive features and nutritive value in ruminants. Studying internal structural make-up of functional groups/feed nutrients is often vital for understanding the digestive behaviors and nutritive values of feeds in ruminant because the intrinsic structure of feed nutrients is more related to its overall absorption. In this article, the detail information on the recent developments in molecular spectroscopic techniques to reveal microstructural information of feed nutrients and the use of nutrition models in regards to ruminant feed research was reviewed. The emphasis of this review was on (1) the technological progress in the use of molecular spectroscopic techniques in ruminant feed research; (2) revealing spectral analysis of functional groups of biomolecules/feed nutrients; (3) the use of advanced nutrition models for better prediction of nutrient availability in ruminant systems; and (4) the application of these molecular techniques and combination of nutrient models in cereals, co-products and pulse crop research. The information described in this article will promote better insight in the progress of research on molecular structural make-up of feed nutrients in ruminants.

RNA-Seq and molecular docking reveal multi-level pesticide resistance in the bed bug

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Mamidala Praveen

2012-01-01

Full Text Available Abstract Background Bed bugs (Cimex lectularius are hematophagous nocturnal parasites of humans that have attained high impact status due to their worldwide resurgence. The sudden and rampant resurgence of C. lectularius has been attributed to numerous factors including frequent international travel, narrower pest management practices, and insecticide resistance. Results We performed a next-generation RNA sequencing (RNA-Seq experiment to find differentially expressed genes between pesticide-resistant (PR and pesticide-susceptible (PS strains of C. lectularius. A reference transcriptome database of 51,492 expressed sequence tags (ESTs was created by combining the databases derived from de novo assembled mRNA-Seq tags (30,404 ESTs and our previous 454 pyrosequenced database (21,088 ESTs. The two-way GLMseq analysis revealed ~15,000 highly significant differentially expressed ESTs between the PR and PS strains. Among the top 5,000 differentially expressed ESTs, 109 putative defense genes (cuticular proteins, cytochrome P450s, antioxidant genes, ABC transporters, glutathione S-transferases, carboxylesterases and acetyl cholinesterase involved in penetration resistance and metabolic resistance were identified. Tissue and development-specific expression of P450 CYP3 clan members showed high mRNA levels in the cuticle, Malpighian tubules, and midgut; and in early instar nymphs, respectively. Lastly, molecular modeling and docking of a candidate cytochrome P450 (CYP397A1V2 revealed the flexibility of the deduced protein to metabolize a broad range of insecticide substrates including DDT, deltamethrin, permethrin, and imidacloprid. Conclusions We developed significant molecular resources for C. lectularius putatively involved in metabolic resistance as well as those participating in other modes of insecticide resistance. RNA-Seq profiles of PR strains combined with tissue-specific profiles and molecular docking revealed multi-level insecticide

Large scale aggregate microarray analysis reveals three distinct molecular subclasses of human preeclampsia.

Science.gov (United States)

Leavey, Katherine; Bainbridge, Shannon A; Cox, Brian J

2015-01-01

Preeclampsia (PE) is a life-threatening hypertensive pathology of pregnancy affecting 3-5% of all pregnancies. To date, PE has no cure, early detection markers, or effective treatments short of the removal of what is thought to be the causative organ, the placenta, which may necessitate a preterm delivery. Additionally, numerous small placental microarray studies attempting to identify "PE-specific" genes have yielded inconsistent results. We therefore hypothesize that preeclampsia is a multifactorial disease encompassing several pathology subclasses, and that large cohort placental gene expression analysis will reveal these groups. To address our hypothesis, we utilized known bioinformatic methods to aggregate 7 microarray data sets across multiple platforms in order to generate a large data set of 173 patient samples, including 77 with preeclampsia. Unsupervised clustering of these patient samples revealed three distinct molecular subclasses of PE. This included a "canonical" PE subclass demonstrating elevated expression of known PE markers and genes associated with poor oxygenation and increased secretion, as well as two other subclasses potentially representing a poor maternal response to pregnancy and an immunological presentation of preeclampsia. Our analysis sheds new light on the heterogeneity of PE patients, and offers up additional avenues for future investigation. Hopefully, our subclassification of preeclampsia based on molecular diversity will finally lead to the development of robust diagnostics and patient-based treatments for this disorder.

Nanomaterials under extreme environments: A study of structural and dynamic properties using reactive molecular dynamics simulations

Science.gov (United States)

Shekhar, Adarsh

Nanotechnology is becoming increasingly important with the continuing advances in experimental techniques. As researchers around the world are trying to expand the current understanding of the behavior of materials at the atomistic scale, the limited resolution of equipment, both in terms of time and space, act as roadblocks to a comprehensive study. Numerical methods, in general and molecular dynamics, in particular act as able compliment to the experiments in our quest for understanding material behavior. In this research work, large scale molecular dynamics simulations to gain insight into the mechano-chemical behavior under extreme conditions of a variety of systems with many real world applications. The body of this work is divided into three parts, each covering a particular system: 1) Aggregates of aluminum nanoparticles are good solid fuel due to high flame propagation rates. Multi-million atom molecular dynamics simulations reveal the mechanism underlying higher reaction rate in a chain of aluminum nanoparticles as compared to an isolated nanoparticle. This is due to the penetration of hot atoms from reacting nanoparticles to an adjacent, unreacted nanoparticle, which brings in external heat and initiates exothermic oxidation reactions. 2) Cavitation bubbles readily occur in fluids subjected to rapid changes in pressure. We use billion-atom reactive molecular dynamics simulations on a 163,840-processor BlueGene/P supercomputer to investigate chemical and mechanical damages caused by shock-induced collapse of nanobubbles in water near amorphous silica. Collapse of an empty nanobubble generates high-speed nanojet, resulting in the formation of a pit on the surface. The pit contains a large number of silanol groups and its volume is found to be directly proportional to the volume of the nanobubble. The gas-filled bubbles undergo partial collapse and consequently the damage on the silica surface is mitigated. 3) The structure and dynamics of water confined in

MMP-13 In-Vivo Molecular Imaging Reveals Early Expression in Lung Adenocarcinoma.

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Mathieu Salaün

Full Text Available Several matrix metalloproteinases (MMPs are overexpressed in lung cancer and may serve as potential targets for the development of bioactivable probes for molecular imaging.To characterize and monitor the activity of MMPs during the progression of lung adenocarcinoma.K-rasLSL-G12D mice were imaged serially during the development of adenocarcinomas using fluorescence molecular tomography (FMT and a probe specific for MMP-2, -3, -9 and -13. Lung tumors were identified using FMT and MRI co-registration, and the probe concentration in each tumor was assessed at each time-point. The expression of Mmp2, -3, -9, -13 was quantified by qRT-PCR using RNA isolated from microdissected tumor cells. Immunohistochemical staining of overexpressed MMPs in animals was assessed on human lung tumors.In mice, 7 adenomas and 5 adenocarcinomas showed an increase in fluorescent signal on successive FMT scans, starting between weeks 4 and 8. qRT-PCR assays revealed significant overexpression of only Mmp-13 in mice lung tumors. In human tumors, a high MMP-13 immunostaining index was found in tumor cells from invasive lesions (24/27, but in none of the non-invasive (0/4 (p=0.001.MMP-13 is detected in early pulmonary invasive adenocarcinomas and may be a potential target for molecular imaging of lung cancer.

MMP-13 In-Vivo Molecular Imaging Reveals Early Expression in Lung Adenocarcinoma

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Salaün, Mathieu; Peng, Jing; Hensley, Harvey H.; Roder, Navid; Flieder, Douglas B.; Houlle-Crépin, Solène; Abramovici-Roels, Olivia; Sabourin, Jean-Christophe; Thiberville, Luc; Clapper, Margie L.

2015-01-01

Introduction Several matrix metalloproteinases (MMPs) are overexpressed in lung cancer and may serve as potential targets for the development of bioactivable probes for molecular imaging. Objective To characterize and monitor the activity of MMPs during the progression of lung adenocarcinoma. Methods K-rasLSL-G12D mice were imaged serially during the development of adenocarcinomas using fluorescence molecular tomography (FMT) and a probe specific for MMP-2, -3, -9 and -13. Lung tumors were identified using FMT and MRI co-registration, and the probe concentration in each tumor was assessed at each time-point. The expression of Mmp2, -3, -9, -13 was quantified by qRT-PCR using RNA isolated from microdissected tumor cells. Immunohistochemical staining of overexpressed MMPs in animals was assessed on human lung tumors. Results In mice, 7 adenomas and 5 adenocarcinomas showed an increase in fluorescent signal on successive FMT scans, starting between weeks 4 and 8. qRT-PCR assays revealed significant overexpression of only Mmp-13 in mice lung tumors. In human tumors, a high MMP-13 immunostaining index was found in tumor cells from invasive lesions (24/27), but in none of the non-invasive (0/4) (p=0.001). Conclusion MMP-13 is detected in early pulmonary invasive adenocarcinomas and may be a potential target for molecular imaging of lung cancer. PMID:26193700

Active mechanics in living oocytes reveal molecular-scale force kinetics

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Ahmed, Wylie; Fodor, Etienne; Almonacid, Maria; Bussonnier, Matthias; Verlhac, Marie-Helene; Gov, Nir; Visco, Paolo; van Wijland, Frederic; Betz, Timo

Unlike traditional materials, living cells actively generate forces at the molecular scale that change their structure and mechanical properties. This nonequilibrium activity is essential for cellular function, and drives processes such as cell division. Single molecule studies have uncovered the detailed force kinetics of isolated motor proteins in-vitro, however their behavior in-vivo has been elusive due to the complex environment inside the cell. Here, we quantify active forces and intracellular mechanics in living oocytes using in-vivo optical trapping and laser interferometry of endogenous vesicles. We integrate an experimental and theoretical framework to connect mesoscopic measurements of nonequilibrium properties to the underlying molecular- scale force kinetics. Our results show that force generation by myosin-V drives the cytoplasmic-skeleton out-of-equilibrium (at frequencies below 300 Hz) and actively softens the environment. In vivo myosin-V activity generates a force of F ~ 0 . 4 pN, with a power-stroke of length Δx ~ 20 nm and duration τ ~ 300 μs, that drives vesicle motion at vv ~ 320 nm/s. This framework is widely applicable to characterize living cells and other soft active materials.

Evolution of molecular phenotypes under stabilizing selection

International Nuclear Information System (INIS)

Nourmohammad, Armita; Schiffels, Stephan; Lässig, Michael

2013-01-01

Molecular phenotypes are important links between genomic information and organismic functions, fitness, and evolution. Complex phenotypes, which are also called quantitative traits, often depend on multiple genomic loci. Their evolution builds on genome evolution in a complicated way, which involves selection, genetic drift, mutations and recombination. Here we develop a coarse-grained evolutionary statistics for phenotypes, which decouples from details of the underlying genotypes. We derive approximate evolution equations for the distribution of phenotype values within and across populations. This dynamics covers evolutionary processes at high and low recombination rates, that is, it applies to sexual and asexual populations. In a fitness landscape with a single optimal phenotype value, the phenotypic diversity within populations and the divergence between populations reach evolutionary equilibria, which describe stabilizing selection. We compute the equilibrium distributions of both quantities analytically and we show that the ratio of mean divergence and diversity depends on the strength of selection in a universal way: it is largely independent of the phenotype’s genomic encoding and of the recombination rate. This establishes a new method for the inference of selection on molecular phenotypes beyond the genome level. We discuss the implications of our findings for the predictability of evolutionary processes. (paper)

Endogenous molecular network reveals two mechanisms of heterogeneity within gastric cancer

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Li, Site; Zhu, Xiaomei; Liu, Bingya; Wang, Gaowei; Ao, Ping

2015-01-01

Intratumor heterogeneity is a common phenomenon and impedes cancer therapy and research. Gastric cancer (GC) cells have generally been classified into two heterogeneous cellular phenotypes, the gastric and intestinal types, yet the mechanisms of maintaining two phenotypes and controlling phenotypic transition are largely unknown. A qualitative systematic framework, the endogenous molecular network hypothesis, has recently been proposed to understand cancer genesis and progression. Here, a minimal network corresponding to such framework was found for GC and was quantified via a stochastic nonlinear dynamical system. We then further extended the framework to address the important question of intratumor heterogeneity quantitatively. The working network characterized main known features of normal gastric epithelial and GC cell phenotypes. Our results demonstrated that four positive feedback loops in the network are critical for GC cell phenotypes. Moreover, two mechanisms that contribute to GC cell heterogeneity were identified: particular positive feedback loops are responsible for the maintenance of intestinal and gastric phenotypes; GC cell progression routes that were revealed by the dynamical behaviors of individual key components are heterogeneous. In this work, we constructed an endogenous molecular network of GC that can be expanded in the future and would broaden the known mechanisms of intratumor heterogeneity. PMID:25962957

Molecular Bases Underlying the Hepatoprotective Effects of Coffee

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Federico Salomone

2017-01-01

Full Text Available Coffee is the most consumed beverage worldwide. Epidemiological studies with prospective cohorts showed that coffee intake is associated with reduced cardiovascular and all-cause mortality independently of caffeine content. Cohort and case-control studies reported an inverse association between coffee consumption and the degree of liver fibrosis as well as the development of liver cancer. Furthermore, the beneficial effects of coffee have been recently confirmed by large meta-analyses. In the last two decades, various in vitro and in vivo studies evaluated the molecular determinants for the hepatoprotective effects of coffee. In the present article, we aimed to critically review experimental evidence regarding the active components and the molecular bases underlying the beneficial role of coffee against chronic liver diseases. Almost all studies highlighted the beneficial effects of this beverage against liver fibrosis with the most solid results indicating a pivot role for both caffeine and chlorogenic acids. In particular, in experimental models of fibrosis, caffeine was shown to inhibit hepatic stellate cell activation by blocking adenosine receptors, and emerging evidence indicated that caffeine may also favorably impact angiogenesis and hepatic hemodynamics. On the other side, chlorogenic acids, potent phenolic antioxidants, suppress liver fibrogenesis and carcinogenesis by reducing oxidative stress and counteract steatogenesis through the modulation of glucose and lipid homeostasis in the liver. Overall, these molecular insights may have translational significance and suggest that coffee components need clinical evaluation.

Placental gene-expression profiles of intrahepatic cholestasis of pregnancy reveal involvement of multiple molecular pathways in blood vessel formation and inflammation.

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Du, QiaoLing; Pan, YouDong; Zhang, YouHua; Zhang, HaiLong; Zheng, YaJuan; Lu, Ling; Wang, JunLei; Duan, Tao; Chen, JianFeng

2014-07-07

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-associated liver disease with potentially deleterious consequences for the fetus, particularly when maternal serum bile-acid concentration >40 μM. However, the etiology and pathogenesis of ICP remain elusive. To reveal the underlying molecular mechanisms for the association of maternal serum bile-acid level and fetal outcome in ICP patients, DNA microarray was applied to characterize the whole-genome expression profiles of placentas from healthy women and women diagnosed with ICP. Thirty pregnant women recruited in this study were categorized evenly into three groups: healthy group; mild ICP, with serum bile-acid concentration ranging from 10-40 μM; and severe ICP, with bile-acid concentration >40 μM. Gene Ontology analysis in combination with construction of gene-interaction and gene co-expression networks were applied to identify the core regulatory genes associated with ICP pathogenesis, which were further validated by quantitative real-time PCR and histological staining. The core regulatory genes were mainly involved in immune response, VEGF signaling pathway and G-protein-coupled receptor signaling, implying essential roles of immune response, vasculogenesis and angiogenesis in ICP pathogenesis. This implication was supported by the observed aggregated immune-cell infiltration and deficient blood vessel formation in ICP placentas. Our study provides a system-level insight into the placental gene-expression profiles of women with mild or severe ICP, and reveals multiple molecular pathways in immune response and blood vessel formation that might contribute to ICP pathogenesis.

Transcriptomic studies reveal a key metabolic pathway contributing to a well-maintained photosynthetic system under drought stress in foxtail millet (Setaria italica L.

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Weiping Shi

2018-05-01

Full Text Available Drought stress is one of the most important abiotic factors limiting crop productivity. A better understanding of the effects of drought on millet (Setaria italica L. production, a model crop for studying drought tolerance, and the underlying molecular mechanisms responsible for drought stress responses is vital to improvement of agricultural production. In this study, we exposed the drought resistant F1 hybrid, M79, and its parental lines E1 and H1 to drought stress. Subsequent physiological analysis demonstrated that M79 showed higher photosynthetic energy conversion efficiency and drought tolerance than its parents. A transcriptomic study using leaves collected six days after drought treatment, when the soil water content was about ∼20%, identified 3066, 1895, and 2148 differentially expressed genes (DEGs in M79, E1 and H1 compared to the respective untreated controls, respectively. Further analysis revealed 17 Gene Ontology (GO enrichments and 14 Kyoto Encyclopedia of Genes and Genomes (KEGG pathways in M79, including photosystem II (PSII oxygen-evolving complex, peroxidase (POD activity, plant hormone signal transduction, and chlorophyll biosynthesis. Co-regulation analysis suggested that these DEGs in M79 contributed to the formation of a regulatory network involving multiple biological processes and pathways including photosynthesis, signal transduction, transcriptional regulation, redox regulation, hormonal signaling, and osmotic regulation. RNA-seq analysis also showed that some photosynthesis-related DEGs were highly expressed in M79 compared to its parental lines under drought stress. These results indicate that various molecular pathways, including photosynthesis, respond to drought stress in M79, and provide abundant molecular information for further analysis of the underlying mechanism responding to this stress.

Transcriptomic studies reveal a key metabolic pathway contributing to a well-maintained photosynthetic system under drought stress in foxtail millet (Setaria italica L.).

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Shi, Weiping; Cheng, Jingye; Wen, Xiaojie; Wang, Jixiang; Shi, Guanyan; Yao, Jiayan; Hou, Liyuan; Sun, Qian; Xiang, Peng; Yuan, Xiangyang; Dong, Shuqi; Guo, Pingyi; Guo, Jie

2018-01-01

Drought stress is one of the most important abiotic factors limiting crop productivity. A better understanding of the effects of drought on millet ( Setaria italica L.) production, a model crop for studying drought tolerance, and the underlying molecular mechanisms responsible for drought stress responses is vital to improvement of agricultural production. In this study, we exposed the drought resistant F 1 hybrid, M79, and its parental lines E1 and H1 to drought stress. Subsequent physiological analysis demonstrated that M79 showed higher photosynthetic energy conversion efficiency and drought tolerance than its parents. A transcriptomic study using leaves collected six days after drought treatment, when the soil water content was about ∼20%, identified 3066, 1895, and 2148 differentially expressed genes (DEGs) in M79, E1 and H1 compared to the respective untreated controls, respectively. Further analysis revealed 17 Gene Ontology (GO) enrichments and 14 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in M79, including photosystem II (PSII) oxygen-evolving complex, peroxidase (POD) activity, plant hormone signal transduction, and chlorophyll biosynthesis. Co-regulation analysis suggested that these DEGs in M79 contributed to the formation of a regulatory network involving multiple biological processes and pathways including photosynthesis, signal transduction, transcriptional regulation, redox regulation, hormonal signaling, and osmotic regulation. RNA-seq analysis also showed that some photosynthesis-related DEGs were highly expressed in M79 compared to its parental lines under drought stress. These results indicate that various molecular pathways, including photosynthesis, respond to drought stress in M79, and provide abundant molecular information for further analysis of the underlying mechanism responding to this stress.

Molecular dynamics modeling on the role of initial void geometry in a thin aluminum film under uniaxial tension

International Nuclear Information System (INIS)

Cui, Yi; Chen, Zengtao

2015-01-01

The effect of initial void geometry on damage progression in a thin aluminum film under uniaxial load is studied via molecular dynamics (MD) method. The embedded voids are with different initial geometries regarding shape, porosity and intervoid ligament distance (ILD). Major simulations are run upon twelve MD geometries with each containing 8–27 million atoms. The corresponding stress–strain relation is monitored during the microstructure evolution of the specimens. The critical stress to trigger the dislocation emission is found in line with the prediction of the Lubarda model. The simulation results reveal that the initial void geometry has substantial impact on the stress–strain relation especially for a specimen with larger initial porosity. (paper)

Unraveling the Root Proteome Changes and Its Relationship to Molecular Mechanism Underlying Salt Stress Response in Radish (Raphanus sativus L.

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Xiaochuan Sun

2017-07-01

Full Text Available To understand the molecular mechanism underlying salt stress response in radish, iTRAQ-based proteomic analysis was conducted to investigate the differences in protein species abundance under different salt treatments. In total, 851, 706, and 685 differential abundance protein species (DAPS were identified between CK vs. Na100, CK vs. Na200, and Na100 vs. Na200, respectively. Functional annotation analysis revealed that salt stress elicited complex proteomic alterations in radish roots involved in carbohydrate and energy metabolism, protein metabolism, signal transduction, transcription regulation, stress and defense and transport. Additionally, the expression levels of nine genes encoding DAPS were further verified using RT-qPCR. The integrative analysis of transcriptomic and proteomic data in conjunction with miRNAs was further performed to strengthen the understanding of radish response to salinity. The genes responsible for signal transduction, ROS scavenging and transport activities as well as several key miRNAs including miR171, miR395, and miR398 played crucial roles in salt stress response in radish. Based on these findings, a schematic genetic regulatory network of salt stress response was proposed. This study provided valuable insights into the molecular mechanism underlying salt stress response in radish roots and would facilitate developing effective strategies toward genetically engineered salt-tolerant radish and other root vegetable crops.

Shapiro like steps reveals molecular nanomagnets’ spin dynamics

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Abdollahipour, Babak; Abouie, Jahanfar; Ebrahimi, Navid

2015-01-01

We present an accurate way to detect spin dynamics of a nutating molecular nanomagnet by inserting it in a tunnel Josephson junction and studying the current voltage (I-V) characteristic. The spin nutation of the molecular nanomagnet is generated by applying two circularly polarized magnetic fields. We demonstrate that modulation of the Josephson current by the nutation of the molecular nanomagnet’s spin appears as a stepwise structure like Shapiro steps in the I-V characteristic of the junction. Width and heights of these Shapiro-like steps are determined by two parameters of the spin nutation, frequency and amplitude of the nutation, which are simply tuned by the applied magnetic fields

Physiological and molecular alterations in plants exposed to high [CO2] under phosphorus stress.

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Pandey, Renu; Zinta, Gaurav; AbdElgawad, Hamada; Ahmad, Altaf; Jain, Vanita; Janssens, Ivan A

2015-01-01

Atmospheric [CO2] has increased substantially in recent decades and will continue to do so, whereas the availability of phosphorus (P) is limited and unlikely to increase in the future. P is a non-renewable resource, and it is essential to every form of life. P is a key plant nutrient controlling the responsiveness of photosynthesis to [CO2]. Increases in [CO2] typically results in increased biomass through stimulation of net photosynthesis, and hence enhance the demand for P uptake. However, most soils contain low concentrations of available P. Therefore, low P is one of the major growth-limiting factors for plants in many agricultural and natural ecosystems. The adaptive responses of plants to [CO2] and P availability encompass alterations at morphological, physiological, biochemical and molecular levels. In general low P reduces growth, whereas high [CO2] enhances it particularly in C3 plants. Photosynthetic capacity is often enhanced under high [CO2] with sufficient P supply through modulation of enzyme activities involved in carbon fixation such as ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco). However, high [CO2] with low P availability results in enhanced dry matter partitioning towards roots. Alterations in below-ground processes including root morphology, exudation and mycorrhizal association are influenced by [CO2] and P availability. Under high P availability, elevated [CO2] improves the uptake of P from soil. In contrast, under low P availability, high [CO2] mainly improves the efficiency with which plants produce biomass per unit P. At molecular level, the spatio-temporal regulation of genes involved in plant adaptation to low P and high [CO2] has been studied individually in various plant species. Genome-wide expression profiling of high [CO2] grown plants revealed hormonal regulation of biomass accumulation through complex transcriptional networks. Similarly, differential transcriptional regulatory networks are involved in P

Non-Newtonian behavior and molecular structure of Cooee bitumen under shear flow

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Lemarchand, Claire; Bailey, Nicholas; Daivis, Peter

2015-01-01

The rheology and molecular structure of a model bitumen (Cooee bitumen) under shear are investigated in the non-Newtonian regime using non-equilibrium molecular dynamics simulations. The shear viscosity, normal stress differences, and pressure of the bitumen mixture are computed at different shear...... rates and different temperatures. The model bitumen is shown to be a shear-thinning fluid at all temperatures. In addition, the Cooee model is able to reproduce experimental results showing the formation of nanoaggregates composed of stacks of flat aromatic molecules in bitumen. These nanoaggregates...

Determination of molecular markers associated with anthesis-silking interval in maize

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Simpson, J.

1998-01-01

Maize lines contrasting in anthesis-silking, interval (ASI), a trait strongly linked to drought tolerance, have been analyzed under different water stress conditions in the field and with molecular markers. Correlation of marker and field data has revealed molecular markers strongly associated with flowering and yield traits. (author)

Photon Upconversion and Molecular Solar Energy Storage by Maximizing the Potential of Molecular Self-Assembly.

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Kimizuka, Nobuo; Yanai, Nobuhiro; Morikawa, Masa-Aki

2016-11-29

The self-assembly of functional molecules into ordered molecular assemblies and the fulfillment of potentials unique to their nanotomesoscopic structures have been one of the central challenges in chemistry. This Feature Article provides an overview of recent progress in the field of molecular self-assembly with the focus on the triplet-triplet annihilation-based photon upconversion (TTA-UC) and supramolecular storage of photon energy. On the basis of the integration of molecular self-assembly and photon energy harvesting, triplet energy migration-based TTA-UC has been achieved in varied molecular systems. Interestingly, some molecular self-assemblies dispersed in solution or organogels revealed oxygen barrier properties, which allowed TTA-UC even under aerated conditions. The elements of molecular self-assembly were also introduced to the field of molecular solar thermal fuel, where reversible photoliquefaction of ionic crystals to ionic liquids was found to double the molecular storage capacity with the simultaneous pursuit of switching ionic conductivity. A future prospect in terms of innovating molecular self-assembly toward molecular systems chemistry is also discussed.

Morphological and molecular features of some freshwater prawn species under genus Macrobrachium Spence Bate, 1868 (Crustacea: Decapoda: Palaemonidae) from Myanmar.

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Mar, Win; Kang, Peng-Fei; Mao, Bin; Wang, Yu-Feng

2018-02-28

Myanmar is abundant in lakes and rivers, yet only a few investigations on the fauna of shrimps and prawns have been conducted and no molecular characteristics of prawn species have been described. This study reveals the morphologically identification of five freshwater prawn species under the genus Macrobrachium, including M. cavernicola, M. australiense, M. johnsoni, M. josephi and Macrobrachium sp.WMY-2017. As there was no previous record and information concerning with M. australiense, M. johnsoni, M. josephi and Macrobrachium sp. WMY-2017, they were regarded as the first record from Myanmar. A fragment of Mitochondrial Cytochrome Oxidase I Gene (COI) was amplified successfully from three studied species: M. australiense, M. josephi, and Macrobrachium sp.WMY-2017. The interspecific divergences of studied species varied from 0.01 to 0.15. The phylogenetic tree based on COI fragment sequences showed that M. australiense was closely related to M. rosenbergii, while Macrobrachium sp. WMY-2017 was closest to M. josephi. The results of molecular phylogeny has clarified the relationship within the genus Macrobrachium and represents the first step toward understanding the pattern of speciation base on molecular approach in Myanmar.

Molecular characteristics of stress overshoot for polymer melts under start-up shear flow.

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Jeong, Sohdam; Kim, Jun Mo; Baig, Chunggi

2017-12-21

Stress overshoot is one of the most important nonlinear rheological phenomena exhibited by polymeric liquids undergoing start-up shear at sufficient flow strengths. Despite considerable previous research, the fundamental molecular characteristics underlying stress overshoot remain unknown. Here, we analyze the intrinsic molecular mechanisms behind the overshoot phenomenon using atomistic nonequilibrium molecular dynamics simulations of entangled linear polyethylene melts under shear flow. Through a detailed analysis of the transient rotational chain dynamics, we identify an intermolecular collision angular regime in the vicinity of the chain orientation angle θ ≈ 20° with respect to the flow direction. The shear stress overshoot occurs via strong intermolecular collisions between chains in the collision regime at θ = 15°-25°, corresponding to a peak strain of 2-4, which is an experimentally well-known value. The normal stress overshoot appears at approximately θ = 10°, at a corresponding peak strain roughly equivalent to twice that for the shear stress. We provide plausible answers to several basic questions regarding the stress overshoot, which may further help understand other nonlinear phenomena of polymeric systems.

The extent of the glass transition from molecular simulation revealing an overcrank effect.

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Godey, François; Fleury, Alexandre; Ghoufi, Aziz; Soldera, Armand

2018-02-15

A deep understanding of the transition between rubber and amorphous state characterized by a glass transition temperature, T g , is still a source of discussions. In this work, we highlight the role of molecular simulation in revealing explicitly this temperature dependent behavior. By reporting the specific volume, the thermal expansion coefficient and the heat capacity versus the temperature, we actually show that the glass transition domain extends to a greater range of temperature, compared with experiments. This significant enlargement width is due to the fast cooling rate, and actually explains the difficulty to locate T g . This result is the manifestation of an overcranking effect used by high-speed cameras to reveal slow-motion. Accordingly, atomistic simulation offers the significant opportunity to show that the transition from the rubber state to the glass phase should be detailed in terms of the degrees of freedom freeze. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Molecular analyses reveal high species diversity of trematodes in a sub-Arctic lake

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Soldánová, Miroslava; Georgieva, Simona; Roháčováa, Jana; Knudsen, Rune; Kuhn, Jesper A.; Henriksen, Eirik H.; Siwertsson, Anna; Shaw, Jenny C.; Kuris, Armand M.; Amundsen, Per-Arne; Scholz, Tomáš; Lafferty, Kevin D.; Kostadinova, Aneta

2017-01-01

To identify trematode diversity and life-cycles in the sub-Arctic Lake Takvatn, Norway, we characterised 120 trematode isolates from mollusc first intermediate hosts, metacercariae from second intermediate host fishes and invertebrates, and adults from fish and invertebrate definitive hosts, using molecular techniques. Phylogenies based on nuclear and/or mtDNA revealed high species richness (24 species or species-level genetic lineages), and uncovered trematode diversity (16 putative new species) from five families typical in lake ecosystems (Allocreadiidae, Diplostomidae, Plagiorchiidae, Schistosomatidae and Strigeidae). Sampling potential invertebrate hosts allowed matching of sequence data for different stages, thus achieving molecular elucidation of trematode life-cycles and exploration of host-parasite interactions. Phylogenetic analyses also helped identify three major mollusc intermediate hosts (Radix balthica, Pisidium casertanum and Sphaerium sp.) in the lake. Our findings increase the known trematode diversity at the sub-Arctic Lake Takvatn, showing that digenean diversity is high in this otherwise depauperate sub-Arctic freshwater ecosystem, and indicating that sub-Arctic and Arctic ecosystems may be characterised by unique trematode assemblages.

Molecular mechanics of silk nanostructures under varied mechanical loading.

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Bratzel, Graham; Buehler, Markus J

2012-06-01

Spider dragline silk is a self-assembling tunable protein composite fiber that rivals many engineering fibers in tensile strength, extensibility, and toughness, making it one of the most versatile biocompatible materials and most inviting for synthetic mimicry. While experimental studies have shown that the peptide sequence and molecular structure of silk have a direct influence on the stiffness, toughness, and failure strength of silk, few molecular-level analyses of the nanostructure of silk assemblies, in particular, under variations of genetic sequences have been reported. In this study, atomistic-level structures of wildtype as well as modified MaSp1 protein from the Nephila clavipes spider dragline silk sequences, obtained using an in silico approach based on replica exchange molecular dynamics and explicit water molecular dynamics, are subjected to simulated nanomechanical testing using different force-control loading conditions including stretch, pull-out, and peel. The authors have explored the effects of the poly-alanine length of the N. clavipes MaSp1 peptide sequence and identify differences in nanomechanical loading conditions on the behavior of a unit cell of 15 strands with 840-990 total residues used to represent a cross-linking β-sheet crystal node in the network within a fibril of the dragline silk thread. The specific loading condition used, representing concepts derived from the protein network connectivity at larger scales, have a significant effect on the mechanical behavior. Our analysis incorporates stretching, pull-out, and peel testing to connect biochemical features to mechanical behavior. The method used in this study could find broad applications in de novo design of silk-like tunable materials for an array of applications. Copyright © 2011 Wiley Periodicals, Inc.

Proteomic-Biostatistic Integrated Approach for Finding the Underlying Molecular Determinants of Hypertension in Human Plasma.

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Gajjala, Prathibha R; Jankowski, Vera; Heinze, Georg; Bilo, Grzegorz; Zanchetti, Alberto; Noels, Heidi; Liehn, Elisa; Perco, Paul; Schulz, Anna; Delles, Christian; Kork, Felix; Biessen, Erik; Narkiewicz, Krzysztof; Kawecka-Jaszcz, Kalina; Floege, Juergen; Soranna, Davide; Zidek, Walter; Jankowski, Joachim

2017-08-01

Despite advancements in lowering blood pressure, the best approach to lower it remains controversial because of the lack of information on the molecular basis of hypertension. We, therefore, performed plasma proteomics of plasma from patients with hypertension to identify molecular determinants detectable in these subjects but not in controls and vice versa. Plasma samples from hypertensive subjects (cases; n=118) and controls (n=85) from the InGenious HyperCare cohort were used for this study and performed mass spectrometric analysis. Using biostatistical methods, plasma peptides specific for hypertension were identified, and a model was developed using least absolute shrinkage and selection operator logistic regression. The underlying peptides were identified and sequenced off-line using matrix-assisted laser desorption ionization orbitrap mass spectrometry. By comparison of the molecular composition of the plasma samples, 27 molecular determinants were identified differently expressed in cases from controls. Seventy percent of the molecular determinants selected were found to occur less likely in hypertensive patients. In cross-validation, the overall R 2 was 0.434, and the area under the curve was 0.891 with 95% confidence interval 0.8482 to 0.9349, P hypertensive patients were found to be -2.007±0.3568 and 3.383±0.2643, respectively, P hypertensives and normotensives. The identified molecular determinants may be the starting point for further studies to clarify the molecular causes of hypertension. © 2017 American Heart Association, Inc.

Molecular Dynamic Simulation of Space and Earth-Grown Crystal Structures of Thermostable T1 Lipase Geobacillus zalihae Revealed a Better Structure.

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Ishak, Siti Nor Hasmah; Aris, Sayangku Nor Ariati Mohamad; Halim, Khairul Bariyyah Abd; Ali, Mohd Shukuri Mohamad; Leow, Thean Chor; Kamarudin, Nor Hafizah Ahmad; Masomian, Malihe; Rahman, Raja Noor Zaliha Raja Abd

2017-09-25

Less sedimentation and convection in a microgravity environment has become a well-suited condition for growing high quality protein crystals. Thermostable T1 lipase derived from bacterium Geobacillus zalihae has been crystallized using the counter diffusion method under space and earth conditions. Preliminary study using YASARA molecular modeling structure program for both structures showed differences in number of hydrogen bond, ionic interaction, and conformation. The space-grown crystal structure contains more hydrogen bonds as compared with the earth-grown crystal structure. A molecular dynamics simulation study was used to provide insight on the fluctuations and conformational changes of both T1 lipase structures. The analysis of root mean square deviation (RMSD), radius of gyration, and root mean square fluctuation (RMSF) showed that space-grown structure is more stable than the earth-grown structure. Space-structure also showed more hydrogen bonds and ion interactions compared to the earth-grown structure. Further analysis also revealed that the space-grown structure has long-lived interactions, hence it is considered as the more stable structure. This study provides the conformational dynamics of T1 lipase crystal structure grown in space and earth condition.

Molecular Chemical Structure of Barley Proteins Revealed by Ultra-Spatially Resolved Synchrotron Light Sourced FTIR Microspectroscopy: Comparison of Barley Varieties

International Nuclear Information System (INIS)

Yu, P.

2007-01-01

Barley protein structure affects the barley quality, fermentation, and degradation behavior in both humans and animals among other factors such as protein matrix. Publications show various biological differences among barley varieties such as Valier and Harrington, which have significantly different degradation behaviors. The objectives of this study were to reveal the molecular structure of barley protein, comparing various varieties (Dolly, Valier, Harrington, LP955, AC Metcalfe, and Sisler), and quantify protein structure profiles using Gaussian and Lorentzian methods of multi-component peak modeling by using the ultra-spatially resolved synchrotron light sourced Fourier transform infrared microspectroscopy (SFTIRM). The items of the protein molecular structure revealed included protein structure α-helices, β-sheets, and others such as β-turns and random coils. The experiment was performed at the National Synchrotron Light Source in Brookhaven National Laboratory (BNL, US Department of Energy, NY). The results showed that with the SFTIRM, the molecular structure of barley protein could be revealed. Barley protein structures exhibited significant differences among the varieties in terms of proportion and ratio of model-fitted α-helices, β-sheets, and others. By using multi-component peaks modeling at protein amide I region of 1710-1576 cm -1 , the results show that barley protein consisted of approximately 18-34% of α-helices, 14-25% of β-sheets, and 44-69% others. AC Metcalfe, Sisler, and LP955 consisted of higher (P 0.05). The ratio of α-helices to others (0.3 to 1.0, P < 0.05) and that of β-sheets to others (0.2 to 0.8, P < 0.05) were different among the barley varieties. It needs to be pointed out that using a multi-peak modeling for protein structure analysis is only for making relative estimates and not exact determinations and only for the comparison purpose between varieties. The principal component analysis showed that protein amide I Fourier

Laminar and dorsoventral molecular organization of the medial entorhinal cortex revealed by large-scale anatomical analysis of gene expression.

Directory of Open Access Journals (Sweden)

Helen L Ramsden

2015-01-01

Full Text Available Neural circuits in the medial entorhinal cortex (MEC encode an animal's position and orientation in space. Within the MEC spatial representations, including grid and directional firing fields, have a laminar and dorsoventral organization that corresponds to a similar topography of neuronal connectivity and cellular properties. Yet, in part due to the challenges of integrating anatomical data at the resolution of cortical layers and borders, we know little about the molecular components underlying this organization. To address this we develop a new computational pipeline for high-throughput analysis and comparison of in situ hybridization (ISH images at laminar resolution. We apply this pipeline to ISH data for over 16,000 genes in the Allen Brain Atlas and validate our analysis with RNA sequencing of MEC tissue from adult mice. We find that differential gene expression delineates the borders of the MEC with neighboring brain structures and reveals its laminar and dorsoventral organization. We propose a new molecular basis for distinguishing the deep layers of the MEC and show that their similarity to corresponding layers of neocortex is greater than that of superficial layers. Our analysis identifies ion channel-, cell adhesion- and synapse-related genes as candidates for functional differentiation of MEC layers and for encoding of spatial information at different scales along the dorsoventral axis of the MEC. We also reveal laminar organization of genes related to disease pathology and suggest that a high metabolic demand predisposes layer II to neurodegenerative pathology. In principle, our computational pipeline can be applied to high-throughput analysis of many forms of neuroanatomical data. Our results support the hypothesis that differences in gene expression contribute to functional specialization of superficial layers of the MEC and dorsoventral organization of the scale of spatial representations.

PREFACE: International Symposium on Molecular Conductors: Novel Functions of Molecular Conductors under Extreme Conditions (ISMC 2008)

Science.gov (United States)

Takahashi, Toshihiro; Suzumura, Yoshikazu

2008-02-01

The International Symposium on Molecular Conductors 2008 (ISMC2008) was held as the second international symposium of the project entitled `Novel Functions of Molecular Conductors under Extreme Conditions', which was supported by the Grant-in-aid for Scientific Research on Priority Areas from the Ministry of Education, Culture, Sports, Science and Technology in Japan. The project lasted from September 2003 to March 2008, and was completed by this symposium held at Okazaki Conference Center, Institute for Molecular Science, Okazaki, Japan (23-25 July 2008), which about 100 scientists attended. During the symposium, five project teams gave summary talks and exciting talks were given on the topics developed recently not only by the members of the project but also by other scientists including invited speakers from abroad, who are doing active research on molecular conductors. It is expected that papers presented in the symposium will give valuable hints for the next step in the research of this field. Therefore the organizers of this symposium decided to publish this proceedings in order to demonstrate these activities, not only for the local community of the project, but also for the broad society of international scientists who are interested in molecular conductors. The editors, who are also the organizers of this symposium, believe that this proceedings provides a significant and relevant contribution to the field of molecular conductors since it is the first time we have published such a proceedings as an electronic journal. We note that all papers published in this volume of Journal of Physics: Conference Series have been peer reviewed by expert referees. Editors made every effort to satisfy the criterion of a proceedings journal published by IOP Publishing. Toshihiro Takahashi and Yoshikazu Suzumura Editors: Toshihiro Takahashi (Gakushuin University) (Chairman) Kazushi Kanoda (University of Tokyo) Seiichi Kagoshima (University of Tokyo) Takehiko Mori (Tokyo

Molecular dynamics simulation of the local concentration and structure in multicomponent aerosol nanoparticles under atmospheric conditions.

Science.gov (United States)

Karadima, Katerina S; Mavrantzas, Vlasis G; Pandis, Spyros N

2017-06-28

Molecular dynamics (MD) simulations were employed to investigate the local structure and local concentration in atmospheric nanoparticles consisting of an organic compound (cis-pinonic acid or n-C 30 H 62 ), sulfate and ammonium ions, and water. Simulations in the isothermal-isobaric (NPT) statistical ensemble under atmospheric conditions with a prespecified number of molecules of the abovementioned compounds led to the formation of a nanoparticle. Calculations of the density profiles of all the chemical species in the nanoparticle, the corresponding radial pair distribution functions, and their mobility inside the nanoparticle revealed strong interactions developing between sulfate and ammonium ions. However, sulfate and ammonium ions prefer to populate the central part of the nanoparticle under the simulated conditions, whereas organic molecules like to reside at its outer surface. Sulfate and ammonium ions were practically immobile; in contrast, the organic molecules exhibited appreciable mobility at the outer surface of the nanoparticle. When the organic compound was a normal alkane (e.g. n-C 30 H 62 ), a well-organized (crystalline-like) phase was rapidly formed at the free surface of the nanoparticle and remained separate from the rest of the species.

Changes in permittivity and density of molecular liquids under high pressure.

Science.gov (United States)

Kiselev, Vladimir D; Kornilov, Dmitry A; Konovalov, Alexander I

2014-04-03

We collected and analyzed the density and permittivity of 57 nonpolar and dipolar molecular liquids at different temperatures (143 sets) and pressures (555 sets). No equation was found that could accurately predict the change to polar liquid permittivity by the change of its density in the range of the pressures and temperatures tested. Consequently, the influence of high hydrostatic pressure and temperature on liquid permittivity may be a more complicated process compared to density changes. The pressure and temperature coefficients of permittivity can be drastically larger than the pressure and temperature coefficients of density, indicating that pressure and particularly temperature significantly affect the structure of molecular liquids. These changes have less influence on the density change but can strongly affect the permittivity change. The clear relationship between the tangent and secant moduli of the permittivity curvatures under pressure for various molecular liquids at different temperatures was obtained, from which one can calculate the Tait equation coefficients from the experimental values of the pressure influence on the permittivity at ambient pressure.

Substrate channel in nitrogenase revealed by a molecular dynamics approach.

Science.gov (United States)

Smith, Dayle; Danyal, Karamatullah; Raugei, Simone; Seefeldt, Lance C

2014-04-15

Mo-dependent nitrogenase catalyzes the biological reduction of N2 to two NH3 molecules at FeMo-cofactor buried deep inside the MoFe protein. Access of substrates, such as N2, to the active site is likely restricted by the surrounding protein, requiring substrate channels that lead from the surface to the active site. Earlier studies on crystallographic structures of the MoFe protein have suggested three putative substrate channels. Here, we have utilized submicrosecond atomistic molecular dynamics simulations to allow the nitrogenase MoFe protein to explore its conformational space in an aqueous solution at physiological ionic strength, revealing a putative substrate channel. The viability of this observed channel was tested by examining the free energy of passage of N2 from the surface through the channel to FeMo-cofactor, resulting in the discovery of a very low energy barrier. These studies point to a viable substrate channel in nitrogenase that appears during thermal motions of the protein in an aqueous environment and that approaches a face of FeMo-cofactor earlier implicated in substrate binding.

Molecular imaging reveals elevated VEGFR-2 expression in retinal capillaries in diabetes: a novel biomarker for early diagnosis

Science.gov (United States)

Sun, Dawei; Nakao, Shintaro; Xie, Fang; Zandi, Souska; Bagheri, Abouzar; Kanavi, Mozhgan Rezaei; Samiei, Shahram; Soheili, Zahra-Soheila; Frimmel, Sonja; Zhang, Zhongyu; Ablonczy, Zsolt; Ahmadieh, Hamid; Hafezi-Moghadam, Ali

2014-01-01

Diabetic retinopathy (DR) is a microvascular complication of diabetes and a leading cause of vision loss. Biomarkers and methods for early diagnosis of DR are urgently needed. Using a new molecular imaging approach, we show up to 94% higher accumulation of custom designed imaging probes against vascular endothelial growth factor receptor 2 (VEGFR-2) in retinal and choroidal vessels of diabetic animals (PM. R., Samiei, S., Soheili, Z.-S., Frimmel, S., Zhang, Z., Ablonczy, Z., Ahmadieh, H., Hafezi-Moghadam, A. Molecular imaging reveals elevated VEGFR-2 expression in retinal capillaries in diabetes: a novel biomarker for early diagnosis. PMID:24903276

Foundational Concepts and Underlying Theories for Majors in "Biochemistry and Molecular Biology"

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Tansey, John T.; Baird, Teaster, Jr.; Cox, Michael M.; Fox, Kristin M.; Knight, Jennifer; Sears, Duane; Bell, Ellis

2013-01-01

Over the past two years, through an NSF RCN UBE grant, the ASBMB has held regional workshops for faculty members and science educators from around the country that focused on identifying: 1) core principles of biochemistry and molecular biology, 2) essential concepts and underlying theories from physics, chemistry, and mathematics, and 3)…

Nullspace Sampling with Holonomic Constraints Reveals Molecular Mechanisms of Protein Gαs.

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Dimitar V Pachov

2015-07-01

Full Text Available Proteins perform their function or interact with partners by exchanging between conformational substates on a wide range of spatiotemporal scales. Structurally characterizing these exchanges is challenging, both experimentally and computationally. Large, diffusional motions are often on timescales that are difficult to access with molecular dynamics simulations, especially for large proteins and their complexes. The low frequency modes of normal mode analysis (NMA report on molecular fluctuations associated with biological activity. However, NMA is limited to a second order expansion about a minimum of the potential energy function, which limits opportunities to observe diffusional motions. By contrast, kino-geometric conformational sampling (KGS permits large perturbations while maintaining the exact geometry of explicit conformational constraints, such as hydrogen bonds. Here, we extend KGS and show that a conformational ensemble of the α subunit Gαs of heterotrimeric stimulatory protein Gs exhibits structural features implicated in its activation pathway. Activation of protein Gs by G protein-coupled receptors (GPCRs is associated with GDP release and large conformational changes of its α-helical domain. Our method reveals a coupled α-helical domain opening motion while, simultaneously, Gαs helix α5 samples an activated conformation. These motions are moderated in the activated state. The motion centers on a dynamic hub near the nucleotide-binding site of Gαs, and radiates to helix α4. We find that comparative NMA-based ensembles underestimate the amplitudes of the motion. Additionally, the ensembles fall short in predicting the accepted direction of the full activation pathway. Taken together, our findings suggest that nullspace sampling with explicit, holonomic constraints yields ensembles that illuminate molecular mechanisms involved in GDP release and protein Gs activation, and further establish conformational coupling between key

Highly distinct chromosomal structures in cowpea (Vigna unguiculata), as revealed by molecular cytogenetic analysis.

Science.gov (United States)

Iwata-Otsubo, Aiko; Lin, Jer-Young; Gill, Navdeep; Jackson, Scott A

2016-05-01

Cowpea (Vigna unguiculata (L.) Walp) is an important legume, particularly in developing countries. However, little is known about its genome or chromosome structure. We used molecular cytogenetics to characterize the structure of pachytene chromosomes to advance our knowledge of chromosome and genome organization of cowpea. Our data showed that cowpea has highly distinct chromosomal structures that are cytologically visible as brightly DAPI-stained heterochromatic regions. Analysis of the repetitive fraction of the cowpea genome present at centromeric and pericentromeric regions confirmed that two retrotransposons are major components of pericentromeric regions and that a 455-bp tandem repeat is found at seven out of 11 centromere pairs in cowpea. These repeats likely evolved after the divergence of cowpea from common bean and form chromosomal structure unique to cowpea. The integration of cowpea genetic and physical chromosome maps reveals potential regions of suppressed recombination due to condensed heterochromatin and a lack of pairing in a few chromosomal termini. This study provides fundamental knowledge on cowpea chromosome structure and molecular cytogenetics tools for further chromosome studies.

Molecular Structural Transformation of 2:1 Clay Minerals by a Constant-Pressure Molecular Dynamics Simulation Method

International Nuclear Information System (INIS)

Wang, J.; Gutierre, M.S.

2010-01-01

This paper presents results of a molecular dynamics simulation study of dehydrated 2:1 clay minerals using the Parrinello-Rahman constant-pressure molecular dynamics method. The method is capable of simulating a system under the most general applied stress conditions by considering the changes of MD cell size and shape. Given the advantage of the method, it is the major goal of the paper to investigate the influence of imposed cell boundary conditions on the molecular structural transformation of 2:1 clay minerals under different normal pressures. Simulation results show that the degrees of freedom of the simulation cell (i.e., whether the cell size or shape change is allowed) determines the final equilibrated crystal structure of clay minerals. Both the MD method and the static method have successfully revealed unforeseen structural transformations of clay minerals upon relaxation under different normal pressures. It is found that large shear distortions of clay minerals occur when full allowance is given to the cell size and shape change. A complete elimination of the interlayer spacing is observed in a static simulation. However, when only the cell size change is allowed, interlayer spacing is retained, but large internal shear stresses also exist.

A molecular perspective on the limits of life: Enzymes under pressure

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Q. Huang

2016-03-01

Full Text Available From a purely operational standpoint, the existence of microbes that can grow under extreme conditions, or "extremophiles", leads to the question of how the molecules making up these microbes can maintain both their structure and function. While microbes that live under extremes of temperature have been heavily studied, those that live under extremes of pressure have been neglected, in part due to the difficulty of collecting samples and performing experiments under the ambient conditions of the microbe. However, thermodynamic arguments imply that the effects of pressure might lead to different organismal solutions than from the effects of temperature. Observationally, some of these solutions might be in the condensed matter properties of the intracellular milieu in addition to genetic modifications of the macromolecules or repair mechanisms for the macromolecules. Here, the effects of pressure on enzymes, which are proteins essential for the growth and reproduction of an organism, and some adaptations against these effects are reviewed and amplified by the results from molecular dynamics simulations. The aim is to provide biological background for soft matter studies of these systems under pressure.

The structure of Lactococcus lactis thioredoxin reductase reveals molecular features of photo-oxidative damage

DEFF Research Database (Denmark)

Skjoldager, Nicklas; Bang, Maria Blanner; Rykær, Martin

2017-01-01

The NADPH-dependent homodimeric flavoenzyme thioredoxin reductase (TrxR) provides reducing equivalents to thioredoxin, a key regulator of various cellular redox processes. Crystal structures of photo-inactivated thioredoxin reductase (TrxR) from the Gram-positive bacterium Lactococcus lactis have...... been determined. These structures reveal novel molecular features that provide further insight into the mechanisms behind the sensitivity of this enzyme toward visible light. We propose that a pocket on the si-face of the isoalloxazine ring accommodates oxygen that reacts with photo-excited FAD...... thus be a widespread feature among bacterial TrxR with the described characteristics, which affords applications in clinical photo-therapy of drug-resistant bacteria....

Synthesis of molecularly imprinted polypyrrole/titanium dioxide nanocomposites and its selective photocatalytic degradation of rhodamine B under visible light irradiation

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M. Q. He

2014-11-01

Full Text Available Highly selective molecularly imprinted nanocomposites MIPRhB-PPy/TiO2 were successfully prepared by surface molecular imprinting technique with rhodamine B (RhB as template molecule. The prepared MIPRhB-PPy/TiO2 coated with a thin imprinted layer could respond to visible light. The static and dynamic binding experiments revealed that MIPRhB-PPy/TiO2 possessed strong affinity, high adsorption capacity and fast adsorption rate for RhB. The selectivity experiments indicated that MIPRhB-PPy/TiO2 had excellent recognition selectivity for RhB. Selective photocatalytic degradation experiments indicated that the apparent rate constant (k for the photodegradation of RhB over MIPRhB-PPy/TiO2 is 0.0158 min–1, being 3.6 times of that over non-imprinted nanocomposites NIPRhB-PPy/TiO2 (0.0044 min–1. Compared with the NIPRhB-PPy/TiO2, MIPRhB-PPy/TiO2 showed higher photocatalytic selectivity toward RhB under visible light, which was attributed the introduction of the imprinted cavities on the surface of MIPRhB-PPy/TiO2. Moreover, MIPRhB-PPy/TiO2 exhibited high reusability and stability. The results indicate that molecularly imprinted nanocomposites MIPRhB-PPy/TiO2 have a promising perspective in industrial wastewater treatment.

Noise-Immune Cavity-Enhanced Optical Heterodyne Molecular Spectrometry Modelling Under Saturated Absorption

Science.gov (United States)

Dupré, Patrick

2015-06-01

The Noise-Immune Cavity-Enhanced Optical Heterodyne Molecular Spectrometry (NICE-OHMS) is a modern technique renowned for its ultimate sensitivity, because it combines long equivalent absorption length provided by a high finesse cavity, and a detection theoretically limited by the sole photon-shot-noise. One fallout of the high finesse is the possibility to accumulating strong intracavity electromagnetic fields (EMF). Under this condition, molecular transitions can be easy saturated giving rise to the usual Lamb dips (or hole burning). However, the unusual shape of the basically trichromatic EMF (due to the RF lateral sidebands) induces nonlinear couplings, i.e., new crossover transitions. An analytical methodology will be presented to calculate spectra provided by NICE-OHMS experiments. It is based on the solutions of the equations of motion of an open two-blocked-level system performed in the frequency-domain (optically thin medium). Knowing the transition dipole moment, the NICE-OHMS signals (``absorption-like'' and ``dispersion-like'') can be simulated by integration over the Doppler shifts and by paying attention to the molecular Zeeman sublevels and to the EMF polarization The approach has been validated by discussion experimental data obtained on two transitions of {C2H2} in the near-infrared under moderated saturation. One of the applications of the saturated absorption is to be able to simultaneously determine the transition intensity and the density number while only one these 2 quantities can only be assessed in nonlinear absorption. J. Opt. Soc. Am. B 32, 838 (2015) Optics Express 16, 14689 (2008)

Biosystems Study of the Molecular Networks Underlying Hippocampal Aging Progression and Anti-aging Treatment in Mice

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Jiao Wang

2017-12-01

Full Text Available Aging progression is a process that an individual encounters as they become older, and usually results from a series of normal physiological changes over time. The hippocampus, which contributes to the loss of spatial and episodic memory and learning in older people, is closely related to the detrimental effects of aging at the morphological and molecular levels. However, age-related genetic changes in hippocampal molecular mechanisms are not yet well-established. To provide additional insight into the aging process, differentially-expressed genes of 3- versus 24- and 29-month old mice were re-analyzed. The results revealed that a large number of immune and inflammatory response-related genes were up-regulated in the aged hippocampus, and membrane receptor-associated genes were down-regulated. The down-regulation of transmembrane receptors may indicate the weaker perception of environmental exposure in older people, since many transmembrane proteins participate in signal transduction. In addition, molecular interaction analysis of the up-regulated immune genes indicated that the hub gene, Ywhae, may play essential roles in immune and inflammatory responses during aging progression, as well as during hippocampal development. Our biological experiments confirmed the conserved roles of Ywhae and its partners between human and mouse. Furthermore, comparison of microarray data between advanced-age mice treated with human umbilical cord blood plasma protein and the phosphate-buffered saline control showed that the genes that contribute to the revitalization of advanced-age mice are different from the genes induced by aging. These results implied that the revitalization of advanced-age mice is not a simple reverse process of normal aging progression. Our data assigned novel roles of genes during aging progression and provided further theoretic evidence for future studies exploring the underlying mechanisms of aging and anti-aging-related disease

Elucidating the molecular mechanisms underlying cellular response to biophysical cues using synthetic biology approaches

NARCIS (Netherlands)

Denning, Denise; Roos, Wouter H

2016-01-01

The use of synthetic surfaces and materials to influence and study cell behavior has vastly progressed our understanding of the underlying molecular mechanisms involved in cellular response to physicochemical and biophysical cues. Reconstituting cytoskeletal proteins and interfacing them with a

Deciphering molecular circuits from genetic variation underlying transcriptional responsiveness to stimuli.

Science.gov (United States)

Gat-Viks, Irit; Chevrier, Nicolas; Wilentzik, Roni; Eisenhaure, Thomas; Raychowdhury, Raktima; Steuerman, Yael; Shalek, Alex K; Hacohen, Nir; Amit, Ido; Regev, Aviv

2013-04-01

Individual genetic variation affects gene responsiveness to stimuli, often by influencing complex molecular circuits. Here we combine genomic and intermediate-scale transcriptional profiling with computational methods to identify variants that affect the responsiveness of genes to stimuli (responsiveness quantitative trait loci or reQTLs) and to position these variants in molecular circuit diagrams. We apply this approach to study variation in transcriptional responsiveness to pathogen components in dendritic cells from recombinant inbred mouse strains. We identify reQTLs that correlate with particular stimuli and position them in known pathways. For example, in response to a virus-like stimulus, a trans-acting variant responds as an activator of the antiviral response; using RNA interference, we identify Rgs16 as the likely causal gene. Our approach charts an experimental and analytic path to decipher the mechanisms underlying genetic variation in circuits that control responses to stimuli.

ESCA and electron diffraction studies of InP surface heated under As molecular beam exposure

International Nuclear Information System (INIS)

Sugiura, Hideo; Yamaguchi, Masafumi; Shibukawa, Atsushi

1983-01-01

Chemical composition of InP substrate surface heattreated under As molecular beam exposure in an ultrahigh vacuum chamber was studied with ESCA, and surface reconstruction of the substrate was examined by in-situ electron diffraction. The InP substrate heated under the exposure of As molecular beam has mirror surface up to 590 0 C while the surface of InP heated above 400 0 C in vacuum is roughened. The ESCA study shows that thin InAs layer (thickness 0 C under the exposure of As. The electron diffraction study indicates that the InP is cleaned at about 500 0 C in As pressures of 10 -7 - 10 -5 Torr. The InP surface is prevented from thermally decomposing by the coverage of the InAs layer, which may be formed through the following process: 2InPO 4 + As 4 → 2InAs + P 2 O 5 + As 2 O 3 . (author)

Transcriptome analysis reveals regulatory networks underlying differential susceptibility to Botrytis cinerea in response to nitrogen availability in Solanum lycopersicum.

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Andrea eVega

2015-11-01

Full Text Available Nitrogen (N is one of the main limiting nutrients for plant growth and crop yield. It is well documented that changes in nitrate availability, the main N source found in agricultural soils, influences a myriad of developmental programs and processes including the plant defense response. Indeed, many agronomical reports indicate that the plant N nutritional status influences their ability to respond effectively when challenged by different pathogens. However, the molecular mechanisms involved in N-modulation of plant susceptibility to pathogens are poorly characterized. In this work, we show that Solanum lycopersicum defense response to the necrotrophic fungus Botrytis cinerea is affected by plant N availability, with higher susceptibility in nitrate-limiting conditions. Global gene expression responses of tomato against B. cinerea under contrasting nitrate conditions reveals that plant primary metabolism is affected by the fungal infection regardless of N regimes. This result suggests that differential susceptibility to pathogen attack under contrasting N conditions is not only explained by a metabolic alteration. We used a systems biology approach to identify the transcriptional regulatory network implicated in plant response to the fungus infection under contrasting nitrate conditions. Interestingly, hub genes in this network are known key transcription factors involved in ethylene and jasmonic acid signaling. This result positions these hormones as key integrators of nitrate and defense against B. cinerea in tomato plants. Our results provide insights into potential crosstalk mechanisms between necrotrophic defense response and N status in plants.

Molecular shape and binding force of Mycoplasma mobile's leg protein Gli349 revealed by an AFM study

International Nuclear Information System (INIS)

Lesoil, Charles; Nonaka, Takahiro; Sekiguchi, Hiroshi; Osada, Toshiya; Miyata, Makoto; Afrin, Rehana; Ikai, Atsushi

2010-01-01

Recent studies of the gliding bacteria Mycoplasma mobile have identified a family of proteins called the Gli family which was considered to be involved in this novel and yet fairly unknown motility system. The 349 kDa protein called Gli349 was successfully isolated and purified from the bacteria, and electron microscopy imaging and antibody experiments led to the hypothesis that it acts as the 'leg' of M. mobile, responsible for attachment to the substrate as well as for gliding motility. However, more precise evidence of the molecular shape and function of this protein was required to asses this theory any further. In this study, an atomic force microscope (AFM) was used both as an imaging and a force measurement device to provide new information about Gli349 and its role in gliding motility. AFM images of the protein were obtained revealing a complex structure with both rigid and flexible parts, consistent with previous electron micrographs of the protein. Single-molecular force spectroscopy experiments were also performed, revealing that Gli349 is able to specifically bind to sialyllactose molecules and withstand unbinding forces around 70 pN. These findings strongly support the idea that Gli349 is the 'leg' protein of M. mobile, responsible for binding and also most probably force generation during gliding motility.

Omics approaches on fresh-cut lettuce reveal global molecular responses to sodium hypochlorite and peracetic acid treatment.

Science.gov (United States)

Daddiego, Loretta; Bianco, Linda; Capodicasa, Cristina; Carbone, Fabrizio; Dalmastri, Claudia; Daroda, Lorenza; Del Fiore, Antonella; De Rossi, Patrizia; Di Carli, Mariasole; Donini, Marcello; Lopez, Loredana; Mengoni, Alessio; Paganin, Patrizia; Perrotta, Gaetano; Bevivino, Annamaria

2018-01-01

Lettuce is a leafy vegetable that is extensively commercialized as a ready-to-eat product because of its widespread use in human nutrition as salad. It is well known that washing treatments can severely affect the quality and shelf-life of ready-to-eat vegetables. The study presented here evaluated the effect of two washing procedures on fresh-cut lettuce during storage. An omics approach was applied to reveal global changes at molecular level induced by peracetic acid washing in comparison with sodium hypochlorite treatment. Microbiological analyses were also performed to quantify total bacterial abundance and composition. The study revealed wide metabolic alterations induced by the two sanitizers. In particular, transcriptomic and proteomic analyses pointed out a number of transcripts and proteins differentially accumulated in response to peracetic acid washing, mainly occurring on the first day of storage. In parallel, different microbiota composition and significant reduction in total bacterial load following washing were also observed. The results provide useful information for the fresh-cut industry to select an appropriate washing procedure preserving fresh-like attributes as much as possible during storage of the end product. Molecular evidence indicated peracetic acid to be a valid alternative to sodium hypochlorite as sanitizer solution. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Molecular evolution and diversification of snake toxin genes, revealed by analysis of intron sequences.

Science.gov (United States)

Fujimi, T J; Nakajyo, T; Nishimura, E; Ogura, E; Tsuchiya, T; Tamiya, T

2003-08-14

The genes encoding erabutoxin (short chain neurotoxin) isoforms (Ea, Eb, and Ec), LsIII (long chain neurotoxin) and a novel long chain neurotoxin pseudogene were cloned from a Laticauda semifasciata genomic library. Short and long chain neurotoxin genes were also cloned from the genome of Laticauda laticaudata, a closely related species of L. semifasciata, by PCR. A putative matrix attached region (MAR) sequence was found in the intron I of the LsIII gene. Comparative analysis of 11 structurally relevant snake toxin genes (three-finger-structure toxins) revealed the molecular evolution of these toxins. Three-finger-structure toxin genes diverged from a common ancestor through two types of evolutionary pathways (long and short types), early in the course of evolution. At a later stage of evolution in each gene, the accumulation of mutations in the exons, especially exon II, by accelerated evolution may have caused the increased diversification in their functions. It was also revealed that the putative MAR sequence found in the LsIII gene was integrated into the gene after the species-level divergence.

Molecular stopwatches, cogwheels and ``spinflakes'': studying the dynamics of molecular superrotors

Science.gov (United States)

Korobenko, Aleksey; Milner, Alexander; Hepburn, John; Milner, Valery

2015-05-01

Using the technique of an optical centrifuge, we excite diatomic molecules to ultrafast synchronous rotation. Femtosecond velocity-map imaging allows us to visualize and study the coherent dynamics of molecular superrotors under field free conditions and in external magnetic field. We demonstrate that when the created rotational wave packet is narrow, its free evolution is nondispersing and follows the motion of a classically rotating dumbbell or a hand of the smallest natural stopwatch. For wider rotational distributions, we observe the breakdown of classical rotation, when a dumbbell shape changes to that of a ``quantum cogwheel'' - a molecular state simultaneously aligned along multiple direction. Our measurements in external magnetic field reveal other peculiar aspects of the rich dynamics of molecular superrotors. The rotation of a non-magnetic molecule interacts with the applied field only weakly, giving rise to slow precession of the molecular angular momentum around the field direction. In contrast, the electronic spin of a paramagnetic superrotor mediates this interaction, causing the initial disk-like angular distribution to split into several spatial components, each precessing with its own frequency determined by the spin projection.

Improved Inhibition of Telomerase by Short Twisted Intercalating Nucleic Acids under Molecular Crowding Conditions

DEFF Research Database (Denmark)

Agarwal, Tani; Pradhan, Devranjan; Géci, Imrich

2012-01-01

Human telomeric DNA has the ability to fold into a 4-stranded G-quadruplex structure. Several G-quadruplex ligands are known to stabilize the structure and thereby inhibit telomerase activity. Such ligands have demonstrated efficient telomerase inhibition in dilute conditions, but under molecular...

Phylogenetic and Molecular Evolutionary Analysis of Mitophagy Receptors under Hypoxic Conditions

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Xiaomei Wu

2017-07-01

Full Text Available As animals evolved to use oxygen as the main strategy to produce ATP through the process of mitochondrial oxidative phosphorylation, the ability to adapt to fluctuating oxygen concentrations is a crucial component of evolutionary pressure. Three mitophagy receptors, FUNDC1, BNIP3 and NIX, induce the removal of dysfunctional mitochondria (mitophagy under prolonged hypoxic conditions in mammalian cells, to maintain oxygen homeostasis and prevent cell death. However, the evolutionary origins and structure-function relationships of these receptors remain poorly understood. Here, we found that FUN14 domain-containing proteins are present in archaeal, bacterial and eukaryotic genomes, while the family of BNIP3 domain-containing proteins evolved from early animals. We investigated conservation patterns of the critical amino acid residues of the human mitophagy receptors. These residues are involved in receptor regulation, mainly through phosphorylation, and in interaction with LC3 on the phagophore. Whereas FUNDC1 may be able to bind to LC3 under the control of post-translational regulations during the early evolution of vertebrates, BINP3 and NIX had already gained the ability for LC3 binding in early invertebrates. Moreover, FUNDC1 and BNIP3 each lack a layer of phosphorylation regulation in fishes that is conserved in land vertebrates. Molecular evolutionary analysis revealed that BNIP3 and NIX, as the targets of oxygen sensing HIF-1α, showed higher rates of substitution in fishes than in mammals. Conversely, FUNDC1 and its regulator MARCH5 showed higher rates of substitution in mammals. Thus, we postulate that the structural traces of mitophagy receptors in land vertebrates and fishes may reflect the process of vertebrate transition from water onto land, during which the changes in atmospheric oxygen concentrations acted as a selection force in vertebrate evolution. In conclusion, our study, combined with previous experimental results, shows that

Thermodynamic coupling between activation and inactivation gating in potassium channels revealed by free energy molecular dynamics simulations.

Science.gov (United States)

Pan, Albert C; Cuello, Luis G; Perozo, Eduardo; Roux, Benoît

2011-12-01

The amount of ionic current flowing through K(+) channels is determined by the interplay between two separate time-dependent processes: activation and inactivation gating. Activation is concerned with the stimulus-dependent opening of the main intracellular gate, whereas inactivation is a spontaneous conformational transition of the selectivity filter toward a nonconductive state occurring on a variety of timescales. A recent analysis of multiple x-ray structures of open and partially open KcsA channels revealed the mechanism by which movements of the inner activation gate, formed by the inner helices from the four subunits of the pore domain, bias the conformational changes at the selectivity filter toward a nonconductive inactivated state. This analysis highlighted the important role of Phe103, a residue located along the inner helix, near the hinge position associated with the opening of the intracellular gate. In the present study, we use free energy perturbation molecular dynamics simulations (FEP/MD) to quantitatively elucidate the thermodynamic basis for the coupling between the intracellular gate and the selectivity filter. The results of the FEP/MD calculations are in good agreement with experiments, and further analysis of the repulsive, van der Waals dispersive, and electrostatic free energy contributions reveals that the energetic basis underlying the absence of inactivation in the F103A mutation in KcsA is the absence of the unfavorable steric interaction occurring with the large Ile100 side chain in a neighboring subunit when the intracellular gate is open and the selectivity filter is in a conductive conformation. Macroscopic current analysis shows that the I100A mutant indeed relieves inactivation in KcsA, but to a lesser extent than the F103A mutant.

Cultivation Versus Molecular Analysis of Banana (Musa sp.) Shoot-Tip Tissue Reveals Enormous Diversity of Normally Uncultivable Endophytic Bacteria.

Science.gov (United States)

Thomas, Pious; Sekhar, Aparna Chandra

2017-05-01

The interior of plants constitutes a unique environment for microorganisms with various organisms inhabiting as endophytes. Unlike subterranean plant parts, aboveground parts are relatively less explored for endophytic microbial diversity. We employed a combination of cultivation and molecular approaches to study the endophytic bacterial diversity in banana shoot-tips. Cultivable bacteria from 20 sucker shoot-tips of cv. Grand Naine included 37 strains under 16 genera and three phyla (Proteobacteria, Actinobacteria, Firmicutes). 16S rRNA gene-ribotyping approach on 799f and 1492r PCR-amplicons to avoid plant organelle sequences was ineffective showing limited bacterial diversity. 16S rRNA metagene profiling targeting the V3-V4 hypervariable region after filtering out the chloroplast (74.2 %), mitochondrial (22.9 %), and unknown sequences (1.1 %) revealed enormous bacterial diversity. Proteobacteria formed the predominant phylum (64 %) succeeded by Firmicutes (12.1 %), Actinobacteria (9.5 %), Bacteroidetes (6.4 %), Planctomycetes, Cyanobacteria, and minor shares (banana shoot-tips (20 phyla, 46 classes) with about 2.6 % of the deciphered 269 genera and 1.5 % of the 656 observed species from the same source of shoot-tips attained through cultivation. The predominant genera included several agriculturally important bacteria. The study reveals an immense ecosystem of endophytic bacteria in banana shoot tissues endorsing the earlier documentation of intracellular "Cytobacts" and "Peribacts" with possible roles in plant holobiome and hologenome.

Molecular Techniques Revealed Highly Diverse Microbial Communities in Natural Marine Biofilms on Polystyrene Dishes for Invertebrate Larval Settlement

KAUST Repository

Lee, On On

2014-01-09

Biofilm microbial communities play an important role in the larval settlement response of marine invertebrates. However, the underlying mechanism has yet to be resolved, mainly because of the uncertainties in characterizing members in the communities using traditional 16S rRNA gene-based molecular methods and in identifying the chemical signals involved. In this study, pyrosequencing was used to characterize the bacterial communities in intertidal and subtidal marine biofilms developed during two seasons. We revealed highly diverse biofilm bacterial communities that varied with season and tidal level. Over 3,000 operational taxonomic units with estimates of up to 8,000 species were recovered in a biofilm sample, which is by far the highest number recorded in subtropical marine biofilms. Nineteen phyla were found, of which Cyanobacteria and Proteobacteria were the most dominant one in the intertidal and subtidal biofilms, respectively. Apart from these, Actinobacteria, Bacteroidetes, and Planctomycetes were the major groups recovered in both intertidal and subtidal biofilms, although their relative abundance varied among samples. Full-length 16S rRNA gene clone libraries were constructed for the four biofilm samples and showed similar bacterial compositions at the phylum level to those revealed by pyrosequencing. Laboratory assays confirmed that cyrids of the barnacle Balanus amphitrite preferred to settle on the intertidal rather than subtidal biofilms. This preference was independent of the biofilm bacterial density or biomass but was probably related to the biofilm community structure, particularly, the Proteobacterial and Cyanobacterial groups. © 2014 Springer Science+Business Media New York.

Solid-state NMR Reveals the Carbon-based Molecular Architecture of Cryptococcus neoformans Fungal Eumelanins in the Cell Wall.

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Chatterjee, Subhasish; Prados-Rosales, Rafael; Itin, Boris; Casadevall, Arturo; Stark, Ruth E

2015-05-29

Melanin pigments protect against both ionizing radiation and free radicals and have potential soil remediation capabilities. Eumelanins produced by pathogenic Cryptococcus neoformans fungi are virulence factors that render the fungal cells resistant to host defenses and certain antifungal drugs. Because of their insoluble and amorphous characteristics, neither the pigment bonding framework nor the cellular interactions underlying melanization of C. neoformans have yielded to comprehensive molecular-scale investigation. This study used the C. neoformans requirement of exogenous obligatory catecholamine precursors for melanization to produce isotopically enriched pigment "ghosts" and applied 2D (13)C-(13)C correlation solid-state NMR to reveal the carbon-based architecture of intact natural eumelanin assemblies in fungal cells. We demonstrated that the aliphatic moieties of solid C. neoformans melanin ghosts include cell-wall components derived from polysaccharides and/or chitin that are associated proximally with lipid membrane constituents. Prior to development of the mature aromatic fungal pigment, these aliphatic moieties form a chemically resistant framework that could serve as the scaffold for melanin synthesis. The indole-based core aromatic moieties show interconnections that are consistent with proposed melanin structures consisting of stacked planar assemblies, which are associated spatially with the aliphatic scaffold. The pyrrole aromatic carbons of the pigments bind covalently to the aliphatic framework via glycoside or glyceride functional groups. These findings establish that the structure of the pigment assembly changes with time and provide the first biophysical information on the mechanism by which melanin is assembled in the fungal cell wall, offering vital insights that can advance the design of bioinspired conductive nanomaterials and novel therapeutics. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

MALDI-TOF mass spectrometry imaging reveals molecular level changes in ultrahigh molecular weight polyethylene joint implants in correlation with lipid adsorption.

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Fröhlich, Sophie M; Archodoulaki, Vasiliki-Maria; Allmaier, Günter; Marchetti-Deschmann, Martina

2014-10-07

Ultrahigh molecular weight polyethylene (PE-UHMW), a material with high biocompatibility and excellent mechanical properties, is among the most commonly used materials for acetabular cup replacement in artificial joint systems. It is assumed that the interaction with synovial fluid in the biocompartment leads to significant changes relevant to material failure. In addition to hyaluronic acid, lipids are particularly relevant for lubrication in an articulating process. This study investigates synovial lipid adsorption on two different PE-UHMW materials (GUR-1050 and vitamin E-doped) in an in vitro model system by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry imaging (MSI). Lipids were identified by high performance thin layer chromatography (HP-TLC) and tandem mass spectrometry (MS/MS) analysis, with an analytical focus on phospholipids and cholesterol, both being species of high importance for lubrication. Scanning electron microscopy (SEM) analysis was applied in the study to correlate molecular information with PE-UHMW material qualities. It is demonstrated that lipid adsorption preferentially occurs in rough or oxidized polymer regions. Polymer modifications were colocalized with adsorbed lipids and found with high density in regions identified by SEM. Explanted, the in vivo polymer material showed comparable and even more obvious polymer damage and lipid adsorption when compared with the static in vitro model. A three-dimensional reconstruction of MSI data from consecutive PE-UHMW slices reveals detailed information about the diffusion process of lipids in the acetabular cup and provides, for the first time, a promising starting point for future studies correlating molecular information with commonly used techniques for material analysis (e.g., Fourier-transform infrared spectroscopy, nanoindentation).

Comparative Transcriptome Analysis of Latex Reveals Molecular Mechanisms Underlying Increased Rubber Yield in Hevea brasiliensis Self-Rooting Juvenile Clones

OpenAIRE

Li, Hui-Liang; Guo, Dong; Zhu, Jia-Hong; Wang, Ying; Chen, Xiong-Ting; Peng, Shi-Qing

2016-01-01

Rubber tree (Hevea brasiliensis) self-rooting juvenile clones (JCs) are promising planting materials for rubber production. In a comparative trial between self-rooting JCs and donor clones (DCs), self-rooting JCs exhibited better performance in rubber yield. To study the molecular mechanism associated with higher rubber yield in self-rooting JCs, we sequenced and comparatively analyzed the latex of rubber tree self-rooting JCs and DCs at the transcriptome level. Total raw reads of 34,632,012 ...

Molecular Dynamics Simulation and Analysis of Interfacial Water at Selected Sulfide Mineral Surfaces under Anaerobic Conditions

Energy Technology Data Exchange (ETDEWEB)

Jin, Jiaqi; Miller, Jan D.; Dang, Liem X.

2014-04-10

In this paper, we report on a molecular dynamics simulation (MDS) study of the behavior of interfacial water at selected sulfide mineral surfaces under anaerobic conditions. The study revealed the interfacial water structure and wetting characteristics of the pyrite (100) surface, galena (100) surface, chalcopyrite (012) surface, sphalerite (110) surface, and molybdenite surfaces (i.e., the face, armchair-edge, and zigzag-edge surfaces), including simulated contact angles, relative number density profiles, water dipole orientations, hydrogen-bonding, and residence times. For force fields of the metal and sulfur atoms in selected sulfide minerals used in the MDS, we used the universal force field (UFF) and another set of force fields optimized by quantum chemical calculations for interactions with interfacial water molecules at selected sulfide mineral surfaces. Simulation results for the structural and dynamic properties of interfacial water molecules indicate the natural hydrophobic character for the selected sulfide mineral surfaces under anaerobic conditions as well as the relatively weak hydrophobicity for the sphalerite (110) surface and two molybdenite edge surfaces. Part of the financial support for this study was provided by the U.S. Department of Energy (DOE) under Basic Science Grant No. DE-FG-03-93ER14315. The Division of Chemical Sciences, Geosciences, and Biosciences, Office of Basic Energy Sciences (BES), of the DOE, funded work performed by Liem X. Dang. Battelle operates Pacific Northwest National Laboratory for DOE. The calculations were carried out using computer resources provided by BES. The authors are grateful to Professor Tsun-Mei Chang for valuable discussions.

Molecular Characterization and Genetic Diversity of the Macaw Palm Ex Situ Germplasm Collection Revealed by Microsatellite Markers

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Fekadu G. Mengistu

2016-10-01

Full Text Available Macaw palm (Acrocomia aculeata is native to tropical forests in South America and highly abundant in Brazil. It is cited as a highly productive oleaginous palm tree presenting high potential for biodiesel production. The aim of this work was to characterize and study the genetic diversity of A. aculeata ex situ collections from different geographical states in Brazil using microsatellite (Simple Sequence Repeats, SSR markers. A total of 192 accessions from 10 provenances were analyzed with 10 SSR, and variations were detected in allelic diversity, polymorphism, and heterozygosity in the collections. Three major groups of accessions were formed using PCoA—principal coordinate analysis, UPGMA—unweighted pair-group method with arithmetic mean, and Tocher. The Mantel test revealed a weak correlation (r = 0.07 between genetic and geographic distances among the provenances reaffirming the result of the grouping. Reduced average heterozygosity (Ho < 50% per locus (or provenance confirmed the predominance of endogamy (or inbreeding in the germplasm collections as evidenced by positive inbreeding coefficient (F > 0 per locus (or per provenance. AMOVA—Analysis of Molecular Variance revealed higher (48.2% genetic variation within population than among populations (36.5%. SSR are useful molecular markers in characterizing A. aculeata germplasm and could facilitate the process of identifying, grouping, and selecting genotypes. Present results could be used to formulate appropriate conservation strategies in the genebank.

Molecular mechanisms underlying formation of long-term reward memories and extinction memories in the honeybee (Apis mellifera)

Science.gov (United States)

2014-01-01

The honeybee (Apis mellifera) has long served as an invertebrate model organism for reward learning and memory research. Its capacity for learning and memory formation is rooted in the ecological need to efficiently collect nectar and pollen during summer to ensure survival of the hive during winter. Foraging bees learn to associate a flower's characteristic features with a reward in a way that resembles olfactory appetitive classical conditioning, a learning paradigm that is used to study mechanisms underlying learning and memory formation in the honeybee. Due to a plethora of studies on appetitive classical conditioning and phenomena related to it, the honeybee is one of the best characterized invertebrate model organisms from a learning psychological point of view. Moreover, classical conditioning and associated behavioral phenomena are surprisingly similar in honeybees and vertebrates, suggesting a convergence of underlying neuronal processes, including the molecular mechanisms that contribute to them. Here I review current thinking on the molecular mechanisms underlying long-term memory (LTM) formation in honeybees following classical conditioning and extinction, demonstrating that an in-depth analysis of the molecular mechanisms of classical conditioning in honeybees might add to our understanding of associative learning in honeybees and vertebrates. PMID:25225299

Signature gene expression reveals novel clues to the molecular mechanisms of dimorphic transition in Penicillium marneffei.

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Ence Yang

2014-10-01

Full Text Available Systemic dimorphic fungi cause more than one million new infections each year, ranking them among the significant public health challenges currently encountered. Penicillium marneffei is a systemic dimorphic fungus endemic to Southeast Asia. The temperature-dependent dimorphic phase transition between mycelium and yeast is considered crucial for the pathogenicity and transmission of P. marneffei, but the underlying mechanisms are still poorly understood. Here, we re-sequenced P. marneffei strain PM1 using multiple sequencing platforms and assembled the genome using hybrid genome assembly. We determined gene expression levels using RNA sequencing at the mycelial and yeast phases of P. marneffei, as well as during phase transition. We classified 2,718 genes with variable expression across conditions into 14 distinct groups, each marked by a signature expression pattern implicated at a certain stage in the dimorphic life cycle. Genes with the same expression patterns tend to be clustered together on the genome, suggesting orchestrated regulations of the transcriptional activities of neighboring genes. Using qRT-PCR, we validated expression levels of all genes in one of clusters highly expressed during the yeast-to-mycelium transition. These included madsA, a gene encoding MADS-box transcription factor whose gene family is exclusively expanded in P. marneffei. Over-expression of madsA drove P. marneffei to undergo mycelial growth at 37°C, a condition that restricts the wild-type in the yeast phase. Furthermore, analyses of signature expression patterns suggested diverse roles of secreted proteins at different developmental stages and the potential importance of non-coding RNAs in mycelium-to-yeast transition. We also showed that RNA structural transition in response to temperature changes may be related to the control of thermal dimorphism. Together, our findings have revealed multiple molecular mechanisms that may underlie the dimorphic transition

Microscopic properties of ionic liquid/organic semiconductor interfaces revealed by molecular dynamics simulations.

Science.gov (United States)

Yokota, Yasuyuki; Miyamoto, Hiroo; Imanishi, Akihito; Takeya, Jun; Inagaki, Kouji; Morikawa, Yoshitada; Fukui, Ken-Ichi

2018-05-09

Electric double-layer transistors based on ionic liquid/organic semiconductor interfaces have been extensively studied during the past decade because of their high carrier densities at low operation voltages. Microscopic structures and the dynamics of ionic liquids likely determine the device performance; however, knowledge of these is limited by a lack of appropriate experimental tools. In this study, we investigated ionic liquid/organic semiconductor interfaces using molecular dynamics to reveal the microscopic properties of ionic liquids. The organic semiconductors include pentacene, rubrene, fullerene, and 7,7,8,8-tetracyanoquinodimethane (TCNQ). While ionic liquids close to the substrate always form the specific layered structures, the surface properties of organic semiconductors drastically alter the ionic dynamics. Ionic liquids at the fullerene interface behave as a two-dimensional ionic crystal because of the energy gain derived from the favorable electrostatic interaction on the corrugated periodic substrate.

DHA-fluorescent probe is sensitive to membrane order and reveals molecular adaptation of DHA in ordered lipid microdomains☆

Science.gov (United States)

Teague, Heather; Ross, Ron; Harris, Mitchel; Mitchell, Drake C.; Shaikh, Saame Raza

2012-01-01

Docosahexaenoic acid (DHA) disrupts the size and order of plasma membrane lipid microdomains in vitro and in vivo. However, it is unknown how the highly disordered structure of DHA mechanistically adapts to increase the order of tightly packed lipid microdomains. Therefore, we studied a novel DHA-Bodipy fluorescent probe to address this issue. We first determined if the DHA-Bodipy probe localized to the plasma membrane of primary B and immortal EL4 cells. Image analysis revealed that DHA-Bodipy localized into the plasma membrane of primary B cells more efficiently than EL4 cells. We then determined if the probe detected changes in plasma membrane order. Quantitative analysis of time-lapse movies established that DHA-Bodipy was sensitive to membrane molecular order. This allowed us to investigate how DHA-Bodipy physically adapted to ordered lipid microdomains. To accomplish this, we employed steady-state and time-resolved fluorescence anisotropy measurements in lipid vesicles of varying composition. Similar to cell culture studies, the probe was highly sensitive to membrane order in lipid vesicles. Moreover, these experiments revealed, relative to controls, that upon incorporation into highly ordered microdomains, DHA-Bodipy underwent an increase in its fluorescence lifetime and molecular order. In addition, the probe displayed a significant reduction in its rotational diffusion compared to controls. Altogether, DHA-Bodipy was highly sensitive to membrane order and revealed for the first time that DHA, despite its flexibility, could become ordered with less rotational motion inside ordered lipid microdomains. Mechanistically, this explains how DHA acyl chains can increase order upon formation of lipid microdomains in vivo. PMID:22841541

Hydration of Watson-Crick base pairs and dehydration of Hoogsteen base pairs inducing structural polymorphism under molecular crowding conditions.

Science.gov (United States)

Miyoshi, Daisuke; Nakamura, Kaori; Tateishi-Karimata, Hisae; Ohmichi, Tatsuo; Sugimoto, Naoki

2009-03-18

It has been revealed recently that molecular crowding, which is one of the largest differences between in vivo and in vitro conditions, is a critical factor determining the structure, stability, and function of nucleic acids. However, the effects of molecular crowding on Watson-Crick and Hoogsteen base pairs remain unclear. In order to investigate directly and quantitatively the molecular crowding effects on base pair types in nucleic acids, we designed intramolecular parallel- and antiparallel-stranded DNA duplexes consisting of Hoogsteen and Watson-Crick base pairs, respectively, as well as an intramolecular parallel-stranded triplex containing both types of base pairs. Thermodynamic analyses demonstrated that the values of free energy change at 25 degrees C for Hoogsteen base-pair formations decreased from +1.45 +/- 0.15 to +1.09 +/- 0.13 kcal mol(-1), and from -1.89 +/- 0.13 to -2.71 +/- 0.11 kcal mol(-1) in the intramolecular duplex and triplex, respectively, when the concentration of PEG 200 (polyethylene glycol with average molecular weight 200) increased from 0 to 20 wt %. However, corresponding values for Watson-Crick formation in the duplex and triplex increased from -10.2 +/- 0.2 to -8.7 +/- 0.1 kcal mol(-1), and from -10.8 +/- 0.2 to -9.2 +/- 0.2 kcal mol(-1), respectively. Furthermore, it was revealed that the opposing effects of molecular crowding on the Hoogsteen and Watson-Crick base pairs were due to different behaviors of water molecules binding to the DNA strands.

Mechanism of the Glycosidic Bond Cleavage of Mismatched Thymine in Human Thymine DNA Glycosylase Revealed by Classical Molecular Dynamics and Quantum Mechanical/Molecular Mechanical Calculations.

Science.gov (United States)

Kanaan, Natalia; Crehuet, Ramon; Imhof, Petra

2015-09-24

Base excision of mismatched or damaged nucleotides catalyzed by glycosylase enzymes is the first step of the base excision repair system, a machinery preserving the integrity of DNA. Thymine DNA glycosylase recognizes and removes mismatched thymine by cleaving the C1'-N1 bond between the base and the sugar ring. Our quantum mechanical/molecular mechanical calculations of this reaction in human thymine DNA glycosylase reveal a requirement for a positive charge in the active site to facilitate C1'-N1 bond scission: protonation of His151 significantly lowers the free energy barrier for C1'-N1 bond dissociation compared to the situation with neutral His151. Shuttling a proton from His151 to the thymine base further reduces the activation free energy for glycosidic bond cleavage. Classical molecular dynamics simulations of the H151A mutant suggest that the mutation to the smaller, neutral, residue increases the water accessibility of the thymine base, rendering direct proton transfer from the bulk feasible. Quantum mechanical/molecular mechanical calculations of the glycosidic bond cleavage reaction in the H151A mutant show that the activation free energy is slightly lower than in the wild-type enzyme, explaining the experimentally observed higher reaction rates in this mutant.

RNA-Seq reveals genotype-specific molecular responses to water deficit in eucalyptus

Science.gov (United States)

2011-01-01

Background In a context of climate change, phenotypic plasticity provides long-lived species, such as trees, with the means to adapt to environmental variations occurring within a single generation. In eucalyptus plantations, water availability is a key factor limiting productivity. However, the molecular mechanisms underlying the adaptation of eucalyptus to water shortage remain unclear. In this study, we compared the molecular responses of two commercial eucalyptus hybrids during the dry season. Both hybrids differ in productivity when grown under water deficit. Results Pyrosequencing of RNA extracted from shoot apices provided extensive transcriptome coverage - a catalog of 129,993 unigenes (49,748 contigs and 80,245 singletons) was generated from 398 million base pairs, or 1.14 million reads. The pyrosequencing data enriched considerably existing Eucalyptus EST collections, adding 36,985 unigenes not previously represented. Digital analysis of read abundance in 14,460 contigs identified 1,280 that were differentially expressed between the two genotypes, 155 contigs showing differential expression between treatments (irrigated vs. non irrigated conditions during the dry season), and 274 contigs with significant genotype-by-treatment interaction. The more productive genotype displayed a larger set of genes responding to water stress. Moreover, stress signal transduction seemed to involve different pathways in the two genotypes, suggesting that water shortage induces distinct cellular stress cascades. Similarly, the response of functional proteins also varied widely between genotypes: the most productive genotype decreased expression of genes related to photosystem, transport and secondary metabolism, whereas genes related to primary metabolism and cell organisation were over-expressed. Conclusions For the most productive genotype, the ability to express a broader set of genes in response to water availability appears to be a key characteristic in the maintenance

Alteration of biomacromolecule in corn by steam flaking in relation to biodegradation kinetics in ruminant, revealed with vibrational molecular spectroscopy

Science.gov (United States)

Xu, Ningning; Liu, Jianxin; Yu, Peiqiang

2018-02-01

Large scale of steam flaked corn has been used in dairy ration to maintain high milk production level. This study aimed to determine effects of steam flaking on processing-induced intrinsic molecular structure changes that were associated with rumen degradation kinetics and nutrients supply. The advanced vibrational molecular spectroscopy was applied to reveal the processing-induced intrinsic structure changes on a molecular basis. The rumen degradation kinetics and nutrient supply were determined using in situ approach in ruminant livestock system. Raw corn grain (RC) and steam flaked corn grain (SFC) were obtained from two different processing plants. The results showed that (1) Compared to RC, SFC had greater truly digestible non-fiber carbohydrate [tdNFC: 86.8 versus 78.0% dry matter (DM)], but lower truly digestible crude protein [tdCP: 7.7 versus 9.0% DM]. (2) The steam flaking increased (P < 0.01) rumen degradable DM (RDDM) and starch (RDSt), but decreased (P < 0.01) rumen degradable protein (RDP). (3) Molecular absorbance intensities of most carbohydrate biopolymers were greater in SFC (P < 0.01), but protein amides associated molecular spectral intensities were lower (P < 0.01) in SFC. (4). The molecular structure and nutrient interactive study showed that carbohydrate spectral intensities were positively (P < 0.10) associated with RDDM and RDSt and protein amide spectral intensities were positively (P < 0.10) associated with RDP. This results indicated that the steam flaking induced molecular structure changes had an interactive relationship with rumen degradation kinetics.

The occurrence of Toxocara species in naturally infected broiler chickens revealed by molecular approaches.

Science.gov (United States)

Zibaei, M; Sadjjadi, S M; Maraghi, S

2017-09-01

Consuming raw and undercooked meat is known to enhance the risk of human toxocariasis because Toxocara species have a wide range of paratenic hosts, including chickens. The aim of this study was to identify species of Toxocara in naturally infected broiler chickens using molecular approaches. A polymerase chain reaction (PCR) method was used for the differentiation of Toxocara canis and Toxocara cati larvae recovered from tissues and organs, and identified by microscopic observations. Thirty-three 35- to 47-day-old broiler chickens were used for examination of Toxocara larvae. The duodenum, liver, lungs, heart, kidneys, skeletal muscles and brain of each chicken were examined using the pepsin method, and DNA from each tissue was extracted as the template for PCR assay. The findings revealed that 5 of 33 (15.2%) broiler chickens were infected with Toxocara larvae. Larvae were recovered from the liver (n = 19), duodenum (n = 8), skeletal muscles (n = 8) and brain (n = 2) of broiler chickens naturally infected with Toxocara spp. The results showed that the frequencies of the species in the chickens were T. canis larvae (n = 5, 83.3%) and T. cati larvae (n = 1, 16.7%). Our data from the present study demonstrated the importance of broiler chickens as a paratenic host for the parasite's life cycle in the environment. The implementation of DNA amplification as a routine diagnostic technique is a specific and alternative method for identification of Toxocara larvae, and allowed the observation of specific species under field conditions within the locations where broiler chickens are typically raised and exposed to Toxocara spp. eggs or larvae.

Energetic changes caused by antigenic module insertion in a virus-like particle revealed by experiment and molecular dynamics simulations.

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Lin Zhang

Full Text Available The success of recombinant virus-like particles (VLPs for human papillomavirus and hepatitis B demonstrates the potential of VLPs as safe and efficacious vaccines. With new modular designs emerging, the effects of antigen module insertion on the self-assembly and structural integrity of VLPs should be clarified so as to better enabling improved design. Previous work has revealed insights into the molecular energetics of a VLP subunit, capsomere, comparing energetics within various solution conditions known to drive or inhibit self-assembly. In the present study, molecular dynamics (MD simulations coupled with the molecular mechanics-Poisson-Boltzmann surface area (MM-PBSA method were performed to examine the molecular interactions and energetics in a modular capsomere of a murine polyomavirus (MPV VLP designed to protect against influenza. Insertion of an influenza antigenic module is found to lower the binding energy within the capsomere, and a more active state is observed in Assembly Buffer as compared with that in Stabilization Buffer, which has been experimentally validated through measurements using differential scanning calorimetry. Further in-depth analysis based on free-energy decomposition indicates that destabilized binding can be attributed to electrostatic interaction induced by the chosen antigen module. These results provide molecular insights into the conformational stability of capsomeres and their abilities to be exploited for antigen presentation, and are expected to be beneficial for the biomolecular engineering of VLP vaccines.

Macroscopic Expressions of Molecular Adiabatic Compressibility of Methyl and Ethyl Caprate under High Pressure and High Temperature

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Fuxi Shi

2014-01-01

Full Text Available The molecular compressibility, which is a macroscopic quantity to reveal the microcompressibility by additivity of molecular constitutions, is considered as a fixed value for specific organic liquids. In this study, we introduced two calculated expressions of molecular adiabatic compressibility to demonstrate its pressure and temperature dependency. The first one was developed from Wada’s constant expression based on experimental data of density and sound velocity. Secondly, by introducing the 2D fitting expressions and their partial derivative of pressure and temperature, molecular compressibility dependency was analyzed further, and a 3D fitting expression was obtained from the calculated data of the first one. The third was derived with introducing the pressure and temperature correction factors based on analogy to Lennard-Jones potential function and energy equipartition theorem. In wide range of temperatures (293molecular compressibility was certified.

Comparative analysis reveals the underlying mechanism of vertebrate seasonal reproduction.

Science.gov (United States)

Ikegami, Keisuke; Yoshimura, Takashi

2016-02-01

Animals utilize photoperiodic changes as a calendar to regulate seasonal reproduction. Birds have highly sophisticated photoperiodic mechanisms and functional genomics analysis in quail uncovered the signal transduction pathway regulating avian seasonal reproduction. Birds detect light with deep brain photoreceptors. Long day (LD) stimulus induces secretion of thyroid-stimulating hormone (TSH) from the pars tuberalis (PT) of the pituitary gland. PT-derived TSH locally activates thyroid hormone (TH) in the hypothalamus, which induces gonadotropin-releasing hormone (GnRH) and hence gonadotropin secretion. However, during winter, low temperatures increase serum TH for adaptive thermogenesis, which accelerates germ cell apoptosis by activating the genes involved in metamorphosis. Therefore, TH has a dual role in the regulation of seasonal reproduction. Studies using TSH receptor knockout mice confirmed the involvement of PT-derived TSH in mammalian seasonal reproduction. In addition, studies in mice revealed that the tissue-specific glycosylation of TSH diversifies its function in the circulation to avoid crosstalk. In contrast to birds and mammals, one of the molecular machineries necessary for the seasonal reproduction of fish are localized in the saccus vasculosus from the photoreceptor to the neuroendocrine output. Thus, comparative analysis is a powerful tool to uncover the universality and diversity of fundamental properties in various organisms. Copyright © 2015 Elsevier Inc. All rights reserved.

Transcriptome analysis reveals self-incompatibility in the tea plant (Camellia sinensis) might be under gametophytic control.

Science.gov (United States)

Zhang, Cheng-Cai; Wang, Li-Yuan; Wei, Kang; Wu, Li-Yun; Li, Hai-Lin; Zhang, Fen; Cheng, Hao; Ni, De-Jiang

2016-05-17

Self-incompatibility (SI) is under genetic control and prevents inbreeding depression in angiosperms. SI mechanisms are quite complicated and still poorly understood in many plants. Tea (Camellia sinensis L.) belonging to the family of Theaceae, exhibits high levels of SI and high heterozygosity. Uncovering the molecular basis of SI of the tea plant may enhance breeding and simplify genomics research for the whole family. The growth of pollen tubes following selfing and crossing was observed using fluorescence microscopy. Self-pollen tubes grew slower than cross treatments from 24 h to 72 h after pollination. RNA-seq was employed to explore the molecular mechanisms of SI and to identify SI-related genes in C. sinensis. Self and cross-pollinated styles were collected at 24 h, 48 h and 72 h after pollination. Six RNA-seq libraries (SP24, SP48, SP72, CP24 CP48 and CP72; SP = self-pollinated, CP = cross-pollinated) were constructed and separately sequenced. In total, 299.327 million raw reads were generated. Following assembly, 63,762 unigenes were identified, and 27,264 (42.76 %) unigenes were annotated in five public databases: NR, KOG, KEGG, Swiss-Port and GO. To identify SI-related genes, the fragments per kb per million mapped reads (FPKM) values of each unigene were evaluated. Comparisons of CP24 vs. SP24, CP48 vs. SP48 and CP72 vs. SP72 revealed differential expression of 3,182, 3,575 and 3,709 genes, respectively. Consequently, several ubiquitin-mediated proteolysis, Ca(2+) signaling, apoptosis and defense-associated genes were obtained. The temporal expression pattern of genes following CP and SP was analyzed; 6 peroxidase, 1 polyphenol oxidase and 7 salicylic acid biosynthetic process-related genes were identified. The RNA-seq data were validated by qRT-PCR of 15 unigenes. Finally, a unigene (CL25983Contig1) with strong homology to the S-RNase was analyzed. It was mainly expressed in styles, with dramatically higher expression in self

Rheology via nonequilibrium molecular dynamics

International Nuclear Information System (INIS)

Hoover, W.G.

1982-10-01

The equilibrium molecular dynamics formulated by Newton, Lagrange, and Hamilton has been modified in order to simulate rheologial molecular flows with fast computers. This modified Nonequilibrium Molecular Dynamics (NEMD) has been applied to fluid and solid deformations, under both homogeneous and shock conditions, as well as to the transport of heat. The irreversible heating associated with dissipation could be controlled by carrying out isothermal NEMD calculations. The new isothermal NEMD equations of motion are consistent with Gauss' 1829 Least-Constraint principle as well as certain microscopic equilibrium and nonequilibrium statistical formulations due to Gibbs and Boltzmann. Application of isothermal NEMD revealed high-frequency and high-strain-rate behavior for simple fluids which resembled the behavior of polymer solutions and melts at lower frequencies and strain rates. For solids NEMD produces plastic flows consistent with experimental observations at much lower strain rates. The new nonequilibrium methods also suggest novel formulations of thermodynamics in nonequilibrium systems and shed light on the failure of the Principle of Material Frame Indifference

Suppression subtractive hybridization reveals transcript profiling of Chlorella under heterotrophy to photoautotrophy transition.

Directory of Open Access Journals (Sweden)

Jianhua Fan

Full Text Available Microalgae have been extensively investigated and exploited because of their competitive nutritive bioproducts and biofuel production ability. Chlorella are green algae that can grow well heterotrophically and photoautotrophically. Previous studies proved that shifting from heterotrophy to photoautotrophy in light-induced environments causes photooxidative damage as well as distinct physiologic features that lead to dynamic changes in Chlorella intracellular components, which have great potential in algal health food and biofuel production. However, the molecular mechanisms underlying the trophic transition remain unclear.In this study, suppression subtractive hybridization strategy was employed to screen and characterize genes that are differentially expressed in response to the light-induced shift from heterotrophy to photoautotrophy. Expressed sequence tags (ESTs were obtained from 770 and 803 randomly selected clones among the forward and reverse libraries, respectively. Sequence analysis identified 544 unique genes in the two libraries. The functional annotation of the assembled unigenes demonstrated that 164 (63.1% from the forward library and 62 (21.8% from the reverse showed significant similarities with the sequences in the NCBI non-redundant database. The time-course expression patterns of 38 selected differentially expressed genes further confirmed their responsiveness to a diverse trophic status. The majority of the genes enriched in the subtracted libraries were associated with energy metabolism, amino acid metabolism, protein synthesis, carbohydrate metabolism, and stress defense.The data presented here offer the first insights into the molecular foundation underlying the diverse microalgal trophic niche. In addition, the results can be used as a reference for unraveling candidate genes associated with the transition of Chlorella from heterotrophy to photoautotrophy, which holds great potential for further improving its lipid and

High-Frequency Observations of Temperature and Dissolved Oxygen Reveal Under-Ice Convection in a Large Lake

Science.gov (United States)

Yang, Bernard; Young, Joelle; Brown, Laura; Wells, Mathew

2017-12-01

Detailed observations of thermal structure over an entire winter in a large lake reveal the presence of large (10-20 m) overturns under the ice, driven by diurnal solar heating. Convection can occur in the early winter, but the most vigorous convection occurred near the end of winter. Both periods are when our lake ice model suggest thinner ice that would have been transparent. This under-ice convection led to a deepening of the mixed layer over time, consistent with previous short-term studies. During periods of vigorous convection under the ice at the end of winter, the dissolved oxygen had become supersaturated from the surface to 23 m below the surface, suggesting abundant algal growth. Analysis of our high-frequency observations over the entire winter of 2015 using the Thorpe-scale method quantified the scale of mixing. Furthermore, it revealed that changes in oxygen concentrations are closely related to the intensity of mixing.

Cellular Molecular Changes in Nerium oleander (L.) Cell Culture Under Gamma Radiation Stress

International Nuclear Information System (INIS)

Salama, I.M.; Abd EL-Megid, M.H.M.

2017-01-01

This study was done to analyze the relationship between the various effects of five different doses of gamma ray treatments (control, 0, 100, 200, 300 and 400 rad) on cell suspension culture of Nerium oleander belonging to the family Apocynaceae, Plant samples were collected from Egyptian flora. The five treatments of the plants were characterized by analyzing variability in frozen biomass cell suspension culture of N. oleander through SDS PAGE and peroxidase is ozymes. The electrophorogram showed a total of 36 bands of proteins with molecular weight ranging from 10 to 225 KDa. The protein diversity analysis was done based on the presence or the absence of bands trhus interpreting their relevance. The his togram analysis clearly showed a high degree of diversity a long these five treatments of the plant. The results of electrophoretic patterns of peroxidase is ozymes that was extracted from frozen biomass cell suspension cultures after receiving the different gamma doses revealed remarkable molecular changes in all treatments. These changes in peroxidase isozymes and protein bands indicate the effect of the different irradiation treatments on the gene expiration

'Ogura'-based 'CMS' lines with different nuclear backgrounds of cabbage revealed substantial diversity at morphological and molecular levels.

Science.gov (United States)

Parkash, Chander; Kumar, Sandeep; Singh, Rajender; Kumar, Ajay; Kumar, Satish; Dey, Shyam Sundar; Bhatia, Reeta; Kumar, Raj

2018-01-01

A comprehensive study on characterization and genetic diversity analysis was carried out in 16 'Ogura'-based 'CMS' lines of cabbage using 14 agro-morphological traits and 29 SSR markers. Agro-morphological characterization depicted considerable variations for different horticultural traits studied. The genotype, ZHA-2, performed better for most of the economically important quantitative traits. Further, gross head weight (0.76), head length (0.60) and head width (0.83) revealed significant positive correlation with net head weight. Dendrogram based on 10 quantitative traits exhibited considerable diversity among different CMS lines and principle component analysis (PCA) indicated that net and gross head weight, and head length and width are the main components of divergence between 16 CMS lines of cabbage. In molecular study, a total of 58 alleles were amplified by 29 SSR primers, averaging to 2.0 alleles in each locus. High mean values of Shannon's Information index (0.62), expected (0.45) and observed (0.32) heterozygosity and polymorphic information content (0.35) depicted substantial polymorphism. Dendrogram based on Jaccard's similarity coefficient constructed two major groups and eight sub-groups, which revealed substantial diversity among different CMS lines. In overall, based on agro-morphological and molecular studies genotype RRMA, ZHA-2 and RCA were found most divergent. Hence, they have immense potential in future breeding programs for the high-yielding hybrid development in cabbage.

The Hidden Diversity of Zanclea Associated with Scleractinians Revealed by Molecular Data.

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Simone Montano

Full Text Available Scleractinian reef corals have recently been acknowledged as the most numerous host group found in association with hydroids belonging to the Zanclea genus. However, knowledge of the molecular phylogenetic relationships among Zanclea species associated with scleractinians is just beginning. This study, using the nuclear 28S rDNA region and the fast-evolving mitochondrial 16S rRNA and COI genes, provides the most comprehensive phylogenetic reconstruction of the genus Zanclea with a particular focus on the genetic diversity among Zanclea specimens associated with 13 scleractinian genera. The monophyly of Zanclea associated with scleractinians was strongly supported in all nuclear and mitochondrial phylogenetic reconstructions. Furthermore, a combined mitochondrial 16S and COI phylogenetic tree revealed a multitude of hidden molecular lineages within this group (Clades I, II, III, V, VI, VII, and VIII, suggesting the existence of both host-generalist and genus-specific lineages of Zanclea associated with scleractinians. In addition to Z. gallii living in association with the genus Acropora, we discovered four well-supported lineages (Clades I, II, III, and VII, each one forming a strict association with a single scleractinian genus, including sequences of Zanclea associated with Montipora from two geographically separated areas (Maldives and Taiwan. Two host-generalist Zanclea lineages were also observed, and one of them was formed by Zanclea specimens symbiotic with seven scleractinian genera (Clade VIII. We also found that the COI gene allows the recognition of separated hidden lineages in agreement with the commonly recommended mitochondrial 16S as a DNA barcoding gene for Hydrozoa and shows reasonable potential for phylogenetic and evolutionary analyses in the genus Zanclea. Finally, as no DNA sequences are available for the majority of the nominal Zanclea species known, we note that they will be necessary to elucidate the diversity of the

The Hidden Diversity of Zanclea Associated with Scleractinians Revealed by Molecular Data

KAUST Repository

Montano, Simone

2015-07-24

Scleractinian reef corals have recently been acknowledged as the most numerous host group found in association with hydroids belonging to the Zanclea genus. However, knowledge of the molecular phylogenetic relationships among Zanclea species associated with scleractinians is just beginning. This study, using the nuclear 28S rDNA region and the fast-evolving mitochondrial 16S rRNA and COI genes, provides the most comprehensive phylogenetic reconstruction of the genus Zanclea with a particular focus on the genetic diversity among Zanclea specimens associated with 13 scleractinian genera. The monophyly of Zanclea associated with scleractinians was strongly supported in all nuclear and mitochondrial phylogenetic reconstructions. Furthermore, a combined mitochondrial 16S and COI phylogenetic tree revealed a multitude of hidden molecular lineages within this group (Clades I, II, III, V, VI, VII, and VIII), suggesting the existence of both host-generalist and genus-specific lineages of Zanclea associated with scleractinians. In addition to Z. gallii living in association with the genus Acropora, we discovered four well-supported lineages (Clades I, II, III, and VII), each one forming a strict association with a single scleractinian genus, including sequences of Zanclea associated with Montipora from two geographically separated areas (Maldives and Taiwan). Two host-generalist Zanclea lineages were also observed, and one of them was formed by Zanclea specimens symbiotic with seven scleractinian genera (Clade VIII). We also found that the COI gene allows the recognition of separated hidden lineages in agreement with the commonly recommended mitochondrial 16S as a DNA barcoding gene for Hydrozoa and shows reasonable potential for phylogenetic and evolutionary analyses in the genus Zanclea. Finally, as no DNA sequences are available for the majority of the nominal Zanclea species known, we note that they will be necessary to elucidate the diversity of the Zanclea

Molecular Epidemiology Reveals Genetic Diversity amongst Isolates of the Cryptococcus neoformans/C. gattii Species Complex in Thailand

Science.gov (United States)

Kaocharoen, Sirada; Ngamskulrungroj, Popchai; Firacative, Carolina; Trilles, Luciana; Piyabongkarn, Dumrongdej; Banlunara, Wijit; Poonwan, Natteewan; Chaiprasert, Angkana; Meyer, Wieland; Chindamporn, Ariya

2013-01-01

To gain a more detailed picture of cryptococcosis in Thailand, a retrospective study of 498 C. neoformans and C. gattii isolates has been conducted. Among these, 386, 83 and 29 strains were from clinical, environmental and veterinary sources, respectively. A total of 485 C. neoformans and 13 C. gattii strains were studied. The majority of the strains (68.9%) were isolated from males (mean age of 37.97 years), 88.5% of C. neoformans and only 37.5% of C. gattii strains were from HIV patients. URA5-RFLP and/or M13 PCR-fingerprinting analysis revealed that the majority of the isolates were C. neoformans molecular type VNI regardless of their sources (94.8%; 94.6% of the clinical, 98.8% of the environmental and 86.2% of the veterinary isolates). In addition, the molecular types VNII (2.4%; 66.7% of the clinical and 33.3% of the veterinary isolates), VNIV (0.2%; 100% environmental isolate), VGI (0.2%; 100% clinical isolate) and VGII (2.4%; 100% clinical isolates) were found less frequently. Multilocus Sequence Type (MLST) analysis using the ISHAM consensus MLST scheme for the C. neoformans/C. gattii species complex identified a total of 20 sequence types (ST) in Thailand combining current and previous data. The Thai isolates are an integrated part of the global cryptococcal population genetic structure, with ST30 for C. gattii and ST82, ST83, ST137, ST141, ST172 and ST173 for C. neoformans being unique to Thailand. Most of the C. gattii isolates were ST7 = VGIIb, which is identical to the less virulent minor Vancouver island outbreak genotype, indicating Thailand as a stepping stone in the global spread of this outbreak strain. The current study revealed a greater genetic diversity and a wider range of major molecular types being present amongst Thai cryptococcal isolates than previously reported. PMID:23861989

Reactive Molecular Dynamics Simulations to Understand Mechanical Response of Thaumasite under Temperature and Strain Rate Effects.

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Hajilar, Shahin; Shafei, Behrouz; Cheng, Tao; Jaramillo-Botero, Andres

2017-06-22

Understanding the structural, thermal, and mechanical properties of thaumasite is of great interest to the cement industry, mainly because it is the phase responsible for the aging and deterioration of civil infrastructures made of cementitious materials attacked by external sources of sulfate. Despite the importance, effects of temperature and strain rate on the mechanical response of thaumasite had remained unexplored prior to the current study, in which the mechanical properties of thaumasite are fully characterized using the reactive molecular dynamics (RMD) method. With employing a first-principles based reactive force field, the RMD simulations enable the description of bond dissociation and formation under realistic conditions. From the stress-strain curves of thaumasite generated in the x, y, and z directions, the tensile strength, Young's modulus, and fracture strain are determined for the three orthogonal directions. During the course of each simulation, the chemical bonds undergoing tensile deformations are monitored to reveal the bonds responsible for the mechanical strength of thaumasite. The temperature increase is found to accelerate the bond breaking rate and consequently the degradation of mechanical properties of thaumasite, while the strain rate only leads to a slight enhancement of them for the ranges considered in this study.

Integrated network analysis reveals potentially novel molecular mechanisms and therapeutic targets of refractory epilepsies.

Directory of Open Access Journals (Sweden)

Hongwei Chu

Full Text Available Epilepsy is a complex neurological disorder and a significant health problem. The pathogenesis of epilepsy remains obscure in a significant number of patients and the current treatment options are not adequate in about a third of individuals which were known as refractory epilepsies (RE. Network medicine provides an effective approach for studying the molecular mechanisms underlying complex diseases. Here we integrated 1876 disease-gene associations of RE and located those genes to human protein-protein interaction (PPI network to obtain 42 significant RE-associated disease modules. The functional analysis of these disease modules showed novel molecular pathological mechanisms of RE, such as the novel enriched pathways (e.g., "presynaptic nicotinic acetylcholine receptors", "signaling by insulin receptor". Further analysis on the relationships between current drug targets and the RE-related disease genes showed the rational mechanisms of most antiepileptic drugs. In addition, we detected ten potential novel drug targets (e.g., KCNA1, KCNA4-6, KCNC3, KCND2, KCNMA1, CAMK2G, CACNB4 and GRM1 located in three RE related disease modules, which might provide novel insights into the new drug discovery for RE therapy.

Molecular Mechanisms Underlying the Epileptogenesis and Seizure Progression in Tuberous Sclerosis Complex 1 Deficient Mouse Models

Science.gov (United States)

2016-10-01

dysregulation in epileptogenesis in the developing brain? 2) What are the molecular mechanisms downstream of mTOR hyperactivation that trigger epileptogenesis...underlying epilepsy. Hopefully, a knowledge of these mechanisms will aid in a rational development of therapies. KEYWORDS Tuberous Sclerosis, Epilepsy

Molecular mechanism of allosteric communication in Hsp70 revealed by molecular dynamics simulations.

Directory of Open Access Journals (Sweden)

Federica Chiappori

Full Text Available Investigating ligand-regulated allosteric coupling between protein domains is fundamental to understand cell-life regulation. The Hsp70 family of chaperones represents an example of proteins in which ATP binding and hydrolysis at the Nucleotide Binding Domain (NBD modulate substrate recognition at the Substrate Binding Domain (SBD. Herein, a comparative analysis of an allosteric (Hsp70-DnaK and a non-allosteric structural homolog (Hsp110-Sse1 of the Hsp70 family is carried out through molecular dynamics simulations, starting from different conformations and ligand-states. Analysis of ligand-dependent modulation of internal fluctuations and local deformation patterns highlights the structural and dynamical changes occurring at residue level upon ATP-ADP exchange, which are connected to the conformational transition between closed and open structures. By identifying the dynamically responsive protein regions and specific cross-domain hydrogen-bonding patterns that differentiate Hsp70 from Hsp110 as a function of the nucleotide, we propose a molecular mechanism for the allosteric signal propagation of the ATP-encoded conformational signal.

A genetic analysis of segregation distortion revealed by molecular ...

Indian Academy of Sciences (India)

Journal of Genetics, Vol. 90, No. ... Segregation analysis was based on 64 molecular markers, including 26 .... FHB of RIL populations was controlled by quantitative trait ... The authors acknowledge financial support by the National Basic.

Revealing vilazodone's binding mechanism underlying its partial agonism to the 5-HT1A receptor in the treatment of major depressive disorder.

Science.gov (United States)

Zheng, Guoxun; Xue, Weiwei; Yang, Fengyuan; Zhang, Yang; Chen, Yuzong; Yao, Xiaojun; Zhu, Feng

2017-11-01

It has been estimated that major depressive disorder (MDD) will become the second largest global burden among all diseases by 2030. Various types of drugs, including selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and serotonin receptor partial agonist/reuptake inhibitors (SPARIs), have been approved and become the primary or first-line medications prescribed for MDD. SPARI was expected to demonstrate more enhanced drug efficacy and a rapid onset of action as compared to SSRI and SNRI. As one of the most famous SPARIs, vilazodone was approved by the FDA for the treatment of MDD. Because of the great clinical importance of vilazodone, its binding mechanism underlying its partial agonism to the 5-HT 1A receptor (5-HT 1A R) could provide valuable information to SPARIs' drug-like properties. However, this mechanism has not been reported to date; consequently, the rational design of new efficacious SPARI-based MDD drugs is severely hampered. To explore the molecular mechanism of vilazodone, an integrated computational strategy was adopted in this study to reveal its binding mechanism and prospective structural feature at the agonist binding site of 5-HT 1A R. As a result, 22 residues of this receptor were identified as hotspots, consistently favoring the binding of vilazodone and its analogues, and a common binding mechanism underlying their partial agonism to 5-HT 1A R was, therefore, discovered. Moreover, three main interaction features between vilazodone and 5-HT 1A R have been revealed and schematically summarized. In summary, this newly identified binding mechanism will provide valuable information for medicinal chemists working in the field of rational design of novel SPARIs for MDD treatment.

Topology of polymer chains under nanoscale confinement.

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Satarifard, Vahid; Heidari, Maziar; Mashaghi, Samaneh; Tans, Sander J; Ejtehadi, Mohammad Reza; Mashaghi, Alireza

2017-08-24

Spatial confinement limits the conformational space accessible to biomolecules but the implications for bimolecular topology are not yet known. Folded linear biopolymers can be seen as molecular circuits formed by intramolecular contacts. The pairwise arrangement of intra-chain contacts can be categorized as parallel, series or cross, and has been identified as a topological property. Using molecular dynamics simulations, we determine the contact order distributions and topological circuits of short semi-flexible linear and ring polymer chains with a persistence length of l p under a spherical confinement of radius R c . At low values of l p /R c , the entropy of the linear chain leads to the formation of independent contacts along the chain and accordingly, increases the fraction of series topology with respect to other topologies. However, at high l p /R c , the fraction of cross and parallel topologies are enhanced in the chain topological circuits with cross becoming predominant. At an intermediate confining regime, we identify a critical value of l p /R c , at which all topological states have equal probability. Confinement thus equalizes the probability of more complex cross and parallel topologies to the level of the more simple, non-cooperative series topology. Moreover, our topology analysis reveals distinct behaviours for ring- and linear polymers under weak confinement; however, we find no difference between ring- and linear polymers under strong confinement. Under weak confinement, ring polymers adopt parallel and series topologies with equal likelihood, while linear polymers show a higher tendency for series arrangement. The radial distribution analysis of the topology reveals a non-uniform effect of confinement on the topology of polymer chains, thereby imposing more pronounced effects on the core region than on the confinement surface. Additionally, our results reveal that over a wide range of confining radii, loops arranged in parallel and cross

Solvent Clathrate Driven Dynamic Stereomutation of a Supramolecular Polymer with Molecular Pockets.

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Kulkarni, Chidambar; Korevaar, Peter A; Bejagam, Karteek K; Palmans, Anja R A; Meijer, E W; George, Subi J

2017-10-04

Control over the helical organization of synthetic supramolecular systems is intensively pursued to manifest chirality in a wide range of applications ranging from electron spin filters to artificial enzymes. Typically, switching the helicity of supramolecular assemblies involves external stimuli or kinetic traps. However, efforts to achieve helix reversal under thermodynamic control and to understand the phenomena at a molecular level are scarce. Here we present a unique example of helix reversal (stereomutation) under thermodynamic control in the self-assembly of a coronene bisimide that has a 3,5-dialkoxy substitution on the imide phenyl groups (CBI-35CH), leading to "molecular pockets" in the assembly. The stereomutation was observed only if the CBI monomer possesses molecular pockets. Detailed chiroptical studies performed in alkane solvents with different molecular structures reveal that solvent molecules intercalate or form clathrates within the molecular pockets of CBI-35CH at low temperature (263 K), thereby triggering the stereomutation. The interplay among the helical assembly, molecular pockets, and solvent molecules is further unraveled by explicit solvent molecular dynamics simulations. Our results demonstrate how the molecular design of self-assembling building blocks can orchestrate the organization of surrounding solvent molecules, which in turn dictates the helical organization of the resulting supramolecular assembly.

Molecular dynamics simulations of the melting curve of NiAl alloy under pressure

OpenAIRE

Wenjin Zhang; Yufeng Peng; Zhongli Liu

2014-01-01

The melting curve of B2-NiAl alloy under pressure has been investigated using molecular dynamics technique and the embedded atom method (EAM) potential. The melting temperatures were determined with two approaches, the one-phase and the two-phase methods. The first one simulates a homogeneous melting, while the second one involves a heterogeneous melting of materials. Both approaches reduce the superheating effectively and their results are close to each other at the applied pressures. By fit...

Transitional Failure of Carbon Nanotube Systems under a Combination of Tension and Torsion

OpenAIRE

Jeong, Byeong-Woo

2012-01-01

Transitional failure envelopes of single- and double-walled carbon nanotubes under combined tension-torsion are predicted using classical molecular dynamics simulations. The observations reveal that while the tensile failure load decreases with combined torsion, the torsional buckling moment increases with combined tension. As a result, the failure envelopes under combined tension-torsion are definitely different from those under pure tension or torsion. In such combined loading, there is a m...

Fluorescence and NMR spectroscopy together with molecular simulations reveal amphiphilic characteristics of a Burkholderia biofilm exopolysaccharide.

Science.gov (United States)

Kuttel, Michelle M; Cescutti, Paola; Distefano, Marco; Rizzo, Roberto

2017-06-30

Biofilms are a collective mode of bacterial life in which a self-produced matrix confines cells in close proximity to each other. Biofilms confer many advantages, including protection from chemicals (including antibiotics), entrapment of useful extracellular enzymes and nutrients, as well as opportunities for efficient recycling of molecules from dead cells. Biofilm matrices are aqueous gel-like structures composed of polysaccharides, proteins, and DNA stabilized by intermolecular interactions that may include non-polar connections. Recently, polysaccharides extracted from biofilms produced by species of the Burkholderia cepacia complex were shown to possess clusters of rhamnose, a 6-deoxy sugar with non-polar characteristics. Molecular dynamics simulations are well suited to characterizing the structure and dynamics of polysaccharides, but only relatively few such studies exist of their interaction with non-polar molecules. Here we report an investigation into the hydrophobic properties of the exopolysaccharide produced by Burkholderia multivorans strain C1576. Fluorescence experiments with two hydrophobic fluorescent probes established that this polysaccharide complexes hydrophobic species, and NMR experiments confirmed these interactions. Molecular simulations to model the hydrodynamics of the polysaccharide and the interaction with guest species revealed a very flexible, amphiphilic carbohydrate chain that has frequent dynamic interactions with apolar molecules; both hexane and a long-chain fatty acid belonging to the quorum-sensing system of B. multivorans were tested. A possible role of the non-polar domains of the exopolysaccharide in facilitating the diffusion of aliphatic species toward specific targets within the biofilm aqueous matrix is proposed. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Characterization of 1577 primary prostate cancers reveals novel biological and clinicopathologic insights into molecular subtypes.

Science.gov (United States)

Tomlins, Scott A; Alshalalfa, Mohammed; Davicioni, Elai; Erho, Nicholas; Yousefi, Kasra; Zhao, Shuang; Haddad, Zaid; Den, Robert B; Dicker, Adam P; Trock, Bruce J; DeMarzo, Angelo M; Ross, Ashley E; Schaeffer, Edward M; Klein, Eric A; Magi-Galluzzi, Cristina; Karnes, R Jeffrey; Jenkins, Robert B; Feng, Felix Y

2015-10-01

Prostate cancer (PCa) molecular subtypes have been defined by essentially mutually exclusive events, including ETS gene fusions (most commonly involving ERG) and SPINK1 overexpression. Clinical assessment may aid in disease stratification, complementing available prognostic tests. To determine the analytical validity and clinicopatholgic associations of microarray-based molecular subtyping. We analyzed Affymetrix GeneChip expression profiles for 1577 patients from eight radical prostatectomy cohorts, including 1351 cases assessed using the Decipher prognostic assay (GenomeDx Biosciences, San Diego, CA, USA) performed in a laboratory with Clinical Laboratory Improvements Amendment certification. A microarray-based (m-) random forest ERG classification model was trained and validated. Outlier expression analysis was used to predict other mutually exclusive non-ERG ETS gene rearrangements (ETS(+)) or SPINK1 overexpression (SPINK1(+)). Associations with clinical features and outcomes by multivariate logistic regression analysis and receiver operating curves. The m-ERG classifier showed 95% accuracy in an independent validation subset (155 samples). Across cohorts, 45% of PCas were classified as m-ERG(+), 9% as m-ETS(+), 8% as m-SPINK1(+), and 38% as triple negative (m-ERG(-)/m-ETS(-)/m-SPINK1(-)). Gene expression profiling supports three underlying molecularly defined groups: m-ERG(+), m-ETS(+), and m-SPINK1(+)/triple negative. On multivariate analysis, m-ERG(+) tumors were associated with lower preoperative serum prostate-specific antigen and Gleason scores, but greater extraprostatic extension (p<0.001). m-ETS(+) tumors were associated with seminal vesicle invasion (p=0.01), while m-SPINK1(+)/triple negative tumors had higher Gleason scores and were more frequent in Black/African American patients (p<0.001). Clinical outcomes were not significantly different among subtypes. A clinically available prognostic test (Decipher) can also assess PCa molecular subtypes

Spatial distribution of intra-molecular water and polymeric components in polyelectrolyte dendrimers revealed by small angle scattering investigations

Science.gov (United States)

Wu, Bin; Li, Xin; Do, Changwoo; Kim, Tae-Hwan; Shew, Chwen-Yang; Liu, Yun; Yang, Jun; Hong, Kunlun; Porcar, Lionel; Chen, Chun-Yu; Liu, Emily L.; Smith, Gregory S.; Herwig, Kenneth W.; Chen, Wei-Ren

2011-10-01

An experimental scheme using contrast variation small angle neutron scattering technique is developed to investigate the structural characteristics of amine-terminated poly(amidoamine) dendrimers solutions. Using this methodology, we present the dependence of both the intra-dendrimer water and the polymer distribution on molecular protonation, which can be precisely adjusted by tuning the pH of the solution. Assuming spherical symmetry of the spatial arrangement of the constituent components of dendrimer, and that the atomic ratio of hydrogen-to-deuterium for the solvent residing within the cavities of dendrimer is identical to that for the solvent outside the dendrimer, the intra-dendrimer water distribution along the radial direction is determined. Our result clearly reveals an outward relocation of the peripheral groups, as well as enhanced intra-dendrimer hydration, upon increasing the molecular protonation and, therefore, allows the determination of segmental backfolding in a quantitative manner. The connection between these charge-induced structural changes and our recently observed progressively active segmental dynamics is also discussed.

A study on EUV reticle surface molecular contamination under different storage conditions in a HVM foundry fab

Science.gov (United States)

Singh, SherJang; Yatzor, Brett; Taylor, Ron; Wood, Obert; Mangat, Pawitter

2017-03-01

The prospect of EUVL (Extreme Ultraviolet Lithography) insertion into HVM (High Volume Manufacturing) has never been this promising. As technology is prepared for "lab to fab" transition, it becomes important to comprehend challenges associated with integrating EUVL infrastructure within existing high volume chip fabrication processes in a foundry fab. The existing 193nm optical lithography process flow for reticle handling and storage in a fab atmosphere is well established and in-fab reticle contamination concerns are mitigated with the reticle pellicle. However EUVL reticle pellicle is still under development and if available, may only provide protection against particles but not molecular contamination. HVM fab atmosphere is known to be contaminated with trace amounts of AMC's (Atmospheric Molecular Contamination). If such contaminants are organic in nature and get absorbed on the reticle surface, EUV photon cause photo-dissociation resulting into carbon generation which is known to reduce multilayer reflectivity and also degrades exposure uniformity. Chemical diffusion and aggregation of other ions is also reported under the e-beam exposure of a EUV reticle which is known to cause haze issues in optical lithography. Therefore it becomes paramount to mitigate absorbed molecular contaminant concerns on EUVL reticle surface. In this paper, we have studied types of molecular contaminants that are absorbed on an EUVL reticle surface under HVM fab storage and handling conditions. Effect of storage conditions (gas purged vs atmospheric) in different storage pods (Dual pods, Reticle Clamshells) is evaluated. Absorption analysis is done both on ruthenium capping layer as well as TaBN absorber. Ru surface chemistry change as a result of storage is also studied. The efficacy of different reticle cleaning processes to remove absorbed contaminant is evaluated as well.

Direct Determination of Molecular Weight Distribution of Calf-Thymus DNAs and Study of Their Fragmentation under Ultrasonic and Low-Energy IR Irradiations. A Charge Detection Mass Spectrometry Investigation.

Science.gov (United States)

Halim, Mohammad A; Bertorelle, Franck; Doussineau, Tristan; Antoine, Rodolphe

2018-06-09

Calf-thymus (CT-DNA) is widely used as binding agent. The commercial samples are known to be "highly polymerized DNA" samples. CT-DNA is known to be fragile in particular upon ultrasonic wave irradiation. Degradation products might have dramatic consequence on its bio-sensing activity, and an accurate determination of the molecular weight distribution and stability of commercial samples is highly demanded. We investigated the sensitivity of charge detection mass spectrometry (CDMS), a single-molecule MS method, both with single-pass and ion trap CDMS ("Benner" trap) modes to the determination of the composition and stability (under multiphoton IR irradiation) of calf-thymus DNAs. We also investigated the changes of molecular weight distributions in the course of sonication by irradiating ultrasonic wave to CT-DNA. We report for the first time, the direct molecular weight (MW) distribution of DNA sodium salt from calf-thymus revealing two populations at high (~10 MDa) and low (~3 MDa) molecular weights. We evidence a transition between the high-MW to the low-MW distribution, confirming that the low-MW distribution results from degradation of CT-DNA. Finally, we report also IRMPD experiments carried out on trapped single-stranded linear DNAs from calf-thymus allowing to extract their activation energy for unimolecular dissociation. We show that single-pass CDMS is a direct, efficient and accurate MS-based approach to determine the composition of calf-thymus DNAs. Furthermore, ion trap CDMS allows us to evaluate the stability (both under multiphoton IR irradiation and in the course of sonication by irradiating ultrasonic wave) of calf-thymus DNAs. This article is protected by copyright. All rights reserved.

Molecular plasmonics: The role of rovibrational molecular states in exciton-plasmon materials under strong-coupling conditions

Science.gov (United States)

Sukharev, Maxim; Charron, Eric

2017-03-01

We extend the model of exciton-plasmon materials to include a rovibrational structure of molecules using wave-packet propagations on electronic potential energy surfaces. Our model replaces conventional two-level emitters with more complex molecules, allowing us to examine the influence of alignment and vibrational dynamics on strong coupling with surface plasmon-polaritons. We apply the model to a hybrid system comprising a thin layer of molecules placed on top of a periodic array of slits. Rigorous simulations are performed for two types of molecular systems described by vibrational bound-bound and bound-continuum electronic transitions. Calculations reveal new features in transmission, reflection, and absorption spectra, including the observation of significantly higher values of the Rabi splitting and vibrational patterns clearly seen in the corresponding spectra. We also examine the influence of anisotropic initial conditions on optical properties of hybrid materials, demonstrating that the optical response of the system is significantly affected by an initial prealignment of the molecules. Our work demonstrates that prealigned molecules could serve as an efficient probe for the subdiffraction characterization of the near-field near metal interfaces.

Thermodynamic properties by equation of state and from Ab initio molecular dynamics of liquid potassium under pressure

Science.gov (United States)

Li, Huaming; Tian, Yanting; Sun, Yongli; Li, Mo; Nonequilibrium materials; physics Team; Computational materials science Team

In this work, we apply a general equation of state of liquid and Ab initio molecular-dynamics method to study thermodynamic properties in liquid potassium under high pressure. Isothermal bulk modulus and molar volume of molten sodium are calculated within good precision as compared with the experimental data. The calculated internal energy data and the calculated values of isobaric heat capacity of molten potassium show the minimum along the isothermal lines as the previous result obtained in liquid sodium. The expressions for acoustical parameter and nonlinearity parameter are obtained based on thermodynamic relations from the equation of state. Both parameters for liquid potassium are calculated under high pressure along the isothermal lines by using the available thermodynamic data and numeric derivations. Furthermore, Ab initio molecular-dynamics simulations are used to calculate some thermodynamic properties of liquid potassium along the isothermal lines. Scientific Research Starting Foundation from Taiyuan university of Technology, Shanxi Provincial government (``100-talents program''), China Scholarship Council and National Natural Science Foundation of China (NSFC) under Grant No. 51602213.

Molecular shape and binding force of Mycoplasma mobile's leg protein Gli349 revealed by an AFM study

Energy Technology Data Exchange (ETDEWEB)

Lesoil, Charles [Department of Life Science, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Nagatsutacho 4259, Midori-ku, Yokohama 226-8501 (Japan); Nonaka, Takahiro [Department of Biology, Graduate School of Science, Osaka City University, Sumiyoshi-ku, Osaka 558-8585 (Japan); Sekiguchi, Hiroshi; Osada, Toshiya [Department of Life Science, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Nagatsutacho 4259, Midori-ku, Yokohama 226-8501 (Japan); Miyata, Makoto [Department of Biology, Graduate School of Science, Osaka City University, Sumiyoshi-ku, Osaka 558-8585 (Japan); Afrin, Rehana [Department of Life Science, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Nagatsutacho 4259, Midori-ku, Yokohama 226-8501 (Japan); Biofrontier Center, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Nagatsutacho 4259, Midori-ku, Yokohama 226-8501 (Japan); Ikai, Atsushi, E-mail: ikai.a.aa@m.titech.ac.jp [Department of Life Science, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Nagatsutacho 4259, Midori-ku, Yokohama 226-8501 (Japan)

2010-01-15

Recent studies of the gliding bacteria Mycoplasma mobile have identified a family of proteins called the Gli family which was considered to be involved in this novel and yet fairly unknown motility system. The 349 kDa protein called Gli349 was successfully isolated and purified from the bacteria, and electron microscopy imaging and antibody experiments led to the hypothesis that it acts as the 'leg' of M. mobile, responsible for attachment to the substrate as well as for gliding motility. However, more precise evidence of the molecular shape and function of this protein was required to asses this theory any further. In this study, an atomic force microscope (AFM) was used both as an imaging and a force measurement device to provide new information about Gli349 and its role in gliding motility. AFM images of the protein were obtained revealing a complex structure with both rigid and flexible parts, consistent with previous electron micrographs of the protein. Single-molecular force spectroscopy experiments were also performed, revealing that Gli349 is able to specifically bind to sialyllactose molecules and withstand unbinding forces around 70 pN. These findings strongly support the idea that Gli349 is the 'leg' protein of M. mobile, responsible for binding and also most probably force generation during gliding motility.

Revealing the Molecular Structural Transformation of Hardwood and Softwood in Dilute Acid Flowthrough Pretreatment

Energy Technology Data Exchange (ETDEWEB)

Zhang, Libing; Pu, Yunqiao; Cort, John R.; Ragauskas, Arthur J.; Yang, Bin

2016-12-05

To better understand the intrinsic recalcitrance of lignocellulosic biomass, the main hurdle to its efficient deconstruction, the effects of dilute acid flowthrough pretreatment on the dissolution chemistry of hemicellulose, cellulose, and lignin for both hardwood (e.g. poplar wood) and softwood (e.g. lodgepole pine wood) were investigated at temperatures of 200 °C to 270 °C and a flow rate of 25 mL/minute with 0.05% (w/w) H2SO4. Results suggested that the softwood cellulose was more readily to be degraded into monomeric sugars than that of hardwood under same pretreatment conditions. However, while the hardwood lignin was completely removed into hydrolysate, ~30% of the softwood lignin remained as solid residues under identical conditions, which was plausibly caused by vigorous C5-active recondensation reactions (C-C5). Unique molecular structural features that pronounced the specific recalcitrance of hardwood and softwood to dilute acid pretreatment were identified for the first time in this study, providing important insights to establish the effective biomass pretreatment.

Phylogeography and molecular diversity analysis of Jatropha curcas L. and the dispersal route revealed by RAPD, AFLP and nrDNA-ITS analysis.

Science.gov (United States)

Sudheer Pamidimarri, D V N; Reddy, Muppala P

2014-05-01

Jatropha curcas L. (Euphorbiaceae) has acquired a great importance as a renewable source of energy with a number of environmental benefits. Very few attempts were made to understand the extent of genetic diversity and its distribution. This study was aimed to study the diversity and deduce the phylogeography of Jatropha curcas L. which is said to be the most primitive species of the genus Jatropha. Here we studied the intraspecific genetic diversity of the species distributed in different parts of the globe. The study also focused to understand the molecular diversity at reported probable center of origin (Mexico), and to reveal the dispersal route to other regions based on random amplified polymorphic DNA, amplified fragment length polymorphism and nrDNA-ITS sequences data. The overall genetic diversity of J. curcas found in the present study was narrow. The highest genetic diversity was observed in the germplasm collected from Mexico and supports the earlier hypothesis based on morphological data and natural distribution, it is the center for origin of the species. Least genetic diversity found in the Indian germplasm and clustering results revealed that the species was introduced simultaneously by two distinct germplasm and subsequently distributed in different parts of India. The present molecular data further revealed that J. curcas might have spread from the center of the origin to Cape Verde, than to Spain, Portuguese to other neighboring countries and simultaneously to Africa. The molecular evidence supports the Burkill et al. (A dictionary of the economic products of the Malay Peninsula, Governments of Malaysia and Singapore by the Ministry of Agriculture and Co-operatives. Kuala Lumpur, Malaysia, 1966) view of Portuguese might have introduced the species to India. The clustering pattern suggests that the distribution was interfered by human activity.

Phylogeography and molecular diversity analysis of Jatropha curcas L. and the dispersal route revealed by RAPD, AFLP and nrDNA-ITS analysis

KAUST Repository

Sudheer Pamidimarri, D. V N

2014-01-29

Jatropha curcas L. (Euphorbiaceae) has acquired a great importance as a renewable source of energy with a number of environmental benefits. Very few attempts were made to understand the extent of genetic diversity and its distribution. This study was aimed to study the diversity and deduce the phylogeography of Jatropha curcas L. which is said to be the most primitive species of the genus Jatropha. Here we studied the intraspecific genetic diversity of the species distributed in different parts of the globe. The study also focused to understand the molecular diversity at reported probable center of origin (Mexico), and to reveal the dispersal route to other regions based on random amplified polymorphic DNA, amplified fragment length polymorphism and nrDNA-ITS sequences data. The overall genetic diversity of J. curcas found in the present study was narrow. The highest genetic diversity was observed in the germplasm collected from Mexico and supports the earlier hypothesis based on morphological data and natural distribution, it is the center for origin of the species. Least genetic diversity found in the Indian germplasm and clustering results revealed that the species was introduced simultaneously by two distinct germplasm and subsequently distributed in different parts of India. The present molecular data further revealed that J. curcas might have spread from the center of the origin to Cape Verde, than to Spain, Portuguese to other neighboring countries and simultaneously to Africa. The molecular evidence supports the Burkill et al. (A dictionary of the economic products of the Malay Peninsula, Governments of Malaysia and Singapore by the Ministry of Agriculture and Co-operatives. Kuala Lumpur, Malaysia, 1966) view of Portuguese might have introduced the species to India. The clustering pattern suggests that the distribution was interfered by human activity. © Springer Science+Business Media 2014.

Yield, Esterification Degree and Molecular Weight Evaluation of Pectins Isolated from Orange and Grapefruit Peels under Different Conditions

Science.gov (United States)

Sayah, Mohamed Yassine; Chabir, Rachida; Benyahia, Hamid; Rodi Kandri, Youssef; Ouazzani Chahdi, Fouad; Touzani, Hanan; Errachidi, Faouzi

2016-01-01

Orange (Citrus sinensis) and grapefruit (Citrus paradise) peels were used as a source of pectin, which was extracted under different conditions. The peels are used under two states: fresh and residual (after essential oil extraction). Organic acid (citric acid) and mineral acid (sulfuric acid) were used in the pectin extraction. The aim of this study is the evaluation the effect of extraction conditions on pectin yield, degree of esterification “DE” and on molecular weight “Mw”. Results showed that the pectin yield was higher using the residual peels. Moreover, both peels allow the obtainment of a high methoxyl pectin with DE >50%. The molecular weight was calculated using Mark-Houwink-Sakurada equation which describes its relationship with intrinsic viscosity. This later was determined using four equations; Huggins equation, kramer, Schulz-Blaschke and Martin equation. The molecular weight varied from 1.538 x1005 to 2.47x1005 g/mol for grapefruit pectin and from 1.639 x1005 to 2.471 x1005 g/mol for orange pectin. PMID:27644093

Structure and Orientation of Bovine Lactoferrampin in the Mimetic Bacterial Membrane as Revealed by Solid-State NMR and Molecular Dynamics Simulation

Science.gov (United States)

Tsutsumi, Atsushi; Javkhlantugs, Namsrai; Kira, Atsushi; Umeyama, Masako; Kawamura, Izuru; Nishimura, Katsuyuki; Ueda, Kazuyoshi; Naito, Akira

2012-01-01

Bovine lactoferrampin (LFampinB) is a newly discovered antimicrobial peptide found in the N1-domain of bovine lactoferrin (268–284), and consists of 17 amino-acid residues. It is important to determine the orientation and structure of LFampinB in bacterial membranes to reveal the antimicrobial mechanism. We therefore performed 13C and 31P NMR, 13C-31P rotational echo double resonance (REDOR), potassium ion-selective electrode, and quartz-crystal microbalance measurements for LFampinB with mimetic bacterial membrane and molecular-dynamics simulation in acidic membrane. 31P NMR results indicated that LFampinB caused a defect in mimetic bacterial membranes. Ion-selective electrode measurements showed that ion leakage occurred for the mimetic bacterial membrane containing cardiolipin. Quartz-crystal microbalance measurements revealed that LFampinB had greater affinity to acidic phospholipids than that to neutral phospholipids. 13C DD-MAS and static NMR spectra showed that LFampinB formed an α-helix in the N-terminus region and tilted 45° to the bilayer normal. REDOR dephasing patterns between carbonyl carbon nucleus in LFampinB and phosphorus nuclei in lipid phosphate groups were measured by 13C-31P REDOR and the results revealed that LFampinB is located in the interfacial region of the membrane. Molecular-dynamics simulation showed the tilt angle to be 42° and the rotation angle to be 92.5° for Leu3, which are in excellent agreement with the experimental values. PMID:23083717

THE MOLECULAR WIND IN THE NEAREST SEYFERT GALAXY CIRCINUS REVEALED BY ALMA

Energy Technology Data Exchange (ETDEWEB)

Zschaechner, Laura K.; Walter, Fabian; Farina, Emanuele P.; Kruijssen, J. M. Diederik [Max Planck Institute für Astronomie—Königstuhl 17, D-69117 Heidelberg (Germany); Bolatto, Alberto; Veilleux, Sylvain [Department of Astronomy and Joint Space Science Institute, University of Maryland, College Park, MD 20642 (United States); Leroy, Adam [Department of Astronomy, The Ohio State University, 140 West 18th Avenue, Columbus, OH 43210 (United States); Meier, David S. [Department of Physics, New Mexico Institute of Mining and Technology, 801 Leroy Place, Socorro, NM 87801 (United States); Ott, Jürgen, E-mail: zschaechner@mpia.de [National Radio Astronomy Observatory—P.O. Box O, 1003 Lopezville Road, Socorro, NM 87801 (United States)

2016-12-01

We present ALMA observations of the inner 1′ (1.2 kpc) of the Circinus galaxy, the nearest Seyfert. We target CO (1–0) in the region associated with a well-known multiphase outflow driven by the central active galactic nucleus (AGN). While the geometry of Circinus and its outflow make disentangling the latter difficult, we see indications of outflowing molecular gas at velocities consistent with the ionized outflow. We constrain the mass of the outflowing molecular gas to be 1.5 × 10{sup 5}−5.1 × 10{sup 6} M {sub ⊙}, yielding a molecular outflow rate of 0.35–12.3 M {sub ⊙} yr{sup −1}. The values within this range are comparable to the star formation (SF) rate in Circinus, indicating that the outflow indeed regulates SF to some degree. The molecular outflow in Circinus is considerably lower in mass and energetics than previously studied AGN-driven outflows, especially given its high ratio of AGN luminosity to bolometric luminosity. The molecular outflow in Circinus is, however, consistent with some trends put forth by Cicone et al., including a linear relation between kinetic power and AGN luminosity, as well as its momentum rate versus bolometric luminosity (although the latter places Circinus among the starburst galaxies in that sample). We detect additional molecular species including CN and C{sup 17}O.

Molecular Dynamics Simulations of Orai Reveal How the Third Transmembrane Segment Contributes to Hydration and Ca2+ Selectivity in Calcium Release-Activated Calcium Channels.

Science.gov (United States)

Alavizargar, Azadeh; Berti, Claudio; Ejtehadi, Mohammad Reza; Furini, Simone

2018-04-26

Calcium release-activated calcium (CRAC) channels open upon depletion of Ca 2+ from the endoplasmic reticulum, and when open, they are permeable to a selective flux of calcium ions. The atomic structure of Orai, the pore domain of CRAC channels, from Drosophila melanogaster has revealed many details about conduction and selectivity in this family of ion channels. However, it is still unclear how residues on the third transmembrane helix can affect the conduction properties of the channel. Here, molecular dynamics and Brownian dynamics simulations were employed to analyze how a conserved glutamate residue on the third transmembrane helix (E262) contributes to selectivity. The comparison between the wild-type and mutated channels revealed a severe impact of the mutation on the hydration pattern of the pore domain and on the dynamics of residues K270, and Brownian dynamics simulations proved that the altered configuration of residues K270 in the mutated channel impairs selectivity to Ca 2+ over Na + . The crevices of water molecules, revealed by molecular dynamics simulations, are perfectly located to contribute to the dynamics of the hydrophobic gate and the basic gate, suggesting a possible role in channel opening and in selectivity function.

Gene expression profiling reveals underlying molecular mechanisms of the early stages of tamoxifen-induced rat hepatocarcinogenesis

International Nuclear Information System (INIS)

Pogribny, Igor P.; Bagnyukova, Tetyana V.; Tryndyak, Volodymyr P.; Muskhelishvili, Levan; Rodriguez-Juarez, Rocio; Kovalchuk, Olga; Han Tao; Fuscoe, James C.; Ross, Sharon A.; Beland, Frederick A.

2007-01-01

Tamoxifen is a widely used anti-estrogenic drug for chemotherapy and, more recently, for the chemoprevention of breast cancer. Despite the indisputable benefits of tamoxifen in preventing the occurrence and re-occurrence of breast cancer, the use of tamoxifen has been shown to induce non-alcoholic steatohepatitis, which is a life-threatening fatty liver disease with a risk of progression to cirrhosis and hepatocellular carcinoma. In recent years, the high-throughput microarray technology for large-scale analysis of gene expression has become a powerful tool for increasing the understanding of the molecular mechanisms of carcinogenesis and for identifying new biomarkers with diagnostic and predictive values. In the present study, we used the high-throughput microarray technology to determine the gene expression profiles in the liver during early stages of tamoxifen-induced rat hepatocarcinogenesis. Female Fisher 344 rats were fed a 420 ppm tamoxifen containing diet for 12 or 24 weeks, and gene expression profiles were determined in liver of control and tamoxifen-exposed rats. The results indicate that early stages of tamoxifen-induced liver carcinogenesis are characterized by alterations in several major cellular pathways, specifically those involved in the tamoxifen metabolism, lipid metabolism, cell cycle signaling, and apoptosis/cell proliferation control. One of the most prominent changes during early stages of tamoxifen-induced hepatocarcinogenesis is dysregulation of signaling pathways in cell cycle progression from the G 1 to S phase, evidenced by the progressive and sustained increase in expression of the Pdgfc, Calb3, Ets1, and Ccnd1 genes accompanied by the elevated level of the PI3K, p-PI3K, Akt1/2, Akt3, and cyclin B, D1, and D3 proteins. The early appearance of these alterations suggests their importance in the mechanism of neoplastic cell transformation induced by tamoxifen

D2+ Molecular complex in non-uniform height quantum ribbon under crossed electric and magnetic fields

Science.gov (United States)

Suaza, Y. A.; Laroze, D.; Fulla, M. R.; Marín, J. H.

2018-05-01

The D2+ molecular complex fundamental properties in a uniform and multi-hilled semiconductor quantum ribbon under orthogonal electric and magnetic fields are theoretically studied. The energy structure is calculated by using adiabatic approximation combined with diagonalization procedure. The D2+ energy structure is more strongly controlled by the geometrical structural hills than the Coulomb interaction. The formation of vibrational and rotational states is discussed. Aharanov-Bohm oscillation patterns linked to rotational states as well as the D2+ molecular complex stability are highly sensitive to the number of hills while electric field breaks the electron rotational symmetry and removes the energy degeneration between low-lying states.

Systematic chemical and molecular profiling of MLL-rearranged infant acute lymphoblastic leukemia reveals efficacy of romidepsin

Science.gov (United States)

Cruickshank, M N; Ford, J; Cheung, L C; Heng, J; Singh, S; Wells, J; Failes, T W; Arndt, G M; Smithers, N; Prinjha, R K; Anderson, D; Carter, K W; Gout, A M; Lassmann, T; O'Reilly, J; Cole, C H; Kotecha, R S; Kees, U R

2017-01-01

To address the poor prognosis of mixed lineage leukemia (MLL)-rearranged infant acute lymphoblastic leukemia (iALL), we generated a panel of cell lines from primary patient samples and investigated cytotoxic responses to contemporary and novel Food and Drug Administration-approved chemotherapeutics. To characterize representation of primary disease within cell lines, molecular features were compared using RNA-sequencing and cytogenetics. High-throughput screening revealed variable efficacy of currently used drugs, however identified consistent efficacy of three novel drug classes: proteasome inhibitors, histone deacetylase inhibitors and cyclin-dependent kinase inhibitors. Gene expression of drug targets was highly reproducible comparing iALL cell lines to matched primary specimens. Histone deacetylase inhibitors, including romidepsin (ROM), enhanced the activity of a key component of iALL therapy, cytarabine (ARAC) in vitro and combined administration of ROM and ARAC to xenografted mice further reduced leukemia burden. Molecular studies showed that ROM reduces expression of cytidine deaminase, an enzyme involved in ARAC deactivation, and enhances the DNA damage–response to ARAC. In conclusion, we present a valuable resource for drug discovery, including the first systematic analysis of transcriptome reproducibility in vitro, and have identified ROM as a promising therapeutic for MLL-rearranged iALL. PMID:27443263

Comparative Phenotypical and Molecular Analyses of Arabidopsis Grown under Fluorescent and LED Light

Directory of Open Access Journals (Sweden)

Franka Seiler

2017-06-01

Full Text Available Comparative analyses of phenotypic and molecular traits of Arabidopsis thaliana grown under standardised conditions is still a challenge using climatic devices supplied with common light sources. These are in most cases fluorescent lights, which have several disadvantages such as heat production at higher light intensities, an invariable spectral output, and relatively rapid “ageing”. This results in non-desired variations of growth conditions and lowers the comparability of data acquired over extended time periods. In this study, we investigated the growth behaviour of Arabidopsis Col0 under different light conditions, applying fluorescent compared to LED lamps, and we conducted physiological as well as gene expression analyses. By changing the spectral composition and/or light intensity of LEDs we can clearly influence the growth behaviour of Arabidopsis and thereby study phenotypic attributes under very specific light conditions that are stable and reproducible, which is not necessarily given for fluorescent lamps. By using LED lights, we can also roughly mimic the sun light emission spectrum, enabling us to study plant growth in a more natural-like light set-up. We observed distinct growth behaviour under the different light regimes which was reflected by physiological properties of the plants. In conclusion, LEDs provide variable emission spectra for studying plant growth under defined, stable light conditions.

Thermal conductivity of graphene nanoribbons under shear deformation: A molecular dynamics simulation

Science.gov (United States)

Zhang, Chao; Hao, Xiao-Li; Wang, Cui-Xia; Wei, Ning; Rabczuk, Timon

2017-01-01

Tensile strain and compress strain can greatly affect the thermal conductivity of graphene nanoribbons (GNRs). However, the effect of GNRs under shear strain, which is also one of the main strain effect, has not been studied systematically yet. In this work, we employ reverse nonequilibrium molecular dynamics (RNEMD) to the systematical study of the thermal conductivity of GNRs (with model size of 4 nm × 15 nm) under the shear strain. Our studies show that the thermal conductivity of GNRs is not sensitive to the shear strain, and the thermal conductivity decreases only 12–16% before the pristine structure is broken. Furthermore, the phonon frequency and the change of the micro-structure of GNRs, such as band angel and bond length, are analyzed to explore the tendency of thermal conductivity. The results show that the main influence of shear strain is on the in-plane phonon density of states (PDOS), whose G band (higher frequency peaks) moved to the low frequency, thus the thermal conductivity is decreased. The unique thermal properties of GNRs under shear strains suggest their great potentials for graphene nanodevices and great potentials in the thermal managements and thermoelectric applications. PMID:28120921

Molecular analyses reveal two geographic and genetic lineages for tapeworms, Taenia solium and Taenia saginata, from Ecuador using mitochondrial DNA.

Science.gov (United States)

Solano, Danilo; Navarro, Juan Carlos; León-Reyes, Antonio; Benítez-Ortiz, Washington; Rodríguez-Hidalgo, Richar

2016-12-01

Tapeworms Taenia solium and Taenia saginata are the causative agents of taeniasis/cysticercosis. These are diseases with high medical and veterinary importance due to their impact on public health and rural economy in tropical countries. The re-emergence of T. solium as a result of human migration, the economic burden affecting livestock industry, and the large variability of symptoms in several human cysticercosis, encourage studies on genetic diversity, and the identification of these parasites with molecular phylogenetic tools. Samples collected from the Ecuadorian provinces: Loja, Guayas, Manabí, Tungurahua (South), and Imbabura, Pichincha (North) from 2000 to 2012 were performed under Maximum Parsimony analyses and haplotype networks using partial sequences of mitochondrial DNA, cytochrome oxidase subunit I (COI) and NADH subunit I (NDI), from Genbank and own sequences of Taenia solium and Taenia saginata from Ecuador. Both species have shown reciprocal monophyly, which confirms its molecular taxonomic identity. The COI and NDI genes results suggest phylogenetic structure for both parasite species from south and north of Ecuador. In T. solium, both genes gene revealed greater geographic structure, whereas in T. saginata, the variability for both genes was low. In conclusion, COI haplotype networks of T. solium suggest two geographical events in the introduction of this species in Ecuador (African and Asian lineages) and occurring sympatric, probably through the most common routes of maritime trade between the XV-XIX centuries. Moreover, the evidence of two NDI geographical lineages in T. solium from the north (province of Imbabura) and the south (province of Loja) of Ecuador derivate from a common Indian ancestor open new approaches for studies on genetic populations and eco-epidemiology. Copyright © 2016 Elsevier Inc. All rights reserved.

Two Antarctic penguin genomes reveal insights into their evolutionary history and molecular changes related to the Antarctic environment.

Science.gov (United States)

Li, Cai; Zhang, Yong; Li, Jianwen; Kong, Lesheng; Hu, Haofu; Pan, Hailin; Xu, Luohao; Deng, Yuan; Li, Qiye; Jin, Lijun; Yu, Hao; Chen, Yan; Liu, Binghang; Yang, Linfeng; Liu, Shiping; Zhang, Yan; Lang, Yongshan; Xia, Jinquan; He, Weiming; Shi, Qiong; Subramanian, Sankar; Millar, Craig D; Meader, Stephen; Rands, Chris M; Fujita, Matthew K; Greenwold, Matthew J; Castoe, Todd A; Pollock, David D; Gu, Wanjun; Nam, Kiwoong; Ellegren, Hans; Ho, Simon Yw; Burt, David W; Ponting, Chris P; Jarvis, Erich D; Gilbert, M Thomas P; Yang, Huanming; Wang, Jian; Lambert, David M; Wang, Jun; Zhang, Guojie

2014-01-01

Penguins are flightless aquatic birds widely distributed in the Southern Hemisphere. The distinctive morphological and physiological features of penguins allow them to live an aquatic life, and some of them have successfully adapted to the hostile environments in Antarctica. To study the phylogenetic and population history of penguins and the molecular basis of their adaptations to Antarctica, we sequenced the genomes of the two Antarctic dwelling penguin species, the Adélie penguin [Pygoscelis adeliae] and emperor penguin [Aptenodytes forsteri]. Phylogenetic dating suggests that early penguins arose ~60 million years ago, coinciding with a period of global warming. Analysis of effective population sizes reveals that the two penguin species experienced population expansions from ~1 million years ago to ~100 thousand years ago, but responded differently to the climatic cooling of the last glacial period. Comparative genomic analyses with other available avian genomes identified molecular changes in genes related to epidermal structure, phototransduction, lipid metabolism, and forelimb morphology. Our sequencing and initial analyses of the first two penguin genomes provide insights into the timing of penguin origin, fluctuations in effective population sizes of the two penguin species over the past 10 million years, and the potential associations between these biological patterns and global climate change. The molecular changes compared with other avian genomes reflect both shared and diverse adaptations of the two penguin species to the Antarctic environment.

RNA-Seq reveals the molecular mechanism of trapping and killing of root-knot nematodes by nematode-trapping fungi.

Science.gov (United States)

Pandit, Ramesh; Patel, Reena; Patel, Namrata; Bhatt, Vaibhav; Joshi, Chaitanya; Singh, Pawan Kumar; Kunjadia, Anju

2017-04-01

Nematode-trapping fungi are well known for their inherent potential to trap and kill nematodes using specialized trapping devices. However, the molecular mechanisms underlying the trapping and subsequent processes are still unclear. Therefore, in this study, we examined differential genes expression in two nematode-trapping fungi after baiting with nematode extracts. In Arthrobotrys conoides, 809 transcripts associated with diverse functions such as signal transduction, morphogenesis, stress response and peroxisomal proteins, proteases, chitinases and genes involved in the host-pathogen interaction showed differential expression with fold change (>±1.5 fold) in the presence of nematode extract with FDR (p-value nematode-trapping fungi for its host. The findings illustrate the molecular mechanism of fungal parasitism in A. conoides which may be helpful in developing a potential biocontrol agent against parasitic nematodes.

Influence of the molecular modifications on the properties of EPDM elastomers under irradiation

Energy Technology Data Exchange (ETDEWEB)

Davenas, J. E-mail: joel.davenas@univ-lyon1.fr; Stevenson, I.; Celette, N.; Vigier, G.; David, L

2003-08-01

The degradation of the mechanical behaviour of EPDM elastomers used as cable insulation materials has been investigated by mechanical spectroscopy and tensile tests for different formulations: unvulcanised EPDM, vulcanised and stabilised elastomer with an antioxidant. In all cases, {gamma}-irradiation of EPDM under oxygen leads to a reduction of the molecular mobility indicated by the shift of the glass transition relaxation temperature towards higher temperatures. Moreover, the molecular flow occurring above T{sub g} is suppressed after irradiation for the unvulcanised EPDM providing evidence of cross-linking. The competition between cross-linking and chain scissions is shown by the decrease of the storage modulus above the crystallites melting temperature ({approx}40 deg. C) at doses larger than 100 kGy. A strong increase of the Young modulus and reduction of the elongation at break of the non-vulcanised EPDM becoming more brittle are shown by stress/strain characterisations performed at 80 deg. C. At the opposite vulcanised EPDM exhibits higher elongation at break after crystallites melting. This evolution is interpreted by the competition between cross-linking and chain scissions, being hindered by the crystallites at room temperature. The intrinsic irradiation effects can be isolated after crystallite melting. The reduction of the molecular mobility can be explained by a chemi-crystallisation process assisted by chain scissions, leading to a more rigid phase upon irradiation.

Influence of the molecular modifications on the properties of EPDM elastomers under irradiation

International Nuclear Information System (INIS)

Davenas, J.; Stevenson, I.; Celette, N.; Vigier, G.; David, L.

2003-01-01

The degradation of the mechanical behaviour of EPDM elastomers used as cable insulation materials has been investigated by mechanical spectroscopy and tensile tests for different formulations: unvulcanised EPDM, vulcanised and stabilised elastomer with an antioxidant. In all cases, γ-irradiation of EPDM under oxygen leads to a reduction of the molecular mobility indicated by the shift of the glass transition relaxation temperature towards higher temperatures. Moreover, the molecular flow occurring above T g is suppressed after irradiation for the unvulcanised EPDM providing evidence of cross-linking. The competition between cross-linking and chain scissions is shown by the decrease of the storage modulus above the crystallites melting temperature (∼40 deg. C) at doses larger than 100 kGy. A strong increase of the Young modulus and reduction of the elongation at break of the non-vulcanised EPDM becoming more brittle are shown by stress/strain characterisations performed at 80 deg. C. At the opposite vulcanised EPDM exhibits higher elongation at break after crystallites melting. This evolution is interpreted by the competition between cross-linking and chain scissions, being hindered by the crystallites at room temperature. The intrinsic irradiation effects can be isolated after crystallite melting. The reduction of the molecular mobility can be explained by a chemi-crystallisation process assisted by chain scissions, leading to a more rigid phase upon irradiation

Negative correlation between rates of molecular evolution and flowering cycles in temperate woody bamboos revealed by plastid phylogenomics.

Science.gov (United States)

Ma, Peng-Fei; Vorontsova, Maria S; Nanjarisoa, Olinirina Prisca; Razanatsoa, Jacqueline; Guo, Zhen-Hua; Haevermans, Thomas; Li, De-Zhu

2017-12-21

Heterogeneous rates of molecular evolution are universal across the tree of life, posing challenges for phylogenetic inference. The temperate woody bamboos (tribe Arundinarieae, Poaceae) are noted for their extremely slow molecular evolutionary rates, supposedly caused by their mysterious monocarpic reproduction. However, the correlation between substitution rates and flowering cycles has not been formally tested. Here we present 15 newly sequenced plastid genomes of temperate woody bamboos, including the first genomes ever sequenced from Madagascar representatives. A data matrix of 46 plastid genomes representing all 12 lineages of Arundinarieae was assembled for phylogenetic and molecular evolutionary analyses. We conducted phylogenetic analyses using different sequences (e.g., coding and noncoding) combined with different data partitioning schemes, revealing conflicting relationships involving internodes among several lineages. A great difference in branch lengths were observed among the major lineages, and topological inconsistency could be attributed to long-branch attraction (LBA). Using clock model-fitting by maximum likelihood and Bayesian approaches, we furthermore demonstrated extensive rate variation among these major lineages. Rate accelerations mainly occurred for the isolated lineages with limited species diversification, totaling 11 rate shifts during the tribe's evolution. Using linear regression analysis, we found a negative correlation between rates of molecular evolution and flowering cycles for Arundinarieae, notwithstanding that the correlation maybe insignificant when taking the phylogenetic structure into account. Using the temperate woody bamboos as an example, we found further evidence that rate heterogeneity is universal in plants, suggesting that this will pose a challenge for phylogenetic reconstruction of bamboos. The bamboos with longer flowering cycles tend to evolve more slowly than those with shorter flowering cycles, in accordance

Observation of molecular level behavior in molecular electronic junction device

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Maitani, Masato

In this dissertation, I utilize AFM based scanning probe measurement and surface enhanced Raman scattering based vibrational spectroscopic analysis to directly characterize topographic, electronic, and chemical properties of molecules confined in the local area of M3 junction to elucidate the molecular level behavior of molecular junction electronic devices. In the introduction, the characterization of molecular electronic devices with different types of metal-molecule-metal (M3) structures based upon self-assembled monolayers (SAMs) is reviewed. A background of the characterization methods I use in this dissertation, conducting probe atomic force microscopy (cp-AFM) and surface enhanced Raman spectroscopy (SERS), is provided in chapter 1. Several attempts are performed to create the ideal top metal contacts on SAMs by metal vapor phase deposition in order to prevent the metal penetration inducing critical defects of the molecular electronic devices. The scanning probe microscopy (SPM), such as cp-AFM, contact mode (c-) AFM and non-contact mode (nc-) AFM, in ultra high vacuum conditions are utilized to study the process of the metal-SAM interface construction in terms of the correlation between the morphological and electrical properties including the metal nucleation and filament generation as a function of the functionalization of long-chain alkane thiolate SAMs on Au. In chapter 2, the nascent condensation process of vapor phase Al deposition on inert and reactive SAMs are studied by SPM. The results of top deposition, penetration, and filament generation of deposited Al are discussed and compared to the results previously observed by spectroscopic measurements. Cp-AFM was shown to provide new insights into Al filament formation which has not been observed by conventional spectroscopic analysis. Additionally, the electronic characteristics of individual Al filaments are measured. Chapter 3 reveals SPM characterization of Au deposition onto --COOH terminated SAMs

Characterization of 1,577 Primary Prostate Cancers Reveals Novel Biological and Clinicopathological Insights into Molecular Subtypes

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Tomlins, Scott A.; Alshalalfa, Mohammed; Davicioni, Elai; Erho, Nicholas; Yousefi, Kasra; Zhao, Shuang; Haddad, Zaid; Den, Robert B.; Dicker, Adam P.; Trock, Bruce; DeMarzo, Angelo; Ross, Ashley; Schaeffer, Edward M.; Klein, Eric A.; Magi-Galluzzi, Cristina; Karnes, Jeffery R.; Jenkins, Robert B.; Feng, Felix Y.

2015-01-01

Background Prostate cancer (PCa) molecular subtypes have been defined by essentially mutually exclusive events, including ETS gene fusions (most commonly involving ERG) and SPINK1 over-expression. Clinical assessment may aid in disease stratification, complementing available prognostic tests. Objective To determine the analytical validity and clinicopatholgical associations of microarray-based molecular subtyping. Design, Setting and Participants We analyzed Affymetrix GeneChip expression profiles for 1,577 patients from eight radical prostatectomy (RP) cohorts, including 1,351 cases assessed using the Decipher prognostic assay (performed in a CLIA-certified laboratory). A microarray-based (m-) random forest ERG classification model was trained and validated. Outlier expression analysis was used to predict other mutually exclusive non-ERG ETS gene rearrangements (ETS+) or SPINK1 over-expression (SPINK1+). Outcome Measurements Associations with clinical features and outcomes by multivariable logistic regression analysis and receiver operating curves. Results and Limitations The m-ERG classifier showed 95% accuracy in an independent validation subset (n=155 samples). Across cohorts, 45%, 9%, 8% and 38% of PCa were classified as m-ERG+, m-ETS+, m-SPINK1+, and triple negative (m-ERG−/m-ETS−/m-SPINK1−), respectively. Gene expression profiling supports three underlying molecularly defined groups (m-ERG+, m-ETS+ and m-SPINK1+/triple negative). On multivariable analysis, m-ERG+ tumors were associated with lower preoperative serum PSA and Gleason scores, but enriched for extraprostatic extension (p<0.001). m-ETS+ tumors were associated with seminal vesicle invasion (p=0.01), while m-SPINK1+/triple negative tumors had higher Gleason scores and were more frequent in Black/African American patients (p<0.001). Clinical outcomes were not significantly different between subtypes. Conclusions A clinically available prognostic test (Decipher) can also assess PCa molecular

Essential concepts and underlying theories from physics, chemistry, and mathematics for "biochemistry and molecular biology" majors.

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Wright, Ann; Provost, Joseph; Roecklein-Canfield, Jennifer A; Bell, Ellis

2013-01-01

Over the past two years, through an NSF RCN UBE grant, the ASBMB has held regional workshops for faculty members from around the country. The workshops have focused on developing lists of Core Principles or Foundational Concepts in Biochemistry and Molecular Biology, a list of foundational skills, and foundational concepts from Physics, Chemistry, and Mathematics that all Biochemistry or Molecular Biology majors must understand to complete their major coursework. The allied fields working group created a survey to validate foundational concepts from Physics, Chemistry, and Mathematics identified from participant feedback at various workshops. One-hundred twenty participants responded to the survey and 68% of the respondents answered yes to the question: "We have identified the following as the core concepts and underlying theories from Physics, Chemistry, and Mathematics that Biochemistry majors or Molecular Biology majors need to understand after they complete their major courses: 1) mechanical concepts from Physics, 2) energy and thermodynamic concepts from Physics, 3) critical concepts of structure from chemistry, 4) critical concepts of reactions from Chemistry, and 5) essential Mathematics. In your opinion, is the above list complete?" Respondents also delineated subcategories they felt should be included in these broad categories. From the results of the survey and this analysis the allied fields working group constructed a consensus list of allied fields concepts, which will help inform Biochemistry and Molecular Biology educators when considering the ASBMB recommended curriculum for Biochemistry or Molecular Biology majors and in the development of appropriate assessment tools to gauge student understanding of how these concepts relate to biochemistry and molecular biology. © 2013 by The International Union of Biochemistry and Molecular Biology.

Recent progress in transition-metal-catalyzed reduction of molecular dinitrogen under ambient reaction conditions.

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Nishibayashi, Yoshiaki

2015-10-05

This paper describes our recent progress in catalytic nitrogen fixation by using transition-metal-dinitrogen complexes as catalysts. Two reaction systems for the catalytic transformation of molecular dinitrogen into ammonia and its equivalent such as silylamine under ambient reaction conditions have been achieved by the molybdenum-, iron-, and cobalt-dinitrogen complexes as catalysts. Many new findings presented here may provide new access to the development of economical nitrogen fixation in place of the Haber-Bosch process.

Post-learning molecular reactivation underlies taste memory consolidation

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Kioko eGuzman-Ramos

2011-09-01

Full Text Available It is considered that memory consolidation is a progressive process that requires post-trial stabilization of the information. In this regard, it has been speculated that waves of receptors activation, expression of immediate early genes and replenishment of receptor subunit pools occur to induce functional or morphological changes to maintain the information for longer periods. In this paper, we will review data related to neuronal changes in the post-acquisition stage of taste aversion learning that could be involved in further stabilization of the memory trace. In order to achieve such stabilization, evidence suggests that the functional integrity of the insular cortex (IC and the amygdala (AMY is required. Particularly the increase of extracellular levels of glutamate and activation of N-methyl-D-aspartate (NMDA receptors within the IC shows a main role in the consolidation process. Additionally the modulatory actions of the dopaminergic system in the IC appear to be involved in the mechanisms that lead to taste aversion memory consolidation through the activation of pathways related to enhancement of protein synthesis such as the Protein Kinase A pathway. In summary, we suggest that post-acquisition molecular and neuronal changes underlying memory consolidation are dependent on the interactions between the AMY and the IC.

Homozygosity mapping and targeted sanger sequencing reveal genetic defects underlying inherited retinal disease in families from pakistan.

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Maleeha Maria

Full Text Available Homozygosity mapping has facilitated the identification of the genetic causes underlying inherited diseases, particularly in consanguineous families with multiple affected individuals. This knowledge has also resulted in a mutation dataset that can be used in a cost and time effective manner to screen frequent population-specific genetic variations associated with diseases such as inherited retinal disease (IRD.We genetically screened 13 families from a cohort of 81 Pakistani IRD families diagnosed with Leber congenital amaurosis (LCA, retinitis pigmentosa (RP, congenital stationary night blindness (CSNB, or cone dystrophy (CD. We employed genome-wide single nucleotide polymorphism (SNP array analysis to identify homozygous regions shared by affected individuals and performed Sanger sequencing of IRD-associated genes located in the sizeable homozygous regions. In addition, based on population specific mutation data we performed targeted Sanger sequencing (TSS of frequent variants in AIPL1, CEP290, CRB1, GUCY2D, LCA5, RPGRIP1 and TULP1, in probands from 28 LCA families.Homozygosity mapping and Sanger sequencing of IRD-associated genes revealed the underlying mutations in 10 families. TSS revealed causative variants in three families. In these 13 families four novel mutations were identified in CNGA1, CNGB1, GUCY2D, and RPGRIP1.Homozygosity mapping and TSS revealed the underlying genetic cause in 13 IRD families, which is useful for genetic counseling as well as therapeutic interventions that are likely to become available in the near future.

Alteration of biomacromolecule in corn by steam flaking in relation to biodegradation kinetics in ruminant, revealed with vibrational molecular spectroscopy.

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Xu, Ningning; Liu, Jianxin; Yu, Peiqiang

2018-02-15

Large scale of steam flaked corn has been used in dairy ration to maintain high milk production level. This study aimed to determine effects of steam flaking on processing-induced intrinsic molecular structure changes that were associated with rumen degradation kinetics and nutrients supply. The advanced vibrational molecular spectroscopy was applied to reveal the processing-induced intrinsic structure changes on a molecular basis. The rumen degradation kinetics and nutrient supply were determined using in situ approach in ruminant livestock system. Raw corn grain (RC) and steam flaked corn grain (SFC) were obtained from two different processing plants. The results showed that (1) Compared to RC, SFC had greater truly digestible non-fiber carbohydrate [tdNFC: 86.8 versus 78.0% dry matter (DM)], but lower truly digestible crude protein [tdCP: 7.7 versus 9.0% DM]. (2) The steam flaking increased (PMolecular absorbance intensities of most carbohydrate biopolymers were greater in SFC (Pmolecular spectral intensities were lower (Pmolecular structure and nutrient interactive study showed that carbohydrate spectral intensities were positively (Pmolecular structure changes had an interactive relationship with rumen degradation kinetics. Copyright © 2017 Elsevier B.V. All rights reserved.

Bio-functions and molecular carbohydrate structure association study in forage with different source origins revealed using non-destructive vibrational molecular spectroscopy techniques.

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Ji, Cuiying; Zhang, Xuewei; Yan, Xiaogang; Mostafizar Rahman, M; Prates, Luciana L; Yu, Peiqiang

2017-08-05

The objectives of this study were to: 1) investigate forage carbohydrate molecular structure profiles; 2) bio-functions in terms of CHO rumen degradation characteristics and hourly effective degradation ratio of N to OM (HED N/OM ), and 3) quantify interactive association between molecular structures, bio-functions and nutrient availability. The vibrational molecular spectroscopy was applied to investigate the structure feature on a molecular basis. Two sourced-origin alfalfa forages were used as modeled forages. The results showed that the carbohydrate molecular structure profiles were highly linked to the bio-functions in terms of rumen degradation characteristics and hourly effective degradation ratio. The molecular spectroscopic technique can be used to detect forage carbohydrate structure features on a molecular basis and can be used to study interactive association between forage molecular structure and bio-functions. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparative Molecular and Morphological Variation Analysis of Siderastrea (Anthozoa, Scleractinia) Reveals the Presence of Siderastrea stellata in the Gulf of Mexico.

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García, Norberto A Colín; Campos, Jorge E; Musi, José L Tello; Forsman, Zac H; Muñoz, Jorge L Montero; Reyes, Alejandro Monsalvo; González, Jesús E Arias

2017-02-01

The genus Siderastrea exhibits high levels of morphological variability. Some of its species share similar morphological characteristics with congeners, making their identification difficult. Siderastrea stellata has been reported as an intermediary of S. siderea and S. radians in the Brazilian reef ecosystem. In an earlier study conducted in Mexico, we detected Siderastrea colonies with morphological features that were not consistent with some siderastreid species previously reported in the Gulf of Mexico. Thus, we performed a combined morphological and molecular analysis to identify Siderastrea species boundaries from the Gulf of Mexico. Some colonies presented high morphologic variability, with characteristics that corresponded to Siderastrea stellata. Molecular analysis, using the nuclear ITS and ITS2 region, corroborated the morphological results, revealing low genetic variability between S. radians and S. stellata. Since the ITS sequences did not distinguish between Siderastrea species, we used the ITS2 region to differentiate S. stellata from S. radians. This is the first report of Siderastrea stellata and its variability in the Gulf of Mexico that is supported by morphological and molecular analyses.

MALDI-TOF mass spectrometry analysis of small molecular weight compounds (under 10 KDa) as biomarkers of rat hearts undergoing arecoline challenge.

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Chen, Tung-Sheng; Chang, Mu-Hsin; Kuo, Wei-Wen; Lin, Yueh-Min; Yeh, Yu-Lan; Day, Cecilia Hsuan; Lin, Chien-Chung; Tsai, Fuu-Jen; Tsai, Chang-Hai; Huang, Chih-Yang

2013-04-01

Statistical and clinical reports indicate that betel nut chewing is strongly associated with progression of oral cancer because some ingredients in betel nuts are potential cancer promoters, especially arecoline. Early diagnosis for cancer biomarkers is the best strategy for prevention of cancer progression. Several methods are suggested for investigating cancer biomarkers. Among these methods, gel-based proteomics approach is the most powerful and recommended tool for investigating biomarkers due to its high-throughput. However, this proteomics approach is not suitable for screening biomarkers with molecular weight under 10 KDa because of the characteristics of gel electrophoresis. This study investigated biomarkers with molecular weight under 10 KDa in rats with arecoline challenge. The centrifuging vials with membrane (10 KDa molecular weight cut-off) played a crucial role in this study. After centrifuging, the filtrate (containing compounds with molecular weight under 10 KDa) was collected and spotted on a sample plate for MALDI-TOF mass spectrometry analysis. Compared to control, three extra peaks (m/z values were 1553.1611, 1668.2097 and 1740.1832, respectively) were found in sera and two extra peaks were found in heart tissue samples (408.9719 and 524.9961, respectively). These small compounds should play important roles and may be potential biomarker candidates in rats with arecoline. This study successfully reports a mass-based method for investigating biomarker candidates with small molecular weight in different types of sample (including serum and tissue). In addition, this reported method is more time-efficient (1 working day) than gel-based proteomics approach (5~7 working days).

Synchrotron-radiation-based X-ray micro-computed tomography reveals dental bur debris under dental composite restorations.

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Hedayat, Assem; Nagy, Nicole; Packota, Garnet; Monteith, Judy; Allen, Darcy; Wysokinski, Tomasz; Zhu, Ning

2016-05-01

Dental burs are used extensively in dentistry to mechanically prepare tooth structures for restorations (fillings), yet little has been reported on the bur debris left behind in the teeth, and whether it poses potential health risks to patients. Here it is aimed to image dental bur debris under dental fillings, and allude to the potential health hazards that can be caused by this debris when left in direct contact with the biological surroundings, specifically when the debris is made of a non-biocompatible material. Non-destructive micro-computed tomography using the BioMedical Imaging & Therapy facility 05ID-2 beamline at the Canadian Light Source was pursued at 50 keV and at a pixel size of 4 µm to image dental bur fragments under a composite resin dental filling. The bur's cutting edges that produced the fragment were also chemically analyzed. The technique revealed dental bur fragments of different sizes in different locations on the floor of the prepared surface of the teeth and under the filling, which places them in direct contact with the dentinal tubules and the dentinal fluid circulating within them. Dispersive X-ray spectroscopy elemental analysis of the dental bur edges revealed that the fragments are made of tungsten carbide-cobalt, which is bio-incompatible.

Family Wide Molecular Adaptations to Underground Life in African Mole-Rats Revealed by Phylogenomic Analysis.

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Davies, Kalina T J; Bennett, Nigel C; Tsagkogeorga, Georgia; Rossiter, Stephen J; Faulkes, Christopher G

2015-12-01

During their evolutionary radiation, mammals have colonized diverse habitats. Arguably the subterranean niche is the most inhospitable of these, characterized by reduced oxygen, elevated carbon dioxide, absence of light, scarcity of food, and a substrate that is energetically costly to burrow through. Of all lineages to have transitioned to a subterranean niche, African mole-rats are one of the most successful. Much of their ecological success can be attributed to a diet of plant storage organs, which has allowed them to colonize climatically varied habitats across sub-Saharan Africa, and has probably contributed to the evolution of their diverse social systems. Yet despite their many remarkable phenotypic specializations, little is known about molecular adaptations underlying these traits. To address this, we sequenced the transcriptomes of seven mole-rat taxa, including three solitary species, and combined new sequences with existing genomic data sets. Alignments of more than 13,000 protein-coding genes encompassed, for the first time, all six genera and the full spectrum of ecological and social variation in the clade. We detected positive selection within the mole-rat clade and along ancestral branches in approximately 700 genes including loci associated with tumorigenesis, aging, morphological development, and sociality. By combining these results with gene ontology annotation and protein-protein networks, we identified several clusters of functionally related genes. This family wide analysis of molecular evolution in mole-rats has identified a suite of positively selected genes, deepening our understanding of the extreme phenotypic traits exhibited by this group. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Structural comparison of tRNA m1A58 methyltransferases revealed different molecular strategies to maintain their oligomeric architecture under extreme conditions

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Guelorget Amandine

2011-12-01

Full Text Available Abstract Background tRNA m1A58 methyltransferases (TrmI catalyze the transfer of a methyl group from S-adenosyl-L-methionine to nitrogen 1 of adenine 58 in the T-loop of tRNAs from all three domains of life. The m1A58 modification has been shown to be essential for cell growth in yeast and for adaptation to high temperatures in thermophilic organisms. These enzymes were shown to be active as tetramers. The crystal structures of five TrmIs from hyperthermophilic archaea and thermophilic or mesophilic bacteria have previously been determined, the optimal growth temperature of these organisms ranging from 37°C to 100°C. All TrmIs are assembled as tetramers formed by dimers of tightly assembled dimers. Results In this study, we present a comparative structural analysis of these TrmIs, which highlights factors that allow them to function over a large range of temperature. The monomers of the five enzymes are structurally highly similar, but the inter-monomer contacts differ strongly. Our analysis shows that bacterial enzymes from thermophilic organisms display additional intermolecular ionic interactions across the dimer interfaces, whereas hyperthermophilic enzymes present additional hydrophobic contacts. Moreover, as an alternative to two bidentate ionic interactions that stabilize the tetrameric interface in all other TrmI proteins, the tetramer of the archaeal P. abyssi enzyme is strengthened by four intersubunit disulfide bridges. Conclusions The availability of crystal structures of TrmIs from mesophilic, thermophilic or hyperthermophilic organisms allows a detailed analysis of the architecture of this protein family. Our structural comparisons provide insight into the different molecular strategies used to achieve the tetrameric organization in order to maintain the enzyme activity under extreme conditions.

Applying Unique Molecular Identifiers in Next Generation Sequencing Reveals a Constrained Viral Quasispecies Evolution under Cross-Reactive Antibody Pressure Targeting Long Alpha Helix of Hemagglutinin

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Hauck, Nastasja C.; Kirpach, Josiane; Kiefer, Christina; Farinelle, Sophie; Morris, Stephen A.; Muller, Claude P.; Lu, I-Na

2018-01-01

To overcome yearly efforts and costs for the production of seasonal influenza vaccines, new approaches for the induction of broadly protective and long-lasting immune responses have been developed in the past decade. To warrant safety and efficacy of the emerging crossreactive vaccine candidates, it is critical to understand the evolution of influenza viruses in response to these new immune pressures. Here we applied unique molecular identifiers in next generation sequencing to analyze the evolution of influenza quasispecies under in vivo antibody pressure targeting the hemagglutinin (HA) long alpha helix (LAH). Our vaccine targeting LAH of hemagglutinin elicited significant seroconversion and protection against homologous and heterologous influenza virus strains in mice. The vaccine not only significantly reduced lung viral titers, but also induced a well-known bottleneck effect by decreasing virus diversity. In contrast to the classical bottleneck effect, here we showed a significant increase in the frequency of viruses with amino acid sequences identical to that of vaccine targeting LAH domain. No escape mutant emerged after vaccination. These results not only support the potential of a universal influenza vaccine targeting the conserved LAH domains, but also clearly demonstrate that the well-established bottleneck effect on viral quasispecies evolution does not necessarily generate escape mutants. PMID:29587397

Applying Unique Molecular Identifiers in Next Generation Sequencing Reveals a Constrained Viral Quasispecies Evolution under Cross-Reactive Antibody Pressure Targeting Long Alpha Helix of Hemagglutinin

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Nastasja C. Hauck

2018-03-01

Full Text Available To overcome yearly efforts and costs for the production of seasonal influenza vaccines, new approaches for the induction of broadly protective and long-lasting immune responses have been developed in the past decade. To warrant safety and efficacy of the emerging crossreactive vaccine candidates, it is critical to understand the evolution of influenza viruses in response to these new immune pressures. Here we applied unique molecular identifiers in next generation sequencing to analyze the evolution of influenza quasispecies under in vivo antibody pressure targeting the hemagglutinin (HA long alpha helix (LAH. Our vaccine targeting LAH of hemagglutinin elicited significant seroconversion and protection against homologous and heterologous influenza virus strains in mice. The vaccine not only significantly reduced lung viral titers, but also induced a well-known bottleneck effect by decreasing virus diversity. In contrast to the classical bottleneck effect, here we showed a significant increase in the frequency of viruses with amino acid sequences identical to that of vaccine targeting LAH domain. No escape mutant emerged after vaccination. These results not only support the potential of a universal influenza vaccine targeting the conserved LAH domains, but also clearly demonstrate that the well-established bottleneck effect on viral quasispecies evolution does not necessarily generate escape mutants.

Molecular mechanisms involved in convergent crop domestication.

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Lenser, Teresa; Theißen, Günter

2013-12-01

Domestication has helped to understand evolution. We argue that, vice versa, novel insights into evolutionary principles could provide deeper insights into domestication. Molecular analyses have demonstrated that convergent phenotypic evolution is often based on molecular changes in orthologous genes or pathways. Recent studies have revealed that during plant domestication the causal mutations for convergent changes in key traits are likely to be located in particular genes. These insights may contribute to defining candidate genes for genetic improvement during the domestication of new plant species. Such efforts may help to increase the range of arable crops available, thus increasing crop biodiversity and food security to help meet the predicted demands of the continually growing global population under rapidly changing environmental conditions. Copyright © 2013 Elsevier Ltd. All rights reserved.

Sterically controlled mechanochemistry under hydrostatic pressure

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Yan, Hao; Yang, Fan; Pan, Ding; Lin, Yu; Hohman, J. Nathan; Solis-Ibarra, Diego; Li, Fei Hua; Dahl, Jeremy E. P.; Carlson, Robert M. K.; Tkachenko, Boryslav A.; Fokin, Andrey A.; Schreiner, Peter R.; Galli, Giulia; Mao, Wendy L.; Shen, Zhi-Xun; Melosh, Nicholas A.

2018-02-01

Mechanical stimuli can modify the energy landscape of chemical reactions and enable reaction pathways, offering a synthetic strategy that complements conventional chemistry. These mechanochemical mechanisms have been studied extensively in one-dimensional polymers under tensile stress using ring-opening and reorganization, polymer unzipping and disulfide reduction as model reactions. In these systems, the pulling force stretches chemical bonds, initiating the reaction. Additionally, it has been shown that forces orthogonal to the chemical bonds can alter the rate of bond dissociation. However, these bond activation mechanisms have not been possible under isotropic, compressive stress (that is, hydrostatic pressure). Here we show that mechanochemistry through isotropic compression is possible by molecularly engineering structures that can translate macroscopic isotropic stress into molecular-level anisotropic strain. We engineer molecules with mechanically heterogeneous components—a compressible (‘soft’) mechanophore and incompressible (‘hard’) ligands. In these ‘molecular anvils’, isotropic stress leads to relative motions of the rigid ligands, anisotropically deforming the compressible mechanophore and activating bonds. Conversely, rigid ligands in steric contact impede relative motion, blocking reactivity. We combine experiments and computations to demonstrate hydrostatic-pressure-driven redox reactions in metal-organic chalcogenides that incorporate molecular elements that have heterogeneous compressibility, in which bending of bond angles or shearing of adjacent chains activates the metal-chalcogen bonds, leading to the formation of the elemental metal. These results reveal an unexplored reaction mechanism and suggest possible strategies for high-specificity mechanosynthesis.

Transcriptional analysis and molecular dynamics simulations reveal the mechanism of toxic metals removal and efflux pumps in Lysinibacillus sphaericus OT4b.31

KAUST Repository

Shaw, Dario Rangel

2017-11-23

Lysinibacillus sphaericus strain OT4b.31 is a bacterium widely applied in bioremediation processes of hydrocarbon and metal polluted environments. In this study, we identified the molecular mechanism underlying the Pb2+ and Cr6+ resistance. Metal uptake and temporal transcription patterns of metal resistance operons were evaluated using reverse-transcribed quantitative PCR amplification. The function of the resistance determinants was studied applying docking and in silico mutagenesis methods. The results revealed that the adaptation of Lysinibacillus sphaericus OT4b.31 to elevated levels of lead and chromium involves the pbr and chr operons which comprise a transcriptional regulatory component (pbrR and chrB) and efflux ATPases (pbrA and chrA) to expel ions from the cytoplasm. Expression of metal resistance genes was constitutive and specifically inducible to the exposure of Pb2+ and Cr6+. The simultaneous presence of cations didn\\'t affect the bioaccumulation of metals, evidencing the multimetal resistance of L. sphaericus. Docking analysis revealed the key metal-protein interactions and the conformational changes after metal or ATP binding. Results showed that residues with aromatic rings or imidazole in the catalytic domain are crucial for metal binding and achievement of the function. To our knowledge, this is the first report of a specific mechanism for lead and chromium resistance in Lysinibacillus genus. From the findings of this study, it is possible to suggest the bacterium as a suitable candidate for rapid toxic metals bioremediation processes.

Metatranscriptomics reveals the molecular mechanism of large granule formation in granular anammox reactor

KAUST Repository

Bagchi, Samik

2016-06-20

Granules enriched with anammox bacteria are essential in enhancing the treatment of ammonia-rich wastewater, but little is known about how anammox bacteria grow and multiply inside granules. Here, we combined metatranscriptomics, quantitative PCR and 16S rRNA gene sequencing to study the changes in community composition, metabolic gene content and gene expression in a granular anammox reactor with the objective of understanding the molecular mechanism of anammox growth and multiplication that led to formation of large granules. Size distribution analysis revealed the spatial distribution of granules in which large granules having higher abundance of anammox bacteria (genus Brocadia) dominated the bottom biomass. Metatranscriptomics analysis detected all the essential transcripts for anammox metabolism. During the later stage of reactor operation, higher expression of ammonia and nitrite transport proteins and key metabolic enzymes mainly in the bottom large granules facilitated anammox bacteria activity. The high activity resulted in higher growth and multiplication of anammox bacteria and expanded the size of the granules. This conceptual model for large granule formation proposed here may assist in the future design of anammox processes for mainstream wastewater treatment.

The gating mechanism of the human aquaporin 5 revealed by molecular dynamics simulations.

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Lorant Janosi

Full Text Available Aquaporins are protein channels located across the cell membrane with the role of conducting water or other small sugar alcohol molecules (aquaglyceroporins. The high-resolution X-ray structure of the human aquaporin 5 (HsAQP5 shows that HsAQP5, as all the other known aquaporins, exhibits tetrameric structure. By means of molecular dynamics simulations we analyzed the role of spontaneous fluctuations on the structural behavior of the human AQP5. We found that different conformations within the tetramer lead to a distribution of monomeric channel structures, which can be characterized as open or closed. The switch between the two states of a channel is a tap-like mechanism at the cytoplasmic end which regulates the water passage through the pore. The channel is closed by a translation of the His67 residue inside the pore. Moreover, water permeation rate calculations revealed that the selectivity filter, located at the other end of the channel, regulates the flow rate of water molecules when the channel is open, by locally modifying the orientation of His173. Furthermore, the calculated permeation rates of a fully open channel are in good agreement with the reported experimental value.

Direct observation, study and control of molecular super rotors

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Korobenko, Aleksey; Milner, Alexander; Hepburn, John; Milner, Valery

2014-05-01

Extremely fast rotating molecules whose rotational energy is comparable with or exceeds the molecular bond strength are known as ``super rotors''. It has been speculated that super rotors may exhibit a number of unique properties, yet only indirect evidence of these molecular objects has been reported to date. We demonstrate the first direct observation of molecular super rotors by detecting coherent unidirectional molecular rotation with extreme frequencies exceeding 10 THz. The technique of an ``optical centrifuge'' is used to control the degree of rotational excitation in an ultra-broad range of rotational quantum numbers, reaching as high as N = 95 in oxygen and N = 60 in nitrogen. State-resolved detection enables us to determine the shape of the excited rotational wave packet and quantify the effect of centrifugal distortion on the rotational spectrum. Femtosecond time resolution reveals coherent rotational dynamics with increasing coherence times at higher angular momentum. We demonstrate that molecular super rotors can be created and observed in dense samples under normal conditions where the effects of ultrafast rotation on many-body interactions, inter-molecular collisions and chemical reactions can be readily explored.

Molecular phenology in plants: in natura systems biology for the comprehensive understanding of seasonal responses under natural environments.

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Kudoh, Hiroshi

2016-04-01

Phenology refers to the study of seasonal schedules of organisms. Molecular phenology is defined here as the study of the seasonal patterns of organisms captured by molecular biology techniques. The history of molecular phenology is reviewed briefly in relation to advances in the quantification technology of gene expression. High-resolution molecular phenology (HMP) data have enabled us to study phenology with an approach of in natura systems biology. I review recent analyses of FLOWERING LOCUS C (FLC), a temperature-responsive repressor of flowering, along the six steps in the typical flow of in natura systems biology. The extensive studies of the regulation of FLC have made this example a successful case in which a comprehensive understanding of gene functions has been progressing. The FLC-mediated long-term memory of past temperatures creates time lags with other seasonal signals, such as photoperiod and short-term temperature. Major signals that control flowering time have a phase lag between them under natural conditions, and hypothetical phase lag calendars are proposed as mechanisms of season detection in plants. Transcriptomic HMP brings a novel strategy to the study of molecular phenology, because it provides a comprehensive representation of plant functions. I discuss future perspectives of molecular phenology from the standpoints of molecular biology, evolutionary biology and ecology. © 2015 The Author. New Phytologist © 2015 New Phytologist Trust.

Translational analysis of mouse and human placental protein and mRNA reveals distinct molecular pathologies in human preeclampsia.

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Cox, Brian; Sharma, Parveen; Evangelou, Andreas I; Whiteley, Kathie; Ignatchenko, Vladimir; Ignatchenko, Alex; Baczyk, Dora; Czikk, Marie; Kingdom, John; Rossant, Janet; Gramolini, Anthony O; Adamson, S Lee; Kislinger, Thomas

2011-12-01

Preeclampsia (PE) adversely impacts ~5% of pregnancies. Despite extensive research, no consistent biomarkers or cures have emerged, suggesting that different molecular mechanisms may cause clinically similar disease. To address this, we undertook a proteomics study with three main goals: (1) to identify a panel of cell surface markers that distinguish the trophoblast and endothelial cells of the placenta in the mouse; (2) to translate this marker set to human via the Human Protein Atlas database; and (3) to utilize the validated human trophoblast markers to identify subgroups of human preeclampsia. To achieve these goals, plasma membrane proteins at the blood tissue interfaces were extracted from placentas using intravascular silica-bead perfusion, and then identified using shotgun proteomics. We identified 1181 plasma membrane proteins, of which 171 were enriched at the maternal blood-trophoblast interface and 192 at the fetal endothelial interface with a 70% conservation of expression in humans. Three distinct molecular subgroups of human preeclampsia were identified in existing human microarray data by using expression patterns of trophoblast-enriched proteins. Analysis of all misexpressed genes revealed divergent dysfunctions including angiogenesis (subgroup 1), MAPK signaling (subgroup 2), and hormone biosynthesis and metabolism (subgroup 3). Subgroup 2 lacked expected changes in known preeclampsia markers (sFLT1, sENG) and uniquely overexpressed GNA12. In an independent set of 40 banked placental specimens, GNA12 was overexpressed during preeclampsia when co-incident with chronic hypertension. In the current study we used a novel translational analysis to integrate mouse and human trophoblast protein expression with human microarray data. This strategy identified distinct molecular pathologies in human preeclampsia. We conclude that clinically similar preeclampsia patients exhibit divergent placental gene expression profiles thus implicating divergent

Revealing time bunching effect in single-molecule enzyme conformational dynamics.

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Lu, H Peter

2011-04-21

In this perspective, we focus our discussion on how the single-molecule spectroscopy and statistical analysis are able to reveal enzyme hidden properties, taking the study of T4 lysozyme as an example. Protein conformational fluctuations and dynamics play a crucial role in biomolecular functions, such as in enzymatic reactions. Single-molecule spectroscopy is a powerful approach to analyze protein conformational dynamics under physiological conditions, providing dynamic perspectives on a molecular-level understanding of protein structure-function mechanisms. Using single-molecule fluorescence spectroscopy, we have probed T4 lysozyme conformational motions under the hydrolysis reaction of a polysaccharide of E. coli B cell walls by monitoring the fluorescence resonant energy transfer (FRET) between a donor-acceptor probe pair tethered to T4 lysozyme domains involving open-close hinge-bending motions. Based on the single-molecule spectroscopic results, molecular dynamics simulation, a random walk model analysis, and a novel 2D statistical correlation analysis, we have revealed a time bunching effect in protein conformational motion dynamics that is critical to enzymatic functions. Bunching effect implies that conformational motion times tend to bunch in a finite and narrow time window. We show that convoluted multiple Poisson rate processes give rise to the bunching effect in the enzymatic reaction dynamics. Evidently, the bunching effect is likely common in protein conformational dynamics involving in conformation-gated protein functions. In this perspective, we will also discuss a new approach of 2D regional correlation analysis capable of analyzing fluctuation dynamics of complex multiple correlated and anti-correlated fluctuations under a non-correlated noise background. Using this new method, we are able to map out any defined segments along the fluctuation trajectories and determine whether they are correlated, anti-correlated, or non-correlated; after which, a

Molecular dynamics simulation on the elastoplastic properties of copper nanowire under torsion

Science.gov (United States)

Yang, Yong; Li, Ying; Yang, Zailin; Zhang, Guowei; Wang, Xizhi; Liu, Jin

2018-02-01

Influences of different factors on the torsion properties of single crystal copper nanowire are studied by molecular dynamics method. The length, torsional rate, and temperature of the nanowire are discussed at the elastic-plastic critical point. According to the average potential energy curve and shear stress curve, the elastic-plastic critical angle is determined. Also, the dislocation at elastoplastic critical points is analyzed. The simulation results show that the single crystal copper nanowire can be strengthened by lengthening the model, decreasing the torsional rate, and lowering the temperature. Moreover, atoms move violently and dislocation is more likely to occur with a higher temperature. This work mainly describes the mechanical behavior of the model under different states.

Molecular Characterization and Germination Analysis of Cotton (Gossypium hirsutum L. Genotypes under Water Deficit Irrigation

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Eminur ELÇİ

2016-09-01

Full Text Available Cotton is an important crop in terms of economic and strategic impacts. Drought stress is one of the most important environmental stress factors which negatively affects growth and yield of plants in Turkey as occurred in many countries in the world. In this study, 11 different cotton cultivars selected based on their agronomical characters were tested under water deficit irrigation strategies. Thus, it was aimed to select and/or determine appropriate new varieties for breeding new national materials resistant to drought stress, and to characterize with the molecular microsatellite markers. According to the different irrigation levels (25%, 50%, 75% and 100% plants were observed under the stressed conditions at the irrigation levels of 50% and 25%. Among the tested varieties, Tamcot Sphinx, Tamcot 94, Tamcot CamdEs and BA525 varieties were found to be more water stress tolerant than others in terms of germination time and germinated plant. The UPGMA (Unweighted Pair-Group Method Using Arithmetic Averages analysis was carried out using 28 markers with average 0.306 polymorphism information content (PIC for molecular characterization studies. Based on the UPGMA results, the varieties were clustered into two groups. It is expected that the results obtained from this study might provide considerable data for improving new drought tolerant varieties.

Changing of Bacteria Catalase Activity Under the Influence of Electro-Magnetic Radiation on a Frequency of Nitric Oxide Absorption and Radiation Molecular Spectrum

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G.M. Shub

2009-09-01

Full Text Available The dynamics of catalase activity degree changing in Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa is described under the influence of electro-magnetic radiation on a frequency of nitric oxide absorption and radiation molecular spectrum. The panoramic spectrometric measuring complex, developed in Central Scientific Research Institute of measuring equipment Public corporation, Saratov, was used while carrying out the research. Electromagnetic vibrations of extremely high frequencies were stimulated in this complex imitating the structure of nitric oxide absorption and radiation molecular spectrum. The growth of activity of the mentioned enzyme of the strains under research was detected. The most significant changes were observed under 60-minutes exposure.

Extended Lagrangian Born-Oppenheimer molecular dynamics simulations of the shock-induced chemistry of phenylacetylene

Energy Technology Data Exchange (ETDEWEB)

Cawkwell, M. J., E-mail: cawkwell@lanl.gov; Niklasson, Anders M. N. [Theoretical Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545 (United States); Dattelbaum, Dana M. [Weapons Experiments Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545 (United States)

2015-02-14

The initial chemical events that occur during the shock compression of liquid phenylacetylene have been investigated using self-consistent tight binding molecular dynamics simulations. The extended Lagrangian Born-Oppenheimer molecular dynamics formalism enabled us to compute microcanonical trajectories with precise conservation of the total energy. Our simulations revealed that the first density-increasing step under shock compression arises from the polymerization of phenylacetylene molecules at the acetylene moiety. The application of electronic structure-based molecular dynamics with long-term conservation of the total energy enabled us to identify electronic signatures of reactivity via monitoring changes in the HOMO-LUMO gap, and to capture directly adiabatic shock heating, transient non-equilibrium states, and changes in temperature arising from exothermic chemistry in classical molecular dynamics trajectories.

Extended Lagrangian Born-Oppenheimer molecular dynamics simulations of the shock-induced chemistry of phenylacetylene.

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Cawkwell, M J; Niklasson, Anders M N; Dattelbaum, Dana M

2015-02-14

The initial chemical events that occur during the shock compression of liquid phenylacetylene have been investigated using self-consistent tight binding molecular dynamics simulations. The extended Lagrangian Born-Oppenheimer molecular dynamics formalism enabled us to compute microcanonical trajectories with precise conservation of the total energy. Our simulations revealed that the first density-increasing step under shock compression arises from the polymerization of phenylacetylene molecules at the acetylene moiety. The application of electronic structure-based molecular dynamics with long-term conservation of the total energy enabled us to identify electronic signatures of reactivity via monitoring changes in the HOMO-LUMO gap, and to capture directly adiabatic shock heating, transient non-equilibrium states, and changes in temperature arising from exothermic chemistry in classical molecular dynamics trajectories.

Revealing Abrupt and Spontaneous Ruptures of Protein Native Structure under picoNewton Compressive Force Manipulation.

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Chowdhury, S Roy; Cao, Jin; He, Yufan; Lu, H Peter

2018-03-27

Manipulating protein conformations for exploring protein structure-function relationship has shown great promise. Although protein conformational changes under pulling force manipulation have been extensively studied, protein conformation changes under a compressive force have not been explored quantitatively. The latter is even more biologically significant and relevant in revealing protein functions in living cells associated with protein crowdedness, distribution fluctuations, and cell osmotic stress. Here we report our experimental observations on abrupt ruptures of protein native structures under compressive force, demonstrated and studied by single-molecule AFM-FRET spectroscopic nanoscopy. Our results show that the protein ruptures are abrupt and spontaneous events occurred when the compressive force reaches a threshold of 12-75 pN, a force amplitude accessible from thermal fluctuations in a living cell. The abrupt ruptures are sensitive to local environment, likely a general and important pathway of protein unfolding in living cells.

Mass spectral chemical fingerprints reveal the molecular dependence of exhaust particulate matters on engine speeds.

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Li, Yi; Zhang, Hua; Zhao, Zongshan; Tian, Yong; Liu, Kun; Jie, Feifan; Zhu, Liang; Chen, Huanwen

2018-05-01

Particulate matters (PMs) emitted by automobile exhaust contribute to a significant fraction of the global PMs. Extractive atmospheric pressure chemical ionization mass spectrometry (EAPCI-MS) was developed to explore the molecular dependence of PMs collected from exhaust gases produced at different vehicle engine speeds. The mass spectral fingerprints of the organic compounds embedded in differentially sized PMs (e.g., 0.22-0.45, 0.45-1.00, 1.00-2.00, 2.00-3.00, 3.00-5.00, and 5.00-10.00μm) generated at different engine speeds (e.g., 1000, 1500, 2000, 2500, and 3000r/min) were chemically profiled in the mass range of mass to charge ratio (m/z) 50-800. Organic compounds, including alcohols, aldehydes, and esters, were detected in all the PMs tested, with varied concentration levels for each individual PM sample. At relatively low engine speeds (≤1500r/min), the total amount of organic species embedded in PMs of 0.22-1.00μm was greater than in PMs of other sizes, while more organic species were found in PMs of 5.00-10.00μm at high engine speeds (≥3000r/min), indicating that the organic compounds distributed in different sizes of PMs strongly correlated with the engine speed. The experimental data showed that the EAPCI-MS technique enables molecular characterization of PMs in exhaust, revealing the chemical dependence of PMs on the engine speeds (i.e., the combustion conditions) of automobiles. Copyright © 2017. Published by Elsevier B.V.

Structure of the CaMKIIdelta/calmodulin complex reveals the molecular mechanism of CaMKII kinase activation.

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Peter Rellos

2010-07-01

Full Text Available Long-term potentiation (LTP, a long-lasting enhancement in communication between neurons, is considered to be the major cellular mechanism underlying learning and memory. LTP triggers high-frequency calcium pulses that result in the activation of Calcium/Calmodulin (CaM-dependent kinase II (CaMKII. CaMKII acts as a molecular switch because it remains active for a long time after the return to basal calcium levels, which is a unique property required for CaMKII function. Here we describe the crystal structure of the human CaMKIIdelta/Ca2+/CaM complex, structures of all four human CaMKII catalytic domains in their autoinhibited states, as well as structures of human CaMKII oligomerization domains in their tetradecameric and physiological dodecameric states. All four autoinhibited human CaMKIIs were monomeric in the determined crystal structures but associated weakly in solution. In the CaMKIIdelta/Ca2+/CaM complex, the inhibitory region adopted an extended conformation and interacted with an adjacent catalytic domain positioning T287 into the active site of the interacting protomer. Comparisons with autoinhibited CaMKII structures showed that binding of calmodulin leads to the rearrangement of residues in the active site to a conformation suitable for ATP binding and to the closure of the binding groove for the autoinhibitory helix by helix alphaD. The structural data, together with biophysical interaction studies, reveals the mechanism of CaMKII activation by calmodulin and explains many of the unique regulatory properties of these two essential signaling molecules.This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3-D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the Web plugin are available in Text S1.

Identification and comparative analysis of differential gene expression in soybean leaf tissue under drought and flooding stress revealed by RNA-Seq

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Soybean is the second largest crop in the US. Its yield directly impacts US agricultural economics. Drought and flooding are two major causes for soybean yield loss. To better understand their underlying molecular regulatory mechanisms, we sequenced the transcriptomes of soybean grown in drought a...

Exploring the molecular mechanisms underlying the potentiation of exogenous growth hormone on alcohol-induced fatty liver diseases in mice

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Tian Ya-ping

2010-11-01

Full Text Available Abstract Background Growth hormone (GH is an essential regulator of intrahepatic lipid metabolism by activating multiple complex hepatic signaling cascades. Here, we examined whether chronic exogenous GH administration (via gene therapy could ameliorate liver steatosis in animal models of alcoholic fatty liver disease (AFLD and explored the underlying molecular mechanisms. Methods Male C57BL/6J mice were fed either an alcohol or a control liquid diet with or without GH therapy for 6 weeks. Biochemical parameters, liver histology, oxidative stress markers, and serum high molecular weight (HMW adiponectin were measured. Quantitative real-time PCR and western blotting were also conducted to determine the underlying molecular mechanism. Results Serum HMW adiponectin levels were significantly higher in the GH1-treated control group than in the control group (3.98 ± 0.71 μg/mL vs. 3.07 ± 0.55 μg/mL; P P P P P Conclusions GH therapy had positive effects on AFLD and may offer a promising approach to prevent or treat AFLD. These beneficial effects of GH on AFLD were achieved through the activation of the hepatic adiponectin-SIRT1-AMPK and PPARα-AMPK signaling systems.

Lipid clustering correlates with membrane curvature as revealed by molecular simulations of complex lipid bilayers.

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Heidi Koldsø

2014-10-01

Full Text Available Cell membranes are complex multicomponent systems, which are highly heterogeneous in the lipid distribution and composition. To date, most molecular simulations have focussed on relatively simple lipid compositions, helping to inform our understanding of in vitro experimental studies. Here we describe on simulations of complex asymmetric plasma membrane model, which contains seven different lipids species including the glycolipid GM3 in the outer leaflet and the anionic lipid, phosphatidylinositol 4,5-bisphophate (PIP2, in the inner leaflet. Plasma membrane models consisting of 1500 lipids and resembling the in vivo composition were constructed and simulations were run for 5 µs. In these simulations the most striking feature was the formation of nano-clusters of GM3 within the outer leaflet. In simulations of protein interactions within a plasma membrane model, GM3, PIP2, and cholesterol all formed favorable interactions with the model α-helical protein. A larger scale simulation of a model plasma membrane containing 6000 lipid molecules revealed correlations between curvature of the bilayer surface and clustering of lipid molecules. In particular, the concave (when viewed from the extracellular side regions of the bilayer surface were locally enriched in GM3. In summary, these simulations explore the nanoscale dynamics of model bilayers which mimic the in vivo lipid composition of mammalian plasma membranes, revealing emergent nanoscale membrane organization which may be coupled both to fluctuations in local membrane geometry and to interactions with proteins.

Molecular sieving through a graphene nanopore: non-equilibrium molecular dynamics simulation

Institute of Scientific and Technical Information of China (English)

Chengzhen Sun; Bofeng Bai

2017-01-01

Two-dimensional graphene nanopores have shown great promise as ultra-permeable molecular sieves based on their size-sieving effects.We design a nitrogen/hydrogen modified graphene nanopore and conduct a transient non-equilibrium molecular dynamics simulation on its molecular sieving effects.The distinct time-varying molecular crossing numbers show that this special nanopore can efficiently sieve CO2 and H2S molecules from CH4 molecules with high selectivity.By analyzing the molecular structure and pore functionalization-related molecular orientation and permeable zone in the nanopore,density distribution in the molecular adsorption layer on the graphene surface,as well as other features,the molecular sieving mechanisms of graphene nanopores are revealed.Finally,several implications on the design of highly-efficient graphene nanopores,especially for determining the porosity and chemical functionalization,as gas separation membranes are summarized based on the identified phenomena and mechanisms.

Molecular portrait of breast cancer in China reveals comprehensive transcriptomic likeness to Caucasian breast cancer and low prevalence of luminal A subtype

International Nuclear Information System (INIS)

Huang, Xiaoyan; Dugo, Matteo; Callari, Maurizio; Sandri, Marco; De Cecco, Loris; Valeri, Barbara; Carcangiu, Maria Luisa; Xue, Jingyan; Bi, Rui; Veneroni, Silvia; Daidone, Maria Grazia; Ménard, Sylvie; Tagliabue, Elda; Shao, Zhimin; Wu, Jiong; Orlandi, Rosaria

2015-01-01

The recent dramatic increase in breast cancer incidence across China with progressive urbanization and economic development has signaled the urgent need for molecular and clinical detailing of breast cancer in the Chinese population. Our analyses of a unique transethnic collection of breast cancer frozen specimens from Shanghai Fudan Cancer Center (Chinese Han) profiled simultaneously with an analogous Caucasian Italian series revealed consistent transcriptomic data lacking in batch effects. The prevalence of Luminal A subtype was significantly lower in Chinese series, impacting the overall prevalence of estrogen receptor (ER)-positive disease in a large cohort of Chinese/Caucasian patients. Unsupervised and supervised comparison of gene and microRNA (miRNA) profiles of Chinese and Caucasian samples revealed extensive similarity in the comprehensive taxonomy of transcriptional elements regulating breast cancer biology. Partition of gene expression data using gene lists relevant to breast cancer as “intrinsic” and “extracellular matrix” genes identified Chinese and Caucasian subgroups with equivalent global gene and miRNA profiles. These findings indicate that in the Chinese and Caucasian groups, breast neoplasia and the surrounding stromal characteristics undergo the same differentiation and molecular processes. Transcriptional similarity across transethnic cohorts may simplify translational medicine approaches and clinical management of breast cancer patients worldwide

Ultra-sensitive molecular MRI of cerebrovascular cell activation enables early detection of chronic central nervous system disorders

International Nuclear Information System (INIS)

Montagne, Axel; Gauberti, Maxime; Jullienne, Amandine; Briens, Aurelien; Docagne, Fabian; Vivien, Denis; Maubert, Eric; Macrez, Richard; Defer, Gilles; Raynaud, Jean-Sebastien; Louin, Gaelle; Buisson, Alain; Haelewyn, Benoit

2012-01-01

Since endothelial cells can be targeted by large contrast-carrying particles, molecular imaging of cerebrovascular cell activation is highly promising to evaluate the underlying inflammation of the central nervous system (CNS). In this study, we aimed to demonstrate that molecular magnetic resonance imaging (MRI) of cerebrovascular cell activation can reveal CNS disorders in the absence of visible lesions and symptoms. To this aim, we optimized contrast carrying particles targeting vascular cell adhesion molecule-1 and MRI protocols through both in vitro and in vivo experiments. Although, pre-contrast MRI images failed to reveal the ongoing pathology, contrast-enhanced MRI revealed hypoperfusion-triggered CNS injury in vascular dementia, unmasked amyloid-induced cerebrovascular activation in Alzheimer's disease and allowed monitoring of disease activity during experimental autoimmune encephalomyelitis. Moreover, contrast-enhanced MRI revealed the cerebrovascular cell activation associated with known risk factors of CNS disorders such as peripheral inflammation, ethanol consumption, hyperglycemia and aging. By providing a dramatically higher sensitivity than previously reported methods and molecular contrast agents, the technology described in the present study opens new avenues of investigation in the field of neuro-inflammation. (authors)

First-principles studies of PETN molecular crystal vibrational frequencies under high pressure

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Perger, Warren; Zhao, Jijun

2005-07-01

The vibrational frequencies of the PETN molecular crystal were calculated using the first-principles CRYSTAL03 program which employs an all-electron LCAO approach and calculates analytic first derivatives of the total energy with respect to atomic displacements. Numerical second derivatives were used to enable calculation of the vibrational frequencies at ambient pressure and under various states of compression. Three different density functionals, B3LYP, PW91, and X3LYP were used to examine the effect of the exchange-correlation functional on the vibrational frequencies. The pressure-induced shift of the vibrational frequencies will be presented and compared with experiment. The average deviation with experimental results is shown to be on the order of 2-3%, depending on the functional used.

Molecular Mechanisms Underlying Renin-Angiotensin-Aldosterone System Mediated Regulation of BK Channels

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Zhen-Ye Zhang

2017-09-01

Full Text Available Large-conductance calcium-activated potassium channels (BK channels belong to a family of Ca2+-sensitive voltage-dependent potassium channels and play a vital role in various physiological activities in the human body. The renin-angiotensin-aldosterone system is acknowledged as being vital in the body's hormone system and plays a fundamental role in the maintenance of water and electrolyte balance and blood pressure regulation. There is growing evidence that the renin-angiotensin-aldosterone system has profound influences on the expression and bioactivity of BK channels. In this review, we focus on the molecular mechanisms underlying the regulation of BK channels mediated by the renin-angiotensin-aldosterone system and its potential as a target for clinical drugs.

Transcriptional analysis and molecular dynamics simulations reveal the mechanism of toxic metals removal and efflux pumps in Lysinibacillus sphaericus OT4b.31

KAUST Repository

Shaw, Dario Rangel; Dussan, Jenny

2017-01-01

Lysinibacillus sphaericus strain OT4b.31 is a bacterium widely applied in bioremediation processes of hydrocarbon and metal polluted environments. In this study, we identified the molecular mechanism underlying the Pb2+ and Cr6+ resistance. Metal

New quantum criticality revealed under pressure

International Nuclear Information System (INIS)

Watanabe, Shinji; Miyake, Kazumasa

2017-01-01

Unconventional quantum critical phenomena observed in Yb-based periodic crystals such as YbRh_2Si_2 and β-YbAlB_4 have been one of the central issues in strongly correlated electron systems. The common criticality has been discovered in the quasicrystal Yb_1_5Au_5_1Al_3_4, which surprisingly persists under pressure at least up to P = 1.5 GPa. The T/H scaling where the magnetic susceptibility can be expressed as a single scaling function of the ratio of the temperature T to the magnetic field H has been discovered in the quasicrystal, which is essentially the same as that observed in β-YbAlB_4. Recently, the T/H scaling as well as the common criticality has also been observed even in the approximant crystal Yb_1_4Au_5_1Al_3_5 under pressure. The theory of critical Yb-valence fluctuation gives a natural explanation for these striking phenomena in a unified way. (author)

Elucidation of molecular mechanisms of physiological variations between bovine subcutaneous and visceral fat depots under different nutritional regimes.

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Romao, Josue Moura; Jin, Weiwu; He, Maolong; McAllister, Tim; Guan, Le Luo

2013-01-01

Adipose tissue plays a critical role in energy homeostasis and metabolism. There is sparse understanding of the molecular regulation at the protein level of bovine adipose tissues, especially within different fat depots under different nutritional regimes. The objective of this study was to analyze the differences in protein expression between bovine subcutaneous and visceral fat depots in steers fed different diets and to identify the potential regulatory molecular mechanisms of protein expression. Subcutaneous and visceral fat tissues were collected from 16 British-continental steers (15.5 month old) fed a high-fat diet (7.1% fat, n=8) or a control diet (2.7% fat, n=8). Protein expression was profiled using label free quantification LC-MS/MS and expression of selected transcripts was evaluated using qRT-PCR. A total of 682 proteins were characterized and quantified with fat depot having more impact on protein expression, altering the level of 51.0% of the detected proteins, whereas diet affected only 5.3%. Functional analysis revealed that energy production and lipid metabolism were among the main functions associated with differentially expressed proteins between fat depots, with visceral fat being more metabolically active than subcutaneous fat as proteins associated with lipid and energy metabolism were upregulated. The expression of several proteins was significantly correlated to subcutaneous fat thickness and adipocyte size, indicating their potential as adiposity markers. A poor correlation (r=0.245) was observed between mRNA and protein levels for 9 genes, indicating that many proteins may be subjected to post-transcriptional regulation. A total of 8 miRNAs were predicted to regulate more than 20% of lipid metabolism proteins differentially expressed between fat depots, suggesting that miRNAs play a role in adipose tissue regulation. Our results show that proteomic changes support the distinct metabolic and physiological characteristics observed between

Multi-Scale Molecular Deconstruction of the Serotonin Neuron System.

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Okaty, Benjamin W; Freret, Morgan E; Rood, Benjamin D; Brust, Rachael D; Hennessy, Morgan L; deBairos, Danielle; Kim, Jun Chul; Cook, Melloni N; Dymecki, Susan M

2015-11-18

Serotonergic (5HT) neurons modulate diverse behaviors and physiology and are implicated in distinct clinical disorders. Corresponding diversity in 5HT neuronal phenotypes is becoming apparent and is likely rooted in molecular differences, yet a comprehensive approach characterizing molecular variation across the 5HT system is lacking, as is concomitant linkage to cellular phenotypes. Here we combine intersectional fate mapping, neuron sorting, and genome-wide RNA-seq to deconstruct the mouse 5HT system at multiple levels of granularity-from anatomy, to genetic sublineages, to single neurons. Our unbiased analyses reveal principles underlying system organization, 5HT neuron subtypes, constellations of differentially expressed genes distinguishing subtypes, and predictions of subtype-specific functions. Using electrophysiology, subtype-specific neuron silencing, and conditional gene knockout, we show that these molecularly defined 5HT neuron subtypes are functionally distinct. Collectively, this resource classifies molecular diversity across the 5HT system and discovers sertonergic subtypes, markers, organizing principles, and subtype-specific functions with potential disease relevance. Copyright © 2015 Elsevier Inc. All rights reserved.

Comprehensive profiling of DNA methylation in colorectal cancer reveals subgroups with distinct clinicopathological and molecular features

International Nuclear Information System (INIS)

Ang, Pei Woon; Soong, Richie; Loh, Marie; Liem, Natalia; Lim, Pei Li; Grieu, Fabienne; Vaithilingam, Aparna; Platell, Cameron; Yong, Wei Peng; Iacopetta, Barry

2010-01-01

Most previous studies of the CpG island methylator phenotype (CIMP) in colorectal cancer (CRC) have been conducted on a relatively small numbers of CpG sites. In the present study we performed comprehensive DNA methylation profiling of CRC with the aim of characterizing CIMP subgroups. DNA methylation at 1,505 CpG sites in 807 cancer-related genes was evaluated using the Illumina GoldenGate ® methylation array in 28 normal colonic mucosa and 91 consecutive CRC samples. Methylation data was analyzed using unsupervised hierarchical clustering. CIMP subgroups were compared for various clinicopathological and molecular features including patient age, tumor site, microsatellite instability (MSI), methylation at a consensus panel of CpG islands and mutations in BRAF and KRAS. A total of 202 CpG sites were differentially methylated between tumor and normal tissue. Unsupervised hierarchical clustering of methylation data from these sites revealed the existence of three CRC subgroups referred to as CIMP-low (CIMP-L, 21% of cases), CIMP-mid (CIMP-M, 14%) and CIMP-high (CIMP-H, 65%). In comparison to CIMP-L tumors, CIMP-H tumors were more often located in the proximal colon and showed more frequent mutation of KRAS and BRAF (P < 0.001). Comprehensive DNA methylation profiling identified three CRC subgroups with distinctive clinicopathological and molecular features. This study suggests that both KRAS and BRAF mutations are involved with the CIMP-H pathway of CRC rather than with distinct CIMP subgroups

Comprehensive profiling of DNA methylation in colorectal cancer reveals subgroups with distinct clinicopathological and molecular features

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Vaithilingam Aparna

2010-05-01

Full Text Available Abstract Background Most previous studies of the CpG island methylator phenotype (CIMP in colorectal cancer (CRC have been conducted on a relatively small numbers of CpG sites. In the present study we performed comprehensive DNA methylation profiling of CRC with the aim of characterizing CIMP subgroups. Methods DNA methylation at 1,505 CpG sites in 807 cancer-related genes was evaluated using the Illumina GoldenGate® methylation array in 28 normal colonic mucosa and 91 consecutive CRC samples. Methylation data was analyzed using unsupervised hierarchical clustering. CIMP subgroups were compared for various clinicopathological and molecular features including patient age, tumor site, microsatellite instability (MSI, methylation at a consensus panel of CpG islands and mutations in BRAF and KRAS. Results A total of 202 CpG sites were differentially methylated between tumor and normal tissue. Unsupervised hierarchical clustering of methylation data from these sites revealed the existence of three CRC subgroups referred to as CIMP-low (CIMP-L, 21% of cases, CIMP-mid (CIMP-M, 14% and CIMP-high (CIMP-H, 65%. In comparison to CIMP-L tumors, CIMP-H tumors were more often located in the proximal colon and showed more frequent mutation of KRAS and BRAF (P Conclusions Comprehensive DNA methylation profiling identified three CRC subgroups with distinctive clinicopathological and molecular features. This study suggests that both KRAS and BRAF mutations are involved with the CIMP-H pathway of CRC rather than with distinct CIMP subgroups.

Molecular profiling reveals biologically discrete subsets and pathways of progression in diffuse glioma

Science.gov (United States)

Ceccarelli, Michele; Barthel, Floris P.; Malta, Tathiane M.; Sabedot, Thais S.; Salama, Sofie R.; Murray, Bradley A.; Morozova, Olena; Newton, Yulia; Radenbaugh, Amie; Pagnotta, Stefano M.; Anjum, Samreen; Wang, Jiguang; Manyam, Ganiraju; Zoppoli, Pietro; Ling, Shiyung; Rao, Arjun A.; Grifford, Mia; Cherniack, Andrew D.; Zhang, Hailei; Poisson, Laila; Carlotti, Carlos Gilberto; Pretti da Cunha Tirapelli, Daniela; Rao, Arvind; Mikkelsen, Tom; Lau, Ching C.; Yung, W.K. Alfred; Rabadan, Raul; Huse, Jason; Brat, Daniel J.; Lehman, Norman L.; Barnholtz-Sloan, Jill S.; Zheng, Siyuan; Hess, Kenneth; Rao, Ganesh; Meyerson, Matthew; Beroukhim, Rameen; Cooper, Lee; Akbani, Rehan; Wrensch, Margaret; Haussler, David; Aldape, Kenneth D.; Laird, Peter W.; Gutmann, David H.; Noushmehr, Houtan; Iavarone, Antonio; Verhaak, Roel G.W.

2015-01-01

SUMMARY Therapy development for adult diffuse glioma is hindered by incomplete knowledge of somatic glioma driving alterations and suboptimal disease classification. We defined the complete set of genes associated with 1,122 diffuse grade II-III-IV gliomas from The Cancer Genome Atlas and used molecular profiles to improve disease classification, identify molecular correlations, and provide insights into the progression from low- to high-grade disease. Whole genome sequencing data analysis determined that ATRX but not TERT promoter mutations are associated with increased telomere length. Recent advances in glioma classification based on IDH mutation and 1p/19q co-deletion status were recapitulated through analysis of DNA methylation profiles, which identified clinically relevant molecular subsets. A subtype of IDH-mutant glioma was associated with DNA demethylation and poor outcome; a group of IDH-wildtype diffuse glioma showed molecular similarity to pilocytic astrocytoma and relatively favorable survival. Understanding of cohesive disease groups may aid improved clinical outcomes. PMID:26824661

Transcriptome Analysis Reveals Molecular Signatures of Luteoloside Accumulation in Senescing Leaves of Lonicera macranthoides

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Zexiong Chen

2018-03-01

Full Text Available Lonicera macranthoides is an important medicinal plant widely used in traditional Chinese medicine. Luteoloside is a critical bioactive compound in L. macranthoides. To date, the molecular mechanisms underlying luteoloside biosynthesis are still largely unknown. In this work, high performance liquid chromatography (HPLC was employed to determine the luteoloside contents in leaves, stems, and flowers at different developmental stages. Results showed that senescing leaves can accumulate large amounts of luteoloside, extremely higher than that in young and semi-lignified leaves and other tissues. RNA-Seq analysis identified that twenty-four differentially expressed unigenes (DEGs associated with luteoloside biosynthesis were significantly up-regulated in senescing leaves, which are positively correlated with luteoloside accumulation. These DEGs include phenylalanine ammonia lyase 2, cinnamate 4-hydroxylase 2, thirteen 4-coumarate-CoA ligases, chalcone synthase 2, six flavonoid 3′-monooxygenase (F3′H and two flavone 7-O-β-glucosyltransferase (UFGT genes. Further analysis demonstrated that two F3′Hs (CL11828.Contig1 and CL11828.Contig2 and two UFGTs (Unigene2918 and Unigene97915 might play vital roles in luteoloside generation. Furthermore, several transcription factors (TFs related to flavonoid biosynthesis including MYB, bHLH and WD40, were differentially expressed during leaf senescence. Among these TFs, MYB12, MYB75, bHLH113 and TTG1 were considered to be key factors involved in the regulation of luteoloside biosynthesis. These findings provide insights for elucidating the molecular signatures of luteoloside accumulation in L. macranthoides.

Revealing the mechanisms of protein disorder and N-glycosylation in CD44-hyaluronan binding using molecular simulation

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Olgun eGuvench

2015-06-01

Full Text Available The extracellular N-terminal hyaluronan binding domain (HABD of CD44 is a small globular domain that confers hyaluronan (HA binding functionality to this large transmembrane glycoprotein. When recombinantly expressed by itself, HABD exists as a globular water-soluble protein that retains the capacity to bind HA. This has enabled atomic-resolution structural biology experiments that have revealed the structure of HABD and its binding mode with oligomeric HA. Such experiments have also pointed to an order-to-disorder transition in HABD that is associated with HA binding. However, it had remained unclear how this structural transition was involved in binding since it occurs in a region of HABD distant from the HA-binding site. Furthermore, HABD is known to be N-glycosylated, and such glycosylation can diminish HA binding when the associated N-glycans are capped with sialic acid residues. The intrinsic flexibility of disordered proteins and of N-glycans makes it difficult to apply experimental structural biology approaches to probe the molecular mechanisms of how the order-to-disorder transition and N-glycosylation can modulate HA binding by HABD. We review recent results from molecular dynamics simulations that provide atomic-resolution mechanistic understanding of such modulation to help bridge gaps between existing experimental binding and structural biology data. Findings from these simulations include: Tyr42 may function as a molecular switch that converts the HA binding site from a low affinity to a high affinity state; in the partially-disordered form of HABD, basic amino acids in the C-terminal region can gain sufficient mobility to form direct contacts with bound HA to further stabilize binding; and terminal sialic acids on covalently-attached N-glycans can form charge-paired hydrogen bonding interactions with basic amino acids that could otherwise bind to HA, thereby blocking HA binding to glycosylated CD44 HABD.

Molecular dynamics simulations revealed structural differences among WRKY domain-DNA interaction in barley (Hordeum vulgare).

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Pandey, Bharati; Grover, Abhinav; Sharma, Pradeep

2018-02-12

The WRKY transcription factors are a class of DNA-binding proteins involved in diverse plant processes play critical roles in response to abiotic and biotic stresses. Genome-wide divergence analysis of WRKY gene family in Hordeum vulgare provided a framework for molecular evolution and functional roles. So far, the crystal structure of WRKY from barley has not been resolved; moreover, knowledge of the three-dimensional structure of WRKY domain is pre-requisites for exploring the protein-DNA recognition mechanisms. Homology modelling based approach was used to generate structures for WRKY DNA binding domain (DBD) and its variants using AtWRKY1 as a template. Finally, the stability and conformational changes of the generated model in unbound and bound form was examined through atomistic molecular dynamics (MD) simulations for 100 ns time period. In this study, we investigated the comparative binding pattern of WRKY domain and its variants with W-box cis-regulatory element using molecular docking and dynamics (MD) simulations assays. The atomic insight into WRKY domain exhibited significant variation in the intermolecular hydrogen bonding pattern, leading to the structural anomalies in the variant type and differences in the DNA-binding specificities. Based on the MD analysis, residual contribution and interaction contour, wild-type WRKY (HvWRKY46) were found to interact with DNA through highly conserved heptapeptide in the pre- and post-MD simulated complexes, whereas heptapeptide interaction with DNA was missing in variants (I and II) in post-MD complexes. Consequently, through principal component analysis, wild-type WRKY was also found to be more stable by obscuring a reduced conformational space than the variant I (HvWRKY34). Lastly, high binding free energy for wild-type and variant II allowed us to conclude that wild-type WRKY-DNA complex was more stable relative to variants I. The results of our study revealed complete dynamic and structural information

Molecular mechanism of catalase activity change under sodium dodecyl sulfate-induced oxidative stress in the mouse primary hepatocytes.

Science.gov (United States)

Wang, Jing; Wang, Jiaxi; Xu, Chi; Liu, Rutao; Chen, Yadong

2016-04-15

Sodium dodecyl sulfate (SDS) contributes to adverse effects of organisms probably because of its ability to induce oxidative stress via changing the activity of antioxidant enzyme catalase (CAT). But the underlying molecular mechanisms still remain unclear. This study characterized the harmful effects of SDS-induced oxidative stress on the mouse primary hepatocytes as well as the structure and function of CAT molecule and investigated the underlying molecular mechanism. After 12h SDS (0.1μM to 0.2mM) exposure, no significant change was observed in CAT activity of the hepatocytes. After 0.5 and 0.8mM SDS exposure, the state of oxidative stress stimulated CAT production in the hepatocytes. The inhibition of CAT activity induced by directly interacting with SDS was unable to catch the synthesis of CAT and therefore resulted in the increased activity and elevated ROS level. Further molecular experiments showed that SDS prefers to bind to the interface with no direct effect on the active site and the structure of heme groups of CAT molecule. When the sites in the interface is saturated, SDS interacts with VAL 73, HIS 74, ASN 147 and PHE 152, the key residues of the enzyme activity, and leads to the decrease of CAT activity. Copyright © 2015 Elsevier B.V. All rights reserved.

Barcoding against a paradox? Combined molecular species delineations reveal multiple cryptic lineages in elusive meiofaunal sea slugs

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Jörger Katharina M

2012-12-01

Full Text Available Abstract Background Many marine meiofaunal species are reported to have wide distributions, which creates a paradox considering their hypothesized low dispersal abilities. Correlated with this paradox is an especially high taxonomic deficit for meiofauna, partly related to a lower taxonomic effort and partly to a high number of putative cryptic species. Molecular-based species delineation and barcoding approaches have been advocated for meiofaunal biodiversity assessments to speed up description processes and uncover cryptic lineages. However, these approaches show sensitivity to sampling coverage (taxonomic and geographic and the success rate has never been explored on mesopsammic Mollusca. Results We collected the meiofaunal sea-slug Pontohedyle (Acochlidia, Heterobranchia from 28 localities worldwide. With a traditional morphological approach, all specimens fall into two morphospecies. However, with a multi-marker genetic approach, we reveal multiple lineages that are reciprocally monophyletic on single and concatenated gene trees in phylogenetic analyses. These lineages are largely concordant with geographical and oceanographic parameters, leading to our primary species hypothesis (PSH. In parallel, we apply four independent methods of molecular based species delineation: General Mixed Yule Coalescent model (GMYC, statistical parsimony, Bayesian Species Delineation (BPP and Automatic Barcode Gap Discovery (ABGD. The secondary species hypothesis (SSH is gained by relying only on uncontradicted results of the different approaches (‘minimum consensus approach’, resulting in the discovery of a radiation of (at least 12 mainly cryptic species, 9 of them new to science, some sympatric and some allopatric with respect to ocean boundaries. However, the meiofaunal paradox still persists in some Pontohedyle species identified here with wide coastal and trans-archipelago distributions. Conclusions Our study confirms extensive, morphologically

Reconstructing genealogies of serial samples under the assumption of a molecular clock using serial-sample UPGMA.

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Drummond, A; Rodrigo, A G

2000-12-01

Reconstruction of evolutionary relationships from noncontemporaneous molecular samples provides a new challenge for phylogenetic reconstruction methods. With recent biotechnological advances there has been an increase in molecular sequencing throughput, and the potential to obtain serial samples of sequences from populations, including rapidly evolving pathogens, is fast being realized. A new method called the serial-sample unweighted pair grouping method with arithmetic means (sUPGMA) is presented that reconstructs a genealogy or phylogeny of sequences sampled serially in time using a matrix of pairwise distances. The resulting tree depicts the terminal lineages of each sample ending at a different level consistent with the sample's temporal order. Since sUPGMA is a variant of UPGMA, it will perform best when sequences have evolved at a constant rate (i.e., according to a molecular clock). On simulated data, this new method performs better than standard cluster analysis under a variety of longitudinal sampling strategies. Serial-sample UPGMA is particularly useful for analysis of longitudinal samples of viruses and bacteria, as well as ancient DNA samples, with the minimal requirement that samples of sequences be ordered in time.

Molecular dynamics simulations of the structure evolutions of Cu-Zr metallic glasses under irradiation

Energy Technology Data Exchange (ETDEWEB)

Lang, Lin [College of Materials Science and Engineering, Hunan University, Changsha 410082 (China); Department of Applied Physics, School of Physics and Electronics, Hunan University, Changsha 410082 (China); Tian, Zean; Xiao, Shifang [Department of Applied Physics, School of Physics and Electronics, Hunan University, Changsha 410082 (China); Deng, Huiqiu, E-mail: hqdeng@hnu.edu.cn [Department of Applied Physics, School of Physics and Electronics, Hunan University, Changsha 410082 (China); Ao, Bingyun [Science and Technology on Surface Physics and Chemistry Laboratory, Mianyang 621907 (China); Chen, Piheng, E-mail: chenpiheng@caep.cn [Science and Technology on Surface Physics and Chemistry Laboratory, Mianyang 621907 (China); Hu, Wangyu [College of Materials Science and Engineering, Hunan University, Changsha 410082 (China)

2017-02-15

Highlights: • The structural evolution of Cu{sub 64.5}Zr{sub 35.5} MG under irradiation was studied. • The structure clusters were analyzed using the LSCA method. • Most of these radiation damages have been self-recovered quickly. - Abstract: Molecular dynamics simulations have been performed to investigate the structural evolution of Cu{sub 64.5}Zr{sub 35.5} metallic glasses under irradiation. The largest standard cluster analysis (LSCA) method was used to quantify the microstructure within the collision cascade regions. It is found that the majority of clusters within the collision cascade regions are full and defective icosahedrons. Not only the smaller structures (common neighbor subcluster) but also primary clusters greatly changed during the collision cascades; while most of these radiation damages self-recover quickly in the following quench states. These findings indicate the Cu-Zr metallic glasses have excellent irradiation-resistance properties.

Organic-based molecular switches for molecular electronics.

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Fuentes, Noelia; Martín-Lasanta, Ana; Alvarez de Cienfuegos, Luis; Ribagorda, Maria; Parra, Andres; Cuerva, Juan M

2011-10-05

In a general sense, molecular electronics (ME) is the branch of nanotechnology which studies the application of molecular building blocks for the fabrication of electronic components. Among the different types of molecules, organic compounds have been revealed as promising candidates for ME, due to the easy access, great structural diversity and suitable electronic and mechanical properties. Thanks to these useful capabilities, organic molecules have been used to emulate electronic devices at the nanoscopic scale. In this feature article, we present the diverse strategies used to develop organic switches towards ME with special attention to non-volatile systems.

The role of stable α-synuclein oligomers in the molecular events underlying amyloid formation

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Lorenzen, Nikolai; Nielsen, Søren Bang; Buell, Alexander K.

2014-01-01

α-synuclein (αSN), whose aggregation is strongly implicated in the development of Parkinson’s disease (PD). The two types of oligomers are both formed under conditions where amyloid fibril formation is observed but differ in molecular weight by an order of magnitude. Both possess a degree of β......, either as precursors of fibrils or as species involved in the fibril elongation process or instead if they are associated with an aggregation process that is distinct from that generating mature fibrils. Here we describe and characterize in detail two well-defined oligomeric species formed by the protein...

Comparative Transcriptomic Exploration Reveals Unique Molecular Adaptations of Neuropathogenic Trichobilharzia to Invade and Parasitize Its Avian Definitive Host.

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Roman Leontovyč

2016-02-01

Full Text Available To date, most molecular investigations of schistosomatids have focused principally on blood flukes (schistosomes of humans. Despite the clinical importance of cercarial dermatitis in humans caused by Trichobilharzia regenti and the serious neuropathologic disease that this parasite causes in its permissive avian hosts and accidental mammalian hosts, almost nothing is known about the molecular aspects of how this fluke invades its hosts, migrates in host tissues and how it interacts with its hosts' immune system. Here, we explored selected aspects using a transcriptomic-bioinformatic approach. To do this, we sequenced, assembled and annotated the transcriptome representing two consecutive life stages (cercariae and schistosomula of T. regenti involved in the first phases of infection of the avian host. We identified key biological and metabolic pathways specific to each of these two developmental stages and also undertook comparative analyses using data available for taxonomically related blood flukes of the genus Schistosoma. Detailed comparative analyses revealed the unique involvement of carbohydrate metabolism, translation and amino acid metabolism, and calcium in T. regenti cercariae during their invasion and in growth and development, as well as the roles of cell adhesion molecules, microaerobic metabolism (citrate cycle and oxidative phosphorylation, peptidases (cathepsins and other histolytic and lysozomal proteins in schistosomula during their particular migration in neural tissues of the avian host. In conclusion, the present transcriptomic exploration provides new and significant insights into the molecular biology of T. regenti, which should underpin future genomic and proteomic investigations of T. regenti and, importantly, provides a useful starting point for a range of comparative studies of schistosomatids and other trematodes.

Disintegration of Ar2+ molecular ions under collisions with electrons in a plasma

International Nuclear Information System (INIS)

Ivanov, V.A.

1992-01-01

A spectroscopic experiment is carried out for investigation of disintegration of Ar 2 + ions by plasma electrons. For the first time in the wide electron temperature range from the room one up to T e ∼ 2 eV is measured the process rate constant. At temperatures lower 0.4 eV the obtained values agree well with published data on the value and temperature dependence of the coefficient of dissociative recombination of Ar 2 + with electrons. When temperature increasing in the range of T e =0.5-2 eV is found substantial rise of the rate of molecular ions disintegration, conditioned by starting dissociation mechanism under collicions with plasma electrons

Nanopore wall-liquid interaction under scope of molecular dynamics study: Review

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Tsukanov, A. A.; Psakhie, S. G.

2017-12-01

The present review is devoted to the analysis of recent molecular dynamics based on the numerical studies of molecular aspects of solid-fluid interaction in nanoscale channels. Nanopore wall-liquid interaction plays the crucial role in such processes as gas separation, water desalination, liquids decontamination, hydrocarbons and water transport in nano-fractured geological formations. Molecular dynamics simulation is one of the most suitable tools to study molecular level effects occurred in such multicomponent systems. The nanopores are classified by their geometry to four groups: nanopore in nanosheet, nanotube-like pore, slit-shaped nanopore and soft-matter nanopore. The review is focused on the functionalized nanopores in boron nitride nanosheets as novel selective membranes and on the slit-shaped nanopores formed by minerals.

Novel cancer gene variants and gene fusions of triple-negative breast cancers (TNBCs) reveal their molecular diversity conserved in the patient-derived xenograft (PDX) model.

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Jung, Jaeyun; Jang, Kiwon; Ju, Jung Min; Lee, Eunji; Lee, Jong Won; Kim, Hee Jung; Kim, Jisun; Lee, Sae Byul; Ko, Beom Seok; Son, Byung Ho; Lee, Hee Jin; Gong, Gyungyup; Ahn, Sei Yeon; Choi, Jung Kyoon; Singh, Shree Ram; Chang, Suhwan

2018-04-20

Despite the improved 5-year survival rate of breast cancer, triple-negative breast cancer (TNBC) remains a challenge due to lack of effective targeted therapy and higher recurrence and metastasis than other subtypes. To identify novel druggable targets and to understand its unique biology, we tried to implement 24 patient-derived xenografts (PDXs) of TNBC. The overall success rate of PDX implantation was 45%, much higher than estrogen receptor (ER)-positive cases. Immunohistochemical analysis revealed conserved ER/PR/Her2 negativity (with two exceptions) between the original and PDX tumors. Genomic analysis of 10 primary tumor-PDX pairs with Ion AmpliSeq CCP revealed high degree of variant conservation (85.0% to 96.9%) between primary and PDXs. Further analysis showed 44 rare variants with a predicted high impact in 36 genes including Trp53, Pten, Notch1, and Col1a1. Among them, we confirmed frequent Notch1 variant. Furthermore, RNA-seq analysis of 24 PDXs revealed 594 gene fusions, of which 163 were in-frame, including AZGP1-GJC3 and NF1-AARSD1. Finally, western blot analysis of oncogenic signaling proteins supporting molecular diversity of TNBC PDXs. Overall, our report provides a molecular basis for the usefulness of the TNBC PDX model in preclinical study. Copyright © 2018. Published by Elsevier B.V.

Molecular Dynamics Simulations Reveal the Conformational Flexibility of Lipid II and Its Loose Association with the Defensin Plectasin in the Staphylococcus aureus Membrane

DEFF Research Database (Denmark)

Witzke, Sarah; Petersen, Michael; Carpenter, Timothy S.

2016-01-01

dynamics simulation study of the conformational dynamics of Lipid II within a detailed model of the Staphylococcus aureus cell membrane. We show that Lipid II is able to adopt a range of conformations, even within the packed lipidic environment of the membrane. Our simulations also reveal dimerization...... the biosynthesis of the cell wall. Given the urgent need for development of novel antibiotics to counter the growing threat of bacterial infection resistance, it is imperative that a thorough molecular-level characterization of the molecules targeted by antibiotics be achieved. To this end, we present a molecular...... of Lipid II mediated by cations. In the presence of the defensin peptide plectasin, the conformational lability of Lipid II allows it to form loose complexes with the protein, via a number of different binding modes....

IgV peptide mapping of native Ro60 autoantibody proteomes in primary Sjögren's syndrome reveals molecular markers of Ro/La diversification.

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Wang, Jing J; Al Kindi, Mahmood A; Colella, Alex D; Dykes, Lukah; Jackson, Michael W; Chataway, Tim K; Reed, Joanne H; Gordon, Tom P

2016-12-01

We have used high-resolution mass spectrometry to sequence precipitating anti-Ro60 proteomes from sera of patients with primary Sjögren's syndrome and compare immunoglobulin variable-region (IgV) peptide signatures in Ro/La autoantibody subsets. Anti-Ro60 were purified by elution from native Ro60-coated ELISA plates and subjected to combined de novo amino acid sequencing and database matching. Monospecific anti-Ro60 Igs comprised dominant public and minor private sets of IgG1 kappa and lambda restricted heavy and light chains. Specific IgV amino acid substitutions stratified anti-Ro60 from anti-Ro60/La responses, providing a molecular fingerprint of Ro60/La determinant spreading and suggesting that different forms of Ro60 antigen drive these responses. Sequencing of linked anti-Ro52 proteomes from individual patients and comparison with their anti-Ro60 partners revealed sharing of a dominant IGHV3-23/IGKV3-20 paired clonotype but with divergent IgV mutational signatures. In summary, anti-Ro60 IgV peptide mapping provides insights into Ro/La autoantibody diversification and reveals serum-based molecular markers of humoral Ro60 autoimmunity. Copyright © 2016 Elsevier Inc. All rights reserved.

Use and trade of bitumen in antiquity and prehistory: molecular archaeology reveals secrets of past civilizations

Science.gov (United States)

Connan, J.

1999-01-01

, shells, mother of pearl, on palm trees, cups, ostrich eggs, musical instruments (e.g. the Queen's lyre) and other items, such as rings, jewellery and games, have been excavated from the Royal tombs in Ur. They are on view in the British Museum. With a special enigmatic material, commonly referred to as 'bitumen mastic', the inhabitants of Susa sculpted masterpieces of art which are today exhibited in the Louvre Museum in Paris. This unique collection is presented in a book by Connan and Deschesne (1996). Last, bitumen was also considered as a powerful remedy in medical practice, especially as a disinfectant and insecticide, and was used by the ancient Egyptians to prepare mixtures to embalm the corpses of their dead. Modern analytical techniques, currently applied in the field of petroleum geochemistry, have been adapted to the study of numerous archaeological bituminous mixtures found in excavations. More than 700 bituminous samples have been analysed during the last decade, using gas chromatography alone and gas chromatography coupled with mass spectrometry and isotopic chemistry (carbon and hydrogen mainly). These powerful tools, focused on the detailed analysis of biomarkers in hydrocarbon fractions, were calibrated on various well-known natural sources of bitumen in Iraq, Syria, Iran, Bahrain and Kuwait. These reference studies have made it possible to establish the origins of bitumen from numerous archaeological sites and to document the bitumen trade routes in the Middle East and the Arabo-Persian Gulf. Using a well-documented case history, Tell el 'Oueili (5800 to 3500 BC) in South Mesopotamia, we will illustrate in this paper how these new molecular and isotopic tools can help us to recognize different sources of bitumen and to trace the ancient trade routes through time. These import routes were found to vary with major cultural and political changes in the area under study. A second example, referring to the prehistoric period, describes bitumen traces on

Molecular and morphological data reveal non-monophyly and speciation in imperiled freshwater mussels (Anodontoides and Strophitus)

Science.gov (United States)

Smith, Chase; Johnson, Nathan A.; Pfeiffer, John M.; Gangloff, Michael M.

2018-01-01

Accurate taxonomic placement is vital to conservation efforts considering many intrinsic biological characteristics of understudied species are inferred from closely related taxa. The rayed creekshell, Anodontoides radiatus (Conrad, 1834), exists in the Gulf of Mexico drainages from western Florida to Louisiana and has been petitioned for listing under the Endangered Species Act. We set out to resolve the evolutionary history of A. radiatus, primarily generic placement and species boundaries, using phylogenetic, morphometric, and geographic information. Our molecular matrix contained 3 loci: cytochrome c oxidase subunit I, NADH dehydrogenase subunit I, and the nuclear-encoded ribosomal internal transcribed spacer I. We employed maximum likelihood and Bayesian inference to estimate a phylogeny and test the monophyly of Anodontoides and Strophitus. We implemented two coalescent-based species delimitation models to test seven species models and evaluate species boundaries within A. radiatus. Concomitant to molecular data, we also employed linear morphometrics and geographic information to further evaluate species boundaries. Molecular and morphological evidence supports the inclusion of A. radiatus in the genus Strophitus, and we resurrect the binomial Strophitus radiatus to reflect their shared common ancestry. We also found strong support for polyphyly in Strophitus and advocate the resurrection of the genus Pseudodontoideus to represent ‘Strophitus’ connasaugaensis and ‘Strophitus’ subvexus. Strophitus radiatus exists in six well-supported clades that were distinguished as evolutionary independent lineages using Bayesian inference, maximum likelihood, and coalescent-based species delimitation models. Our integrative approach found evidence for as many as 4 evolutionary divergent clades within S. radiatus. Therefore, we formally describe two new species from the S. radiatus species complex (Strophitus williamsi and Strophitus pascagoulaensis) and recognize

Non-sensitized selective photochemical reduction of CO2 to CO under visible light with an iron molecular catalyst.

Science.gov (United States)

Rao, Heng; Bonin, Julien; Robert, Marc

2017-03-02

A substituted tetraphenyl iron porphyrin, bearing positively charged trimethylammonio groups at the para position of each phenyl ring, demonstrates its ability as a homogeneous molecular catalyst to selectively reduce CO 2 to CO under visible light irradiation in organic media without the assistance of a sensitizer and no competitive hydrogen evolution for several days.

Molecular profiling of ALDH1+ colorectal cancer stem cells reveals preferential activation of MAPK, FAK, and oxidative stress prosurvival signalling pathways

DEFF Research Database (Denmark)

Vishnubalaji, Radhakrishnan; Manikandan, Muthurangan; Fahad, Mohamed

2018-01-01

enrichment related to DNA damage, MAPK, FAK, oxidative stress response, and Wnt signalling. ALDH+ cells showed enhanced ROS stress resistance, whereas MAPK/FAK pathway pharmacologic inhibition limited their survival. Conversely, 5-fluorouracil increased the ALDH+ cell fraction among the SW403, HCT116 and SW.......006) and poor DFS (p = 0.05), thus implicating ALDH1A1 and POU5F1 in CRC prognosis. Our data reveal distinct molecular signature of ALDH+ CSCs in CRC and suggest pathways relevant for successful targeted therapies and management of CRC....

Synthesis of Molecularly Imprinted Polymer for Sterol Separation

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Yuangsawad Ratanaporn

2016-01-01

Full Text Available Molecular imprinted polymer (MIP was prepared by bulk polymerization in acetone using acrylamide as a functional monomer, ethylene glycol dimethacrylate as a crosslinker, stigmasterol as a template and benzoyl peroxide as an initiator. The obtained MIPs were characterized using a scanning electron microscope and a fourier transform infrared spectrophotometer. Performance in sterol adsorption of MIPs prepared under various conditions was investigated using a model solution of phytosterols in heptane, comparing with a nonimprinted polymer (NIP. Statistical analysis revealed that the amounts of crosslinker and template strongly affected the performance of MIP while the amount of solvent slightly affected the performance of MIP. MIP synthesized under the optimal condition had adsorption capacity of 1.28 mgsterols/gads which were 1.13 times of NIP.

Molecular spectrum of laterally coupled quantum rings under intense terahertz radiation.

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Baghramyan, Henrikh M; Barseghyan, Manuk G; Laroze, David

2017-09-05

We study the influence of intense THz laser radiation and electric field on molecular states of laterally coupled quantum rings. Laser radiation shows the capability to dissociate quantum ring molecule and add 2-fold degeneracy to the molecular states at the fixed value of the overlapping size between rings. It is shown that coupled to decoupled molecular states phase transition points form almost a straight line with a slope equal to two. In addition, the electric field direction dependent energy spectrum shows unexpected oscillations, demonstrating strong coupling between molecular states. Besides, intraband absorption is considered, showing both blue and redshifts in its spectrum. The obtained results can be useful for the controlling of degeneracy of the discrete energy spectrum of nanoscale structures and in the tunneling effects therein.

Transcriptome dynamics of a susceptible wheat upon Fusarium head blight reveals that molecular responses to Fusarium graminearum infection fit over the grain development processes.

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Chetouhi, Cherif; Bonhomme, Ludovic; Lasserre-Zuber, Pauline; Cambon, Florence; Pelletier, Sandra; Renou, Jean-Pierre; Langin, Thierry

2016-03-01

In many plant/pathogen interactions, host susceptibility factors are key determinants of disease development promoting pathogen growth and spreading in plant tissues. In the Fusarium head blight (FHB) disease, the molecular basis of wheat susceptibility is still poorly understood while it could provide new insights into the understanding of the wheat/Fusarium graminearum (Fg) interaction and guide future breeding programs to produce cultivars with sustainable resistance. To identify the wheat grain candidate genes, a genome-wide gene expression profiling was performed in the French susceptible wheat cultivar, Recital. Gene-specific two-way ANOVA of about 40 K transcripts at five grain developmental stages identified 1309 differentially expressed genes. Out of these, 536 were impacted by the Fg effect alone. Most of these Fg-responsive genes belonged to biological and molecular functions related to biotic and abiotic stresses indicating the activation of common stress pathways during susceptibility response of wheat grain to FHB. This analysis revealed also 773 other genes displaying either specific Fg-responsive profiles along with grain development stages or synergistic adjustments with the grain development effect. These genes were involved in various molecular pathways including primary metabolism, cell death, and gene expression reprogramming. An increasingly complex host response was revealed, as was the impact of both Fg infection and grain ontogeny on the transcription of wheat genes. This analysis provides a wealth of candidate genes and pathways involved in susceptibility responses to FHB and depicts new clues to the understanding of the susceptibility determinism in plant/pathogen interactions.

Degradation of Poly (lactic acid under Simulated Landfill Conditions

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Chomnutcha Boonmee

2017-03-01

Full Text Available In this study, the physical and chemical properties change of poly(lactic acid after burying in the mixture of soil and sludge under thermophilic (61 °C oxygen limited conditions were investigated using various analytical techniques. The environmental factors under these setting conditions and microbial activities accelerated the degradation process of PLA. Under tested conditions, PLA loss their weight about 90% at the burying time of 90 days. During the degradation process, PLA samples were continuously broken to small fragile fragments and showed the size less than 1 mm at the end of degradation test. Change of the surface morphology change was revealed by scanning electron microscopy (SEM. Many pores, cracks and irregular roughness were presented on the PLA surface. Thermal decomposition was decreased from 387.8 to 289.2 °C. The percentage of carbon content in molecular structure decreased from 49.46% to 45.42%. In addition, the Fourier transformed infrared spectroscopy (FTIR revealed the change of ester bonds. This study can be used for developing PLA waste management process.

Molecular structure of self-assembled chiral nanoribbons and nanotubules revealed in the hydrated state.

Science.gov (United States)

Oda, Reiko; Artzner, Franck; Laguerre, Michel; Huc, Ivan

2008-11-05

A detailed molecular organization of racemic 16-2-16 tartrate self-assembled multi-bilayer ribbons in the hydrated state is proposed where 16-2-16 amphiphiles, tartrate ions, and water molecules are all accurately positioned by comparing experimental X-ray powder diffraction and diffraction patterns derived from modeling studies. X-ray diffuse scattering studies show that molecular organization is not fundamentally altered when comparing the flat ribbons of the racemate to chirally twisted or helical ribbons of the pure tartrate enantiomer. Essential features of the three-dimensional molecular organizations of these structures include interdigitation of alkyl chains within each bilayer and well-defined networks of ionic and hydrogen bonds between cations, anions, and water molecules between bilayers. The detailed study of diffraction patterns also indicated that the gemini headgroups are oriented parallel to the long edge of the ribbons. The structure thus possesses a high cohesion and good crystallinity, and for the first time, we could relate the packing of the chiral molecules to the expression of the chirality at a mesoscopic scale. The organization of the ribbons at the molecular level sheds light on a number of their macroscopic features. Among these are the reason why enantiomerically pure 16-2-16 tartrate forms ribbons that consist of exactly two bilayers, and a plausible mechanism by which a chirally twisted or helical shape may emerge from the packing of chiral tartrate ions. Importantly, the distinction between commonly observed helical and twisted morphologies could be related to a subtle symmetry breaking. These results demonstrate that accurately solving the molecular structure of self-assembled soft materials--a process rarely achieved--is within reach, that it is a valid approach to correlate molecular parameters to macroscopic properties, and thus that it offers opportunities to modulate properties through molecular design.

Solid-state NMR Reveals the Carbon-based Molecular Architecture of Cryptococcus neoformans Fungal Eumelanins in the Cell Wall*

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Chatterjee, Subhasish; Prados-Rosales, Rafael; Itin, Boris; Casadevall, Arturo; Stark, Ruth E.

2015-01-01

Melanin pigments protect against both ionizing radiation and free radicals and have potential soil remediation capabilities. Eumelanins produced by pathogenic Cryptococcus neoformans fungi are virulence factors that render the fungal cells resistant to host defenses and certain antifungal drugs. Because of their insoluble and amorphous characteristics, neither the pigment bonding framework nor the cellular interactions underlying melanization of C. neoformans have yielded to comprehensive molecular-scale investigation. This study used the C. neoformans requirement of exogenous obligatory catecholamine precursors for melanization to produce isotopically enriched pigment “ghosts” and applied 2D 13C-13C correlation solid-state NMR to reveal the carbon-based architecture of intact natural eumelanin assemblies in fungal cells. We demonstrated that the aliphatic moieties of solid C. neoformans melanin ghosts include cell-wall components derived from polysaccharides and/or chitin that are associated proximally with lipid membrane constituents. Prior to development of the mature aromatic fungal pigment, these aliphatic moieties form a chemically resistant framework that could serve as the scaffold for melanin synthesis. The indole-based core aromatic moieties show interconnections that are consistent with proposed melanin structures consisting of stacked planar assemblies, which are associated spatially with the aliphatic scaffold. The pyrrole aromatic carbons of the pigments bind covalently to the aliphatic framework via glycoside or glyceride functional groups. These findings establish that the structure of the pigment assembly changes with time and provide the first biophysical information on the mechanism by which melanin is assembled in the fungal cell wall, offering vital insights that can advance the design of bioinspired conductive nanomaterials and novel therapeutics. PMID:25825492

The rise of a novel classification system for endometrial carcinoma; integration of molecular subclasses.

Science.gov (United States)

McAlpine, Jessica; Leon-Castillo, Alicia; Bosse, Tjalling

2018-04-01

Endometrial cancer is a clinically heterogeneous disease and it is becoming increasingly clear that this heterogeneity may be a function of the diversity of the underlying molecular alterations. Recent large-scale genomic studies have revealed that endometrial cancer can be divided into at least four distinct molecular subtypes, with well-described underlying genomic aberrations. These subtypes can be reliably delineated and carry significant prognostic as well as predictive information; embracing and incorporating them into clinical practice is thus attractive. The road towards the integration of molecular features into current classification systems is not without obstacles. Collaborative studies engaging research teams from across the world are working to define pragmatic assays, improve risk stratification systems by combining molecular features and traditional clinicopathological parameters, and determine how molecular classification can be optimally utilized to direct patient care. Pathologists and clinicians caring for women with endometrial cancer need to engage with and understand the possibilities and limitations of this new approach, because integration of molecular classification of endometrial cancers is anticipated to become an essential part of gynaecological pathology practice. This review will describe the challenges in current systems of endometrial carcinoma classification, the evolution of new molecular technologies that define prognostically distinct molecular subtypes, and potential applications of molecular classification as a step towards precision medicine and refining care for individuals with the most common gynaecological cancer in the developed world. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Survival under stress: molecular mechanisms of metabolic rate ...

African Journals Online (AJOL)

Studies in my laboratory are analysing the molecular mechanisms and regulatory events that underlie transitions to and from hypometabolic states In systems including anoxia-tolerant turtles and molluscs, estivating snails and toads, hibernating small mammals, and freeze tolerant frogs and insects. Our newest research ...

Revealing Amphiphilic Nanodornains of Anti-Biofouling Polymer Coatings

Energy Technology Data Exchange (ETDEWEB)

Amadei, CA; Yang, R; Chiesa, M; Gleason, KK; Santos, S

2014-04-09

Undesired bacterial adhesion and biofilm formation on wetted surfaces leads to significant economic and environmental costs in various industries. Amphiphilic coatings with molecular hydrophilic and hydrophobic patches can mitigate such biofouling effectively in an environmentally friendly manner. The coatings are synthesized by copolymerizing (Hydroxyethyl)methacrylate and perfluorodecylacrylate via initiated chemical vapor deposition (iCVD). In previous studies, the size of the patches was estimated to be similar to 1.4-1.75 nm by fitting protein adsorption data to a theoretical model. However, no direct observations of the molecular heterogeneity exist and therefore the origin of the fouling resistance of amphiphilic coatings remains unclear. Here, the amphiphilic nature is investigated by amplitude modulation atomic force microscopy (AM-AFM). High-resolution images obtained by penetrating and oscillating the AFM tip under the naturally present water layer with sub-nanometer amplitudes reveal, for the first time, the existence of amphiphilic nanodomains (1-2 nm(2)). Compositional heterogeneity at the nanoscale is further corroborated by a statistical analysis on the data obtained with dynamic AM-AFM force spectroscopy. Variations in the long range attractive forces, responsible for water affinity, are also identified. These nanoscopic results on the polymers wettability are also confirmed by contact angle measurements (i.e., static and dynamic). The unprecedented ability to visualize the amphiphilic nanodomains as well as sub-nanometer crystalline structures provides strong evidence for the existence of previously postulated nanostructures, and sheds light on the underlying antifouling mechanism of amphiphilic chemistry.

Investigation of tribological properties of graphene oxide reinforced ultrahigh molecular weight polyethylene under artificial seawater lubricating condition

Science.gov (United States)

Pang, Wenchao; Ni, Zifeng; Wu, JiaLiang; Zhao, Yongwu

2018-03-01

A range of ultrahigh molecular weight polyethylene (UHMWPE)/graphene oxide (GO) nanocomposites were fabricated using liquid-phase ultrasonication mixing followed by hot-pressing. The wettability, water absorption and corrosion resistance of composites were studied to prove the composites were suitable for application in liquid environment. The tribological properties of composites under dry, deionized water and seawater lubricating condition were investigated. The results showed that the incorporation of GO decreased the wear rate of UHMWPE under different lubricating conditions and with the increase of GO addition, the wear rate of UHMWPE/GO composites decreased. UHMWPE/GO composites exhibited better tribological behaviors under seawater lubricating condition than other conditions, because good corrosion resistance and excellent wear resistance of UHMWPE/GO composites, and the lubricating effect of seawater is also indispensable.

Dynamic coherence in excitonic molecular complexes under various excitation conditions

Energy Technology Data Exchange (ETDEWEB)

Chenu, Aurélia; Malý, Pavel; Mančal, Tomáš, E-mail: mancal@karlov.mff.cuni.cz

2014-08-17

Highlights: • Dynamic coherence does not improve energy transfer efficiency in natural conditions. • Photo-induced quantum jumps are discussed in classical context. • Natural time scale of a light excitation event is identified. • Coherence in FMO complex averages out under excitation by neighboring antenna. • This result is valid even in absence of dissipation. - Abstract: We investigate the relevance of dynamic quantum coherence in the energy transfer efficiency of molecular aggregates. We derive the time evolution of the density matrix for an open quantum system excited by light or by a neighboring antenna. Unlike in the classical case, the quantum description does not allow for a formal decomposition of the dynamics into sudden jumps in an observable quantity – an expectation value. Rather, there is a natural finite time-scale associated with the excitation process. We propose a simple experiment to test the influence of this time scale on the yield of photosynthesis. We demonstrate, using typical parameters of the Fenna–Matthews–Olson (FMO) complex and a typical energy transfer rate from the chlorosome baseplate, that dynamic coherences are averaged out in the complex even when the FMO model is completely free of all dissipation and dephasing.

Molecular and Silica-Supported Molybdenum Alkyne Metathesis Catalysts: Influence of Electronics and Dynamics on Activity Revealed by Kinetics, Solid-State NMR, and Chemical Shift Analysis.

Science.gov (United States)

Estes, Deven P; Gordon, Christopher P; Fedorov, Alexey; Liao, Wei-Chih; Ehrhorn, Henrike; Bittner, Celine; Zier, Manuel Luca; Bockfeld, Dirk; Chan, Ka Wing; Eisenstein, Odile; Raynaud, Christophe; Tamm, Matthias; Copéret, Christophe

2017-12-06

Molybdenum-based molecular alkylidyne complexes of the type [MesC≡Mo{OC(CH 3 ) 3-x (CF 3 ) x } 3 ] (MoF 0 , x = 0; MoF 3 , x = 1; MoF 6 , x = 2; MoF 9 , x = 3; Mes = 2,4,6-trimethylphenyl) and their silica-supported analogues are prepared and characterized at the molecular level, in particular by solid-state NMR, and their alkyne metathesis catalytic activity is evaluated. The 13 C NMR chemical shift of the alkylidyne carbon increases with increasing number of fluorine atoms on the alkoxide ligands for both molecular and supported catalysts but with more shielded values for the supported complexes. The activity of these catalysts increases in the order MoF 0 molecular and supported species. Detailed solid-state NMR analysis of molecular and silica-supported metal alkylidyne catalysts coupled with DFT/ZORA calculations rationalize the NMR spectroscopic signatures and discernible activity trends at the frontier orbital level: (1) increasing the number of fluorine atoms lowers the energy of the π*(M≡C) orbital, explaining the more deshielded chemical shift values; it also leads to an increased electrophilicity and higher reactivity for catalysts up to MoF 6 , prior to a sharp decrease in reactivity for MoF 9 due to the formation of stable metallacyclobutadiene intermediates; (2) the silica-supported catalysts are less active than their molecular analogues because they are less electrophilic and dynamic, as revealed by their 13 C NMR chemical shift tensors.

Charge transport through molecular rods with reduced pi-conjugation.

Science.gov (United States)

Lörtscher, Emanuel; Elbing, Mark; Tschudy, Meinrad; von Hänisch, Carsten; Weber, Heiko B; Mayor, Marcel; Riel, Heike

2008-10-24

A series of oligophenylene rods of increasing lengths is synthesized to investigate the charge-transport mechanisms. Methyl groups are attached to the phenyl rings to weaken the electronic overlap of the pi-subsystems along the molecular backbones. Out-of-plane rotation of the phenyl rings is confirmed in the solid state by means of X-ray analysis and in solution by using UV/Vis spectroscopy. The influence of the reduced pi-conjugation on the resonant charge transport is studied at the single-molecule level by using the mechanically controllable break-junction technique. Experiments are performed under ultra-high-vacuum conditions at low temperature (50 K). A linear increase of the conductance gap with increasing number of phenyl rings (from 260 meV for one ring to 580 meV for four rings) is revealed. In addition, the absolute conductance of the first resonant peaks does not depend on the length of the molecular wire. Resonant transport through the first molecular orbital is found to be dominated by charge-carrier injection into the molecule, rather than by the intrinsic resistance of the molecular wire length.

Molecular phenotyping of multiple mouse strains under metabolic challenge uncovers a role for Elovl2 in glucose-induced insulin secretion

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Céline Cruciani-Guglielmacci

2017-04-01

Conclusion: Our results suggest a role for Elovl2 in ensuring normal insulin secretory responses to glucose. Moreover, the large comprehensive dataset and integrative network-based approach provides a new resource to dissect the molecular etiology of β cell failure under metabolic stress.

Molecular HIV screening.

Science.gov (United States)

Bourlet, Thomas; Memmi, Meriam; Saoudin, Henia; Pozzetto, Bruno

2013-09-01

Nuclear acid testing is more and more used for the diagnosis of infectious diseases. This paper focuses on the use of molecular tools for HIV screening. The term 'screening' will be used under the meaning of first-line HIV molecular techniques performed on a routine basis, which excludes HIV molecular tests designed to confirm or infirm a newly discovered HIV-seropositive patient or other molecular tests performed for the follow-up of HIV-infected patients. The following items are developed successively: i) presentation of the variety of molecular tools used for molecular HIV screening, ii) use of HIV molecular tools for the screening of blood products, iii) use of HIV molecular tools for the screening of organs and tissue from human origin, iv) use of HIV molecular tools in medically assisted procreation and v) use of HIV molecular tools in neonates from HIV-infected mothers.

Quantitative proteomic analysis of human testis reveals system-wide molecular and cellular pathways associated with non-obstructive azoospermia.

Science.gov (United States)

Alikhani, Mehdi; Mirzaei, Mehdi; Sabbaghian, Marjan; Parsamatin, Pouria; Karamzadeh, Razieh; Adib, Samane; Sodeifi, Niloofar; Gilani, Mohammad Ali Sadighi; Zabet-Moghaddam, Masoud; Parker, Lindsay; Wu, Yunqi; Gupta, Vivek; Haynes, Paul A; Gourabi, Hamid; Baharvand, Hossein; Salekdeh, Ghasem Hosseini

2017-06-06

Male infertility accounts for half of the infertility problems experienced by couples. Azoospermia, having no measurable level of sperm in seminal fluid, is one of the known conditions resulting in male infertility. In order to elucidate the complex molecular mechanisms causing male azoospermia, label-free quantitative shotgun proteomics was carried out on testicular tissue specimens from patients with obstructive azoospermia and non-obstructive azoospermia, including maturation arrest (MA) and Sertoli cell only syndrome (SCOS). The abundance of 520 proteins was significantly changed across three groups of samples. We were able to identify several functional biological pathways enriched in azoospermia samples and confirm selected differentially abundant proteins, using multiple histological methods. The results revealed that cell cycle and proteolysis, and RNA splicing were the most significant biological processes impaired by the substantial suppression of proteins related to the aforementioned categories in SCOS tissues. In the MA patient testes, generation of precursor metabolites and energy as well as oxidation-reduction were the most significantly altered processes. Novel candidate proteins identified in this study include key transcription factors, many of which have not previously been shown to be associated with azoospermia. Our findings can provide substantial insights into the molecular regulation of spermatogenesis and human reproduction. The obtained data showed a drastic suppression of proteins involved in spliceosome, cell cycle and proteasome proteins, as well as energy and metabolic production in Sertoli cell only syndrome testis tissue, and to a lesser extent in maturation arrest samples. Moreover, we identified new transcription factors that are highly down-regulated in SCOS and MA patients, thus helping to understand the molecular complexity of spermatogenesis in male infertility. Our findings provide novel candidate protein targets associated

A probe to study the toxic interaction of tartrazine with bovine hemoglobin at the molecular level.

Science.gov (United States)

Li, Yating; Wei, Haoran; Liu, Rutao

2014-03-01

Tartrazine is an artificial azo dye commonly used in food products, but tartrazine in the environment is potentially harmful. The toxic interaction between tartrazine and bovine hemoglobin (BHb) was investigated using fluorescence, synchronous fluorescence, UV-vis absorption, circular dichroism (CD) and molecular modeling techniques under simulated physiological conditions. The fluorescence data showed that tartrazine can bind with BHb to form a complex. The binding process was a spontaneous molecular interaction, in which van der Waals' forces and hydrogen bonds played major roles. Molecular docking results showed that the hydrogen bonds exist between the oxygen atoms at position 31 of tartrazine and the nitrogen atom NZ7 on Lys99, and also between the oxygen atoms at position 15 of tartrazine and the nitrogen atom NZ7 on Lys104, Lys105. The results of UV-vis and CD spectra revealed that tartrazine led to conformational changes in BHb, including loosening of the skeleton structure and decreasing α helix in the secondary structure. The synchronous fluorescence experiment revealed that tartrazine binds into the hemoglobin central cavity, and this was verified using a molecular modeling study. Copyright © 2013 John Wiley & Sons, Ltd.

Molecular profiling of synchronous and metachronous cancers of the pancreas reveal molecular mimicry between samples from the same patient.

Science.gov (United States)

Talbott, Vanessa A; Yeo, Charles J; Brody, Jonathan R; Witkiewicz, Agnieszka K

2012-07-01

Pancreatic ductal adenocarcinoma (PDA) is rarely a survivable disease. In rare cases, separate synchronous tumors are discovered at the time of resection, while in others, patients present with a metachronous cancer after prior surgical resection. Studying molecular markers of synchronous and metachronous lesions may aid to clarify the biology of this often deadly disease. Two patients presented with synchronous tumors (each one with a tumor in the pancreatic head/neck and the other in the tail, designated patients A and B). An additional patient (patient C) underwent an R0 resection for PDA of the head and recurred 1.5 y later with PDA in the tail. Genomic DNA was laser capture microdissected (LCM) from the tumor and molecular analysis was performed. K-ras status and loss of heterozygosity (LOH) were determined from multiple specimens for each case. All samples from each patient harbored identical K-ras mutations. In patient A, the tumor at the head of the pancreas had more clonal genetic instability as reflected by LOH analysis over multiple LCM samples. Patient B had more genetic instability in the tail lesion compared with the neck. Patient C had virtually the identical molecular profile in both tumors, supporting the notion that both tumors were related. We conclude that the synchronous and metachronous tumors likely are initiated from identical precursor lesions and/or events (i.e., K-ras mutations). Future studies will need to investigate if these tumors will respond similarly to adjuvant therapies targeted against the clonal molecular events in the tumor. Copyright © 2012 Elsevier Inc. All rights reserved.

Molecular imaging reveals elevated VEGFR-2 expression in retinal capillaries in diabetes: a novel biomarker for early diagnosis.

Science.gov (United States)

Sun, Dawei; Nakao, Shintaro; Xie, Fang; Zandi, Souska; Bagheri, Abouzar; Kanavi, Mozhgan Rezaei; Samiei, Shahram; Soheili, Zahra-Soheila; Frimmel, Sonja; Zhang, Zhongyu; Ablonczy, Zsolt; Ahmadieh, Hamid; Hafezi-Moghadam, Ali

2014-09-01

Diabetic retinopathy (DR) is a microvascular complication of diabetes and a leading cause of vision loss. Biomarkers and methods for early diagnosis of DR are urgently needed. Using a new molecular imaging approach, we show up to 94% higher accumulation of custom designed imaging probes against vascular endothelial growth factor receptor 2 (VEGFR-2) in retinal and choroidal vessels of diabetic animals (P<0.01), compared to normal controls. More than 80% of the VEGFR-2 in the diabetic retina was in the capillaries, compared to 47% in normal controls (P<0.01). Angiography in rabbit retinas revealed microvascular capillaries to be the location for VEGF-A-induced leakage, as expressed by significantly higher rate of fluorophore spreading with VEGF-A injection when compared to vehicle control (26±2 vs. 3±1 μm/s, P<0.05). Immunohistochemistry showed VEGFR-2 expression in capillaries of diabetic animals but not in normal controls. Macular vessels from diabetic patients (n=7) showed significantly more VEGFR-2 compared to nondiabetic controls (n=5) or peripheral retinal regions of the same retinas (P<0.01 in both cases). Here we introduce a new approach for early diagnosis of DR and VEGFR-2 as a molecular marker. VEGFR-2 could become a key diagnostic target, one that might help to prevent retinal vascular leakage and proliferation in diabetic patients. © FASEB.

Design principles and optimal performance for molecular motors under realistic constraints

Science.gov (United States)

Tu, Yuhai; Cao, Yuansheng

2018-02-01

The performance of a molecular motor, characterized by its power output and energy efficiency, is investigated in the motor design space spanned by the stepping rate function and the motor-track interaction potential. Analytic results and simulations show that a gating mechanism that restricts forward stepping in a narrow window in configuration space is needed for generating high power at physiologically relevant loads. By deriving general thermodynamics laws for nonequilibrium motors, we find that the maximum torque (force) at stall is less than its theoretical limit for any realistic motor-track interactions due to speed fluctuations. Our study reveals a tradeoff for the motor-track interaction: while a strong interaction generates a high power output for forward steps, it also leads to a higher probability of wasteful spontaneous back steps. Our analysis and simulations show that this tradeoff sets a fundamental limit to the maximum motor efficiency in the presence of spontaneous back steps, i.e., loose-coupling. Balancing this tradeoff leads to an optimal design of the motor-track interaction for achieving a maximum efficiency close to 1 for realistic motors that are not perfectly coupled with the energy source. Comparison with existing data and suggestions for future experiments are discussed.

Transcriptome profiling in engrailed-2 mutant mice reveals common molecular pathways associated with autism spectrum disorders.

Science.gov (United States)

Sgadò, Paola; Provenzano, Giovanni; Dassi, Erik; Adami, Valentina; Zunino, Giulia; Genovesi, Sacha; Casarosa, Simona; Bozzi, Yuri

2013-12-19

Transcriptome analysis has been used in autism spectrum disorder (ASD) to unravel common pathogenic pathways based on the assumption that distinct rare genetic variants or epigenetic modifications affect common biological pathways. To unravel recurrent ASD-related neuropathological mechanisms, we took advantage of the En2-/- mouse model and performed transcriptome profiling on cerebellar and hippocampal adult tissues. Cerebellar and hippocampal tissue samples from three En2-/- and wild type (WT) littermate mice were assessed for differential gene expression using microarray hybridization followed by RankProd analysis. To identify functional categories overrepresented in the differentially expressed genes, we used integrated gene-network analysis, gene ontology enrichment and mouse phenotype ontology analysis. Furthermore, we performed direct enrichment analysis of ASD-associated genes from the SFARI repository in our differentially expressed genes. Given the limited number of animals used in the study, we used permissive criteria and identified 842 differentially expressed genes in En2-/- cerebellum and 862 in the En2-/- hippocampus. Our functional analysis revealed that the molecular signature of En2-/- cerebellum and hippocampus shares convergent pathological pathways with ASD, including abnormal synaptic transmission, altered developmental processes and increased immune response. Furthermore, when directly compared to the repository of the SFARI database, our differentially expressed genes in the hippocampus showed enrichment of ASD-associated genes significantly higher than previously reported. qPCR was performed for representative genes to confirm relative transcript levels compared to those detected in microarrays. Despite the limited number of animals used in the study, our bioinformatic analysis indicates the En2-/- mouse is a valuable tool for investigating molecular alterations related to ASD.

Nanostructure characterization of beta-sheet crystals in silk under various temperatures

Directory of Open Access Journals (Sweden)

Zhang Yan

2014-01-01

Full Text Available This paper studies the nanostructure characterizations of β-sheet in silk fiber with different reaction temperatures. A molecular dynamic model is developed and simulated by Gromacs software packages. The results reveal the change rules of the number of hydrogen bonds in β-sheet under different temperatures. The best reaction temperature for the β-sheet crystals is also found. This work provides theoretical basis for the designing of materials based on silk.

Shape Changing Nonlocal Molecular Deformations in a Nematic Liquid Crystal

International Nuclear Information System (INIS)

Kavitha, L.; Venkatesh, M.; Gopi, D.

2010-07-01

The nature of nonlinear molecular deformations in a homeotropically aligned nematic liquid crystal (NLC) is presented. We start from the basic dynamical equation for the director axis of a NLC with elastic deformation mapped onto an integro-differential perturbed Nonlinear Schroedinger equation which includes the nonlocal term. By invoking the modified extended tangent hyperbolic function method aided with symbolic computation, we obtain a series of solitary wave solutions. Under the influence of the nonlocality induced by the reorientation nonlinearity due to fluctuations in the molecular orientation, the solitary wave exhibits shape changing property for different choices of parameters. This intriguing property, as a result of the relation between the coherence of the solitary deformation and the nonlocality, reveals a strong need for deeper understanding in the theory of self-localization in NLC systems. (author)

Molecular evolutionary patterns of NAD+/Sirtuin aging signaling pathway across taxa.

Directory of Open Access Journals (Sweden)

Uma Gaur

Full Text Available A deeper understanding of the conserved molecular mechanisms in different taxa have been made possible only because of the evolutionary conservation of crucial signaling pathways. In the present study, we explored the molecular evolutionary pattern of selection signatures in 51 species for 10 genes which are important components of NAD+/Sirtuin pathway and have already been directly linked to lifespan extension in worms and mice. Selection pressure analysis using PAML program revealed that MRPS5 and PPARGC1A were under significant constraints because of their functional significance. FOXO3a also displayed strong purifying selection. All three sirtuins, which were SIRT1, SIRT2 and SIRT6, displayed a great degree of conservation between taxa, which is consistent with the previous report. A significant evolutionary constraint is seen on the anti-oxidant gene, SOD3. As expected, TP53 gene was under significant selection pressure in mammals, owing to its major role in tumor progression. Poly-ADP-ribose polymerase (PARP genes displayed the most sites under positive selection. Further 3D structural analysis of PARP1 and PARP2 protein revealed that some of these positively selected sites caused a change in the electrostatic potential of the protein structure, which may allow a change in its interaction with other proteins and molecules ultimately leading to difference in the function. Although the functional significance of the positively selected sites could not be established in the variants databases, yet it will be interesting to see if these sites actually affect the function of PARP1 and PARP2.

Genes and (Common) Pathways Underlying Drug Addiction

Science.gov (United States)

Li, Chuan-Yun; Mao, Xizeng; Wei, Liping

2008-01-01

Drug addiction is a serious worldwide problem with strong genetic and environmental influences. Different technologies have revealed a variety of genes and pathways underlying addiction; however, each individual technology can be biased and incomplete. We integrated 2,343 items of evidence from peer-reviewed publications between 1976 and 2006 linking genes and chromosome regions to addiction by single-gene strategies, microrray, proteomics, or genetic studies. We identified 1,500 human addiction-related genes and developed KARG (http://karg.cbi.pku.edu.cn), the first molecular database for addiction-related genes with extensive annotations and a friendly Web interface. We then performed a meta-analysis of 396 genes that were supported by two or more independent items of evidence to identify 18 molecular pathways that were statistically significantly enriched, covering both upstream signaling events and downstream effects. Five molecular pathways significantly enriched for all four different types of addictive drugs were identified as common pathways which may underlie shared rewarding and addictive actions, including two new ones, GnRH signaling pathway and gap junction. We connected the common pathways into a hypothetical common molecular network for addiction. We observed that fast and slow positive feedback loops were interlinked through CAMKII, which may provide clues to explain some of the irreversible features of addiction. PMID:18179280

Genes and (common pathways underlying drug addiction.

Directory of Open Access Journals (Sweden)

Chuan-Yun Li

2008-01-01

Full Text Available Drug addiction is a serious worldwide problem with strong genetic and environmental influences. Different technologies have revealed a variety of genes and pathways underlying addiction; however, each individual technology can be biased and incomplete. We integrated 2,343 items of evidence from peer-reviewed publications between 1976 and 2006 linking genes and chromosome regions to addiction by single-gene strategies, microrray, proteomics, or genetic studies. We identified 1,500 human addiction-related genes and developed KARG (http://karg.cbi.pku.edu.cn, the first molecular database for addiction-related genes with extensive annotations and a friendly Web interface. We then performed a meta-analysis of 396 genes that were supported by two or more independent items of evidence to identify 18 molecular pathways that were statistically significantly enriched, covering both upstream signaling events and downstream effects. Five molecular pathways significantly enriched for all four different types of addictive drugs were identified as common pathways which may underlie shared rewarding and addictive actions, including two new ones, GnRH signaling pathway and gap junction. We connected the common pathways into a hypothetical common molecular network for addiction. We observed that fast and slow positive feedback loops were interlinked through CAMKII, which may provide clues to explain some of the irreversible features of addiction.

A transcriptomic computational analysis of mastic oil-treated Lewis lung carcinomas reveals molecular mechanisms targeting tumor cell growth and survival

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Roussos Charis

2009-12-01

Full Text Available Abstract Background Mastic oil from Pistacia lentiscus variation chia, a blend of bioactive terpenes with recognized medicinal properties, has been recently shown to exert anti-tumor growth activity through inhibition of cancer cell proliferation, survival, angiogenesis and inflammatory response. However, no studies have addressed its mechanisms of action at genome-wide gene expression level. Methods To investigate molecular mechanisms triggered by mastic oil, Lewis Lung Carcinoma cells were treated with mastic oil or DMSO and RNA was collected at five distinct time points (3-48 h. Microarray expression profiling was performed using Illumina mouse-6 v1 beadchips, followed by computational analysis. For a number of selected genes, RT-PCR validation was performed in LLC cells as well as in three human cancer cell lines of different origin (A549, HCT116, K562. PTEN specific inhibition by a bisperovanadium compound was applied to validate its contribution to mastic oil-mediated anti-tumor growth effects. Results In this work we demonstrated that exposure of Lewis lung carcinomas to mastic oil caused a time-dependent alteration in the expression of 925 genes. GO analysis associated expression profiles with several biological processes and functions. Among them, modifications on cell cycle/proliferation, survival and NF-κB cascade in conjunction with concomitant regulation of genes encoding for PTEN, E2F7, HMOX1 (up-regulation and NOD1 (down-regulation indicated some important mechanistic links underlying the anti-proliferative, pro-apoptotic and anti-inflammatory effects of mastic oil. The expression profiles of Hmox1, Pten and E2f7 genes were similarly altered by mastic oil in the majority of test cancer cell lines. Inhibition of PTEN partially reversed mastic oil effects on tumor cell growth, indicating a multi-target mechanism of action. Finally, k-means clustering, organized the significant gene list in eight clusters demonstrating a similar

Noncanonical structures and their thermodynamics of DNA and RNA under molecular crowding: beyond the Watson-Crick double helix.

Science.gov (United States)

Sugimoto, Naoki

2014-01-01

How does molecular crowding affect the stability of nucleic acid structures inside cells? Water is the major solvent component in living cells, and the properties of water in the highly crowded media inside cells differ from that in buffered solution. As it is difficult to measure the thermodynamic behavior of nucleic acids in cells directly and quantitatively, we recently developed a cell-mimicking system using cosolutes as crowding reagents. The influences of molecular crowding on the structures and thermodynamics of various nucleic acid sequences have been reported. In this chapter, we discuss how the structures and thermodynamic properties of nucleic acids differ under various conditions such as highly crowded environments, compartment environments, and in the presence of ionic liquids, and the major determinants of the crowding effects on nucleic acids are discussed. The effects of molecular crowding on the activities of ribozymes and riboswitches on noncanonical structures of DNA- and RNA-like quadruplexes that play important roles in transcription and translation are also described. © 2014 Elsevier Inc. All rights reserved.

Elucidation of molecular mechanisms of physiological variations between bovine subcutaneous and visceral fat depots under different nutritional regimes.

Directory of Open Access Journals (Sweden)

Josue Moura Romao

Full Text Available Adipose tissue plays a critical role in energy homeostasis and metabolism. There is sparse understanding of the molecular regulation at the protein level of bovine adipose tissues, especially within different fat depots under different nutritional regimes. The objective of this study was to analyze the differences in protein expression between bovine subcutaneous and visceral fat depots in steers fed different diets and to identify the potential regulatory molecular mechanisms of protein expression. Subcutaneous and visceral fat tissues were collected from 16 British-continental steers (15.5 month old fed a high-fat diet (7.1% fat, n=8 or a control diet (2.7% fat, n=8. Protein expression was profiled using label free quantification LC-MS/MS and expression of selected transcripts was evaluated using qRT-PCR. A total of 682 proteins were characterized and quantified with fat depot having more impact on protein expression, altering the level of 51.0% of the detected proteins, whereas diet affected only 5.3%. Functional analysis revealed that energy production and lipid metabolism were among the main functions associated with differentially expressed proteins between fat depots, with visceral fat being more metabolically active than subcutaneous fat as proteins associated with lipid and energy metabolism were upregulated. The expression of several proteins was significantly correlated to subcutaneous fat thickness and adipocyte size, indicating their potential as adiposity markers. A poor correlation (r=0.245 was observed between mRNA and protein levels for 9 genes, indicating that many proteins may be subjected to post-transcriptional regulation. A total of 8 miRNAs were predicted to regulate more than 20% of lipid metabolism proteins differentially expressed between fat depots, suggesting that miRNAs play a role in adipose tissue regulation. Our results show that proteomic changes support the distinct metabolic and physiological characteristics

Stability of large-area molecular junctions

NARCIS (Netherlands)

Akkerman, Hylke B.; Kronemeijer, Auke J.; Harkema, Jan; van Hal, Paul A.; Smits, Edsger C. P.; de Leeuw, Dago M.; Blom, Paul W. M.

The stability of molecular junctions is crucial for any application of molecular electronics. Degradation of molecular junctions when exposed to ambient conditions is regularly observed. In this report the stability of large-area molecular junctions under ambient conditions for more than two years

Mg doping of GaN grown by plasma-assisted molecular beam epitaxy under nitrogen-rich conditions

International Nuclear Information System (INIS)

Zhang Meng; Bhattacharya, Pallab; Guo Wei; Banerjee, Animesh

2010-01-01

Acceptor doping of GaN with Mg during plasma-assisted molecular beam epitaxy, under N-rich conditions and a relatively high growth temperature of 740 deg. C, was investigated. The p-doping level steadily increases with increasing Mg flux. The highest doping level achieved, determined from Hall measurements, is 2.1x10 18 cm -3 . The corresponding doping efficiency and hole mobility are ∼4.9% and 3.7 cm 2 /V s at room temperature. Cross-sectional transmission electron microscopy and photoluminescence measurements confirm good crystalline and optical quality of the Mg-doped layers. An InGaN/GaN quantum dot light emitting diode (λ peak =529 nm) with p-GaN contact layers grown under N-rich condition exhibits a low series resistance of 9.8 Ω.

Global transcriptomic profiling of aspen trees under elevated [CO2] to identify potential molecular mechanisms responsible for enhanced radial growth.

Science.gov (United States)

Wei, Hairong; Gou, Jiqing; Yordanov, Yordan; Zhang, Huaxin; Thakur, Ramesh; Jones, Wendy; Burton, Andrew

2013-03-01

Aspen (Populus tremuloides) trees growing under elevated [CO(2)] at a free-air CO(2) enrichment (FACE) site produced significantly more biomass than control trees. We investigated the molecular mechanisms underlying the observed increase in biomass by producing transcriptomic profiles of the vascular cambium zone (VCZ) and leaves, and then performed a comparative study to identify significantly changed genes and pathways after 12 years exposure to elevated [CO(2)]. In leaves, elevated [CO(2)] enhanced expression of genes related to Calvin cycle activity and linked pathways. In the VCZ, the pathways involved in cell growth, cell division, hormone metabolism, and secondary cell wall formation were altered while auxin conjugation, ABA synthesis, and cytokinin glucosylation and degradation were inhibited. Similarly, the genes involved in hemicellulose and pectin biosynthesis were enhanced, but some genes that catalyze important steps in lignin biosynthesis pathway were inhibited. Evidence from systemic analysis supported the functioning of multiple molecular mechanisms that underpin the enhanced radial growth in response to elevated [CO(2)].

Unfolding mechanism of thrombin-binding aptamer revealed by molecular dynamics simulation and Markov State Model.

Science.gov (United States)

Zeng, Xiaojun; Zhang, Liyun; Xiao, Xiuchan; Jiang, Yuanyuan; Guo, Yanzhi; Yu, Xinyan; Pu, Xuemei; Li, Menglong

2016-04-05

Thrombin-binding aptamer (TBA) with the sequence 5'GGTTGGTGTGGTTGG3' could fold into G-quadruplex, which correlates with functionally important genomic regionsis. However, unfolding mechanism involved in the structural stability of G-quadruplex has not been satisfactorily elucidated on experiments so far. Herein, we studied the unfolding pathway of TBA by a combination of molecular dynamics simulation (MD) and Markov State Model (MSM). Our results revealed that the unfolding of TBA is not a simple two-state process but proceeds along multiple pathways with multistate intermediates. One high flux confirms some observations from NMR experiment. Another high flux exhibits a different and simpler unfolding pathway with less intermediates. Two important intermediate states were identified. One is similar to the G-triplex reported in the folding of G-quadruplex, but lack of H-bonding between guanines in the upper plane. More importantly, another intermediate state acting as a connector to link the folding region and the unfolding one, was the first time identified, which exhibits higher population and stability than the G-triplex-like intermediate. These results will provide valuable information for extending our understanding the folding landscape of G-quadruplex formation.

Molecular gas in the x-ray bright group NGC 5044 as revealed by ALMA

Energy Technology Data Exchange (ETDEWEB)

David, Laurence P.; Forman, William; Vrtilek, Jan; Jones, Christine; O' Sullivan, Ewan [Harvard-Smithsonian Center for Astrophysics, 60 Garden St., Cambridge, MA 02138 (United States); Lim, Jeremy [Department of Physics, University of Hong Kong, Pokfulam Road (Hong Kong); Combes, Francoise [Observatoire de Paris, LERMA, CNRS, 61 Avenue de l' Observatoire, F-75014 Paris (France); Salome, Philippe [LERMA Observatoire de paris, CNRS, 61 rue de l' Observatoire, F-75014 Paris (France); Edge, Alastair; Hamer, Stephen [Institute for Computational Cosmology, Department of Physics, Durham University, South Road, Durham DH1 3LE (United Kingdom); Sun, Ming [Department of Physics, University of Alabama in Huntsville, Huntsville, AL 35899 (United States); Gastaldello, Fabio; Bardelli, Sandro [INAF - IASF-Milano, Via E. Bassini 15, I-20133 Milano (Italy); Temi, Pasquale [Astrophysics Branch, NASA/Ames Research Center, MS 245-6, Moffett Field, CA 94035 (United States); Schmitt, Henrique [Remote Sensing Division, Naval Research Laboratory, 4555 Overlook Avenue SW, Washington, DC 20375 (United States); Ohyama, Youichi [Academia Sinica, Institute of Astronomy and Astrophysics, Taiwan (China); Mathews, William [University of California Observatories/Lick Observatory, Department of Astronomy and Astrophysics, University of California, Santa Cruz, CA 95064 (United States); Brighenti, Fabrizio [Dipartimento di Astronomia, Universit di Bologna, via Ranzani 1, I-40127 Bologna (Italy); Giacintucci, Simona [Department of Astronomy, University of Maryland, College Park, MD 20742 (United States); Trung, Dinh-V, E-mail: ldavid@head.cfa.harvard.edu [Institute of Physics, Vietnamese Academy of Science and Technology, 10 DaoTan Street, BaDinh, Hanoi (Viet Nam)

2014-09-10

An ALMA observation of the early-type galaxy NGC 5044, which resides at the center of an X-ray bright group with a moderate cooling flow, detected 24 molecular structures within the central 2.5 kpc. The masses of the molecular structures vary from 3 × 10{sup 5} M {sub ☉} to 10{sup 7} M {sub ☉} and the CO(2-1) linewidths vary from 15 to 65 km s{sup –1}. Given the large CO(2-1) linewidths, the observed structures are likely giant molecular associations (GMAs) and not individual giant molecular clouds (GMCs). Only a few of the GMAs are spatially resolved and the average density of these GMAs yields a GMC volume filling factor of about 15%. The masses of the resolved GMAs are insufficient for them to be gravitationally bound, however, the most massive GMA does contain a less massive component with a linewidth of 5.5 km s{sup –1} (typical of an individual virialized GMC). We also show that the GMAs cannot be pressure confined by the hot gas. Given the CO(2-1) linewidths of the GMAs (i.e., the velocity dispersion of the embedded GMCs) they should disperse on a timescale of about 12 Myr. No disk-like molecular structures are detected and all indications suggest that the molecular gas follows ballistic trajectories after condensing out of the thermally unstable hot gas. The 230 GHz luminosity of the central continuum source is 500 times greater than its low frequency radio luminosity and probably reflects a recent accretion event. The spectrum of the central continuum source also exhibits an absorption feature with a linewidth typical of an individual GMC and an infalling velocity of 250 km s{sup –1}.

Molecular Force Spectroscopy on Cells

Science.gov (United States)

Liu, Baoyu; Chen, Wei; Zhu, Cheng

2015-04-01

Molecular force spectroscopy has become a powerful tool to study how mechanics regulates biology, especially the mechanical regulation of molecular interactions and its impact on cellular functions. This force-driven methodology has uncovered a wealth of new information of the physical chemistry of molecular bonds for various biological systems. The new concepts, qualitative and quantitative measures describing bond behavior under force, and structural bases underlying these phenomena have substantially advanced our fundamental understanding of the inner workings of biological systems from the nanoscale (molecule) to the microscale (cell), elucidated basic molecular mechanisms of a wide range of important biological processes, and provided opportunities for engineering applications. Here, we review major force spectroscopic assays, conceptual developments of mechanically regulated kinetics of molecular interactions, and their biological relevance. We also present current challenges and highlight future directions.

Incorporation of Eu(III) into calcite under recrystallization conditions

International Nuclear Information System (INIS)

Hellebrandt, S.E.; Jordan, Norbert; Barkleit, Astrid; Schmidt, Moritz; Hofmann, S.

2017-01-01

The interaction of three calcite powders with Eu(III) under recrystallization conditions was studied on the molecular level using site-selective time-resolved laser fluorescence spectroscopy (TRLFS). Batch contact studies with reaction times from 1 week up to 3 years revealed that the speciation differs from that observed previously in co-precipitation experiments and is dominated by a newly identified species ''γ''. The speed of formation of this species was found to depend greatly on the recrystallization rate of the studied minerals.

Incorporation of Eu(III) into calcite under recrystallization conditions

Energy Technology Data Exchange (ETDEWEB)

Hellebrandt, S.E. [Helmholtz-Zentrum Dresden-Rossendorf e.V., Dresden (Germany). Inst. of Resource Ecology; Jordan, Norbert [Helmholtz-Zentrum Dresden-Rossendorf e.V., Dresden (Germany). Surface Processes; Barkleit, Astrid [Helmholtz-Zentrum Dresden-Rossendorf e.V., Dresden (Germany). Chemistry of the F-Elements; Schmidt, Moritz [Helmholtz-Zentrum Dresden-Rossendorf e.V., Dresden (Germany). HGF Young Investigator Group; Hofmann, S.

2017-06-01

The interaction of three calcite powders with Eu(III) under recrystallization conditions was studied on the molecular level using site-selective time-resolved laser fluorescence spectroscopy (TRLFS). Batch contact studies with reaction times from 1 week up to 3 years revealed that the speciation differs from that observed previously in co-precipitation experiments and is dominated by a newly identified species ''γ''. The speed of formation of this species was found to depend greatly on the recrystallization rate of the studied minerals.

Confocal imaging of whole vertebrate embryos reveals novel insights into molecular and cellular mechanisms of organ development

Science.gov (United States)

Hadel, Diana M.; Keller, Bradley B.; Sandell, Lisa L.

2014-03-01

Confocal microscopy has been an invaluable tool for studying cellular or sub-cellular biological processes. The study of vertebrate embryology is based largely on examination of whole embryos and organs. The application of confocal microscopy to immunostained whole mount embryos, combined with three dimensional (3D) image reconstruction technologies, opens new avenues for synthesizing molecular, cellular and anatomical analysis of vertebrate development. Optical cropping of the region of interest enables visualization of structures that are morphologically complex or obscured, and solid surface rendering of fluorescent signal facilitates understanding of 3D structures. We have applied these technologies to whole mount immunostained mouse embryos to visualize developmental morphogenesis of the mammalian inner ear and heart. Using molecular markers of neuron development and transgenic reporters of neural crest cell lineage we have examined development of inner ear neurons that originate from the otic vesicle, along with the supporting glial cells that derive from the neural crest. The image analysis reveals a previously unrecognized coordinated spatial organization between migratory neural crest cells and neurons of the cochleovestibular nerve. The images also enable visualization of early cochlear spiral nerve morphogenesis relative to the developing cochlea, demonstrating a heretofore unknown association of neural crest cells with extending peripheral neurite projections. We performed similar analysis of embryonic hearts in mouse and chick, documenting the distribution of adhesion molecules during septation of the outflow tract and remodeling of aortic arches. Surface rendering of lumen space defines the morphology in a manner similar to resin injection casting and micro-CT.

A combined cryo-EM and molecular dynamics approach reveals the mechanism of ErmBL-mediated translation arrest

Science.gov (United States)

Arenz, Stefan; Bock, Lars V.; Graf, Michael; Innis, C. Axel; Beckmann, Roland; Grubmüller, Helmut; Vaiana, Andrea C.; Wilson, Daniel N.

2016-07-01

Nascent polypeptides can induce ribosome stalling, regulating downstream genes. Stalling of ErmBL peptide translation in the presence of the macrolide antibiotic erythromycin leads to resistance in Streptococcus sanguis. To reveal this stalling mechanism we obtained 3.6-Å-resolution cryo-EM structures of ErmBL-stalled ribosomes with erythromycin. The nascent peptide adopts an unusual conformation with the C-terminal Asp10 side chain in a previously unseen rotated position. Together with molecular dynamics simulations, the structures indicate that peptide-bond formation is inhibited by displacement of the peptidyl-tRNA A76 ribose from its canonical position, and by non-productive interactions of the A-tRNA Lys11 side chain with the A-site crevice. These two effects combine to perturb peptide-bond formation by increasing the distance between the attacking Lys11 amine and the Asp10 carbonyl carbon. The interplay between drug, peptide and ribosome uncovered here also provides insight into the fundamental mechanism of peptide-bond formation.

mRNA-Seq Reveals Novel Molecular Mechanisms and a Robust Fingerprint in Graves' Disease

Science.gov (United States)

Sachidanandam, Ravi; Morshed, Syed; Latif, Rauf; Shi, Ruijin; Davies, Terry F.

2014-01-01

Context: The immune response in autoimmune thyroid disease has been shown to occur primarily within the thyroid gland in which the most abundant antigens can be found. A variety of capture molecules are known to be expressed by thyroid epithelial cells and serve to attract and help retain an intrathyroidal immune infiltrate. Objective: To explore the entire repertoire of expressed genes in human thyroid tissue, we have deep sequenced the transcriptome (referred to as mRNA-Seq). Design and Patients: We applied mRNA-Seq to thyroid tissue from nine patients with Graves' disease subjected to total thyroidectomy and compared the data with 12 samples of normal thyroid tissue obtained from patients having a thyroid nodule removed. The expression for each gene was calculated from the sequencing data by taking the median of the coverage across the length of the gene. The expression levels were quantile normalized and a gene signature was derived from these. Results: On comparison of expression levels in tissues derived from Graves' patients and controls, there was clear evidence for overexpression of the antigen presentation pathway consisting of HLA and associated genes. We also found a robust disease signature and discovered active innate and adaptive immune signaling networks. Conclusions: These data reveal an active immune defense system in Graves' disease, which involves novel molecular mechanisms in its pathogenesis and development. PMID:24971664

Molecular characterization of HCV in a Swedish county over 8 years (2002–2009 reveals distinct transmission patterns

Directory of Open Access Journals (Sweden)

Josefine Ederth

2016-02-01

Full Text Available Background: Hepatitis C virus (HCV is a major public health concern and data on its molecular epidemiology in Sweden is scarce. We carried out an 8-year population-based study of newly diagnosed HCV cases in one of Sweden's centrally situated counties, Södermanland (D-county. The aim was to characterize the HCV strains circulating, analyze their genetic relatedness to detect networks, and in combination with demographic data learn more about transmission. Methods: Molecular analyses of serum samples from 91% (N=557 of all newly notified cases in D-county, 2002–2009, were performed. Phylogenetic analysis (NS5B gene, 300 bp was linked to demographic data from the national surveillance database, SmiNet, to characterize D-county transmission clusters. The linear-by-linear association test (LBL was used to analyze trends over time. Results: The most prevalent subtypes were 1a (38% and 3a (34%. Subtype 1a was most prevalent among cases transmitted via sexual contact, via contaminated blood, or blood products, while subtype 3a was most prevalent among people who inject drugs (PWIDs. Phylogenetic analysis revealed that the subtype 3a sequences formed more and larger transmission clusters (50% of the sequences clustered, while the 1a sequences formed smaller clusters (19% of the sequences clustered, possibly suggesting different epidemics. Conclusion: We found different transmission patterns in D-county which may, from a public health perspective, have implications for how to control virus infections by targeted interventions.

Transcriptomic Analysis Reveals the Molecular Mechanisms of Drought-Stress-Induced Decreases in Camellia sinensis Leaf Quality

Science.gov (United States)

Wang, Weidong; Xin, Huahong; Wang, Mingle; Ma, Qingping; Wang, Le; Kaleri, Najeeb A.; Wang, Yuhua; Li, Xinghui

2016-01-01

The tea plant [Camellia sinensis (L.) O. Kuntze] is an important commercial crop rich in bioactive ingredients, especially catechins, caffeine, theanine and other free amino acids, which the quality of tea leaves depends on. Drought is the most important environmental stress affecting the yield and quality of this plant. In this study, the effects of drought stress on the phenotype, physiological characteristics and major bioactive ingredients accumulation of C. sinensis leaves were examined, and the results indicated that drought stress resulted in dehydration and wilt of the leaves, and significant decrease in the total polyphenols and free amino acids and increase in the total flavonoids. In addition, HPLC analysis showed that the catechins, caffeine, theanine and some free amino acids in C. sinensis leaves were significantly reduced in response to drought stress, implying that drought stress severely decreased the quality of C. sinensis leaves. Furthermore, differentially expressed genes (DEGs) related to amino acid metabolism and secondary metabolism were identified and quantified in C. sinensis leaves under drought stress using high-throughput Illumina RNA-Seq technology, especially the key regulatory genes of the catechins, caffeine, and theanine biosynthesis pathways. The expression levels of key regulatory genes were consistent with the results from the HPLC analysis, which indicate a potential molecular mechanism for the above results. Taken together, these data provide further insights into the mechanisms underlying the change in the quality of C. sinensis leaves under environmental stress, which involve changes in the accumulation of major bioactive ingredients, especially catechins, caffeine, theanine and other free amino acids. PMID:27066035

Integrative Bioinformatic Analysis of Transcriptomic Data Identifies Conserved Molecular Pathways Underlying Ionizing Radiation-Induced Bystander Effects (RIBE

Directory of Open Access Journals (Sweden)

Constantinos Yeles

2017-11-01

Full Text Available Ionizing radiation-induced bystander effects (RIBE encompass a number of effects with potential for a plethora of damages in adjacent non-irradiated tissue. The cascade of molecular events is initiated in response to the exposure to ionizing radiation (IR, something that may occur during diagnostic or therapeutic medical applications. In order to better investigate these complex response mechanisms, we employed a unified framework integrating statistical microarray analysis, signal normalization, and translational bioinformatics functional analysis techniques. This approach was applied to several microarray datasets from Gene Expression Omnibus (GEO related to RIBE. The analysis produced lists of differentially expressed genes, contrasting bystander and irradiated samples versus sham-irradiated controls. Furthermore, comparative molecular analysis through BioInfoMiner, which integrates advanced statistical enrichment and prioritization methodologies, revealed discrete biological processes, at the cellular level. For example, the negative regulation of growth, cellular response to Zn2+-Cd2+, and Wnt and NIK/NF-kappaB signaling, thus refining the description of the phenotypic landscape of RIBE. Our results provide a more solid understanding of RIBE cell-specific response patterns, especially in the case of high-LET radiations, like α-particles and carbon-ions.

Molecular dynamics simulation of ZnO wurtzite phase under high and low pressures and temperatures

Science.gov (United States)

Chergui, Y.; Aouaroun, T.; Hadley, M. J.; Belkada, R.; Chemam, R.; Mekki, D. E.

2017-11-01

Isothermal and isobaric ensembles behaviours of ZnO wurtzite phase have been investigated, by parallel molecular dynamics method and using Buckingham potential, which contains long-range Coulomb, repulsive exponential, and attractive dispersion terms. To conduct our calculations, we have used dl_poly 4 software, under which the method is implemented. We have examined the influence of the temperature and pressure on molar volume in the ranges of 300-3000 K and 0-200 GPa. Isothermal-isobaric relationships, fluctuations, standard error, equilibrium time, molar volume and its variation versus time are predicted and analyzed. Our results are close to available experimental data and theoretical results.

Molecular Dynamics Simulation of Damage to Coiled Carbon Nanotubes under C Ion Irradiation

International Nuclear Information System (INIS)

Zhou Bin; Zhang Wei; Gong Wen-Bin; Wang Song; Ren Cui-Lan; Wang Cheng-Bin; Zhu Zhi-Yuan; Huai Ping

2013-01-01

The stability of coiled carbon nanotubes under C ion irradiation is investigated by molecular dynamics simulations. The defect statistics shows that small curvature coiled carbon nanotubes have better radiation tolerance than normal straight carbon nanotubes. To understand the effect of the curvature on defect production, the threshold displacement energies for the upper and lower walls, as well as those for the side parts, are calculated. The results show that the lower wall has better radiation tolerance than the upper wall. For the upper wall, a small increase in the curvature of nanotube axis gives rise to an increase in the radiation tolerance and then a decrease with the curvature becomes larger. However, for the lower wall, as the curvature of the nanotube axis increases, the radiation tolerance increases as the bonds compressed slightly in our simulation

Formation of truncated proteins and high-molecular-mass aggregates upon soft illumination of photosynthetic proteins

DEFF Research Database (Denmark)

Rinalducci, Sara; Campostrini, Natascia; Antonioli, Paolo

2005-01-01

Different spot profiles were observed in 2D gel electrophoresis of thylakoid membranes performed either under complete darkness or by leaving the sample for a short time to low visible light. In the latter case, a large number of new spots with lower molecular masses, ranging between 15,000 and 25......,000 Da, were observed, and high-molecular-mass aggregates, seen as a smearing in the upper part of the gel, appeared in the region around 250 kDa. Identification of protein(s) contained in these new spots by MS/MS revealed that most of them are simply truncated proteins deriving from native ones...

Ultrafast isomerization dynamics of a unidirectional molecular rotor revealed by femtosecond stimulated raman spectroscopy (FSRS)

NARCIS (Netherlands)

Hall, Christopher R.; Conyard, Jamie; Laptenok, Siarhei; Browne, Wesley R.; Feringa, Ben L.; Heisler, Ismael A.; Meech, Stephen R.

2016-01-01

Unidirectional molecular rotors based on chiral overcrowded alkenes operate via sequential photochemical- and thermal-activated steps. Over the last decade the rotation rate limiting thermal step has been optimized through modification of the molecular structure. In recent years we have shown the

High-frequency microrheology reveals cytoskeleton dynamics in living cells

Science.gov (United States)

Rigato, Annafrancesca; Miyagi, Atsushi; Scheuring, Simon; Rico, Felix

2017-08-01

Living cells are viscoelastic materials, dominated by an elastic response on timescales longer than a millisecond. On shorter timescales, the dynamics of individual cytoskeleton filaments are expected to emerge, but active microrheology measurements on cells accessing this regime are scarce. Here, we develop high-frequency microrheology experiments to probe the viscoelastic response of living cells from 1 Hz to 100 kHz. We report the viscoelasticity of different cell types under cytoskeletal drug treatments. On previously inaccessible short timescales, cells exhibit rich viscoelastic responses that depend on the state of the cytoskeleton. Benign and malignant cancer cells revealed remarkably different scaling laws at high frequencies, providing a unique mechanical fingerprint. Microrheology over a wide dynamic range--up to the frequency characterizing the molecular components--provides a mechanistic understanding of cell mechanics.

Molecular ferromagnetism

International Nuclear Information System (INIS)

Epstein, A.J.

1990-01-01

This past year has been one of substantial advancement in both the physics and chemistry of molecular and polymeric ferromagnets. The specific heat studies of (DMeFc)(TCNE) have revealed a cusp at the three-dimensional ferromagnetic transition temperature with a crossover to primarily 1-D behavior at higher temperatures. This paper discusses these studies

Adaptation to High Ethanol Reveals Complex Evolutionary Pathways.

Directory of Open Access Journals (Sweden)

Karin Voordeckers

2015-11-01

Full Text Available Tolerance to high levels of ethanol is an ecologically and industrially relevant phenotype of microbes, but the molecular mechanisms underlying this complex trait remain largely unknown. Here, we use long-term experimental evolution of isogenic yeast populations of different initial ploidy to study adaptation to increasing levels of ethanol. Whole-genome sequencing of more than 30 evolved populations and over 100 adapted clones isolated throughout this two-year evolution experiment revealed how a complex interplay of de novo single nucleotide mutations, copy number variation, ploidy changes, mutator phenotypes, and clonal interference led to a significant increase in ethanol tolerance. Although the specific mutations differ between different evolved lineages, application of a novel computational pipeline, PheNetic, revealed that many mutations target functional modules involved in stress response, cell cycle regulation, DNA repair and respiration. Measuring the fitness effects of selected mutations introduced in non-evolved ethanol-sensitive cells revealed several adaptive mutations that had previously not been implicated in ethanol tolerance, including mutations in PRT1, VPS70 and MEX67. Interestingly, variation in VPS70 was recently identified as a QTL for ethanol tolerance in an industrial bio-ethanol strain. Taken together, our results show how, in contrast to adaptation to some other stresses, adaptation to a continuous complex and severe stress involves interplay of different evolutionary mechanisms. In addition, our study reveals functional modules involved in ethanol resistance and identifies several mutations that could help to improve the ethanol tolerance of industrial yeasts.

An update on potential molecular mechanisms underlying the actions of snake venom L-amino acid oxidases (LAAOs).

Science.gov (United States)

Paloschi, Mauro Valentino; Pontes, Adriana Silva; Soares, Andreimar Martins; Zuliani, Juliana Pavan

2017-11-08

LAAOs (EC 1.4.3.2) are found in concentrations that vary according to each species of snakes; Viperidae, Crotalidae and Elapidae contain 1-9% of this enzyme in their venoms. This review focuses on an update on molecular mechanisms, platelet activities, antimicrobial, antiprotozoal, induction of apoptosis and inflammatory potential underlying the actions of SV-LAAOs. Snake venom LAAOs (SV-LAAOs) have become an interesting subject for pharmacological, structural and molecular studies. Although the mechanisms of action of these enzymes are not well understood they are a subject of a variety of studies, because LAAOs are multifunctional enzymes exhibiting a wide range of pharmacological effects, including the inhibition or induction of platelet aggregation, hemolysis and hemorrhage, in addition to the stimulation of apoptosis, the activation of leukocytes and the formation of edema. Moreover, SV-LAAOs play an important role in bactericidal, cytotoxic, anti-parasitic, anti-tumor, and antiviral activities. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Isolation of glia from Alzheimer's mice reveals inflammation and dysfunction

NARCIS (Netherlands)

Orre, Marie; Kamphuis, Willem; Osborn, Lana M; Jansen, Anne H P; Kooijman, Lieneke; Bossers, Koen; Hol, Elly M

2014-01-01

Reactive astrocytes and microglia are associated with amyloid plaques in Alzheimer's disease (AD). Yet, not much is known about the molecular alterations underlying this reactive phenotype. To get an insight into the molecular changes underlying AD induced astrocyte and microglia reactivity, we

ALMA REVEALS THE ANATOMY OF THE mm-SIZED DUST AND MOLECULAR GAS IN THE HD 97048 DISK

Energy Technology Data Exchange (ETDEWEB)

Walsh, Catherine; Maud, Luke T. [Leiden Observatory, Leiden University, P.O. Box 9531, 2300 RA Leiden (Netherlands); Juhász, Attila [Institute of Astronomy, University of Cambridge, Madingley Road, Cambridge CB3 0HA (United Kingdom); Meeus, Gwendolyn [Departamento de Física Teórica, Universidad Autonoma de Madrid, Campus Cantoblanco, E-28049 Madrid (Spain); Dent, William R. F. [Joint ALMA Observatory (JAO), Alonso de Córdova 3107, Vitacura, Santiago (Chile); Aikawa, Yuri [Center for Computer Sciences, University of Tsukuba, 305-8577 Tsukuba (Japan); Millar, Tom J. [School of Mathematics and Physics, Queen’s University Belfast, University Road, Belfast BT7 1NN (United Kingdom); Nomura, Hideko, E-mail: cwalsh@strw.leidenuniv.nl, E-mail: c.walsh1@leeds.ac.uk [Department of Earth and Planetary Science, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro-ku, 152-8551 Tokyo (Japan)

2016-11-10

Transitional disks show a lack of excess emission at infrared wavelengths due to a large dust cavity, that is often corroborated by spatially resolved observations at ∼ mm wavelengths. We present the first spatially resolved ∼ mm-wavelength images of the disk around the Herbig Ae/Be star, HD 97048. Scattered light images show that the disk extends to ≈640 au. ALMA data reveal a circular-symmetric dusty disk extending to ≈350 au, and a molecular disk traced in CO J = 3-2 emission, extending to ≈750 au. The CO emission arises from a flared layer with an opening angle ≈30°–40°. HD 97048 is another source for which the large (∼ mm-sized) dust grains are more centrally concentrated than the small (∼ μ m-sized) grains and molecular gas, likely due to radial drift. The images and visibility data modeling suggest a decrement in continuum emission within ≈50 au, consistent with the cavity size determined from mid-infrared imaging (34 ± 4 au). The extracted continuum intensity profiles show ring-like structures with peaks at ≈50, 150, and 300 au, with associated gaps at ≈100 and 250 au. This structure should be confirmed in higher-resolution images (FWHM ≈ 10–20 au). These data confirm the classification of HD 97048 as a transitional disk that also possesses multiple ring-like structures in the dust continuum emission. Additional data are required at multiple and well-separated frequencies to fully characterize the disk structure, and thereby constrain the mechanism(s) responsible for sculpting the HD 97048 disk.

ALMA Reveals the Anatomy of the mm-sized Dust and Molecular Gas in the HD 97048 Disk

Science.gov (United States)

Walsh, Catherine; Juhász, Attila; Meeus, Gwendolyn; Dent, William R. F.; Maud, Luke T.; Aikawa, Yuri; Millar, Tom J.; Nomura, Hideko

2016-11-01

Transitional disks show a lack of excess emission at infrared wavelengths due to a large dust cavity, that is often corroborated by spatially resolved observations at ˜ mm wavelengths. We present the first spatially resolved ˜ mm-wavelength images of the disk around the Herbig Ae/Be star, HD 97048. Scattered light images show that the disk extends to ≈640 au. ALMA data reveal a circular-symmetric dusty disk extending to ≈350 au, and a molecular disk traced in CO J = 3-2 emission, extending to ≈750 au. The CO emission arises from a flared layer with an opening angle ≈30°-40°. HD 97048 is another source for which the large (˜ mm-sized) dust grains are more centrally concentrated than the small (˜μm-sized) grains and molecular gas, likely due to radial drift. The images and visibility data modeling suggest a decrement in continuum emission within ≈50 au, consistent with the cavity size determined from mid-infrared imaging (34 ± 4 au). The extracted continuum intensity profiles show ring-like structures with peaks at ≈50, 150, and 300 au, with associated gaps at ≈100 and 250 au. This structure should be confirmed in higher-resolution images (FWHM ≈ 10-20 au). These data confirm the classification of HD 97048 as a transitional disk that also possesses multiple ring-like structures in the dust continuum emission. Additional data are required at multiple and well-separated frequencies to fully characterize the disk structure, and thereby constrain the mechanism(s) responsible for sculpting the HD 97048 disk.

ALMA REVEALS THE ANATOMY OF THE mm-SIZED DUST AND MOLECULAR GAS IN THE HD 97048 DISK

International Nuclear Information System (INIS)

Walsh, Catherine; Maud, Luke T.; Juhász, Attila; Meeus, Gwendolyn; Dent, William R. F.; Aikawa, Yuri; Millar, Tom J.; Nomura, Hideko

2016-01-01

Transitional disks show a lack of excess emission at infrared wavelengths due to a large dust cavity, that is often corroborated by spatially resolved observations at ∼ mm wavelengths. We present the first spatially resolved ∼ mm-wavelength images of the disk around the Herbig Ae/Be star, HD 97048. Scattered light images show that the disk extends to ≈640 au. ALMA data reveal a circular-symmetric dusty disk extending to ≈350 au, and a molecular disk traced in CO J = 3-2 emission, extending to ≈750 au. The CO emission arises from a flared layer with an opening angle ≈30°–40°. HD 97048 is another source for which the large (∼ mm-sized) dust grains are more centrally concentrated than the small (∼ μ m-sized) grains and molecular gas, likely due to radial drift. The images and visibility data modeling suggest a decrement in continuum emission within ≈50 au, consistent with the cavity size determined from mid-infrared imaging (34 ± 4 au). The extracted continuum intensity profiles show ring-like structures with peaks at ≈50, 150, and 300 au, with associated gaps at ≈100 and 250 au. This structure should be confirmed in higher-resolution images (FWHM ≈ 10–20 au). These data confirm the classification of HD 97048 as a transitional disk that also possesses multiple ring-like structures in the dust continuum emission. Additional data are required at multiple and well-separated frequencies to fully characterize the disk structure, and thereby constrain the mechanism(s) responsible for sculpting the HD 97048 disk.

Molecular authentication of Pargo fillets Lutjanus purpureus (Perciformes: Lutjanidae by DNA barcoding reveals commercial fraud

Directory of Open Access Journals (Sweden)

Ivana Veneza

2018-03-01

Full Text Available ABSTRACT The Caribbean Red Snapper (Pargo Lutjanus purpureus is the most economically important snapper in Brazil, which is sold, among other forms, as frozen fillets. During the process of transformation into fillets there is the removal of the distinctive morphological traits, being able to favor the substitution by less valued species. In addition, there is no national legislation requiring the insertion of the specific name on the product label. However, according to a Normative Instruction (IN N ° 29/2015 MAPA that correlates the common and specific names of the products destined to the national trade, in Brazil only L. purpureus and L. campechanus can be denominated “Pargo”. Thus, the DNA barcode tool was used to identify the fillets sold in north of Brazil, labeled “Pargo”, with the aid of sequences from the public and control databases. The results showed that among 142 fillets examined, 78% was identified as L. purpureus and 22% as Rhomboplites aurorubens, a snapper with low commercial value in the country, revealing commercial fraud. The molecular identification method successfully used in this study to authenticate fillets snappers may also be used by surveillance authorities in the quality control of processed fish products, towards ensuring consumer rights.

Proteomics approach reveals mechanism underlying susceptibility of loquat fruit to sunburn during color changing period.

Science.gov (United States)

Jiang, Ji-Mou; Lin, Yong-Xiang; Chen, Yi-Yong; Deng, Chao-Jun; Gong, Hui-Wen; Xu, Qi-Zhi; Zheng, Shao-Quan; Chen, Wei

2015-06-01

The objective of this work was to investigate why loquat fruit peels are more sensitive to high temperature and strong sunlight, making them highly susceptible to sunburn, during the color changing period (CCP). Two dimensional gel electrophoresis (2-DE) of the fruit peel proteins was performed over three developmental periods, namely green fruit period (GFP), color changing period and yellow ripening period (YRP). Fifty-five protein spots with at least 2-fold differences in abundance were successfully identified by MALDI-TOF-TOF/MS. The identified proteins were divided into categories related to heat-shock response, stress response and defense, energy metabolism, photosynthesis and protein biosynthesis. The results showed that expression of proteins related to anaerobic respiration and photorespiration were increased while the proteins related to ROS scavenging, polyamine biosynthesis, defense pathogens and photosynthesis were decreased during CCP under heat stress. Our findings provide new insights into the molecular mechanism of loquat fruit susceptible to sunburn during CCP. Copyright © 2014 Elsevier Ltd. All rights reserved.

Molecular diversity and phylogeny of Triticum-Aegilops species possessing D genome revealed by SSR and ISSR markers

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Moradkhani Hoda

2015-12-01

Full Text Available The aim of this study is investigation the applicability of SSR and ISSR markers in evaluating the genetic relationships in twenty accessions of Aegilops and Triticum species with D genome in different ploidy levels. Totally, 119 bands and 46 alleles were detected using ten primers for ISSR and SSR markers, respectively. Polymorphism Information Content values for all primers ranged from 0.345 to 0.375 with an average of 0.367 for SSR, and varied from 0.29 to 0.44 with the average 0.37 for ISSR marker. Analysis of molecular variance (AMOVA revealed that 81% (ISSR and 84% (SSR of variability was partitioned among individuals within populations. Comparing the genetic diversity of Aegilops and Triticum accessions, based on genetic parameters, shows that genetic variation of Ae. crassa and Ae. tauschii species are higher than other species, especially in terms of Nei’s gene diversity. Cluster analysis, based on both markers, separated total accessions in three groups. However, classification based on SSR marker data was not conformed to classification according to ISSR marker data. Principal co-ordinate analysis (PCoA for SSR and ISSR data showed that, the first two components clarified 53.48% and 49.91% of the total variation, respectively. This analysis (PCoA, also, indicated consistent patterns of genetic relationships for ISSR data sets, however, the grouping of accessions was not completely accorded to their own geographical origins. Consequently, a high level of genetic diversity was revealed from the accessions sampled from different eco-geographical regions of Iran.

Molecular dynamics simulation of Cu/Au thin films under temperature gradient

International Nuclear Information System (INIS)

Li, Qibin; Peng, Xianghe; Peng, Tiefeng; Tang, Qizhong; Zhang, Xiaomin; Huang, Cheng

2015-01-01

Graphical abstract: Heat transportation in the thin films. - Highlights: • The coherent lattice interface is found at thin films after annealing. • The vacancies are observed clearly in the deposit thin films. • The defect and component will influence the energy transportation in the coatings. • The vacancies and lattice mismatch can enlarge the mobility of atoms. • The phonon transportation in thin films has no apparent rule. - Abstract: Three modulation period thin films, 1.8 nm Cu/3.6 nm Au, 2.7 nm Cu/2.7 nm Au and 3.6 nm Cu/1.8 nm Au, are obtained from deposition method and ideal modeling based on lattice constant, to examine their structures and thermophysical characteristics under temperature gradient. The coherent lattice interface is found both at deposit and ideal thin films after annealing. Also, the vacancies are observed clearly in the deposit thin films. The defect and component of thin films will influence the energy transportation in the coatings. The vacancies and lattice mismatch can enlarge the mobility of atoms and result in the failure of coating under the thermal stress. The power spectrum of atoms’ movement has no apparent rule for phonon transportation in thin films. The results are helpful to reveal the micro-mechanism and provide reasonable basis for the failure of metallic coatings.

Molecular dynamics simulation of Cu/Au thin films under temperature gradient

Energy Technology Data Exchange (ETDEWEB)

Li, Qibin, E-mail: qibinli@cqu.edu.cn [College of Aerospace Engineering, Chongqing University, Chongqing 400030 (China); State Key Laboratory of Coal Mine Disaster Dynamics and Control, Chongqing University, Chongqing 400030 (China); Chongqing Key Laboratory of Heterogeneous Material Mechanics, Chongqing University, Chongqing 400030 (China); Peng, Xianghe [College of Aerospace Engineering, Chongqing University, Chongqing 400030 (China); State Key Laboratory of Coal Mine Disaster Dynamics and Control, Chongqing University, Chongqing 400030 (China); Peng, Tiefeng, E-mail: pengtiefeng@cqu.edu.cn [State Key Laboratory of Coal Mine Disaster Dynamics and Control, Chongqing University, Chongqing 400030 (China); Tang, Qizhong [College of Aerospace Engineering, Chongqing University, Chongqing 400030 (China); Zhang, Xiaomin [College of Aerospace Engineering, Chongqing University, Chongqing 400030 (China); Chongqing Key Laboratory of Heterogeneous Material Mechanics, Chongqing University, Chongqing 400030 (China); Huang, Cheng [College of Aerospace Engineering, Chongqing University, Chongqing 400030 (China)

2015-12-01

Graphical abstract: Heat transportation in the thin films. - Highlights: • The coherent lattice interface is found at thin films after annealing. • The vacancies are observed clearly in the deposit thin films. • The defect and component will influence the energy transportation in the coatings. • The vacancies and lattice mismatch can enlarge the mobility of atoms. • The phonon transportation in thin films has no apparent rule. - Abstract: Three modulation period thin films, 1.8 nm Cu/3.6 nm Au, 2.7 nm Cu/2.7 nm Au and 3.6 nm Cu/1.8 nm Au, are obtained from deposition method and ideal modeling based on lattice constant, to examine their structures and thermophysical characteristics under temperature gradient. The coherent lattice interface is found both at deposit and ideal thin films after annealing. Also, the vacancies are observed clearly in the deposit thin films. The defect and component of thin films will influence the energy transportation in the coatings. The vacancies and lattice mismatch can enlarge the mobility of atoms and result in the failure of coating under the thermal stress. The power spectrum of atoms’ movement has no apparent rule for phonon transportation in thin films. The results are helpful to reveal the micro-mechanism and provide reasonable basis for the failure of metallic coatings.

Molecular analysis of clinical isolates previously diagnosed as Mycobacterium intracellulare reveals incidental findings of "Mycobacterium indicus pranii" genotypes in human lung infection.

Science.gov (United States)

Kim, Su-Young; Park, Hye Yun; Jeong, Byeong-Ho; Jeon, Kyeongman; Huh, Hee Jae; Ki, Chang-Seok; Lee, Nam Yong; Han, Seung-Jung; Shin, Sung Jae; Koh, Won-Jung

2015-09-30

Mycobacterium intracellulare is a major cause of Mycobacterium avium complex lung disease in many countries. Molecular studies have revealed several new Mycobacteria species that are closely related to M. intracellulare. The aim of this study was to re-identify and characterize clinical isolates from patients previously diagnosed with M. intracellulare lung disease at the molecular level. Mycobacterial isolates from 77 patients, initially diagnosed with M. intracellulare lung disease were re-analyzed by multi-locus sequencing and pattern of insertion sequences. Among the 77 isolates, 74 (96 %) isolates were designated as M. intracellulare based on multigene sequence-based analysis. Interestingly, the three remaining strains (4 %) were re-identified as "Mycobacterium indicus pranii" according to distinct molecular phylogenetic positions in rpoB and hsp65 sequence-based typing. In hsp65 sequevar analysis, code 13 was found in the majority of cases and three unreported codes were identified. In 16S-23S rRNA internal transcribed spacer (ITS) sequevar analysis, all isolates of both species were classified within the Min-A ITS sequevar. Interestingly, four of the M. intracellulare isolates harbored IS1311, a M. avium-specific element. Two of three patients infected with "M. indicus pranii" had persistent positive sputum cultures after antibiotic therapy, indicating the clinical relevance of this study. This analysis highlights the importance of precise identification of clinical isolates genetically close to Mycobacterium species, and suggests that greater attention should be paid to nontuberculous mycobacteria lung disease caused by "M. indicus pranii".

Molecular Pathogenesis and Diagnostic, Prognostic and Predictive Molecular Markers in Sarcoma.

Science.gov (United States)

Mariño-Enríquez, Adrián; Bovée, Judith V M G

2016-09-01

Sarcomas are infrequent mesenchymal neoplasms characterized by notable morphological and molecular heterogeneity. Molecular studies in sarcoma provide refinements to morphologic classification, and contribute diagnostic information (frequently), prognostic stratification (rarely) and predict therapeutic response (occasionally). Herein, we summarize the major molecular mechanisms underlying sarcoma pathogenesis and present clinically useful diagnostic, prognostic and predictive molecular markers for sarcoma. Five major molecular alterations are discussed, illustrated with representative sarcoma types, including 1. the presence of chimeric transcription factors, in vascular tumors; 2. abnormal kinase signaling, in gastrointestinal stromal tumor; 3. epigenetic deregulation, in chondrosarcoma, chondroblastoma, and other tumors; 4. deregulated cell survival and proliferation, due to focal copy number alterations, in dedifferentiated liposarcoma; 5. extreme genomic instability, in conventional osteosarcoma as a representative example of sarcomas with highly complex karyotype. Copyright © 2016 Elsevier Inc. All rights reserved.

Molecular evolution of pentatricopeptide repeat genes reveals truncation in species lacking an editing target and structural domains under distinct selective pressures

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Hayes Michael L

2012-05-01

Full Text Available Abstract Background Pentatricopeptide repeat (PPR proteins are required for numerous RNA processing events in plant organelles including C-to-U editing, splicing, stabilization, and cleavage. Fifteen PPR proteins are known to be required for RNA editing at 21 sites in Arabidopsis chloroplasts, and belong to the PLS class of PPR proteins. In this study, we investigate the co-evolution of four PPR genes (CRR4, CRR21, CLB19, and OTP82 and their six editing targets in Brassicaceae species. PPR genes are composed of approximately 10 to 20 tandem repeats and each repeat has two α-helical regions, helix A and helix B, that are separated by short coil regions. Each repeat and structural feature was examined to determine the selective pressures on these regions. Results All of the PPR genes examined are under strong negative selection. Multiple independent losses of editing site targets are observed for both CRR21 and OTP82. In several species lacking the known editing target for CRR21, PPR genes are truncated near the 17th PPR repeat. The coding sequences of the truncated CRR21 genes are maintained under strong negative selection; however, the 3’ UTR sequences beyond the truncation site have substantially diverged. Phylogenetic analyses of four PPR genes show that sequences corresponding to helix A are high compared to helix B sequences. Differential evolutionary selection of helix A versus helix B is observed in both plant and mammalian PPR genes. Conclusion PPR genes and their cognate editing sites are mutually constrained in evolution. Editing sites are frequently lost by replacement of an edited C with a genomic T. After the loss of an editing site, the PPR genes are observed with three outcomes: first, few changes are detected in some cases; second, the PPR gene is present as a pseudogene; and third, the PPR gene is present but truncated in the C-terminal region. The retention of truncated forms of CRR21 that are maintained under strong negative

Molecular evolution of pentatricopeptide repeat genes reveals truncation in species lacking an editing target and structural domains under distinct selective pressures.

Science.gov (United States)

Hayes, Michael L; Giang, Karolyn; Mulligan, R Michael

2012-05-14

Pentatricopeptide repeat (PPR) proteins are required for numerous RNA processing events in plant organelles including C-to-U editing, splicing, stabilization, and cleavage. Fifteen PPR proteins are known to be required for RNA editing at 21 sites in Arabidopsis chloroplasts, and belong to the PLS class of PPR proteins. In this study, we investigate the co-evolution of four PPR genes (CRR4, CRR21, CLB19, and OTP82) and their six editing targets in Brassicaceae species. PPR genes are composed of approximately 10 to 20 tandem repeats and each repeat has two α-helical regions, helix A and helix B, that are separated by short coil regions. Each repeat and structural feature was examined to determine the selective pressures on these regions. All of the PPR genes examined are under strong negative selection. Multiple independent losses of editing site targets are observed for both CRR21 and OTP82. In several species lacking the known editing target for CRR21, PPR genes are truncated near the 17th PPR repeat. The coding sequences of the truncated CRR21 genes are maintained under strong negative selection; however, the 3' UTR sequences beyond the truncation site have substantially diverged. Phylogenetic analyses of four PPR genes show that sequences corresponding to helix A are high compared to helix B sequences. Differential evolutionary selection of helix A versus helix B is observed in both plant and mammalian PPR genes. PPR genes and their cognate editing sites are mutually constrained in evolution. Editing sites are frequently lost by replacement of an edited C with a genomic T. After the loss of an editing site, the PPR genes are observed with three outcomes: first, few changes are detected in some cases; second, the PPR gene is present as a pseudogene; and third, the PPR gene is present but truncated in the C-terminal region. The retention of truncated forms of CRR21 that are maintained under strong negative selection even in the absence of an editing site target

Abrupt deceleration of molecular evolution linked to the origin of arborescence in ferns.

Science.gov (United States)

Korall, Petra; Schuettpelz, Eric; Pryer, Kathleen M

2010-09-01

Molecular rate heterogeneity, whereby rates of molecular evolution vary among groups of organisms, is a well-documented phenomenon. Nonetheless, its causes are poorly understood. For animals, generation time is frequently cited because longer-lived species tend to have slower rates of molecular evolution than their shorter-lived counterparts. Although a similar pattern has been uncovered in flowering plants, using proxies such as growth form, the underlying process has remained elusive. Here, we find a deceleration of molecular evolutionary rate to be coupled with the origin of arborescence in ferns. Phylogenetic branch lengths within the “tree fern” clade are considerably shorter than those of closely related lineages, and our analyses demonstrate that this is due to a significant difference in molecular evolutionary rate. Reconstructions reveal that an abrupt rate deceleration coincided with the evolution of the long-lived tree-like habit at the base of the tree fern clade. This suggests that a generation time effect may well be ubiquitous across the green tree of life, and that the search for a responsible mechanism must focus on characteristics shared by all vascular plants. Discriminating among the possibilities will require contributions from various biological disciplines,but will be necessary for a full appreciation of molecular evolution.

Molecular mechanisms underlying the close association between soil Burkholderia and fungi

Science.gov (United States)

Stopnisek, Nejc; Zühlke, Daniela; Carlier, Aurélien; Barberán, Albert; Fierer, Noah; Becher, Dörte; Riedel, Katharina; Eberl, Leo; Weisskopf, Laure

2016-01-01

Bacterial species belonging to the genus Burkholderia have been repeatedly reported to be associated with fungi but the extent and specificity of these associations in soils remain undetermined. To assess whether associations between Burkholderia and fungi are widespread in soils, we performed a co-occurrence analysis in an intercontinental soil sample collection. This revealed that Burkholderia significantly co-occurred with a wide range of fungi. To analyse the molecular basis of the interaction, we selected two model fungi frequently co-occurring with Burkholderia, Alternaria alternata and Fusarium solani, and analysed the proteome changes caused by cultivation with either fungus in the widespread soil inhabitant B. glathei, whose genome we sequenced. Co-cultivation with both fungi led to very similar changes in the B. glathei proteome. Our results indicate that B. glathei significantly benefits from the interaction, which is exemplified by a lower abundance of several starvation factors that were highly expressed in pure culture. However, co-cultivation also gave rise to stress factors, as indicated by the increased expression of multidrug efflux pumps and proteins involved in oxidative stress response. Our data suggest that the ability of Burkholderia to establish a close association with fungi mainly lies in the capacities to utilize fungal-secreted metabolites and to overcome fungal defense mechanisms. This work indicates that beneficial interactions with fungi might contribute to the survival strategy of Burkholderia species in environments with sub-optimal conditions, including acidic soils. PMID:25989372

Molecular mechanisms underlying the close association between soil Burkholderia and fungi.

Science.gov (United States)

Stopnisek, Nejc; Zühlke, Daniela; Carlier, Aurélien; Barberán, Albert; Fierer, Noah; Becher, Dörte; Riedel, Katharina; Eberl, Leo; Weisskopf, Laure

2016-01-01

Bacterial species belonging to the genus Burkholderia have been repeatedly reported to be associated with fungi but the extent and specificity of these associations in soils remain undetermined. To assess whether associations between Burkholderia and fungi are widespread in soils, we performed a co-occurrence analysis in an intercontinental soil sample collection. This revealed that Burkholderia significantly co-occurred with a wide range of fungi. To analyse the molecular basis of the interaction, we selected two model fungi frequently co-occurring with Burkholderia, Alternaria alternata and Fusarium solani, and analysed the proteome changes caused by cultivation with either fungus in the widespread soil inhabitant B. glathei, whose genome we sequenced. Co-cultivation with both fungi led to very similar changes in the B. glathei proteome. Our results indicate that B. glathei significantly benefits from the interaction, which is exemplified by a lower abundance of several starvation factors that were highly expressed in pure culture. However, co-cultivation also gave rise to stress factors, as indicated by the increased expression of multidrug efflux pumps and proteins involved in oxidative stress response. Our data suggest that the ability of Burkholderia to establish a close association with fungi mainly lies in the capacities to utilize fungal-secreted metabolites and to overcome fungal defense mechanisms. This work indicates that beneficial interactions with fungi might contribute to the survival strategy of Burkholderia species in environments with sub-optimal conditions, including acidic soils.

Molecular characterization of a novel intracellular ADP-ribosyl cyclase.

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Dev Churamani

2007-08-01

Full Text Available ADP-ribosyl cyclases are remarkable enzymes capable of catalyzing multiple reactions including the synthesis of the novel and potent intracellular calcium mobilizing messengers, cyclic ADP-ribose and NAADP. Not all ADP-ribosyl cyclases however have been characterized at the molecular level. Moreover, those that have are located predominately at the outer cell surface and thus away from their cytosolic substrates.Here we report the molecular cloning of a novel expanded family of ADP-ribosyl cyclases from the sea urchin, an extensively used model organism for the study of inositol trisphosphate-independent calcium mobilization. We provide evidence that one of the isoforms (SpARC1 is a soluble protein that is targeted exclusively to the endoplasmic reticulum lumen when heterologously expressed. Catalytic activity of the recombinant protein was readily demonstrable in crude cell homogenates, even under conditions where luminal continuity was maintained.Our data reveal a new intracellular location for ADP-ribosyl cyclases and suggest that production of calcium mobilizing messengers may be compartmentalized.

Synthesis and Molecular Modeling of Thermally Stable DNA G-Quadruplexes with Anthraquinone Insertions

DEFF Research Database (Denmark)

Gouda, Alaa S.; Amine, Mahasen S.; Pedersen, Erik Bjerregaard

2017-01-01

Two new phosphoramidite building blocks for DNA synthesis were synthesized from 1,5- and 2,6-dihydroxyanthraquinones through alkylation with 3-bromo-1-propanol followed by DMT-protection. The novel synthesized 1,5- and 2,6-disubstituted anthraquinone monomers H15 and H26 are incorporated into a G...... anthraquinone-modified quadruplexes revealed no change of the antiparallel structure when compared with the wild type under potassium buffer conditions. The significantly increased thermostabilities were interpreted by molecular modeling of anthraquinone-modified G-quadruplexes....

Early molecular events involved in Pinus pinaster Ait. somatic embryo development under reduced water availability: transcriptomic and proteomic analyses.

Science.gov (United States)

Morel, Alexandre; Teyssier, Caroline; Trontin, Jean-François; Eliášová, Kateřina; Pešek, Bedřich; Beaufour, Martine; Morabito, Domenico; Boizot, Nathalie; Le Metté, Claire; Belal-Bessai, Leila; Reymond, Isabelle; Harvengt, Luc; Cadene, Martine; Corbineau, Françoise; Vágner, Martin; Label, Philippe; Lelu-Walter, Marie-Anne

2014-09-01

Maritime pine somatic embryos (SEs) require a reduction in water availability (high gellan gum concentration in the maturation medium) to reach the cotyledonary stage. This key switch, reported specifically for pine species, is not yet well understood. To facilitate the use of somatic embryogenesis for mass propagation of conifers, we need a better understanding of embryo development. Comparison of both transcriptome (Illumina RNA sequencing) and proteome [two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis with mass spectrometry (MS) identification] of immature SEs, cultured on either high (9G) or low (4G) gellan gum concentration, was performed, together with analysis of water content, fresh and dry mass, endogenous abscisic acid (ABA; gas chromatography-MS), soluble sugars (high-pressure liquid chromatography), starch and confocal laser microscope observations. This multiscale, integrated analysis was used to unravel early molecular and physiological events involved in SE development. Under unfavorable conditions (4G), the glycolytic pathway was enhanced, possibly in relation to cell proliferation that may be antagonistic to SE development. Under favorable conditions (9G), SEs adapted to culture constraint by activating specific protective pathways, and ABA-mediated molecular and physiological responses promoting embryo development. Our results suggest that on 9G, germin-like protein and ubiquitin-protein ligase could be used as predictive markers of SE development, whereas protein phosphatase 2C could be a biomarker for culture adaptive responses. This is the first characterization of early molecular mechanisms involved in the development of pine SEs following an increase in gellan gum concentration in the maturation medium, and it is also the first report on somatic embryogenesis in conifers combining transcriptomic and proteomic datasets. © 2014 Scandinavian Plant Physiology Society.

Different routes, same pathways: Molecular mechanisms under silver ion and nanoparticle exposures in the soil sentinel Eisenia fetida

International Nuclear Information System (INIS)

Novo, Marta; Lahive, Elma; Díez-Ortiz, María; Matzke, Marianne; Morgan, Andrew J.; Spurgeon, David J.; Svendsen, Claus; Kille, Peter

2015-01-01

Use of nanotechnology products is increasing; with silver (Ag) nanoparticles particularly widely used. A key uncertainty surrounding the risk assessment of AgNPs is whether their effects are driven through the same mechanism of action that underlies the toxic effects of Ag ions. We present the first full transcriptome study of the effects of Ag ions and NPs in an ecotoxicological model soil invertebrate, the earthworm Eisenia fetida. Gene expression analyses indicated similar mechanisms for both silver forms with toxicity being exerted through pathways related to ribosome function, sugar and protein metabolism, molecular stress, disruption of energy production and histones. The main difference seen between Ag ions and NPs was associated with potential toxicokinetic effects related to cellular internalisation and communication, with pathways related to endocytosis and cilia being significantly enriched. These results point to a common final toxicodynamic response, but initial internalisation driven by different exposure routes and toxicokinetic mechanisms. - Highlights: • Molecular effects underlying Ag ions and NPs exposure were studied in Eisenia fetida. • Full transcriptomic study of a genetically characterised lineage. • NPs and ions presented a similar toxicodynamic response. • Internalisation of the two Ag forms by different toxicokinetic mechanisms. - Transcriptomic analyses after exposure of earthworms to silver NPs or ions showed a final common toxicodynamic response, but internalisation by different toxicokinetic mechanisms

The structure of molecular liquids. Neutron diffraction and molecular dynamics simulations

International Nuclear Information System (INIS)

Bianchi, L.

2000-05-01

obtained from the X-rays. Nevertheless, comparisons between the MD and ND results for the C-H and H-H pdfs show significant discrepancies, which highlight the need to further refine the existing force field models. Neutron diffraction (ND) measurements were also performed on benzene-methanol liquid mixture (molar ratio 1:2) under ambient conditions. The H/D isotopic substitution technique on the hydrogens of both the hydroxyl group of methanol (Ho) and benzene (HB) was used to extract the solvent-solvent, solute-solute and solute-solvent correlations. The ND structural results of the mixture are interpreted with the help of the experimental results of its pure components. The results reveal that the self-association of methanol due to hydrogen bonding is hardly disrupted by the addition of benzene. Investigations of the solute-solvent and solute-solute correlations show that although a weak association exists between benzene and methanol molecules, there is no evidence to suggest the formation of a π-hydrogen bond between them in the liquid state. The benzene molecules thus, play the role of an inert solute in the mixture. The experimental structural results for the benzene-methanol liquid mixture are compared with those obtained from molecular dynamics (MD) simulations performed with an inter-molecular potential model built from the two force field models used in simulating the behaviour of the two pure components. The simulated structural results of the mixture are interpreted with the help of the simulated results of the pure components. Although an overall agreement is obtained between the simulated and experimental inter-molecular rdfs, a comparison of the partial distribution functions reveals that model potentials for the mixture need to be refined. (author)

Joint operation of TSTA under the collaboration between JAERI and DOE

International Nuclear Information System (INIS)

Konishi, Satoshi; O-hira, Shigeru; Inoue, Masahiko

1993-03-01

Under the Annex IV of the US-Japan Collaboration Program, loop test of the TSTA was performed in October, 1990. This test is focused on the Isotope Separation System with 3 distillation columns operated. The system was stably operated and DT products were continuously obtained. Composition profile along the columns were successfully measured with the Gas Chromatograph. In the Fuel Cleanup System, amount of adsorbed tritium on the cold molecular sieve beds were measured and a large impact of this phenomena on inventory was revealed. (author)

[Advance in molecular biology of Dendrobium (Orchidaceae)].

Science.gov (United States)

Li, Qing; Li, Biao; Guo, Shun-Xing

2016-08-01

With the development of molecular biology, the process in molecular biology research of Dendrobium is going fast. Not only did it provide new ways to identify Dendrobium quickly, reveal the genetic diversity and relationship of Dendrobium, but also lay the vital foundation for explaining the mechanism of Dendrobium growth and metabolism. The present paper reviews the recent process in molecular biology research of Dendrobium from three aspects, including molecular identification, genetic diversity and functional genes. And this review will facilitate the development of this research area and Dendrobium. Copyright© by the Chinese Pharmaceutical Association.

Dissecting molecular stress networks: identifying nodes of divergence between life-history phenotypes.

Science.gov (United States)

Schwartz, Tonia S; Bronikowski, Anne M

2013-02-01

The complex molecular network that underlies physiological stress response is comprised of nodes (proteins, metabolites, mRNAs, etc.) whose connections span cells, tissues and organs. Variable nodes are points in the network upon which natural selection may act. Thus, identifying variable nodes will reveal how this molecular stress network may evolve among populations in different habitats and how it might impact life-history evolution. Here, we use physiological and genetic assays to test whether laboratory-born juveniles from natural populations of garter snakes (Thamnophis elegans), which have diverged in their life-history phenotypes, vary concomitantly at candidate nodes of the stress response network, (i) under unstressed conditions and (ii) in response to an induced stress. We found that two common measures of stress (plasma corticosterone and liver gene expression of heat shock proteins) increased under stress in both life-history phenotypes. In contrast, the phenotypes diverged at four nodes both under unstressed conditions and in response to stress: circulating levels of reactive oxygen species (superoxide, H(2)O(2)); liver gene expression of GPX1 and erythrocyte DNA damage. Additionally, allele frequencies for SOD2 diverge from neutral markers, suggesting diversifying selection on SOD2 alleles. This study supports the hypothesis that these life-history phenotypes have diverged at the molecular level in how they respond to stress, particularly in nodes regulating oxidative stress. Furthermore, the differences between the life-history phenotypes were more pronounced in females. We discuss the responses to stress in the context of the associated life-history phenotype and the evolutionary pressures thought to be responsible for divergence between the phenotypes. © 2012 Blackwell Publishing Ltd.

Sexual polyploidization in plants--cytological mechanisms and molecular regulation.

Science.gov (United States)

De Storme, Nico; Geelen, Danny

2013-05-01

In the plant kingdom, events of whole genome duplication or polyploidization are generally believed to occur via alterations of the sexual reproduction process. Thereby, diploid pollen and eggs are formed that contain the somatic number of chromosomes rather than the gametophytic number. By participating in fertilization, these so-called 2n gametes generate polyploid offspring and therefore constitute the basis for the establishment of polyploidy in plants. In addition, diplogamete formation, through meiotic restitution, is an essential component of apomixis and also serves as an important mechanism for the restoration of F1 hybrid fertility. Characterization of the cytological mechanisms and molecular factors underlying 2n gamete formation is therefore not only relevant for basic plant biology and evolution, but may also provide valuable cues for agricultural and biotechnological applications (e.g. reverse breeding, clonal seeds). Recent data have provided novel insights into the process of 2n pollen and egg formation and have revealed multiple means to the same end. Here, we summarize the cytological mechanisms and molecular regulatory networks underlying 2n gamete formation, and outline important mitotic and meiotic processes involved in the ectopic induction of sexual polyploidization. © 2013 Ghent University. New Phytologist © 2013 New Phytologist Trust.

Generative mechanistic explanation building in undergraduate molecular and cellular biology

Science.gov (United States)

Southard, Katelyn M.; Espindola, Melissa R.; Zaepfel, Samantha D.; Bolger, Molly S.

2017-09-01

When conducting scientific research, experts in molecular and cellular biology (MCB) use specific reasoning strategies to construct mechanistic explanations for the underlying causal features of molecular phenomena. We explored how undergraduate students applied this scientific practice in MCB. Drawing from studies of explanation building among scientists, we created and applied a theoretical framework to explore the strategies students use to construct explanations for 'novel' biological phenomena. Specifically, we explored how students navigated the multi-level nature of complex biological systems using generative mechanistic reasoning. Interviews were conducted with introductory and upper-division biology students at a large public university in the United States. Results of qualitative coding revealed key features of students' explanation building. Students used modular thinking to consider the functional subdivisions of the system, which they 'filled in' to varying degrees with mechanistic elements. They also hypothesised the involvement of mechanistic entities and instantiated abstract schema to adapt their explanations to unfamiliar biological contexts. Finally, we explored the flexible thinking that students used to hypothesise the impact of mutations on multi-leveled biological systems. Results revealed a number of ways that students drew mechanistic connections between molecules, functional modules (sets of molecules with an emergent function), cells, tissues, organisms and populations.

Molecular Mechanisms Underlying γ-Aminobutyric Acid (GABA) Accumulation in Giant Embryo Rice Seeds.

Science.gov (United States)

Zhao, Guo-Chao; Xie, Mi-Xue; Wang, Ying-Cun; Li, Jian-Yue

2017-06-21

To uncover the molecular mechanisms underlying GABA accumulation in giant embryo rice seeds, we analyzed the expression levels of GABA metabolism genes and contents of GABA and GABA metabolic intermediates in developing grains and germinated brown rice of giant embryo rice 'Shangshida No. 5' and normal embryo rice 'Chao2-10' respectively. In developing grains, the higher GABA contents in 'Shangshida No. 5' were accompanied with upregulation of gene transcripts and intermediate contents in the polyamine pathway and downregulation of GABA catabolic gene transcripts, as compared with those in 'Chao2-10'. In germinated brown rice, the higher GABA contents in 'Shangshida No. 5' were parallel with upregulation of OsGAD and polyamine pathway gene transcripts and Glu and polyamine pathway intermediate contents and downregulation of GABA catabolic gene transcripts. These results are the first to indicate that polyamine pathway and GABA catabolic genes play a crucial role in GABA accumulation in giant embryo rice seeds.

Surface functionalization of SPR chip for specific molecular interaction analysis under flow condition

Directory of Open Access Journals (Sweden)

Tao Ma

2017-03-01

Full Text Available Surface functionalization of sensor chip for probe immobilization is crucial for the biosensing applications of surface plasmon resonance (SPR sensors. In this paper, we report a method circulating the dopamine aqueous solution to coat polydopamine film on sensing surface for surface functionalization of SPR chip. The polydopamine film with available thickness can be easily prepared by controlling the circulation time and the biorecognition elements can be immobilized on the polydopamine film for specific molecular interaction analysis. These operations are all performed under flow condition in the fluidic system, and have the advantages of easy implementation, less time consuming, and low cost, because the reagents and devices used in the operations are routinely applied in most laboratories. In this study, the specific absorption between the protein A probe immobilized on the sensing surface and human immunoglobulin G in the buffer is monitored based on this surface functionalization strategy to demonstrated its feasibility for SPR biosensing applications.

Phylogenetic estimates of diversification rate are affected by molecular rate variation.

Science.gov (United States)

Duchêne, D A; Hua, X; Bromham, L

2017-10-01

Molecular phylogenies are increasingly being used to investigate the patterns and mechanisms of macroevolution. In particular, node heights in a phylogeny can be used to detect changes in rates of diversification over time. Such analyses rest on the assumption that node heights in a phylogeny represent the timing of diversification events, which in turn rests on the assumption that evolutionary time can be accurately predicted from DNA sequence divergence. But there are many influences on the rate of molecular evolution, which might also influence node heights in molecular phylogenies, and thus affect estimates of diversification rate. In particular, a growing number of studies have revealed an association between the net diversification rate estimated from phylogenies and the rate of molecular evolution. Such an association might, by influencing the relative position of node heights, systematically bias estimates of diversification time. We simulated the evolution of DNA sequences under several scenarios where rates of diversification and molecular evolution vary through time, including models where diversification and molecular evolutionary rates are linked. We show that commonly used methods, including metric-based, likelihood and Bayesian approaches, can have a low power to identify changes in diversification rate when molecular substitution rates vary. Furthermore, the association between the rates of speciation and molecular evolution rate can cause the signature of a slowdown or speedup in speciation rates to be lost or misidentified. These results suggest that the multiple sources of variation in molecular evolutionary rates need to be considered when inferring macroevolutionary processes from phylogenies. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.

Genomic analysis reveals the molecular basis for capsule loss in the group B Streptococcus population.

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Roberto Rosini

Full Text Available The human and bovine bacterial pathogen Streptococcus agalactiae (Group B Streptococcus, GBS expresses a thick polysaccharide capsule that constitutes a major virulence factor and vaccine target. GBS can be classified into ten distinct serotypes differing in the chemical composition of their capsular polysaccharide. However, non-typeable strains that do not react with anti-capsular sera are frequently isolated from colonized and infected humans and cattle. To gain a comprehensive insight into the molecular basis for the loss of capsule expression in GBS, a collection of well-characterized non-typeable strains was investigated by genome sequencing. Genome based phylogenetic analysis extended to a wide population of sequenced strains confirmed the recently observed high clonality among GBS lineages mainly containing human strains, and revealed a much higher degree of diversity in the bovine population. Remarkably, non-typeable strains were equally distributed in all lineages. A number of distinct mutations in the cps operon were identified that were apparently responsible for inactivation of capsule synthesis. The most frequent genetic alterations were point mutations leading to stop codons in the cps genes, and the main target was found to be cpsE encoding the portal glycosyl transferase of capsule biosynthesis. Complementation of strains carrying missense mutations in cpsE with a wild-type gene restored capsule expression allowing the identification of amino acid residues essential for enzyme activity.

Comparative Circadian Metabolomics Reveal Differential Effects of Nutritional Challenge in the Serum and Liver.

Science.gov (United States)

Abbondante, Serena; Eckel-Mahan, Kristin L; Ceglia, Nicholas J; Baldi, Pierre; Sassone-Corsi, Paolo

2016-02-05

Diagnosis and therapeutic interventions in pathological conditions rely upon clinical monitoring of key metabolites in the serum. Recent studies show that a wide range of metabolic pathways are controlled by circadian rhythms whose oscillation is affected by nutritional challenges, underscoring the importance of assessing a temporal window for clinical testing and thereby questioning the accuracy of the reading of critical pathological markers in circulation. We have been interested in studying the communication between peripheral tissues under metabolic homeostasis perturbation. Here we present a comparative circadian metabolomic analysis on serum and liver in mice under high fat diet. Our data reveal that the nutritional challenge induces a loss of serum metabolite rhythmicity compared with liver, indicating a circadian misalignment between the tissues analyzed. Importantly, our results show that the levels of serum metabolites do not reflect the circadian liver metabolic signature or the effect of nutritional challenge. This notion reveals the possibility that misleading reads of metabolites in circulation may result in misdiagnosis and improper treatments. Our findings also demonstrate a tissue-specific and time-dependent disruption of metabolic homeostasis in response to altered nutrition. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

RNA sequencing of Populus x canadensis roots identifies key molecular mechanisms underlying physiological adaption to excess zinc.

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Andrea Ariani

Full Text Available Populus x canadensis clone I-214 exhibits a general indicator phenotype in response to excess Zn, and a higher metal uptake in roots than in shoots with a reduced translocation to aerial parts under hydroponic conditions. This physiological adaptation seems mainly regulated by roots, although the molecular mechanisms that underlie these processes are still poorly understood. Here, differential expression analysis using RNA-sequencing technology was used to identify the molecular mechanisms involved in the response to excess Zn in root. In order to maximize specificity of detection of differentially expressed (DE genes, we consider the intersection of genes identified by three distinct statistical approaches (61 up- and 19 down-regulated and validate them by RT-qPCR, yielding an agreement of 93% between the two experimental techniques. Gene Ontology (GO terms related to oxidation-reduction processes, transport and cellular iron ion homeostasis were enriched among DE genes, highlighting the importance of metal homeostasis in adaptation to excess Zn by P. x canadensis clone I-214. We identified the up-regulation of two Populus metal transporters (ZIP2 and NRAMP1 probably involved in metal uptake, and the down-regulation of a NAS4 gene involved in metal translocation. We identified also four Fe-homeostasis transcription factors (two bHLH38 genes, FIT and BTS that were differentially expressed, probably for reducing Zn-induced Fe-deficiency. In particular, we suggest that the down-regulation of FIT transcription factor could be a mechanism to cope with Zn-induced Fe-deficiency in Populus. These results provide insight into the molecular mechanisms involved in adaption to excess Zn in Populus spp., but could also constitute a starting point for the identification and characterization of molecular markers or biotechnological targets for possible improvement of phytoremediation performances of poplar trees.

Atomic-scale structure of dislocations revealed by scanning tunneling microscopy and molecular dynamics

DEFF Research Database (Denmark)

Christiansen, Jesper; Morgenstern, K.; Schiøtz, Jakob

2002-01-01

The intersection between dislocations and a Ag(111) surface has been studied using an interplay of scanning tunneling microscopy (STM) and molecular dynamics. Whereas the STM provides atomically resolved information about the surface structure and Burgers vectors of the dislocations, the simulati......The intersection between dislocations and a Ag(111) surface has been studied using an interplay of scanning tunneling microscopy (STM) and molecular dynamics. Whereas the STM provides atomically resolved information about the surface structure and Burgers vectors of the dislocations......, the simulations can be used to determine dislocation structure and orientation in the near-surface region. In a similar way, the subsurface structure of other extended defects can be studied. The simulations show dislocations to reorient the partials in the surface region leading to an increased splitting width...

Melting curves of molecular hydrogen and molecular deuterium under high pressures between 20 and 373 K

International Nuclear Information System (INIS)

Diatschenko, V.; Chu, C.W.; Liebenberg, D.H.; Young, D.A.; Ross, M.; Mills, R.L.

1985-01-01

We determined the melting curve of molecular hydrogen and molecular deuterium at closely spaced intervals from 20 to 373 K by two different techniques using high-pressure diamond cells. The cells were loaded with liquid at low temperature or with compressed gas at room temperature. Empirical functions for the melting curves were evaluated from least-squares fits of the data. Values of the compressibility and Debye temperature were computed at melting, and the results are compared with those calculated from various theoretical models. The good agreement shows that the models are generally valid, although small systematic deviations may point the way toward refinements in modeling. Our study also demonstrates the need to determine a one-piece intermolecular potential valid over a wide pressure range by refitting all experimental data, including the shock data recently made available

Genome-wide characterization of the WRKY gene family in radish (Raphanus sativus L.) reveals its critical functions under different abiotic stresses.

Science.gov (United States)

Karanja, Bernard Kinuthia; Fan, Lianxue; Xu, Liang; Wang, Yan; Zhu, Xianwen; Tang, Mingjia; Wang, Ronghua; Zhang, Fei; Muleke, Everlyne M'mbone; Liu, Liwang

2017-11-01

The radish WRKY gene family was genome-widely identified and played critical roles in response to multiple abiotic stresses. The WRKY is among the largest transcription factors (TFs) associated with multiple biological activities for plant survival, including control response mechanisms against abiotic stresses such as heat, salinity, and heavy metals. Radish is an important root vegetable crop and therefore characterization and expression pattern investigation of WRKY transcription factors in radish is imperative. In the present study, 126 putative WRKY genes were retrieved from radish genome database. Protein sequence and annotation scrutiny confirmed that RsWRKY proteins possessed highly conserved domains and zinc finger motif. Based on phylogenetic analysis results, RsWRKYs candidate genes were divided into three groups (Group I, II and III) with the number 31, 74, and 20, respectively. Additionally, gene structure analysis revealed that intron-exon patterns of the WRKY genes are highly conserved in radish. Linkage map analysis indicated that RsWRKY genes were distributed with varying densities over nine linkage groups. Further, RT-qPCR analysis illustrated the significant variation of 36 RsWRKY genes under one or more abiotic stress treatments, implicating that they might be stress-responsive genes. In total, 126 WRKY TFs were identified from the R. sativus genome wherein, 35 of them showed abiotic stress-induced expression patterns. These results provide a genome-wide characterization of RsWRKY TFs and baseline for further functional dissection and molecular evolution investigation, specifically for improving abiotic stress resistances with an ultimate goal of increasing yield and quality of radish.

Molecular Clues to Physiological and Premature Ageing Revealed | Center for Cancer Research

Science.gov (United States)

There are many theories about the molecular basis of ageing. One of the most popular ones postulates that organisms age by accumulating damage to their tissues, cells, and molecules. On the cellular level, ageing is associated with progressive changes in chromatin (a combination of DNA and proteins that makes up chromosomes). These changes include loss of chromatin structure,

Structural phase transition and failure of nanographite sheets under high pressure: a molecular dynamics study

International Nuclear Information System (INIS)

Zhang Bin; Liang Yongcheng; Sun Huiyu

2007-01-01

Nanographite sheets under high compressive stresses at ambient temperature have been investigated through molecular dynamics simulations using the Tersoff-Brenner potential. Nanographite undergoes a soft to hard phase transition at a certain compressive stress, about 15 GPa. With increasing compressions, the bonding structures of nanographite are changed, interlayer sp 3 -bonds are formed, and nanographite transforms into a superhard carbon phase (SCP). Further compressions lead to the instabilities of the SCP. Although the detailed lattice structure of the SCP remains elusive, its compressive strength can approach 150 GPa, comparable to that of diamond. The maximum failure stresses of nanographite sheets are sensitive to the inter-and intra-layer interstices. Our results may explain paradoxical experimental results in the available literature

Molecular interaction of PCB153 to human serum albumin: Insights from spectroscopic and molecular modeling studies

Energy Technology Data Exchange (ETDEWEB)

Han, Chao; Fang, Senbiao; Cao, Huiming; Lu, Yan; Ma, Yaqiong [School of Pharmacy, Lanzhou University, Lanzhou 730000 (China); Wei, Dongfeng [Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700 (China); Xie, Xiaoyun [College of Earth and Environmental Science, Lanzhou University, Lanzhou 730000 (China); Liu, Xiaohua [School of Pharmacy, Lanzhou University, Lanzhou 730000 (China); Li, Xin [College of Food and Bioengineering, Henan University of Science and Technology, Luoyang 471003 (China); Fei, Dongqing [School of Pharmacy, Lanzhou University, Lanzhou 730000 (China); Zhao, Chunyan, E-mail: zhaochy07@lzu.edu.cn [School of Pharmacy, Lanzhou University, Lanzhou 730000 (China)

2013-03-15

Highlights: ► We identify the binding mode of PCB153 to human serum albumin (HSA). ► Spectroscopic and molecular modeling results reveal that PCB153 binds at the site II. ► The interaction is mainly governed by hydrophobic and hydrogen bond forces. ► The work helps to probe transporting, distribution and toxicity effect of PCBs. -- Abstract: Polychlorinated biphenyls (PCBs) possessed much potential hazard to environment because of its chemical stability and biological toxicity. Here, we identified the binding mode of a representative compound, PCB153, to human serum albumin (HSA) using fluorescence and molecular dynamics simulation methods. The fluorescence study showed that the intrinsic fluorescence of HSA was quenched by addition of PCB153 through a static quenching mechanism. The thermodynamic analysis proved the binding behavior was mainly governed by hydrophobic force. Furthermore, as evidenced by site marker displacement experiments using two probe compounds, it revealed that PCB153 acted exactly on subdomain IIIA (site II) of HSA. On the other hand, the molecular dynamics studies as well as free energy calculations made another important contribution to understand the conformational changes of HSA and the stability of HSA-PCB153 system. Molecular docking revealed PCB153 can bind in a large hydrophobic activity of subdomain IIIA by the hydrophobic interaction and hydrogen bond interactions between chlorine atoms and residue ASN391. The present work provided reasonable models helping us further understand the transporting, distribution and toxicity effect of PCBs when it spread into human blood serum.

Systematically Altering Bacterial SOS Activity under Stress Reveals Therapeutic Strategies for Potentiating Antibiotics.

Science.gov (United States)

Mo, Charlie Y; Manning, Sara A; Roggiani, Manuela; Culyba, Matthew J; Samuels, Amanda N; Sniegowski, Paul D; Goulian, Mark; Kohli, Rahul M

2016-01-01

promoting survival and the evolution of resistance under antibiotic stress. As a result, targeting the SOS response has been proposed as an adjuvant strategy to revitalize our current antibiotic arsenal. However, the optimal molecular targets and partner antibiotics for such an approach remain unclear. In this study, focusing on the two key regulators of the SOS response, LexA and RecA, we provide the first comprehensive assessment of how to target the SOS response in order to increase bacterial susceptibility and reduce mutagenesis under antibiotic treatment.

Computational Analysis of Molecular Interaction Networks Underlying Change of HIV-1 Resistance to Selected Reverse Transcriptase Inhibitors.

Science.gov (United States)

Kierczak, Marcin; Dramiński, Michał; Koronacki, Jacek; Komorowski, Jan

2010-12-12

Despite more than two decades of research, HIV resistance to drugs remains a serious obstacle in developing efficient AIDS treatments. Several computational methods have been developed to predict resistance level from the sequence of viral proteins such as reverse transcriptase (RT) or protease. These methods, while powerful and accurate, give very little insight into the molecular interactions that underly acquisition of drug resistance/hypersusceptibility. Here, we attempt at filling this gap by using our Monte Carlo feature selection and interdependency discovery method (MCFS-ID) to elucidate molecular interaction networks that characterize viral strains with altered drug resistance levels. We analyzed a number of HIV-1 RT sequences annotated with drug resistance level using the MCFS-ID method. This let us expound interdependency networks that characterize change of drug resistance to six selected RT inhibitors: Abacavir, Lamivudine, Stavudine, Zidovudine, Tenofovir and Nevirapine. The networks consider interdependencies at the level of physicochemical properties of mutating amino acids, eg,: polarity. We mapped each network on the 3D structure of RT in attempt to understand the molecular meaning of interacting pairs. The discovered interactions describe several known drug resistance mechanisms and, importantly, some previously unidentified ones. Our approach can be easily applied to a whole range of problems from the domain of protein engineering. A portable Java implementation of our MCFS-ID method is freely available for academic users and can be obtained at: http://www.ipipan.eu/staff/m.draminski/software.htm.

Molecular profiling reveals frequent gain of MYCN and anaplasia-specific loss of 4q and 14q in Wilms tumor.

Science.gov (United States)

Williams, Richard D; Al-Saadi, Reem; Natrajan, Rachael; Mackay, Alan; Chagtai, Tasnim; Little, Suzanne; Hing, Sandra N; Fenwick, Kerry; Ashworth, Alan; Grundy, Paul; Anderson, James R; Dome, Jeffrey S; Perlman, Elizabeth J; Jones, Chris; Pritchard-Jones, Kathy

2011-12-01

Anaplasia in Wilms tumor, a distinctive histology characterized by abnormal mitoses, is associated with poor patient outcome. While anaplastic tumors frequently harbour TP53 mutations, little is otherwise known about their molecular biology. We have used array comparative genomic hybridization (aCGH) and cDNA microarray expression profiling to compare anaplastic and favorable histology Wilms tumors to determine their common and differentiating features. In addition to changes on 17p, consistent with TP53 deletion, recurrent anaplasia-specific genomic loss and under-expression were noted in several other regions, most strikingly 4q and 14q. Further aberrations, including gain of 1q and loss of 16q were common to both histologies. Focal gain of MYCN, initially detected by high resolution aCGH profiling in 6/61 anaplastic samples, was confirmed in a significant proportion of both tumor types by a genomic quantitative PCR survey of over 400 tumors. Overall, these results are consistent with a model where anaplasia, rather than forming an entirely distinct molecular entity, arises from the general continuum of Wilms tumor by the acquisition of additional genomic changes at multiple loci. Copyright © 2011 Wiley Periodicals, Inc.

Mechanistic Insights on Human Phosphoglucomutase Revealed by Transition Path Sampling and Molecular Dynamics Calculations.

Science.gov (United States)

Brás, Natércia F; Fernandes, Pedro A; Ramos, Maria J; Schwartz, Steven D

2018-02-06

Human α-phosphoglucomutase 1 (α-PGM) catalyzes the isomerization of glucose-1-phosphate into glucose-6-phosphate (G6P) through two sequential phosphoryl transfer steps with a glucose-1,6-bisphosphate (G16P) intermediate. Given that the release of G6P in the gluconeogenesis raises the glucose output levels, α-PGM represents a tempting pharmacological target for type 2 diabetes. Here, we provide the first theoretical study of the catalytic mechanism of human α-PGM. We performed transition-path sampling simulations to unveil the atomic details of the two catalytic chemical steps, which could be key for developing transition state (TS) analogue molecules with inhibitory properties. Our calculations revealed that both steps proceed through a concerted S N 2-like mechanism, with a loose metaphosphate-like TS. Even though experimental data suggests that the two steps are identical, we observed noticeable differences: 1) the transition state ensemble has a well-defined TS region and a late TS for the second step, and 2) larger coordinated protein motions are required to reach the TS of the second step. We have identified key residues (Arg23, Ser117, His118, Lys389), and the Mg 2+ ion that contribute in different ways to the reaction coordinate. Accelerated molecular dynamics simulations suggest that the G16P intermediate may reorient without leaving the enzymatic binding pocket, through significant conformational rearrangements of the G16P and of specific loop regions of the human α-PGM. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Transitional Failure of Carbon Nanotube Systems under a Combination of Tension and Torsion

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Byeong-Woo Jeong

2012-01-01

Full Text Available Transitional failure envelopes of single- and double-walled carbon nanotubes under combined tension-torsion are predicted using classical molecular dynamics simulations. The observations reveal that while the tensile failure load decreases with combined torsion, the torsional buckling moment increases with combined tension. As a result, the failure envelopes under combined tension-torsion are definitely different from those under pure tension or torsion. In such combined loading, there is a multitude of failure modes (tensile failure and torsional buckling, and the failure consequently exhibits the feature of transitional failure envelopes. In addition, the safe region of double-walled carbon nanotubes is significantly larger than that of single-walled carbon nanotubes due to the differences in the onset of torsional buckling.

Investigation of molecular markers related to fecundity in local egyptian sheep

International Nuclear Information System (INIS)

Hassanin, W.F.E.

2011-01-01

The present experimental work aimed to investigate a number of molecular makers that influence fecundity in local Egyptian sheep. In the present study, twenty two (11 twin producing crossbred ewes, 7 single lamb producing crossbred ewes, 2 crossbred rams from twin producing ewes and 2 pure bred rams from twin producing ewes) were tested. They were carefully selected from the records of the Egyptian Nuclear Research Centre. The ewes were selected for their twin production in three repetitive production cycles while the rams were selected for being produced from prolific ewes as above. The presence of the booroola fecundity gene (FecB) (FecB mutation in bone morphogenic protein receptor gene 1B (BMPR1B)) and the Inverdale gene (FecX I ) (FecX I mutation in bone morphogenic receptor gene (BMP15)) using Forced restriction PCR of the FecB and FecX I mutations, 190 base pair (bp) was amplified using specific primer which was forward (5 ' -CCAGAGGACAATAGCAAAGCAAA -3 ' ) and reverse (5 ' -CAAGATGTTTTCATGCCTCATCAACAGGTC -3 ' ) and designed to introduce a point mutation in the resulting PCR products with FecB carrier sheep containing an AvaII restriction site (G|GACC). The FecB DNA test showed that there were no carriers for the FecB mutation in the selected prolific sheep sample. When a specific primer which was forward (5 ' -GAAGTAACCAGTGTTCCCTCCACCCTTTTCT-3 ' ) and reverse (5 ' -CATGATTGGGAGAATTGAGACC-3 ' ) used to test the presence of FecX I mutation no amplification resulted from DNA samples of the twin producing ewes while two amplified DNA fragments of molecular size 154 bp and 120 bp resulted from the single lamb producing females and male sheep under study. Serum samples were collected from sheep under study and tested using totallab 120 computer software analyses for Native protein gel images. Gel images revealed a protein pattern in twin producing ewe samples characterized by the presence of three bands with molecular weights 679.7, 524.3, and 431.1 kd and the

Optogenetic dissection reveals multiple rhythmogenic modules underlying locomotion

DEFF Research Database (Denmark)

Hägglund, Martin; Dougherty, Kimberly J.; Borgius, Lotta

2013-01-01

flexor motor neuron pools can be recruited into bursting without any activity in other nearby flexor motor neuron pools. Our experiments differentiate among several proposed models for rhythm generation in the vertebrates and show that the basic structure underlying the locomotor network has...

Assessment of molecular events during in vitro re-epithelialization under honey-alginate matrix ambience

Energy Technology Data Exchange (ETDEWEB)

Barui, Ananya [Centre for Healthcare Science and Technology, BESU, Shibpur, Howrah 711103, West Bengal (India); Mandal, Naresh [Dept. of Electronics and Telecommunication Engg., BESU, Shibpur, Howrah 711103, West Bengal (India); Majumder, Subhadipa [Department of Biochemistry, University of Calcutta Ballygunge, Circular Road, Kolkata 700 019, West Bengal (India); Das, Raunak Kumar [School of Medical Science and Technology, IIT, Kharagpur 721 302, West Bengal (India); Sengupta, Sanghamitra [Department of Biochemistry, University of Calcutta Ballygunge, Circular Road, Kolkata 700 019, West Bengal (India); Banerjee, Provas [School of Medical Science and Technology, IIT, Kharagpur 721 302, West Bengal (India); Ray, Ajoy Kumar; RoyChaudhuri, Chirosree [Dept. of Electronics and Telecommunication Engg., BESU, Shibpur, Howrah 711103, West Bengal (India); Chatterjee, Jyotirmoy, E-mail: jchatterjee@smst.iitkgp.ernet.in [School of Medical Science and Technology, IIT, Kharagpur 721 302, West Bengal (India)

2013-08-01

Re-epithelialization is one of the most important stages of cutaneous regeneration and its success requires supportive micro-ambience which may be provided with suitable bio-matrix. Biocompatibility and efficacy of such bio-matrix in re-epithelialization could be explored by multimodal analysis of structural and functional attributes of in vitro wound healing model including evaluation of prime molecular expressions of the epithelial cells during repair. Present study examines the influence of honey-alginate and alginate matrices on re-epithelialization in keratinocyte (HaCaT) population in a 2-D wound model. Cellular viability, proliferation and cell–cell adhesion status were assessed during wound closure using live/dead cell assay and by evaluating expressions of Ki67, p63 and E-cadherin along-with % change in cellular electrical impedance. Efficacy of honey-alginate matrix in comparison to only alginate one was demonstrated by a quicker reduction in wound gap, improved cellular viability, enhanced expressions of Ki67, p63 and its isoforms (TAp63, ΔNp63) as well as E-cadherin. Faster restoration of electrical attribute (% of impedance change) after wounding also indicated better impact of honey-alginate matrix in re-epithelialization. - Highlights: • Role of honey based matrix is evaluated in wound re-epithelialization. • Healing impact of matrix studied in 2D in vitro keratinocyte (HaCaT) wound model. • Faster impedance restoration indicated rapid healing rate of HaCaT under honey. • PCR observations showed faster initiation of cell proliferation under honey. • ICC study indicated better up-regulation of healing markers under honey matrix.

Assessment of molecular events during in vitro re-epithelialization under honey-alginate matrix ambience

International Nuclear Information System (INIS)

Barui, Ananya; Mandal, Naresh; Majumder, Subhadipa; Das, Raunak Kumar; Sengupta, Sanghamitra; Banerjee, Provas; Ray, Ajoy Kumar; RoyChaudhuri, Chirosree; Chatterjee, Jyotirmoy

2013-01-01

Re-epithelialization is one of the most important stages of cutaneous regeneration and its success requires supportive micro-ambience which may be provided with suitable bio-matrix. Biocompatibility and efficacy of such bio-matrix in re-epithelialization could be explored by multimodal analysis of structural and functional attributes of in vitro wound healing model including evaluation of prime molecular expressions of the epithelial cells during repair. Present study examines the influence of honey-alginate and alginate matrices on re-epithelialization in keratinocyte (HaCaT) population in a 2-D wound model. Cellular viability, proliferation and cell–cell adhesion status were assessed during wound closure using live/dead cell assay and by evaluating expressions of Ki67, p63 and E-cadherin along-with % change in cellular electrical impedance. Efficacy of honey-alginate matrix in comparison to only alginate one was demonstrated by a quicker reduction in wound gap, improved cellular viability, enhanced expressions of Ki67, p63 and its isoforms (TAp63, ΔNp63) as well as E-cadherin. Faster restoration of electrical attribute (% of impedance change) after wounding also indicated better impact of honey-alginate matrix in re-epithelialization. - Highlights: • Role of honey based matrix is evaluated in wound re-epithelialization. • Healing impact of matrix studied in 2D in vitro keratinocyte (HaCaT) wound model. • Faster impedance restoration indicated rapid healing rate of HaCaT under honey. • PCR observations showed faster initiation of cell proliferation under honey. • ICC study indicated better up-regulation of healing markers under honey matrix

Molecular type channeling of relativistic electrons in crystals

International Nuclear Information System (INIS)

Vyatkin, E.G.; Filimonov, Yu.M.; Taratin, A.M.; Vorobiev, S.A.

1983-01-01

Channeling of relativistic electrons in direction in a diamond crystal and the channeling radiation spectra are investigated using computer simulation by the binary collision model and using the model of a continuum potential of the atomic rows. In a computer experiment the atomic- and molecular-type states of channeled elcetrons are revealed, and the orientational dependence of the electron trapping probability in these states is obtained. The peculiarities revealed of the angular distributions and radiation spectra of electrons in the molecular-type states allow to discover these states in the experiment. (author)

Potential Role of the Last Half Repeat in TAL Effectors Revealed by a Molecular Simulation Study

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Hua Wan

2016-01-01

Full Text Available TAL effectors (TALEs contain a modular DNA-binding domain that is composed of tandem repeats. In all naturally occurring TALEs, the end of tandem repeats is invariantly a truncated half repeat. To investigate the potential role of the last half repeat in TALEs, we performed comparative molecular dynamics simulations for the crystal structure of DNA-bound TALE AvrBs3 lacking the last half repeat and its modeled structure having the last half repeat. The structural stability analysis indicates that the modeled system is more stable than the nonmodeled system. Based on the principle component analysis, it is found that the AvrBs3 increases its structural compactness in the presence of the last half repeat. The comparison of DNA groove parameters of the two systems implies that the last half repeat also causes the change of DNA major groove binding efficiency. The following calculation of hydrogen bond reveals that, by stabilizing the phosphate binding with DNA at the C-terminus, the last half repeat helps to adopt a compact conformation at the protein-DNA interface. It further mediates more contacts between TAL repeats and DNA nucleotide bases. Finally, we suggest that the last half repeat is required for the high-efficient recognition of DNA by TALE.

Equations of states for an ionic liquid under high pressure: A molecular dynamics simulation study

International Nuclear Information System (INIS)

Ribeiro, Mauro C.C.; Pádua, Agílio A.H.; Gomes, Margarida F.C.

2014-01-01

Highlights: • We compare different equation of states, EoS, for an ionic liquid under high pressure. • Molecular dynamics, MD, simulations have been used to evaluate the best EoS. • MD simulations show that a group contribution model can be extrapolated to P ∼ 1.0 GPa. • A perturbed hard-sphere EoS also fits the densities calculated by MD simulations. - Abstract: The high-pressure dependence of density given by empirical equation of states (EoS) for the ionic liquid 1-butyl-3-methylimidazolium trifluoromethanesulfonate (or triflate), [C 4 C 1 im][TfO], is compared with results obtained by molecular dynamics (MD) simulations. Two EoS proposed for [C 4 C 1 im][TfO] in the pressure range of tens of MPa, which give very different densities when extrapolated to pressures beyond the original experiments, are compared with a group contribution model (GCM). The MD simulations provide support that one of the empirical EoS and the GCM is valid in the pressure range of hundreds of MPa. As an alternative to these EoS that are based on modified Tait equations, it is shown that a perturbed hard-sphere EoS based on the Carnahan–Starling–van der Waals equation also fits the densities calculated by MD simulations of [C 4 C 1 im][TfO] up to ∼1.0 GPa

Shuttlecock-Shaped Molecular Rectifier: Asymmetric Electron Transport Coupled with Controlled Molecular Motion.

Science.gov (United States)

Ryu, Taekhee; Lansac, Yves; Jang, Yun Hee

2017-07-12

A fullerene derivative with five hydroxyphenyl groups attached around a pentagon, (4-HOC 6 H 4 ) 5 HC 60 (1), has shown an asymmetric current-voltage (I-V) curve in a conducting atomic force microscopy experiment on gold. Such molecular rectification has been ascribed to the asymmetric distribution of frontier molecular orbitals over its shuttlecock-shaped structure. Our nonequilibrium Green's function (NEGF) calculations based on density functional theory (DFT) indeed exhibit an asymmetric I-V curve for 1 standing up between two Au(111) electrodes, but the resulting rectification ratio (RR ∼ 3) is insufficient to explain the wide range of RR observed in experiments performed under a high bias voltage. Therefore, we formulate a hypothesis that high RR (>10) may come from molecular orientation switching induced by a strong electric field applied between two electrodes. Indeed, molecular dynamics simulations of a self-assembled monolayer of 1 on Au(111) show that the orientation of 1 can be switched between standing-up and lying-on-the-side configurations in a manner to align its molecular dipole moment with the direction of the applied electric field. The DFT-NEGF calculations taking into account such field-induced reorientation between up and side configurations indeed yield RR of ∼13, which agrees well with the experimental value obtained under a high bias voltage.

Renal Effects and Underlying Molecular Mechanisms of Long-Term Salt Content Diets in Spontaneously Hypertensive Rats

Science.gov (United States)

Berger, Rebeca Caldeira Machado; Vassallo, Paula Frizera; Crajoinas, Renato de Oliveira; Oliveira, Marilene Luzia; Martins, Flávia Letícia; Nogueira, Breno Valentim; Motta-Santos, Daisy; Araújo, Isabella Binotti; Forechi, Ludimila; Girardi, Adriana Castello Costa; Santos, Robson Augusto Souza; Mill, José Geraldo

2015-01-01

Several evidences have shown that salt excess is an important determinant of cardiovascular and renal derangement in hypertension. The present study aimed to investigate the renal effects of chronic high or low salt intake in the context of hypertension and to elucidate the molecular mechanisms underlying such effects. To this end, newly weaned male SHR were fed with diets only differing in NaCl content: normal salt (NS: 0.3%), low salt (LS: 0.03%), and high salt diet (HS: 3%) until 7 months of age. Analysis of renal function, morphology, and evaluation of the expression of the main molecular components involved in the renal handling of albumin, including podocyte slit-diaphragm proteins and proximal tubule endocytic receptors were performed. The relationship between diets and the balance of the renal angiotensin-converting enzyme (ACE) and ACE2 enzymes was also examined. HS produced glomerular hypertrophy and decreased ACE2 and nephrin expressions, loss of morphological integrity of the podocyte processes, and increased proteinuria, characterized by loss of albumin and high molecular weight proteins. Conversely, severe hypertension was attenuated and renal dysfunction was prevented by LS since proteinuria was much lower than in the NS SHRs. This was associated with a decrease in kidney ACE/ACE2 protein and activity ratio and increased cubilin renal expression. Taken together, these results suggest that LS attenuates hypertension progression in SHRs and preserves renal function. The mechanisms partially explaining these findings include modulation of the intrarenal ACE/ACE2 balance and the increased cubilin expression. Importantly, HS worsens hypertensive kidney injury and decreases the expression nephrin, a key component of the slit diaphragm. PMID:26495970

Renal Effects and Underlying Molecular Mechanisms of Long-Term Salt Content Diets in Spontaneously Hypertensive Rats.

Directory of Open Access Journals (Sweden)

Rebeca Caldeira Machado Berger

Full Text Available Several evidences have shown that salt excess is an important determinant of cardiovascular and renal derangement in hypertension. The present study aimed to investigate the renal effects of chronic high or low salt intake in the context of hypertension and to elucidate the molecular mechanisms underlying such effects. To this end, newly weaned male SHR were fed with diets only differing in NaCl content: normal salt (NS: 0.3%, low salt (LS: 0.03%, and high salt diet (HS: 3% until 7 months of age. Analysis of renal function, morphology, and evaluation of the expression of the main molecular components involved in the renal handling of albumin, including podocyte slit-diaphragm proteins and proximal tubule endocytic receptors were performed. The relationship between diets and the balance of the renal angiotensin-converting enzyme (ACE and ACE2 enzymes was also examined. HS produced glomerular hypertrophy and decreased ACE2 and nephrin expressions, loss of morphological integrity of the podocyte processes, and increased proteinuria, characterized by loss of albumin and high molecular weight proteins. Conversely, severe hypertension was attenuated and renal dysfunction was prevented by LS since proteinuria was much lower than in the NS SHRs. This was associated with a decrease in kidney ACE/ACE2 protein and activity ratio and increased cubilin renal expression. Taken together, these results suggest that LS attenuates hypertension progression in SHRs and preserves renal function. The mechanisms partially explaining these findings include modulation of the intrarenal ACE/ACE2 balance and the increased cubilin expression. Importantly, HS worsens hypertensive kidney injury and decreases the expression nephrin, a key component of the slit diaphragm.

Differentiation of molecular chain entanglement structure through laser Raman spectrum measurement of High strength PET fibers under stress

Science.gov (United States)

Go, D.; Takarada, W.; Kikutani, T.

2017-10-01

The aim of this study was to investigate the mechanism for the improvement of mechanical properties of poly(ethylene terephthalate) (PET) fibers based on the concept of controlling the state of molecular entanglement. For this purpose, five different PET fibers were prepared through either the conventional melt spinning and drawing/annealing process or the high-speed melt spinning process. In both cases, the melt spinning process was designed so as to realize different Deborah number conditions. The prepared fibers were subjected to the laser Raman spectroscopy measurement and the characteristics of the scattering peak at around 1616 cm-1, which corresponds to the C-C/C=C stretching mode of the aromatic ring in the main chain, were investigated in detail. It was revealed that the fibers drawn and annealed after the melt spinning process of lower Deborah number showed higher tensile strength as well as lower value of full width at half maximum (FWHM) in the laser Raman spectrum. Narrow FWHM was considered to represent the homogeneous state of entanglement structure, which may lead to the higher strength and toughness of fibers because individual molecular chains tend to bare similar level of tensile stress when the fiber is stretched. In case of high-speed spun fibers prepared with a high Deborah number condition, the FWHM was narrow presumably because much lower tensile stress in comparison with the drawing/annealing process was applied when the fiber structure was developed, however the value increased significantly upon applying tensile load to the fibers during the laser Raman spectrum measurement. From these results, it was concluded that the Laser Raman spectroscopy could differentiate molecular chain entanglement structure of various fiber samples, in that low FWHM, which corresponds to either homogeneous state of molecular entanglement or lower level of mean residual stress, and small increase of FWTH upon applying tensile stress are considered to be the key

Molecular dynamics for irradiation driven chemistry

DEFF Research Database (Denmark)

Sushko, Gennady B.; Solov'yov, Ilia A.; Solov'yov, Andrey V.

2016-01-01

A new molecular dynamics (MD) approach for computer simulations of irradiation driven chemical transformations of complex molecular systems is suggested. The approach is based on the fact that irradiation induced quantum transformations can often be treated as random, fast and local processes...... that describe the classical MD of complex molecular systems under irradiation. The proposed irradiation driven molecular dynamics (IDMD) methodology is designed for the molecular level description of the irradiation driven chemistry. The IDMD approach is implemented into the MBN Explorer software package...... involving small molecules or molecular fragments. We advocate that the quantum transformations, such as molecular bond breaks, creation and annihilation of dangling bonds, electronic charge redistributions, changes in molecular topologies, etc., could be incorporated locally into the molecular force fields...

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

Science.gov (United States)

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

2018-03-01

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

Transport in aluminized RDX under shock compression explored using molecular dynamics simulations

International Nuclear Information System (INIS)

Losada, M; Chaudhuri, S

2014-01-01

Shock response of energetic materials is controlled by a combination of mechanical response, thermal, transport, and chemical properties. How these properties interplay in condensed-phase energetic materials is of fundamental interest for improving predictive capabilities. Due to unknown nature of chemistry during the evolution and growth of high-temperature regions within the energetic material (so called hot spots), the connection between reactive and unreactive equations of state contain a high degree of empiricism. In particular, chemistry in materials with high degree of heterogeneity such as aluminized HE is of interest. In order to identify shock compression states and transport properties in high-pressure/temperature (HP-HT) conditions, we use molecular dynamics (MD) simulations in conjunction with the multi-scale shock technique (MSST). Mean square displacement calculations enabled us to track the diffusivity of stable gas products. Among decomposition products, H 2 O and CO 2 are found to be the dominant diffusing species under compression conditions. Heat transport and diffusion rates in decomposed RDX are compared and the comparison shows that around 2000 K, transport can be a major contribution during propagation of the reaction front.

An Investigation of Molecular Docking and Molecular Dynamic Simulation on Imidazopyridines as B-Raf Kinase Inhibitors

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Huiding Xie

2015-11-01

Full Text Available In the recent cancer treatment, B-Raf kinase is one of key targets. Nowadays, a group of imidazopyridines as B-Raf kinase inhibitors have been reported. In order to investigate the interaction between this group of inhibitors and B-Raf kinase, molecular docking, molecular dynamic (MD simulation and binding free energy (ΔGbind calculation were performed in this work. Molecular docking was carried out to identify the key residues in the binding site, and MD simulations were performed to determine the detail binding mode. The results obtained from MD simulation reveal that the binding site is stable during the MD simulations, and some hydrogen bonds (H-bonds in MD simulations are different from H-bonds in the docking mode. Based on the obtained MD trajectories, ΔGbind was computed by using Molecular Mechanics Generalized Born Surface Area (MM-GBSA, and the obtained energies are consistent with the activities. An energetic analysis reveals that both electrostatic and van der Waals contributions are important to ΔGbind, and the unfavorable polar solvation contribution results in the instability of the inhibitor with the lowest activity. These results are expected to understand the binding between B-Raf and imidazopyridines and provide some useful information to design potential B-Raf inhibitors.

Clustering the Orion B giant molecular cloud based on its molecular emission.

Science.gov (United States)

Bron, Emeric; Daudon, Chloé; Pety, Jérôme; Levrier, François; Gerin, Maryvonne; Gratier, Pierre; Orkisz, Jan H; Guzman, Viviana; Bardeau, Sébastien; Goicoechea, Javier R; Liszt, Harvey; Öberg, Karin; Peretto, Nicolas; Sievers, Albrecht; Tremblin, Pascal

2018-02-01

Previous attempts at segmenting molecular line maps of molecular clouds have focused on using position-position-velocity data cubes of a single molecular line to separate the spatial components of the cloud. In contrast, wide field spectral imaging over a large spectral bandwidth in the (sub)mm domain now allows one to combine multiple molecular tracers to understand the different physical and chemical phases that constitute giant molecular clouds (GMCs). We aim at using multiple tracers (sensitive to different physical processes and conditions) to segment a molecular cloud into physically/chemically similar regions (rather than spatially connected components), thus disentangling the different physical/chemical phases present in the cloud. We use a machine learning clustering method, namely the Meanshift algorithm, to cluster pixels with similar molecular emission, ignoring spatial information. Clusters are defined around each maximum of the multidimensional Probability Density Function (PDF) of the line integrated intensities. Simple radiative transfer models were used to interpret the astrophysical information uncovered by the clustering analysis. A clustering analysis based only on the J = 1 - 0 lines of three isotopologues of CO proves suffcient to reveal distinct density/column density regimes ( n H ~ 100 cm -3 , ~ 500 cm -3 , and > 1000 cm -3 ), closely related to the usual definitions of diffuse, translucent and high-column-density regions. Adding two UV-sensitive tracers, the J = 1 - 0 line of HCO + and the N = 1 - 0 line of CN, allows us to distinguish two clearly distinct chemical regimes, characteristic of UV-illuminated and UV-shielded gas. The UV-illuminated regime shows overbright HCO + and CN emission, which we relate to a photochemical enrichment effect. We also find a tail of high CN/HCO + intensity ratio in UV-illuminated regions. Finer distinctions in density classes ( n H ~ 7 × 10 3 cm -3 ~ 4 × 10 4 cm -3 ) for the densest regions are also

A hypothesis regarding the molecular mechanism underlying dietary soy-induced effects on seizure propensity.

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Cara Jean Westmark

2014-09-01

Full Text Available Numerous neurological disorders including fragile X syndrome, Down syndrome, autism and Alzheimer’s disease are comorbid with epilepsy. We have observed elevated seizure propensity in mouse models of these disorders dependent on diet. Specifically, soy-based diets exacerbate audiogenic-induced seizures in juvenile mice. We have also found potential associations between the consumption of soy-based infant formula and seizure incidence, epilepsy comorbidity and autism diagnostic scores in autistic children by retrospective analyses of medical record data. In total, these data suggest that consumption of high levels of soy protein during postnatal development may affect neuronal excitability. Herein, we present our theory regarding the molecular mechanism underlying soy-induced effects on seizure propensity. We hypothesize that soy phytoestrogens interfere with metabotropic glutamate receptor signaling through an estrogen receptor-dependent mechanism, which results in elevated production of key synaptic proteins and decreased seizure threshold.

Virus Infection Triggers MAVS Polymers of Distinct Molecular Weight

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Natalia Zamorano Cuervo

2018-01-01

Full Text Available The mitochondrial antiviral signaling (MAVS adaptor protein is a central signaling hub required for cells to mount an antiviral response following virus sensing by retinoic acid-inducible gene I (RIG-I-like receptors. MAVS localizes in the membrane of mitochondria and peroxisomes and in mitochondrial-associated endoplasmic reticulum membranes. Structural and functional studies have revealed that MAVS activity relies on the formation of functional high molecular weight prion-like aggregates. The formation of protein aggregates typically relies on a dynamic transition between oligomerization and aggregation states. The existence of intermediate state(s of MAVS polymers, other than aggregates, has not yet been documented. Here, we used a combination of non-reducing SDS-PAGE and semi-denaturing detergent agarose gel electrophoresis (SDD-AGE to resolve whole cell extract preparations to distinguish MAVS polymerization states. While SDD-AGE analysis of whole cell extracts revealed the formation of previously described high molecular weight prion-like aggregates upon constitutively active RIG-I ectopic expression and virus infection, non-reducing SDS-PAGE allowed us to demonstrate the induction of lower molecular weight oligomers. Cleavage of MAVS using the NS3/4A protease revealed that anchoring to intracellular membranes is required for the appropriate polymerization into active high molecular weight aggregates. Altogether, our data suggest that RIG-I-dependent MAVS activation involves the coexistence of MAVS polymers with distinct molecular weights.

A concurrent multiscale micromorphic molecular dynamics

International Nuclear Information System (INIS)

Li, Shaofan; Tong, Qi

2015-01-01

In this work, we have derived a multiscale micromorphic molecular dynamics (MMMD) from first principle to extend the (Andersen)-Parrinello-Rahman molecular dynamics to mesoscale and continuum scale. The multiscale micromorphic molecular dynamics is a con-current three-scale dynamics that couples a fine scale molecular dynamics, a mesoscale micromorphic dynamics, and a macroscale nonlocal particle dynamics together. By choosing proper statistical closure conditions, we have shown that the original Andersen-Parrinello-Rahman molecular dynamics is the homogeneous and equilibrium case of the proposed multiscale micromorphic molecular dynamics. In specific, we have shown that the Andersen-Parrinello-Rahman molecular dynamics can be rigorously formulated and justified from first principle, and its general inhomogeneous case, i.e., the three scale con-current multiscale micromorphic molecular dynamics can take into account of macroscale continuum mechanics boundary condition without the limitation of atomistic boundary condition or periodic boundary conditions. The discovered multiscale scale structure and the corresponding multiscale dynamics reveal a seamless transition from atomistic scale to continuum scale and the intrinsic coupling mechanism among them based on first principle formulation

Pronounced low-frequency vibrational thermal transport in C60 fullerite realized through pressure-dependent molecular dynamics simulations

Science.gov (United States)

Giri, Ashutosh; Hopkins, Patrick E.

2017-12-01

Fullerene condensed-matter solids can possess thermal conductivities below their minimum glassy limit while theorized to be stiffer than diamond when crystallized under pressure. These seemingly disparate extremes in thermal and mechanical properties raise questions into the pressure dependence on the thermal conductivity of C60 fullerite crystals, and how the spectral contributions to vibrational thermal conductivity changes under applied pressure. To answer these questions, we investigate the effect of strain on the thermal conductivity of C60 fullerite crystals via pressure-dependent molecular dynamics simulations under the Green-Kubo formalism. We show that the thermal conductivity increases rapidly with compressive strain, which demonstrates a power-law relationship similar to their stress-strain relationship for the C60 crystals. Calculations of the density of states for the crystals under compressive strains reveal that the librational modes characteristic in the unstrained case are diminished due to densification of the molecular crystal. Over a large compression range (0-20 GPa), the Leibfried-Schlömann equation is shown to adequately describe the pressure dependence of thermal conductivity, suggesting that low-frequency intermolecular vibrations dictate heat flow in the C60 crystals. A spectral decomposition of the thermal conductivity supports this hypothesis.

Molecular control of rodent spermatogenesis

NARCIS (Netherlands)

Jan, Sabrina Z.; Hamer, Geert; Repping, Sjoerd; de Rooij, Dirk G.; van Pelt, Ans M. M.; Vormer, Tinke L.

2012-01-01

Spermatogenesis is a complex developmental process that ultimately generates mature spermatozoa. This process involves a phase of proliferative expansion, meiosis, and cytodifferentiation. Mouse models have been widely used to study spermatogenesis and have revealed many genes and molecular

Genome-Wide Association Study Reveals Natural Variations Contributing to Drought Resistance in Crops

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Hongwei Wang

2017-06-01

Full Text Available Crops are often cultivated in regions where they will face environmental adversities; resulting in substantial yield loss which can ultimately lead to food and societal problems. Thus, significant efforts have been made to breed stress tolerant cultivars in an attempt to minimize these problems and to produce more stability with respect to crop yields across broad geographies. Since stress tolerance is a complex and multi-genic trait, advancements with classical breeding approaches have been challenging. On the other hand, molecular breeding, which is based on transgenics, marker-assisted selection and genome editing technologies; holds great promise to enable farmers to better cope with these challenges. However, identification of the key genetic components underlying the trait is critical and will serve as the foundation for future crop genetic improvement. Recently, genome-wide association studies have made significant contributions to facilitate the discovery of natural variation contributing to stress tolerance in crops. From these studies, the identified loci can serve as targets for genomic selection or editing to enable the molecular design of new cultivars. Here, we summarize research progress on this issue and focus on the genetic basis of drought tolerance as revealed by genome-wide association studies and quantitative trait loci mapping. Although many favorable loci have been identified, elucidation of their molecular mechanisms contributing to increased stress tolerance still remains a challenge. Thus, continuous efforts are still required to functionally dissect this complex trait through comprehensive approaches, such as system biological studies. It is expected that proper application of the acquired knowledge will enable the development of stress tolerant cultivars; allowing agricultural production to become more sustainable under dynamic environmental conditions.

Molecular mechanisms underlying memory consolidation of taste information in the cortex.

Science.gov (United States)

Gal-Ben-Ari, Shunit; Rosenblum, Kobi

2011-01-01

The senses of taste and odor are both chemical senses. However, whereas an organism can detect an odor at a relatively long distance from its source, taste serves as the ultimate proximate gatekeeper of food intake: it helps in avoiding poisons and consuming beneficial substances. The automatic reaction to a given taste has been developed during evolution and is well adapted to conditions that may occur with high probability during the lifetime of an organism. However, in addition to this automatic reaction, animals can learn and remember tastes, together with their positive or negative values, with high precision and in light of minimal experience. This ability of mammalians to learn and remember tastes has been studied extensively in rodents through application of reasonably simple and well defined behavioral paradigms. The learning process follows a temporal continuum similar to those of other memories: acquisition, consolidation, retrieval, relearning, and reconsolidation. Moreover, inhibiting protein synthesis in the gustatory cortex (GC) specifically affects the consolidation phase of taste memory, i.e., the transformation of short- to long-term memory, in keeping with the general biochemical definition of memory consolidation. This review aims to present a general background of taste learning, and to focus on recent findings regarding the molecular mechanisms underlying taste-memory consolidation in the GC. Specifically, the roles of neurotransmitters, neuromodulators, immediate early genes, and translation regulation are addressed.

Molecular mechanisms underlying memory consolidation of taste information in the cortex

Directory of Open Access Journals (Sweden)

Shunit eGal-Ben-Ari

2012-01-01

Full Text Available The senses of taste and odor are both chemical senses. However, whereas an organism can detect an odor at a relatively long distance from its source, taste serves as the ultimate proximate gatekeeper of food intake: it helps in avoiding poisons and consuming beneficial substances. The automatic reaction to a given taste has been developed during evolution and is well adapted to conditions that may occur with high probability during the lifetime of an organism. However, in addition to this automatic reaction, animals can learn and remember tastes, together with their positive or negative values, with high precision and in light of minimal experience. This ability of mammalians to learn and remember tastes has been studied extensively in rodents through application of reasonably simple and well defined behavioral paradigms. The learning process follows a temporal continuum similar to those of other memories: acquisition, consolidation, retrieval, relearning, and reconsolidation. Moreover, inhibiting protein synthesis in the gustatory cortex specifically affects the consolidation phase of taste memory, i.e., the transformation of short- to long-term memory, in keeping with the general biochemical definition of memory consolidation. This review aims to present a general background of taste learning, and to focus on recent findings regarding the molecular mechanisms underlying taste memory consolidation in the gustatory cortex. Specifically, the role of neurotransmitters, meuromodulators, immediate early genes, and translation regulation are addressed.

Latent memory facilitates relearning through molecular signaling mechanisms that are distinct from original learning.

Science.gov (United States)

Menges, Steven A; Riepe, Joshua R; Philips, Gary T

2015-09-01

A highly conserved feature of memory is that it can exist in a latent, non-expressed state which is revealed during subsequent learning by its ability to significantly facilitate (savings) or inhibit (latent inhibition) subsequent memory formation. Despite the ubiquitous nature of latent memory, the mechanistic nature of the latent memory trace and its ability to influence subsequent learning remains unclear. The model organism Aplysia californica provides the unique opportunity to make strong links between behavior and underlying cellular and molecular mechanisms. Using Aplysia, we have studied the mechanisms of savings due to latent memory for a prior, forgotten experience. We previously reported savings in the induction of three distinct temporal domains of memory: short-term (10min), intermediate-term (2h) and long-term (24h). Here we report that savings memory formation utilizes molecular signaling pathways that are distinct from original learning: whereas the induction of both original intermediate- and long-term memory in naïve animals requires mitogen activated protein kinase (MAPK) activation and ongoing protein synthesis, 2h savings memory is not disrupted by inhibitors of MAPK or protein synthesis, and 24h savings memory is not dependent on MAPK activation. Collectively, these findings reveal that during forgetting, latent memory for the original experience can facilitate relearning through molecular signaling mechanisms that are distinct from original learning. Copyright © 2015 Elsevier Inc. All rights reserved.

Molecular mechanism for inhibition of twinfilin by phosphoinositides

DEFF Research Database (Denmark)

Hakala, Markku; Kalimeri, Maria; Enkavi, Giray

2018-01-01

actin-depolymerizing factor (ADF)/cofilin-like ADF homology domains of twinfilin bind phosphoinositides only with low affinity. Mutagenesis and biochemical experiments combined with atomistic molecular dynamics simulations reveal that the C-terminal tail of twinfilin interacts with membranes through......Membrane phosphoinositides control organization and dynamics of the actin cytoskeleton by regulating the activities of several key actin-binding proteins. Twinfilin is an evolutionarily conserved protein that contributes to cytoskeletal dynamics by interacting with actin monomers, filaments......, and the heterodimeric capping protein. Twinfilin also binds phosphoinositides, which inhibit its interactions with actin, but the underlying mechanism has remained unknown. Here, we show that the high-affinity binding site of twinfilin for phosphoinositides is located at the C-terminal tail region, whereas the two...

Molecular characterization of larval development from fertilization to metamorphosis in a reef-building coral.

Science.gov (United States)

Strader, Marie E; Aglyamova, Galina V; Matz, Mikhail V

2018-01-04

Molecular mechanisms underlying coral larval competence, the ability of larvae to respond to settlement cues, determine their dispersal potential and are potential targets of natural selection. Here, we profiled competence, fluorescence and genome-wide gene expression in embryos and larvae of the reef-building coral Acropora millepora daily throughout 12 days post-fertilization. Gene expression associated with competence was positively correlated with transcriptomic response to the natural settlement cue, confirming that mature coral larvae are "primed" for settlement. Rise of competence through development was accompanied by up-regulation of sensory and signal transduction genes such as ion channels, genes involved in neuropeptide signaling, and G-protein coupled receptor (GPCRs). A drug screen targeting components of GPCR signaling pathways confirmed a role in larval settlement behavior and metamorphosis. These results gives insight into the molecular complexity underlying these transitions and reveals receptors and pathways that, if altered by changing environments, could affect dispersal capabilities of reef-building corals. In addition, this dataset provides a toolkit for asking broad questions about sensory capacity in multicellular animals and the evolution of development.

Raman spectroscopy of triolein under high pressures

Science.gov (United States)

Tefelski, D. B.; Jastrzębski, C.; Wierzbicki, M.; Siegoczyński, R. M.; Rostocki, A. J.; Wieja, K.; Kościesza, R.

2010-03-01

This article presents results of the high pressure Raman spectroscopy of triolein. Triolein, a triacylglyceride (TAG) of oleic acid, is an unsaturated fat, present in natural oils such as olive oil. As a basic food component and an energy storage molecule, it has considerable importance for food and fuel industries. To generate pressure in the experiment, we used a high-pressure cylindrical chamber with sapphire windows, presented in (R.M. Siegoczyński, R. Kościesza, D.B. Tefelski, and A. Kos, Molecular collapse - modification of the liquid structure induced by pressure in oleic acid, High Press. Res. 29 (2009), pp. 61-66). Pressure up to 750 MPa was applied. A Raman spectrometer in "macro"-configuration was employed. Raman spectroscopy provides information on changes of vibrational modes related to structural changes of triolein under pressure. Interesting changes in the triglyceride C‒H stretching region at 2650-3100 cm-1 were observed under high-pressures. Changes were also observed in the ester carbonyl (C˭ O) stretching region 1700-1780 cm-1 and the C‒C stretching region at 1050-1150 cm-1. The overall luminescence of the sample decreased under pressure, making it possible to set longer spectrum acquisition time and obtain more details of the spectrum. The registered changes suggest that the high-pressure solid phase of triolein is organized as β-polymorphic, as was reported in (C. Akita, T. Kawaguchi, and F. Kaneko, Structural study on polymorphism of cis-unsaturated triacylglycerol: Triolein, J. Phys. Chem. B 110 (2006), pp. 4346-4353; E. Da Silva and D. Rousseau, Molecular order and thermodynamics of the solid-liquid transition in triglycerides via Raman spectroscopy, Phys. Chem. Chem. Phys. 10 (2008), pp. 4606-4613) (with temperature-induced phase transitions). The research has shown that Raman spectroscopy in TAGs under pressure reveals useful information about its structural changes.

Molecular similarity measures.

Science.gov (United States)

Maggiora, Gerald M; Shanmugasundaram, Veerabahu

2011-01-01

Molecular similarity is a pervasive concept in chemistry. It is essential to many aspects of chemical reasoning and analysis and is perhaps the fundamental assumption underlying medicinal chemistry. Dissimilarity, the complement of similarity, also plays a major role in a growing number of applications of molecular diversity in combinatorial chemistry, high-throughput screening, and related fields. How molecular information is represented, called the representation problem, is important to the type of molecular similarity analysis (MSA) that can be carried out in any given situation. In this work, four types of mathematical structure are used to represent molecular information: sets, graphs, vectors, and functions. Molecular similarity is a pairwise relationship that induces structure into sets of molecules, giving rise to the concept of chemical space. Although all three concepts - molecular similarity, molecular representation, and chemical space - are treated in this chapter, the emphasis is on molecular similarity measures. Similarity measures, also called similarity coefficients or indices, are functions that map pairs of compatible molecular representations that are of the same mathematical form into real numbers usually, but not always, lying on the unit interval. This chapter presents a somewhat pedagogical discussion of many types of molecular similarity measures, their strengths and limitations, and their relationship to one another. An expanded account of the material on chemical spaces presented in the first edition of this book is also provided. It includes a discussion of the topography of activity landscapes and the role that activity cliffs in these landscapes play in structure-activity studies.

Peltier cooling in molecular junctions

Science.gov (United States)

Cui, Longji; Miao, Ruijiao; Wang, Kun; Thompson, Dakotah; Zotti, Linda Angela; Cuevas, Juan Carlos; Meyhofer, Edgar; Reddy, Pramod

2018-02-01

The study of thermoelectricity in molecular junctions is of fundamental interest for the development of various technologies including cooling (refrigeration) and heat-to-electricity conversion1-4. Recent experimental progress in probing the thermopower (Seebeck effect) of molecular junctions5-9 has enabled studies of the relationship between thermoelectricity and molecular structure10,11. However, observations of Peltier cooling in molecular junctions—a critical step for establishing molecular-based refrigeration—have remained inaccessible. Here, we report direct experimental observations of Peltier cooling in molecular junctions. By integrating conducting-probe atomic force microscopy12,13 with custom-fabricated picowatt-resolution calorimetric microdevices, we created an experimental platform that enables the unified characterization of electrical, thermoelectric and energy dissipation characteristics of molecular junctions. Using this platform, we studied gold junctions with prototypical molecules (Au-biphenyl-4,4'-dithiol-Au, Au-terphenyl-4,4''-dithiol-Au and Au-4,4'-bipyridine-Au) and revealed the relationship between heating or cooling and charge transmission characteristics. Our experimental conclusions are supported by self-energy-corrected density functional theory calculations. We expect these advances to stimulate studies of both thermal and thermoelectric transport in molecular junctions where the possibility of extraordinarily efficient energy conversion has been theoretically predicted2-4,14.

Structure of a molecular liquid GeI4

International Nuclear Information System (INIS)

Fuchizaki, Kazuhiro; Sakagami, Takahiro; Kohara, Shinji; Mizuno, Akitoshi; Asano, Yuta; Hamaya, Nozomu

2016-01-01

A molecular liquid GeI 4 is a candidate that undergoes a pressure-induced liquid-to-liquid phase transition. This study establishes the reference structure of the low-pressure liquid phase. Synchrotron x-ray diffraction measurements were carried out at several temperatures between the melting and the boiling points under ambient pressure. The molecule has regular tetrahedral symmetry, and the intramolecular Ge–I length of 2.51 Å is almost temperature-independent within the measured range. A reverse Monte Carlo (RMC) analysis is employed to find that the distribution of molecular centers remains self-similar against heating, and thus justifying the length-scaling method adopted in determining the density. The RMC analysis also reveals that the vertex-to-face orientation of the nearest molecules are not straightly aligned, but are inclined at about 20 degrees, thereby making the closest intermolecular I–I distance definitely shorter than the intramolecular one. The prepeak observed at  ∼1 Å −1 in the structural factor slightly shifts and increases in height with increasing temperature. The origin of the prepeak is clearly identified to be traces of the 111 diffraction peak in the crystalline state. The prepeak, assuming the residual spatial correlation between germanium sites in the densest direction, thus shifts toward lower wavenumbers with thermal expansion. The aspect that a relative reduction in molecular size associated with the volume expansion is responsible for the increase in the prepeak’s height is confirmed by a simulation, in which the molecular size is changed. (paper)

Exome sequencing in Jewish and Arab patients with rhabdomyolysis reveals single-gene etiology in 43% of cases.

Science.gov (United States)

Vivante, Asaf; Ityel, Hadas; Pode-Shakked, Ben; Chen, Jing; Shril, Shirlee; van der Ven, Amelie T; Mann, Nina; Schmidt, Johanna Magdalena; Segel, Reeval; Aran, Adi; Zeharia, Avraham; Staretz-Chacham, Orna; Bar-Yosef, Omer; Raas-Rothschild, Annick; Landau, Yuval E; Lifton, Richard P; Anikster, Yair; Hildebrandt, Friedhelm

2017-12-01

Rhabdomyolysis is a clinical emergency that may cause acute kidney injury (AKI). It can be acquired or due to monogenic mutations. Around 60 different rare monogenic forms of rhabdomyolysis have been reported to date. In the clinical setting, identifying the underlying molecular diagnosis is challenging due to nonspecific presentation, the high number of causative genes, and current lack of data on the prevalence of monogenic forms. We employed whole exome sequencing (WES) to reveal the percentage of rhabdomyolysis cases explained by single-gene (monogenic) mutations in one of 58 candidate genes. We investigated a cohort of 21 unrelated families with rhabdomyolysis, in whom no underlying etiology had been previously established. Using WES, we identified causative mutations in candidate genes in nine of the 21 families (43%). We detected disease-causing mutations in eight of 58 candidate genes, grouped into the following categories: (1) disorders of fatty acid metabolism (CPT2), (2) disorders of glycogen metabolism (PFKM and PGAM2), (3) disorders of abnormal skeletal muscle relaxation and contraction (CACNA1S, MYH3, RYR1 and SCN4A), and (4) disorders of purine metabolism (AHCY). Our findings demonstrate a very high detection rate for monogenic etiologies using WES and reveal broad genetic heterogeneity for rhabdomyolysis. These results highlight the importance of molecular genetic diagnostics for establishing an etiologic diagnosis. Because these patients are at risk for recurrent episodes of rhabdomyolysis and subsequent risk for AKI, WES allows adequate prophylaxis and treatment for these patients and their family members and enables a personalized medicine approach.

Molecular clouds and galactic spiral structure

International Nuclear Information System (INIS)

Dame, T.M.

1984-02-01

Galactic CO line emission at 115 GHz was surveyed in order to study the distribution of molecular clouds in the inner galaxy. Comparison of this survey with similar H1 data reveals a detailed correlation with the most intense 21 cm features. To each of the classical 21 cm H1 spiral arms of the inner galaxy there corresponds a CO molecular arm which is generally more clearly defined and of higher contrast. A simple model is devised for the galactic distribution of molecular clouds. The modeling results suggest that molecular clouds are essentially transient objects, existing for 15 to 40 million years after their formation in a spiral arm, and are largely confined to spiral features about 300 pc wide

Revealing the Molecular Portrait of Triple Negative Breast Tumors in an Understudied Population through Omics Analysis of Formalin-Fixed and Paraffin-Embedded Tissues.

Science.gov (United States)

Vaca-Paniagua, Felipe; Alvarez-Gomez, Rosa María; Maldonado-Martínez, Hector Aquiles; Pérez-Plasencia, Carlos; Fragoso-Ontiveros, Veronica; Lasa-Gonsebatt, Federico; Herrera, Luis Alonso; Cantú, David; Bargallo-Rocha, Enrique; Mohar, Alejandro; Durand, Geoffroy; Forey, Nathalie; Voegele, Catherine; Vallée, Maxime; Le Calvez-Kelm, Florence; McKay, James; Ardin, Maude; Villar, Stéphanie; Zavadil, Jiri; Olivier, Magali

2015-01-01

Triple negative breast cancer (TNBC), defined by the lack of expression of the estrogen receptor, progesterone receptor and human epidermal receptor 2, is an aggressive form of breast cancer that is more prevalent in certain populations, in particular in low- and middle-income regions. The detailed molecular features of TNBC in these regions remain unexplored as samples are mostly accessible as formalin-fixed paraffin embedded (FFPE) archived tissues, a challenging material for advanced genomic and transcriptomic studies. Using dedicated reagents and analysis pipelines, we performed whole exome sequencing and miRNA and mRNA profiling of 12 FFPE tumor tissues collected from pathological archives in Mexico. Sequencing analyses of the tumor tissues and their blood pairs identified TP53 and RB1 genes as the most frequently mutated genes, with a somatic mutation load of 1.7 mutations/exome Mb on average. Transcriptional analyses revealed an overexpression of growth-promoting signals (EGFR, PDGFR, VEGF, PIK3CA, FOXM1), a repression of cell cycle control pathways (TP53, RB1), a deregulation of DNA-repair pathways, and alterations in epigenetic modifiers through miRNA:mRNA network de-regulation. The molecular programs identified were typical of those described in basal-like tumors in other populations. This work demonstrates the feasibility of using archived clinical samples for advanced integrated genomics analyses. It thus opens up opportunities for investigating molecular features of tumors from regions where only FFPE tissues are available, allowing retrospective studies on the search for treatment strategies or on the exploration of the geographic diversity of breast cancer.

Molecular-dynamics Simulation-based Cohesive Zone Representation of Intergranular Fracture Processes in Aluminum

Science.gov (United States)

Yamakov, Vesselin I.; Saether, Erik; Phillips, Dawn R.; Glaessgen, Edward H.

2006-01-01

A traction-displacement relationship that may be embedded into a cohesive zone model for microscale problems of intergranular fracture is extracted from atomistic molecular-dynamics simulations. A molecular-dynamics model for crack propagation under steady-state conditions is developed to analyze intergranular fracture along a flat 99 [1 1 0] symmetric tilt grain boundary in aluminum. Under hydrostatic tensile load, the simulation reveals asymmetric crack propagation in the two opposite directions along the grain boundary. In one direction, the crack propagates in a brittle manner by cleavage with very little or no dislocation emission, and in the other direction, the propagation is ductile through the mechanism of deformation twinning. This behavior is consistent with the Rice criterion for cleavage vs. dislocation blunting transition at the crack tip. The preference for twinning to dislocation slip is in agreement with the predictions of the Tadmor and Hai criterion. A comparison with finite element calculations shows that while the stress field around the brittle crack tip follows the expected elastic solution for the given boundary conditions of the model, the stress field around the twinning crack tip has a strong plastic contribution. Through the definition of a Cohesive-Zone-Volume-Element an atomistic analog to a continuum cohesive zone model element - the results from the molecular-dynamics simulation are recast to obtain an average continuum traction-displacement relationship to represent cohesive zone interaction along a characteristic length of the grain boundary interface for the cases of ductile and brittle decohesion. Keywords: Crack-tip plasticity; Cohesive zone model; Grain boundary decohesion; Intergranular fracture; Molecular-dynamics simulation

Integrative Transcriptomic and Metabonomic Molecular Profiling of Colonic Mucosal Biopsies Indicates a Unique Molecular Phenotype for Ulcerative Colitis

DEFF Research Database (Denmark)

Rantalainen, Mattias; Bjerrum, Jacob Tveiten; Olsen, Jørgen

2015-01-01

characterized the molecular phenotype of ulcerative colitis through transcriptomic and metabonomic profiling of colonic mucosal biopsies from patients and controls. We have characterized the extent to which metabonomic and transcriptomic molecular phenotypes are associated with ulcerative colitis versus...... transcriptomic and metabonomic data have previously been shown to predict the clinical course of ulcerative colitis and related clinical phenotypes, indicating that molecular phenotypes reveal molecular changes associated with the disease. Our analyses indicate that variables of both transcriptomics...... and metabonomics are associated with disease case and control status, that a large proportion of transcripts are associated with at least one metabolite in mucosal colonic biopsies, and that multiple pathways are connected to disease-related metabolites and transcripts....

Striking Plasticity of CRISPR-Cas9 and Key Role of Non-target DNA, as Revealed by Molecular Simulations.

Science.gov (United States)

Palermo, Giulia; Miao, Yinglong; Walker, Ross C; Jinek, Martin; McCammon, J Andrew

2016-10-26

The CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 system recently emerged as a transformative genome-editing technology that is innovating basic bioscience and applied medicine and biotechnology. The endonuclease Cas9 associates with a guide RNA to match and cleave complementary sequences in double stranded DNA, forming an RNA:DNA hybrid and a displaced non-target DNA strand. Although extensive structural studies are ongoing, the conformational dynamics of Cas9 and its interplay with the nucleic acids during association and DNA cleavage are largely unclear. Here, by employing multi-microsecond time scale molecular dynamics, we reveal the conformational plasticity of Cas9 and identify key determinants that allow its large-scale conformational changes during nucleic acid binding and processing. We show how the "closure" of the protein, which accompanies nucleic acid binding, fundamentally relies on highly coupled and specific motions of the protein domains, collectively initiating the prominent conformational changes needed for nucleic acid association. We further reveal a key role of the non-target DNA during the process of activation of the nuclease HNH domain, showing how the nontarget DNA positioning triggers local conformational changes that favor the formation of a catalytically competent Cas9. Finally, a remarkable conformational plasticity is identified as an intrinsic property of the HNH domain, constituting a necessary element that allows for the HNH repositioning. These novel findings constitute a reference for future experimental studies aimed at a full characterization of the dynamic features of the CRISPR-Cas9 system, and-more importantly-call for novel structure engineering efforts that are of fundamental importance for the rational design of new genome-engineering applications.

Functional and structural insights revealed by molecular dynamics simulations of an essential RNA editing ligase in Trypanosoma brucei.

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Rommie E Amaro

2007-11-01

Full Text Available RNA editing ligase 1 (TbREL1 is required for the survival of both the insect and bloodstream forms of Trypanosoma brucei, the parasite responsible for the devastating tropical disease African sleeping sickness. The type of RNA editing that TbREL1 is involved in is unique to the trypanosomes, and no close human homolog is known to exist. In addition, the high-resolution crystal structure revealed several unique features of the active site, making this enzyme a promising target for structure-based drug design. In this work, two 20 ns atomistic molecular dynamics (MD simulations are employed to investigate the dynamics of TbREL1, both with and without the ATP substrate present. The flexibility of the active site, dynamics of conserved residues and crystallized water molecules, and the interactions between TbREL1 and the ATP substrate are investigated and discussed in the context of TbREL1's function. Differences in local and global motion upon ATP binding suggest that two peripheral loops, unique to the trypanosomes, may be involved in interdomain signaling events. Notably, a significant structural rearrangement of the enzyme's active site occurs during the apo simulations, opening an additional cavity adjacent to the ATP binding site that could be exploited in the development of effective inhibitors directed against this protozoan parasite. Finally, ensemble averaged electrostatics calculations over the MD simulations reveal a novel putative RNA binding site, a discovery that has previously eluded scientists. Ultimately, we use the insights gained through the MD simulations to make several predictions and recommendations, which we anticipate will help direct future experimental studies and structure-based drug discovery efforts against this vital enzyme.

Microarray Analysis Reveals the Molecular Basis of Antiarthritic Activity of Huo-Luo-Xiao-Ling Dan

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Hua Yu

2013-01-01

Full Text Available Rheumatoid arthritis (RA is a chronic inflammatory disease of autoimmune origin. Huo-luo-xiao-ling dan (HLXL is an herbal mixture that has been used in traditional Chinese medicine over several decades to treat chronic inflammatory diseases including RA. However, the mechanism of the anti-arthritic action of this herbal remedy is poorly understood at the molecular level. In this study, we determined by microarray analysis the effects of HLXL on the global gene expression profile of the draining lymph node cells (LNC in the rat adjuvant arthritis (AA model of human RA. In LNC restimulated in vitro with the disease-related antigen mycobacterial heat-shock protein 65 (Bhsp65, 84 differentially expressed genes (DEG (64 upregulated and 20 downregulated versus 120 DEG (94 upregulated and 26 downregulated were identified in HLXL-treated versus vehicle (Water-treated rats, respectively, and 62 DEG (45 upregulated and 17 downregulated were shared between the two groups. The most affected pathways in response to HLXL treatment included immune response, inflammation, cellular proliferation and apoptosis, and metabolic processes, many of which are directly relevant to arthritis pathogenesis. These results would advance our understanding of the mechanisms underlying the anti-arthritic activity of HLXL.

Molecular dynamics simulations of polyelectrolyte brushes under poor solvent conditions: origins of bundle formation.

Science.gov (United States)

He, Gui-Li; Merlitz, Holger; Sommer, Jens-Uwe

2014-03-14

Molecular dynamics simulations are applied to investigate salt-free planar polyelectrolyte brushes under poor solvent conditions. Starting above the Θ-point with a homogeneous brush and then gradually reducing the temperature, the polymers initially display a lateral structure formation, forming vertical bundles of chains. A further reduction of the temperature (or solvent quality) leads to a vertical collapse of the brush. By varying the size and selectivity of the counterions, we show that lateral structure formation persists and therefore demonstrate that the entropy of counterions being the dominant factor for the formation of the bundle phase. By applying an external compression force on the brush we calculate the minimal work done on the polymer phase only and prove that the entropy gain of counterions in the bundle state, as compared to the homogeneously collapsed state at the same temperature, is responsible for the lateral microphase segregation. As a consequence, the observed lateral structure formation has to be regarded universal for osmotic polymer brushes below the Θ-point.

Electrostatic point charge fitting as an inverse problem: Revealing the underlying ill-conditioning

International Nuclear Information System (INIS)

Ivanov, Maxim V.; Talipov, Marat R.; Timerghazin, Qadir K.

2015-01-01

Atom-centered point charge (PC) model of the molecular electrostatics—a major workhorse of the atomistic biomolecular simulations—is usually parameterized by least-squares (LS) fitting of the point charge values to a reference electrostatic potential, a procedure that suffers from numerical instabilities due to the ill-conditioned nature of the LS problem. To reveal the origins of this ill-conditioning, we start with a general treatment of the point charge fitting problem as an inverse problem and construct an analytical model with the point charges spherically arranged according to Lebedev quadrature which is naturally suited for the inverse electrostatic problem. This analytical model is contrasted to the atom-centered point-charge model that can be viewed as an irregular quadrature poorly suited for the problem. This analysis shows that the numerical problems of the point charge fitting are due to the decay of the curvatures corresponding to the eigenvectors of LS sum Hessian matrix. In part, this ill-conditioning is intrinsic to the problem and is related to decreasing electrostatic contribution of the higher multipole moments, that are, in the case of Lebedev grid model, directly associated with the Hessian eigenvectors. For the atom-centered model, this association breaks down beyond the first few eigenvectors related to the high-curvature monopole and dipole terms; this leads to even wider spread-out of the Hessian curvature values. Using these insights, it is possible to alleviate the ill-conditioning of the LS point-charge fitting without introducing external restraints and/or constraints. Also, as the analytical Lebedev grid PC model proposed here can reproduce multipole moments up to a given rank, it may provide a promising alternative to including explicit multipole terms in a force field

Measurement of incident molecular temperature in the formation of organic thin films

Science.gov (United States)

Abe, Takahiro; Matsubara, Ryosuke; Hayakawa, Munetaka; Shimoyama, Akifumi; Tanaka, Takaaki; Tsuji, Akira; Takahashi, Yoshikazu; Kubono, Atsushi

2018-03-01

To investigate the effects of incident molecular temperature on organic-thin-film growth by vacuum evaporation, quantitative analysis of molecular temperature is required. In this study, we propose a method of determining molecular temperature based on the heat exchange between a platinum filament and molecular vapor. Molecular temperature is estimated from filament temperature, which remains unchanged even under molecular vapor supply. The results indicate that our method has sufficient sensitivity to evaluate the molecular temperature under the typical growth rate used for fabrication of functional organic thin films.

A model of lipid-free apolipoprotein A-I revealed by iterative molecular dynamics simulation.

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Xing Zhang

Full Text Available Apolipoprotein A-I (apo A-I, the major protein component of high-density lipoprotein, has been proven inversely correlated to cardiovascular risk in past decades. The lipid-free state of apo A-I is the initial stage which binds to lipids forming high-density lipoprotein. Molecular models of lipid-free apo A-I have been reported by methods like X-ray crystallography and chemical cross-linking/mass spectrometry (CCL/MS. Through structural analysis we found that those current models had limited consistency with other experimental results, such as those from hydrogen exchange with mass spectrometry. Through molecular dynamics simulations, we also found those models could not reach a stable equilibrium state. Therefore, by integrating various experimental results, we proposed a new structural model for lipid-free apo A-I, which contains a bundled four-helix N-terminal domain (1-192 that forms a variable hydrophobic groove and a mobile short hairpin C-terminal domain (193-243. This model exhibits an equilibrium state through molecular dynamics simulation and is consistent with most of the experimental results known from CCL/MS on lysine pairs, fluorescence resonance energy transfer and hydrogen exchange. This solution-state lipid-free apo A-I model may elucidate the possible conformational transitions of apo A-I binding with lipids in high-density lipoprotein formation.

Source-sink interaction: a century old concept under the light of modern molecular systems biology.

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Chang, Tian-Gen; Zhu, Xin-Guang; Raines, Christine

2017-07-20

Many approaches to engineer source strength have been proposed to enhance crop yield potential. However, a well-co-ordinated source-sink relationship is required finally to realize the promised increase in crop yield potential in the farmer's field. Source-sink interaction has been intensively studied for decades, and a vast amount of knowledge about the interaction in different crops and under different environments has been accumulated. In this review, we first introduce the basic concepts of source, sink and their interactions, then summarize current understanding of how source and sink can be manipulated through both environmental control and genetic manipulations. We show that the source-sink interaction underlies the diverse responses of crops to the same perturbations and argue that development of a molecular systems model of source-sink interaction is required towards a rational manipulation of the source-sink relationship for increased yield. We finally discuss both bottom-up and top-down routes to develop such a model and emphasize that a community effort is needed for development of this model. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Molecular dynamics simulations of ejecta production from sinusoidal tin surfaces under supported and unsupported shocks

Science.gov (United States)

Wu, Bao; Wu, FengChao; Zhu, YinBo; Wang, Pei; He, AnMin; Wu, HengAn

2018-04-01

Micro-ejecta, an instability growth process, occurs at metal/vacuum or metal/gas interface when compressed shock wave releases from the free surface that contains surface defects. We present molecular dynamics (MD) simulations to investigate the ejecta production from tin surface shocked by supported and unsupported waves with pressures ranging from 8.5 to 60.8 GPa. It is found that the loading waveforms have little effect on spike velocity while remarkably affect the bubble velocity. The bubble velocity of unsupported shock loading remains nonzero constant value at late time as observed in experiments. Besides, the time evolution of ejected mass in the simulations is compared with the recently developed ejecta source model, indicating the suppressed ejection of unmelted or partial melted materials. Moreover, different reference positions are chosen to characterize the amount of ejecta under different loading waveforms. Compared with supported shock case, the ejected mass of unsupported shock case saturates at lower pressure. Through the analysis on unloading path, we find that the temperature of tin sample increases quickly from tensile stress state to zero pressure state, resulting in the melting of bulk tin under decaying shock. Thus, the unsupported wave loading exhibits a lower threshold pressure causing the solid-liquid phase transition on shock release than the supported shock loading.

DNA under Force: Mechanics, Electrostatics, and Hydration

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Jingqiang Li

2015-02-01

Full Text Available Quantifying the basic intra- and inter-molecular forces of DNA has helped us to better understand and further predict the behavior of DNA. Single molecule technique elucidates the mechanics of DNA under applied external forces, sometimes under extreme forces. On the other hand, ensemble studies of DNA molecular force allow us to extend our understanding of DNA molecules under other forces such as electrostatic and hydration forces. Using a variety of techniques, we can have a comprehensive understanding of DNA molecular forces, which is crucial in unraveling the complex DNA functions in living cells as well as in designing a system that utilizes the unique properties of DNA in nanotechnology.

MinePath: Mining for Phenotype Differential Sub-paths in Molecular Pathways

Science.gov (United States)

Koumakis, Lefteris; Kartsaki, Evgenia; Chatzimina, Maria; Zervakis, Michalis; Vassou, Despoina; Marias, Kostas; Moustakis, Vassilis; Potamias, George

2016-01-01

Pathway analysis methodologies couple traditional gene expression analysis with knowledge encoded in established molecular pathway networks, offering a promising approach towards the biological interpretation of phenotype differentiating genes. Early pathway analysis methodologies, named as gene set analysis (GSA), view pathways just as plain lists of genes without taking into account either the underlying pathway network topology or the involved gene regulatory relations. These approaches, even if they achieve computational efficiency and simplicity, consider pathways that involve the same genes as equivalent in terms of their gene enrichment characteristics. Most recent pathway analysis approaches take into account the underlying gene regulatory relations by examining their consistency with gene expression profiles and computing a score for each profile. Even with this approach, assessing and scoring single-relations limits the ability to reveal key gene regulation mechanisms hidden in longer pathway sub-paths. We introduce MinePath, a pathway analysis methodology that addresses and overcomes the aforementioned problems. MinePath facilitates the decomposition of pathways into their constituent sub-paths. Decomposition leads to the transformation of single-relations to complex regulation sub-paths. Regulation sub-paths are then matched with gene expression sample profiles in order to evaluate their functional status and to assess phenotype differential power. Assessment of differential power supports the identification of the most discriminant profiles. In addition, MinePath assess the significance of the pathways as a whole, ranking them by their p-values. Comparison results with state-of-the-art pathway analysis systems are indicative for the soundness and reliability of the MinePath approach. In contrast with many pathway analysis tools, MinePath is a web-based system (www.minepath.org) offering dynamic and rich pathway visualization functionality, with the

Molecular medicine: a path towards a personalized medicine.

Science.gov (United States)

Miranda, Debora Marques de; Mamede, Marcelo; Souza, Bruno Rezende de; Almeida Barros, Alexandre Guimarães de; Magno, Luiz Alexandre; Alvim-Soares, Antônio; Rosa, Daniela Valadão; Castro, Célio José de; Malloy-Diniz, Leandro; Gomez, Marcus Vinícius; Marco, Luiz Armando De; Correa, Humberto; Romano-Silva, Marco Aurélio

2012-03-01

Psychiatric disorders are among the most common human illnesses; still, the molecular and cellular mechanisms underlying their complex pathophysiology remain to be fully elucidated. Over the past 10 years, our group has been investigating the molecular abnormalities in major signaling pathways involved in psychiatric disorders. Recent evidences obtained by the Instituto Nacional de Ciência e Tecnologia de Medicina Molecular (National Institute of Science and Technology - Molecular Medicine, INCT-MM) and others using behavioral analysis of animal models provided valuable insights into the underlying molecular alterations responsible for many complex neuropsychiatric disorders, suggesting that "defects" in critical intracellular signaling pathways have an important role in regulating neurodevelopment, as well as in pathophysiology and treatment efficacy. Resources from the INCT have allowed us to start doing research in the field of molecular imaging. Molecular imaging is a research discipline that visualizes, characterizes, and quantifies the biologic processes taking place at cellular and molecular levels in humans and other living systems through the results of image within the reality of the physiological environment. In order to recognize targets, molecular imaging applies specific instruments (e.g., PET) that enable visualization and quantification in space and in real-time of signals from molecular imaging agents. The objective of molecular medicine is to individualize treatment and improve patient care. Thus, molecular imaging is an additional tool to achieve our ultimate goal.

Revealing molecular mechanisms by integrating high-dimensional functional screens with protein interaction data.

Directory of Open Access Journals (Sweden)

Angela Simeone

2014-09-01

Full Text Available Functional genomics screens using multi-parametric assays are powerful approaches for identifying genes involved in particular cellular processes. However, they suffer from problems like noise, and often provide little insight into molecular mechanisms. A bottleneck for addressing these issues is the lack of computational methods for the systematic integration of multi-parametric phenotypic datasets with molecular interactions. Here, we present Integrative Multi Profile Analysis of Cellular Traits (IMPACT. The main goal of IMPACT is to identify the most consistent phenotypic profile among interacting genes. This approach utilizes two types of external information: sets of related genes (IMPACT-sets and network information (IMPACT-modules. Based on the notion that interacting genes are more likely to be involved in similar functions than non-interacting genes, this data is used as a prior to inform the filtering of phenotypic profiles that are similar among interacting genes. IMPACT-sets selects the most frequent profile among a set of related genes. IMPACT-modules identifies sub-networks containing genes with similar phenotype profiles. The statistical significance of these selections is subsequently quantified via permutations of the data. IMPACT (1 handles multiple profiles per gene, (2 rescues genes with weak phenotypes and (3 accounts for multiple biases e.g. caused by the network topology. Application to a genome-wide RNAi screen on endocytosis showed that IMPACT improved the recovery of known endocytosis-related genes, decreased off-target effects, and detected consistent phenotypes. Those findings were confirmed by rescreening 468 genes. Additionally we validated an unexpected influence of the IGF-receptor on EGF-endocytosis. IMPACT facilitates the selection of high-quality phenotypic profiles using different types of independent information, thereby supporting the molecular interpretation of functional screens.

Thermal force approach to molecular evolution.

Science.gov (United States)

Braun, Dieter; Libchaber, Albert

2004-06-01

Recent experiments are discussed where temperature gradients across mesoscopic pores are shown to provide essential mechanisms for autonomous molecular evolution. On the one hand, laminar thermal convection can drive DNA replication as the molecules are continuously cycled between hot and cold regions of a chamber. On the other hand, thermophoresis can accumulate charged biopolymers in similar convection settings. The experiments show that temperature differences analogous to those across porous rocks present a robust nonequilibrium boundary condition to feed the replication and accumulation of evolving molecules. It is speculated that similar nonequilibrium conditions near porous submarine hydrothermal mounds could have triggered the origin of life. In such a scenario, the encapsulation of cells with membranes would be a later development. It is expected that detailed studies of mesoscopic boundary conditions under nonequilibrium conditions will reveal new connecting pieces in the fascinating puzzle of the origins of life.

Gorilla gorilla gorilla gut: a potential reservoir of pathogenic bacteria as revealed using culturomics and molecular tools.

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Bittar, Fadi; Keita, Mamadou B; Lagier, Jean-Christophe; Peeters, Martine; Delaporte, Eric; Raoult, Didier

2014-11-24

Wild apes are considered to be the most serious reservoir and source of zoonoses. However, little data are available about the gut microbiota and pathogenic bacteria in gorillas. For this propose, a total of 48 fecal samples obtained from 21 Gorilla gorilla gorilla individuals (as revealed via microsatellite analysis) were screened for human bacterial pathogens using culturomics and molecular techniques. By applying culturomics to one index gorilla and using specific media supplemented by plants, we tested 12,800 colonies and identified 147 different bacterial species, including 5 new species. Many opportunistic pathogens were isolated, including 8 frequently associated with human diseases; Mycobacterium bolletii, Proteus mirabilis, Acinetobacter baumannii, Klebsiella pneumoniae, Serratia marcescens, Escherichia coli, Staphylococcus aureus and Clostridium botulinum. The genus Treponema accounted for 27.4% of the total reads identified at the genus level via 454 pyrosequencing. Using specific real-time PCR on 48 gorilla fecal samples, in addition to classical human pathogens, we also observed the fastidious bacteria Bartonella spp. Borrelia spp., Coxiella burnetii and Tropheryma whipplei in the gorilla population. We estimated that the prevalence of these pathogens vary between 4.76% and 85.7%. Therefore, gorillas share many bacterial pathogens with humans suggesting that they could be a reservoir for their emergence.

Molecular Outflow and Feedback in an Obscured Quasar at z˜1.5 Revealed by ALMA

Science.gov (United States)

Brusa, Marcella

2017-11-01

We imaged with ALMA and ARGOS/LUCI the molecular gas and the dust and stellar continuum in XID2028, an obscured QSO at z=1.593, where the presence of a massive outflow in the ionized gas component traced by the [O III]5007 emission has been resolved up to 10 kpc. This target does represent a unique test case to study QSO 'feedback in action' at the peak epoch of AGN- galaxy coevolution. The QSO has been detected both in the CO(5-4) transition and in the 1.3mm continuum, with emissions confined in the central ( consumption conditions in XID2028, possibly due to feedback effects on the host galaxy. Finally, we observe an asymmetric profile of the CO(5-4) line, which suggests the presence of high velocity gas up to 700 km/s. An image of the blueshfited and redshifted CO wings provides the first detection of a spatially resolved, galaxy-scale molecular outflow at high-z, extended in opposite directions with the approaching component spatially coincident with the ionised gas outflow. The resolved, molecular outflow appear to be cospatial with the component observed int the ionised gas. XID2028 therefore represents the first example of molecular and ionised kpc scales outflows at high-z.

Molecular weights and molecular weight distributions of irradiated cellulose fibers by gel permeation chromatography

International Nuclear Information System (INIS)

Kusama, Y.; Kageyama, E.; Shimada, M.; Nakamura, Y.

1976-01-01

Radiation degradation of cellulose fibers was investigated by gel permeation chromatography (GPC). Scoured cotton of Mexican variety (cellulose I), Polynosic rayon (cellulose II), and their microcrystalline celluloses obtained by hydrolysis of the original fibers were irradiated by Co-60 γ-rays under vacuum or humid conditions. The irradiated samples were then nitrated under nondegradative conditions. The molecular weights and molecular weight distributions were measured by GPC using tetrahydrofuran as solvent. The relationship between molecular weight and elution count was obtained with cellulose trinitrate standards fractionated by preparative GPC. The degree of polymerization of the fibers decreased with increasing irradiation dose, but their microcrystalline celluloses were only slightly degraded by irradiation, especially in microcrystalline cellulose from cellulose I. Degradation of the fibers irradiated under humid conditions was less than that irradiated under vacuum. It was found that the G-values for main-chain scission for the irradiated cellulose I, cellulose II, microcrystalline cellulose I, and microcrystalline cellulose II were 2.8, 2.9, less than 1, and 2.9, respectively, but the G-value for main-chain scission for the irradiated cellulose II was increased to 11.2 at irradiation doses above 3 Mrad. Consequently, it is inferred that cellulose molecules in the amorphous regions are degraded more readily, and the well-aligned molecules in crystalline regions are not as easily degraded by irradiation

Molecular cogs of the insect circadian clock.

Science.gov (United States)

Shirasu, Naoto; Shimohigashi, Yasuyuki; Tominaga, Yoshiya; Shimohigashi, Miki

2003-08-01

During the last five years, enormous progress has been made in understanding the molecular basis of circadian systems, mainly by molecular genetic studies using the mouse and fly. Extensive evidence has revealed that the core clock machinery involves "clock genes" and "clock proteins" functioning as molecular cogs. These participate in transcriptional/translational feedback loops and many homologous clock-components in the fruit fly Drosophila are also expressed in mammalian clock tissues with circadian rhythms. Thus, the mechanisms of the central clock seem to be conserved across animal kingdom. However, some recent studies imply that the present widely accepted molecular models of circadian clocks may not always be supported by the experimental evidence.

Electrospray soft-landing for the construction of non-covalent molecular nanostructures using charged droplets under ambient conditions.

Science.gov (United States)

Hou, Jian; Zheng, Qingna; Badu-Tawiah, Abraham K; Xiong, Caiqiao; Guan, Cuizhong; Chen, Suming; Nie, Zongxiu; Wang, Dong; Wan, Lijun

2016-11-17

An electrospray soft-landing (SL) technique was utilized to create 2D nano-networks on HOPG under ambient conditions. A 2,3,6,7,10,11-hexahydroxy-triphenylene close-packing structure was observed by STM instead of unorganized clusters, as well as amine and acid nanostructures. On C 18 H 37 NH 2 networks, C 18 H 37 NH 3 + was identified by XPS analysis revealing retaining of charges on the SL-modified surface.

Transcriptomic Profiling Reveals Complex Molecular Regulation in Cotton Genic Male Sterile Mutant Yu98-8A.

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Weiping Fang

Full Text Available Although cotton genic male sterility (GMS plays an important role in the utilization of hybrid vigor, its precise molecular mechanism remains unclear. To characterize the molecular events of pollen abortion, transcriptome analysis, combined with histological observations, was conducted in the cotton GMS line, Yu98-8A. A total of 2,412 genes were identified as significant differentially expressed genes (DEGs before and during the critical pollen abortion stages. Bioinformatics and biochemical analysis showed that the DEGs mainly associated with sugars and starch metabolism, oxidative phosphorylation, and plant endogenous hormones play a critical and complicated role in pollen abortion. These findings extend a better understanding of the molecular events involved in the regulation of pollen abortion in genic male sterile cotton, which may provide a foundation for further research studies on cotton heterosis breeding.

Transient β-hairpin formation in α-synuclein monomer revealed by coarse-grained molecular dynamics simulation

Energy Technology Data Exchange (ETDEWEB)

Yu, Hang; Ma, Wen [Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801 (United States); Center for Biophysics and Computational Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801 (United States); Han, Wei [Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801 (United States); Department of Physics, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801 (United States); Schulten, Klaus, E-mail: kschulte@ks.uiuc.edu [Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801 (United States); Center for Biophysics and Computational Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801 (United States); Department of Physics, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801 (United States)

2015-12-28

Parkinson’s disease, originating from the intrinsically disordered peptide α-synuclein, is a common neurodegenerative disorder that affects more than 5% of the population above age 85. It remains unclear how α-synuclein monomers undergo conformational changes leading to aggregation and formation of fibrils characteristic for the disease. In the present study, we perform molecular dynamics simulations (over 180 μs in aggregated time) using a hybrid-resolution model, Proteins with Atomic details in Coarse-grained Environment (PACE), to characterize in atomic detail structural ensembles of wild type and mutant monomeric α-synuclein in aqueous solution. The simulations reproduce structural properties of α-synuclein characterized in experiments, such as secondary structure content, long-range contacts, chemical shifts, and {sup 3}J(H{sub N}H{sub C{sub α}})-coupling constants. Most notably, the simulations reveal that a short fragment encompassing region 38-53, adjacent to the non-amyloid-β component region, exhibits a high probability of forming a β-hairpin; this fragment, when isolated from the remainder of α-synuclein, fluctuates frequently into its β-hairpin conformation. Two disease-prone mutations, namely, A30P and A53T, significantly accelerate the formation of a β-hairpin in the stated fragment. We conclude that the formation of a β-hairpin in region 38-53 is a key event during α-synuclein aggregation. We predict further that the G47V mutation impedes the formation of a turn in the β-hairpin and slows down β-hairpin formation, thereby retarding α-synuclein aggregation.

Genome-Wide Transcription and Functional Analyses Reveal Heterogeneous Molecular Mechanisms Driving Pyrethroids Resistance in the Major Malaria Vector Anopheles funestus Across Africa.

Science.gov (United States)

Riveron, Jacob M; Ibrahim, Sulaiman S; Mulamba, Charles; Djouaka, Rousseau; Irving, Helen; Wondji, Murielle J; Ishak, Intan H; Wondji, Charles S

2017-06-07

Pyrethroid resistance in malaria vector, An. funestus is increasingly reported across Africa, threatening the sustainability of pyrethroid-based control interventions, including long lasting insecticidal nets (LLINs). Managing this problem requires understanding of the molecular basis of the resistance from different regions of the continent, to establish whether it is being driven by a single or independent selective events. Here, using a genome-wide transcription profiling of pyrethroid resistant populations from southern (Malawi), East (Uganda), and West Africa (Benin), we investigated the molecular basis of resistance, revealing strong differences between the different African regions. The duplicated cytochrome P450 genes ( CYP6P9a and CYP6P9b ) which were highly overexpressed in southern Africa are not the most upregulated in other regions, where other genes are more overexpressed, including GSTe2 in West (Benin) and CYP9K1 in East (Uganda). The lack of directional selection on both CYP6P9a and CYP6P9b in Uganda in contrast to southern Africa further supports the limited role of these genes outside southern Africa. However, other genes such as the P450 CYP9J11 are commonly overexpressed in all countries across Africa. Here, CYP9J11 is functionally characterized and shown to confer resistance to pyrethroids and moderate cross-resistance to carbamates (bendiocarb). The consistent overexpression of GSTe2 in Benin is coupled with a role of allelic variation at this gene as GAL4-UAS transgenic expression in Drosophila flies showed that the resistant 119F allele is highly efficient in conferring both DDT and permethrin resistance than the L119. The heterogeneity in the molecular basis of resistance and cross-resistance to insecticides in An. funestus populations throughout sub-Saharan African should be taken into account in designing resistance management strategies. Copyright © 2017 Riveron et al.

Genome-Wide Transcription and Functional Analyses Reveal Heterogeneous Molecular Mechanisms Driving Pyrethroids Resistance in the Major Malaria Vector Anopheles funestus Across Africa

Science.gov (United States)

Riveron, Jacob M.; Ibrahim, Sulaiman S.; Mulamba, Charles; Djouaka, Rousseau; Irving, Helen; Wondji, Murielle J.; Ishak, Intan H.; Wondji, Charles S.

2017-01-01

Pyrethroid resistance in malaria vector, An. funestus is increasingly reported across Africa, threatening the sustainability of pyrethroid-based control interventions, including long lasting insecticidal nets (LLINs). Managing this problem requires understanding of the molecular basis of the resistance from different regions of the continent, to establish whether it is being driven by a single or independent selective events. Here, using a genome-wide transcription profiling of pyrethroid resistant populations from southern (Malawi), East (Uganda), and West Africa (Benin), we investigated the molecular basis of resistance, revealing strong differences between the different African regions. The duplicated cytochrome P450 genes (CYP6P9a and CYP6P9b) which were highly overexpressed in southern Africa are not the most upregulated in other regions, where other genes are more overexpressed, including GSTe2 in West (Benin) and CYP9K1 in East (Uganda). The lack of directional selection on both CYP6P9a and CYP6P9b in Uganda in contrast to southern Africa further supports the limited role of these genes outside southern Africa. However, other genes such as the P450 CYP9J11 are commonly overexpressed in all countries across Africa. Here, CYP9J11 is functionally characterized and shown to confer resistance to pyrethroids and moderate cross-resistance to carbamates (bendiocarb). The consistent overexpression of GSTe2 in Benin is coupled with a role of allelic variation at this gene as GAL4-UAS transgenic expression in Drosophila flies showed that the resistant 119F allele is highly efficient in conferring both DDT and permethrin resistance than the L119. The heterogeneity in the molecular basis of resistance and cross-resistance to insecticides in An. funestus populations throughout sub-Saharan African should be taken into account in designing resistance management strategies. PMID:28428243

Autophagy regulation revealed by SapM-induced block of autophagosome-lysosome fusion via binding RAB7

International Nuclear Information System (INIS)

Hu, Dong; Wu, Jing; Wang, Wan; Mu, Min; Zhao, Runpeng; Xu, Xuewei; Chen, Zhaoquan; Xiao, Jian; Hu, Fengyu; Yang, Yabo; Zhang, Rongbo

2015-01-01

The mechanism underlying autophagy alteration by mycobacterium tuberculosis remains unclear. Our previous study shows LpqH, a lipoprotein of mycobacterium tuberculosis, can cause autophagosomes accumulation in murine macrophages. It is well known that SapM, another virulence factor, plays an important role in blocking phagosome-endosome fusion. However, the mechanism that SapM interferes with autophagy remains poorly defined. In this study, we report that SapM suppresses the autophagy flux by blocking autophagosome fusion with lysosome. Exposure to SapM results in accumulations of autophagosomes and decreased co-localization of autophagosome with lysosome. Molecularly, Rab7, a small GTPase, is blocked by SapM through its CT domain and is prevented from involvement of autophagosome-lysosome fusion. In conclusion, our study reveals that SapM takes Rab7 as a previously unknown target to govern a distinct molecular mechanism underlying autophagosome-lysosome fusion, which may bring light to a new thought about developing potential drugs or vaccines against tuberculosis. - Highlights: • A mechanism for disrupting autophagosome-lysosome fusion induced by SapM. • Rab7 is involved in SapM-inhibited autophagy. • SapM interacts with Rab7 by CT-domain. • CT-domain is indispensable to SapM-inhibited autophagy

Autophagy regulation revealed by SapM-induced block of autophagosome-lysosome fusion via binding RAB7

Energy Technology Data Exchange (ETDEWEB)

Hu, Dong, E-mail: austhudong@126.com [Institute of Infection and Immunology, Department of Medical Immunology, Medical School, Anhui University of Science and Technology, Huainan (China); Wu, Jing, E-mail: wujing8008@126.com [Institute of Infection and Immunology, Department of Medical Immunology, Medical School, Anhui University of Science and Technology, Huainan (China); Wang, Wan; Mu, Min; Zhao, Runpeng; Xu, Xuewei; Chen, Zhaoquan [Institute of Infection and Immunology, Department of Medical Immunology, Medical School, Anhui University of Science and Technology, Huainan (China); Xiao, Jian [School of Pharmacy, Wenzhou Medical College, Wenzhou (China); Hu, Fengyu; Yang, Yabo [Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou (China); Zhang, Rongbo, E-mail: lory456@126.com [Institute of Infection and Immunology, Department of Medical Immunology, Medical School, Anhui University of Science and Technology, Huainan (China)

2015-05-29

The mechanism underlying autophagy alteration by mycobacterium tuberculosis remains unclear. Our previous study shows LpqH, a lipoprotein of mycobacterium tuberculosis, can cause autophagosomes accumulation in murine macrophages. It is well known that SapM, another virulence factor, plays an important role in blocking phagosome-endosome fusion. However, the mechanism that SapM interferes with autophagy remains poorly defined. In this study, we report that SapM suppresses the autophagy flux by blocking autophagosome fusion with lysosome. Exposure to SapM results in accumulations of autophagosomes and decreased co-localization of autophagosome with lysosome. Molecularly, Rab7, a small GTPase, is blocked by SapM through its CT domain and is prevented from involvement of autophagosome-lysosome fusion. In conclusion, our study reveals that SapM takes Rab7 as a previously unknown target to govern a distinct molecular mechanism underlying autophagosome-lysosome fusion, which may bring light to a new thought about developing potential drugs or vaccines against tuberculosis. - Highlights: • A mechanism for disrupting autophagosome-lysosome fusion induced by SapM. • Rab7 is involved in SapM-inhibited autophagy. • SapM interacts with Rab7 by CT-domain. • CT-domain is indispensable to SapM-inhibited autophagy.

Potential relationship between phenotypic and molecular characteristics in revealing livestock-associated Staphylococcus aureus in Chinese humans without occupational livestock contact

Directory of Open Access Journals (Sweden)

Yanping Fan

2016-09-01

Full Text Available While some studies have defined Staphylococcus aureus based on its clonal complex and resistance pattern, few have explored the relations between the genetic lineages and antibiotic resistance patterns and immune evasion cluster (IEC genes. Our aim was to investigate the potential relationship between phenotypic and molecular characteristics so as to reveal livestock-associated S. aureus in humans. The study participants were interviewed, and they provided two nasal swabs for S. aureus analysis. All S. aureus and methicillin-resistant S. aureus (MRSA were tested for antibiotic susceptibility, multilocus sequence type and IEC genes. Of the 1162 participants, 9.3% carried S. aureus, including MRSA (1.4% and multidrug-resistant S. aureus (MDRSA, 2.8%. The predominant multidrug-resistant pattern among MDRSA isolates was nonsusceptibility to erythromycin, clindamycin and tetracycline. The most common S. aureus genotypes were ST7, ST6, ST188 and ST59, and the predominant MRSA genotype was ST7. Notably, the livestock-associated S. aureus isolates (IEC-negative CC9, IEC-negative tetracycline-resistant CC398, and IEC-negative tetracycline-resistant CC5 were found in people with no occupational livestock contact. These findings reveal a potential relationship between S. aureus CCs and IEC genes and antibiotic resistance patterns in defining livestock-associated S. aureus in humans and support growing concern about the potential livestock-to-human transmission of livestock-associated S. aureus by non-occupational livestock contact.

75 FR 340 - Approval for Expansion of Subzone 22F, Abbott Molecular, Inc. (Pharmaceutical and Molecular...

Science.gov (United States)

2010-01-05

... DEPARTMENT OF COMMERCE Foreign-Trade Zones Board [Order No. 1654] Approval for Expansion of Subzone 22F, Abbott Molecular, Inc. (Pharmaceutical and Molecular Diagnostic Products), Chicago, IL, Area Pursuant to its authority under the Foreign-Trade Zones Act of June 18, 1934, as amended (19 U.S.C. 81a-81u...

Molecular dynamics simulation of UO2 nanocrystals melting under isolated and periodic boundary conditions

International Nuclear Information System (INIS)

Boyarchenkov, A.S.; Potashnikov, S.I.; Nekrasov, K.A.; Kupryazhkin, A.Ya.

2012-01-01

Highlights: ► We perform MD simulation of UO 2 nanocrystals melting (in range of 768–49 152 ions). ► T(P) melting curves intersect zero near −20 GPa and saturate near 25 GPa. ► Reciprocal size dependences of nanocrystal melting point decrease nonlinearly. ► Linear and parabolic extrapolations to macroscopic values are considered. ► Melting point and density jump are reproduced, but heat of fusion is underestimated. - Abstract: Melting of uranium dioxide (UO 2 ) nanocrystals has been studied by molecular dynamics (MD) simulation. Ten recent and widely used sets of pair potentials were assessed in the rigid ion approximation. Both isolated (in vacuum) and periodic boundary conditions (PBC) were explored. Using barostat under PBC the pressure dependences of melting point were obtained. These curves intersected zero near −20 GPa, saturated near 25 GPa and increased nonlinearly in between. Using simulation of surface under isolated boundary conditions (IBC) recommended melting temperature and density jump were successfully reproduced. However, the heat of fusion is still underestimated. These melting characteristics were calculated for nanocrystals of cubic shape in the range of 768–49 152 particles (volume range of 10–1000 nm 3 ). The obtained reciprocal size dependences decreased nonlinearly. Linear and parabolic extrapolations to macroscopic values are considered. The parabolic one is found to be better suited for analysis of the data on temperature and heat of melting.

Molecular cardiovascular imaging

International Nuclear Information System (INIS)

Schaefers, M.

2007-01-01

Although huge and long-lasting research efforts have been spent on the development of new diagnostic techniques investigating cardiovascular diseases, still fundamental challenges exist; the main challenge being the diagnosis of a suspected or known coronary artery disease or its consequences (myocardial infarction, heart failure etc.). Beside morphological techniques, functional imaging modalities are available in clinical diagnostic algorithms, whereas molecular cardiovascular imaging techniques are still under development. This review summarizes clinical-diagnostical challenges of modern cardiovascular medicine as well as the potential of new molecular imaging techniques to face these. (orig.)

Noncovalent Molecular Electronics.

Science.gov (United States)

Gryn'ova, G; Corminboeuf, C

2018-05-03

Molecular electronics covers several distinctly different conducting architectures, including organic semiconductors and single-molecule junctions. The noncovalent interactions, abundant in the former, are also often found in the latter, i.e., the dimer junctions. In the present work, we draw the parallel between the two types of noncovalent molecular electronics for a range of π-conjugated heteroaromatic molecules. In silico modeling allows us to distill the factors that arise from the chemical nature of their building blocks and from their mutual arrangement. We find that the same compounds are consistently the worst and the best performers in the two types of electronic assemblies, emphasizing the universal imprint of the underlying chemistry of the molecular cores on their diverse charge transport characteristics. The interplay between molecular and intermolecular factors creates a spectrum of noncovalent conductive architectures, which can be manipulated using the design strategies based upon the established relationships between chemistry and transport.

The molecular spin filter constructed from 1D organic chain

International Nuclear Information System (INIS)

Chen, Wei; Xu, Ning; Wang, Baolin; Bian, Baoan

2014-01-01

We proposed a molecular spin filter, which is constructed from the 1D metallic organic chain (Fe n+1 (C 6 H 4 ) n ). The spin-polarized transport properties of the molecular spin filter are explored by combining density functional theory with nonequilibrium Green's function formalism. Theoretical results reveal that Fe n+1 (C 6 H 4 ) n molecular chain exhibits robust spin filtering effect, and only the spin-down electrons can transmit through the molecular chain. At the given bias voltage window [−1 eV,1 eV], the calculated spin filter efficiency is close to 100% in the case of n≥3. We find that the effect of spin polarization origin from both Fe n+1 and (C 6 H 4 ) n . In addition, negative difference resistance behavior appears in Fe n+1 (C 6 H 4 ) n molecular chain. The results can help us understand the spin transport properties of organic molecular chain. - Highlights: • Theoretical results reveal that Fe n+1 (C 6 H 4 ) n molecular chain exhibits robust spin filtering effect. • The effect of spin polarization origin from both of Fe n+1 and (C 6 H 4 ) n . • Negative difference resistance behavior appears in Fe n+1 (C 6 H 4 ) n molecular chain

The influence of 150-cavity binders on the dynamics of influenza A neuraminidases as revealed by molecular dynamics simulations and combined clustering.

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Kyle T Greenway

Full Text Available Neuraminidase inhibitors are the main pharmaceutical agents employed for treatments of influenza infections. The neuraminidase structures typically exhibit a 150-cavity, an exposed pocket that is adjacent to the catalytic site. This site offers promising additional contact points for improving potency of existing pharmaceuticals, as well as generating entirely new candidate inhibitors. Several inhibitors based on known compounds and designed to interact with 150-cavity residues have been reported. However, the dynamics of any of these inhibitors remains unstudied and their viability remains unknown. This work reports the outcome of long-term, all-atom molecular dynamics simulations of four such inhibitors, along with three standard inhibitors for comparison. Each is studied in complex with four representative neuraminidase structures, which are also simulated in the absence of ligands for comparison, resulting in a total simulation time of 9.6 µs. Our results demonstrate that standard inhibitors characteristically reduce the mobility of these dynamic proteins, while the 150-binders do not, instead giving rise to many unique conformations. We further describe an improved RMSD-based clustering technique that isolates these conformations--the structures of which are provided to facilitate future molecular docking studies--and reveals their interdependence. We find that this approach confers many advantages over previously described techniques, and the implications for rational drug design are discussed.

The curse of the prey: Sarcoptes mite molecular analysis reveals potential prey-to-predator parasitic infestation in wild animals from Masai Mara, Kenya

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Soriguer Ramón C

2011-10-01

Full Text Available Abstract Background Recently, there have been attempts to understand the molecular epidemiology of Sarcoptes scabiei, to evaluate the gene flow between isolates of S. scabiei from different hosts and geographic regions. However, to our knowledge, a molecular study has not been carried out to assess the molecular diversity and gene flow of Sarcoptes mite in a predator/prey ecosystem. Results Our study revealed an absence of gene flow between the two herbivore (Thomson's gazelle and wildebeest- and between the two carnivore (lion and cheetah-derived Sarcoptes populations from Masai Mara (Kenya, which is in discrepancy with the host-taxon law described for wild animals in Europe. Lion- and wildebeest-derived Sarcoptes mite populations were similar yet different from the Thomson's gazelle-derived Sarcoptes population. This could be attributed to Sarcoptes cross-infestation from wildebeest ("favourite prey" of the lion, but not from Thomson's gazelle. The cheetah-derived Sarcoptes population had different subpopulations: one is cheetah-private, one similar to the wildebeest- and lion-derived Sarcoptes populations, and another similar to the Thomson's gazelle-derived Sarcoptes mite population, where both wildebeest and Thomson's gazelle are "favourite preys" for the cheetah. Conclusions In a predator/prey ecosystem, like Masai Mara in Kenya, it seems that Sarcoptes infestation in wild animals is prey-to-predator-wise, depending on the predator's "favourite prey". More studies on the lion and cheetah diet and behaviour could be of great help to clarify the addressed hypotheses. This study could have further ramification in the epidemiological studies and the monitoring protocols of the neglected Sarcoptes mite in predator/prey ecosystems.

Molecular imaging in patients with mood disorders: a review of PET findings

International Nuclear Information System (INIS)

Chen, Qiaozhen; Liu, Weibo; Li, Huichun; Zhang, Hong; Tian, Mei

2011-01-01

Mood disorders are chronic, recurrent psychiatric disorders with high morbidity rates that cause severe disability. Researchers have used molecular imaging extensively in studies of mood disorders. In this article, we concisely and selectively review the major findings of positron emission tomography studies of patients with mood disorders. Specifically, we describe findings from cerebral blood flow, cerebral glucose/oxygen metabolism, and radioligand studies in both cross-sectional and longitudinal investigations. Patients with mood disorders have mood-correlated regional metabolism changes and molecular abnormalities in several neurotransmitter systems. Although the findings of these studies are not completely consistent and confounding factors, including drug effects and specific methodology, should be strictly controlled, these results reveal the pathophysiology of mood disorders and aid the development of novel treatment approaches for mood disorders. Future positron emission tomography research will benefit greatly from the development of better radioligands to simultaneously identify multiple neurotransmitter systems in the specific brain region and the integration of more detecting methods in specifying the neurobiological predictors of treatment response in patients with mood disorders. Understanding the molecular mechanisms in underlying mood disorders will result in aetiological diagnosis and individualization of treatment of these disorders. (orig.)

Molecular imaging in patients with mood disorders: a review of PET findings

Energy Technology Data Exchange (ETDEWEB)

Chen, Qiaozhen [Zhejiang University, Department of Nuclear Medicine, Second Affiliated Hospital, School of Medicine, Hangzhou, Zhejiang (China); Zhejiang University, Department of Psychiatry, Second Affiliated Hospital, School of Medicine, Hangzhou (China); Zhejiang University, Medical PET Center, Hangzhou (China); Zhejiang University, Institute of Nuclear Medicine and Molecular Imaging, Hangzhou (China); Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Hangzhou (China); Liu, Weibo; Li, Huichun [Zhejiang University, Department of Psychiatry, Second Affiliated Hospital, School of Medicine, Hangzhou (China); Zhang, Hong [Zhejiang University, Department of Nuclear Medicine, Second Affiliated Hospital, School of Medicine, Hangzhou, Zhejiang (China); Zhejiang University, Medical PET Center, Hangzhou (China); Zhejiang University, Institute of Nuclear Medicine and Molecular Imaging, Hangzhou (China); Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Hangzhou (China); Tian, Mei [The University of Texas MD Anderson Cancer Center, Department of Experimental Diagnostic Imaging, Houston, TX (United States)

2011-07-15

Mood disorders are chronic, recurrent psychiatric disorders with high morbidity rates that cause severe disability. Researchers have used molecular imaging extensively in studies of mood disorders. In this article, we concisely and selectively review the major findings of positron emission tomography studies of patients with mood disorders. Specifically, we describe findings from cerebral blood flow, cerebral glucose/oxygen metabolism, and radioligand studies in both cross-sectional and longitudinal investigations. Patients with mood disorders have mood-correlated regional metabolism changes and molecular abnormalities in several neurotransmitter systems. Although the findings of these studies are not completely consistent and confounding factors, including drug effects and specific methodology, should be strictly controlled, these results reveal the pathophysiology of mood disorders and aid the development of novel treatment approaches for mood disorders. Future positron emission tomography research will benefit greatly from the development of better radioligands to simultaneously identify multiple neurotransmitter systems in the specific brain region and the integration of more detecting methods in specifying the neurobiological predictors of treatment response in patients with mood disorders. Understanding the molecular mechanisms in underlying mood disorders will result in aetiological diagnosis and individualization of treatment of these disorders. (orig.)

Molecular dynamics study of radiation damage and microstructure evolution of zigzag single-walled carbon nanotubes under carbon ion incidence

Science.gov (United States)

Li, Huan; Tang, Xiaobin; Chen, Feida; Huang, Hai; Liu, Jian; Chen, Da

2016-07-01

The radiation damage and microstructure evolution of different zigzag single-walled carbon nanotubes (SWCNTs) were investigated under incident carbon ion by molecular dynamics (MD) simulations. The radiation damage of SWCNTs under incident carbon ion with energy ranging from 25 eV to 1 keV at 300 K showed many differences at different incident sites, and the defect production increased to the maximum value with the increase in incident ion energy, and slightly decreased but stayed fairly stable within the majority of the energy range. The maximum damage of SWCNTs appeared when the incident ion energy reached 200 eV and the level of damage was directly proportional to incident ion fluence. The radiation damage was also studied at 100 K and 700 K and the defect production decreased distinctly with rising temperature because radiation-induced defects would anneal and recombine by saturating dangling bonds and reconstructing carbon network at the higher temperature. Furthermore, the stability of a large-diameter tube surpassed that of a thin one under the same radiation environments.

STICK AND SLIP BEHAVIOR OF CONFINED OLIGOMER MELTS UNDER SHEAR - A MOLECULAR-DYNAMICS STUDY

NARCIS (Netherlands)

MANIAS, E; HADZIIOANNOU, G; BITSANIS, [No Value; TENBRINKE, G

1993-01-01

The flow behaviour of melts of short chains, confined in molecularly thin Couette flow geometries, is studied with molecular-dynamics simulations. The effect of wall attraction and confinement on the density and velocity profiles is analysed. In these highly inhomogeneous films, a strong correlation

On the theory of frequency-shifted secondary emission of light-harvesting molecular systems

International Nuclear Information System (INIS)

Morozov, V.A.

2001-01-01

The expressions are obtained for the intensity of the frequency-shifted secondary emission of a chromophore playing the role of a reaction center in the simplest model three-chromophore molecular 'light-harvesting' antenna, which is constructed and oriented in space so that the incident photons coherently excite two of its chromophore pigments. The quantum-field formalism was used, which takes into account the generalized (quantum-electrodynamic) dipole-dipole, as well as radiative and nonradiative dissipative interactions between pigments and the reaction center of the antenna. The special features of the excitation spectrum of the Raman scattering line and the frequency-shifted fluorescence spectrum of the reaction center of the molecular antenna under study are discussed. A comparison of the expressions obtained for the excitation and fluorescence spectra and with the corresponding expressions obtained for a bichromophore molecular system, which differs from a three-chromophore antenna by the absence of one of the pigments, revealed the properties of the mechanism of action of light-harvesting molecular antennas that have not been found earlier. In particular, it is shown that 'the light-harvesting' caused by the collective dissipative interactions of pigments with the reaction center of the antenna can substantially exceed a sum of contributions from separate pigments

Molecular biology of Plasmodiophora brassicae

DEFF Research Database (Denmark)

Siemens, Johannes; Bulman, Simon; Rehn, Frank

2009-01-01

of several genes have been revealed, and the expression of those genes has been linked to development of clubroot to some extent. In addition, the sequence data have reinforced the inclusion of the plasmodiophorids within the Cercozoa. The recent successes in molecular biology have produced new approaches...

What Controls Thermo-osmosis? Molecular Simulations Show the Critical Role of Interfacial Hydrodynamics

Science.gov (United States)

Fu, Li; Merabia, Samy; Joly, Laurent

2017-11-01

Thermo-osmotic and related thermophoretic phenomena can be found in many situations from biology to colloid science, but the underlying molecular mechanisms remain largely unexplored. Using molecular dynamics simulations, we measure the thermo-osmosis coefficient by both mechanocaloric and thermo-osmotic routes, for different solid-liquid interfacial energies. The simulations reveal, in particular, the crucial role of nanoscale interfacial hydrodynamics. For nonwetting surfaces, thermo-osmotic transport is largely amplified by hydrodynamic slip at the interface. For wetting surfaces, the position of the hydrodynamic shear plane plays a key role in determining the amplitude and sign of the thermo-osmosis coefficient. Finally, we measure a giant thermo-osmotic response of the water-graphene interface, which we relate to the very low interfacial friction displayed by this system. These results open new perspectives for the design of efficient functional interfaces for, e.g., waste-heat harvesting.

What Controls Thermo-osmosis? Molecular Simulations Show the Critical Role of Interfacial Hydrodynamics.

Science.gov (United States)

Fu, Li; Merabia, Samy; Joly, Laurent

2017-11-24

Thermo-osmotic and related thermophoretic phenomena can be found in many situations from biology to colloid science, but the underlying molecular mechanisms remain largely unexplored. Using molecular dynamics simulations, we measure the thermo-osmosis coefficient by both mechanocaloric and thermo-osmotic routes, for different solid-liquid interfacial energies. The simulations reveal, in particular, the crucial role of nanoscale interfacial hydrodynamics. For nonwetting surfaces, thermo-osmotic transport is largely amplified by hydrodynamic slip at the interface. For wetting surfaces, the position of the hydrodynamic shear plane plays a key role in determining the amplitude and sign of the thermo-osmosis coefficient. Finally, we measure a giant thermo-osmotic response of the water-graphene interface, which we relate to the very low interfacial friction displayed by this system. These results open new perspectives for the design of efficient functional interfaces for, e.g., waste-heat harvesting.

Episodic sexual transmission of HIV revealed by molecular phylodynamics.

Directory of Open Access Journals (Sweden)

Fraser Lewis

2008-03-01

Full Text Available The structure of sexual contact networks plays a key role in the epidemiology of sexually transmitted infections, and their reconstruction from interview data has provided valuable insights into the spread of infection. For HIV, the long period of infectivity has made the interpretation of contact networks more difficult, and major discrepancies have been observed between the contact network and the transmission network revealed by viral phylogenetics. The high rate of HIV evolution in principle allows for detailed reconstruction of links between virus from different individuals, but often sampling has been too sparse to describe the structure of the transmission network. The aim of this study was to analyze a high-density sample of an HIV-infected population using recently developed techniques in phylogenetics to infer the short-term dynamics of the epidemic among men who have sex with men (MSM.Sequences of the protease and reverse transcriptase coding regions from 2,126 patients, predominantly MSM, from London were compared: 402 of these showed a close match to at least one other subtype B sequence. Nine large clusters were identified on the basis of genetic distance; all were confirmed by Bayesian Monte Carlo Markov chain (MCMC phylogenetic analysis. Overall, 25% of individuals with a close match with one sequence are linked to 10 or more others. Dated phylogenies of the clusters using a relaxed clock indicated that 65% of the transmissions within clusters took place between 1995 and 2000, and 25% occurred within 6 mo after infection. The likelihood that not all members of the clusters have been identified renders the latter observation conservative.Reconstruction of the HIV transmission network using a dated phylogeny approach has revealed the HIV epidemic among MSM in London to have been episodic, with evidence of multiple clusters of transmissions dating to the late 1990s, a period when HIV prevalence is known to have doubled in this

Diffusion Modelling Reveals the Decision Making Processes Underlying Negative Judgement Bias in Rats.

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Claire A Hales

Full Text Available Human decision making is modified by emotional state. Rodents exhibit similar biases during interpretation of ambiguous cues that can be altered by affective state manipulations. In this study, the impact of negative affective state on judgement bias in rats was measured using an ambiguous-cue interpretation task. Acute treatment with an anxiogenic drug (FG7142, and chronic restraint stress and social isolation both induced a bias towards more negative interpretation of the ambiguous cue. The diffusion model was fit to behavioural data to allow further analysis of the underlying decision making processes. To uncover the way in which parameters vary together in relation to affective state manipulations, independent component analysis was conducted on rate of information accumulation and distances to decision threshold parameters for control data. Results from this analysis were applied to parameters from negative affective state manipulations. These projected components were compared to control components to reveal the changes in decision making processes that are due to affective state manipulations. Negative affective bias in rodents induced by either FG7142 or chronic stress is due to a combination of more negative interpretation of the ambiguous cue, reduced anticipation of the high reward and increased anticipation of the low reward.

Diffusion Modelling Reveals the Decision Making Processes Underlying Negative Judgement Bias in Rats.

Science.gov (United States)

Hales, Claire A; Robinson, Emma S J; Houghton, Conor J

2016-01-01

Human decision making is modified by emotional state. Rodents exhibit similar biases during interpretation of ambiguous cues that can be altered by affective state manipulations. In this study, the impact of negative affective state on judgement bias in rats was measured using an ambiguous-cue interpretation task. Acute treatment with an anxiogenic drug (FG7142), and chronic restraint stress and social isolation both induced a bias towards more negative interpretation of the ambiguous cue. The diffusion model was fit to behavioural data to allow further analysis of the underlying decision making processes. To uncover the way in which parameters vary together in relation to affective state manipulations, independent component analysis was conducted on rate of information accumulation and distances to decision threshold parameters for control data. Results from this analysis were applied to parameters from negative affective state manipulations. These projected components were compared to control components to reveal the changes in decision making processes that are due to affective state manipulations. Negative affective bias in rodents induced by either FG7142 or chronic stress is due to a combination of more negative interpretation of the ambiguous cue, reduced anticipation of the high reward and increased anticipation of the low reward.

Molecular Cloning and Expression Analysis of Cu/Zn SOD Gene from Gynura bicolor DC.

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Xin Xu

2017-01-01

Full Text Available Superoxide dismutase is an important antioxidant enzyme extensively existing in eukaryote, which scavenges reactive oxygen species (ROS and plays an essential role in stress tolerance of higher plants. A full-length cDNA encoding Cu/Zn SOD was cloned from leaves of Gynura bicolor DC. by rapid amplification of cDNA ends (RACE. The full-length cDNA of Cu/Zn SOD is 924 bp and has a 681 bp open reading frame encoding 227 amino acids. Bioinformatics analysis revealed that belonged to the plant SOD super family. Cu/Zn SODs of the Helianthus annuus, Mikania micrantha, and Solidago canadensis var. scabra all have 86% similarity to the G. bicolor Cu/Zn SOD. Analysis of the expression of Cu/Zn SOD under different treatments revealed that Cu/Zn SOD was a stress-responsive gene, especially to 1-MCP. It indicates that the Cu/Zn SOD gene would be an important gene in the resistance to stresses and will be helpful in providing evidence for future research on underlying molecular mechanism and choosing proper postharvest treatments for G. bicolor.

Deciphering the molecular mechanisms underlying sea urchin reversible adhesion: A quantitative proteomics approach.

Science.gov (United States)

Lebesgue, Nicolas; da Costa, Gonçalo; Ribeiro, Raquel Mesquita; Ribeiro-Silva, Cristina; Martins, Gabriel G; Matranga, Valeria; Scholten, Arjen; Cordeiro, Carlos; Heck, Albert J R; Santos, Romana

2016-04-14

Marine bioadhesives have unmatched performances in wet environments, being an inspiration for biomedical applications. In sea urchins specialized adhesive organs, tube feet, mediate reversible adhesion, being composed by a disc, producing adhesive and de-adhesive secretions, and a motile stem. After tube foot detachment, the secreted adhesive remains bound to the substratum as a footprint. Sea urchin adhesive is composed by proteins and sugars, but so far only one protein, Nectin, was shown to be over-expressed as a transcript in tube feet discs, suggesting its involvement in sea urchin adhesion. Here we use high-resolution quantitative mass-spectrometry to perform the first study combining the analysis of the differential proteome of an adhesive organ, with the proteome of its secreted adhesive. This strategy allowed us to identify 163 highly over-expressed disc proteins, specifically involved in sea urchin reversible adhesion; to find that 70% of the secreted adhesive components fall within five protein groups, involved in exocytosis and microbial protection; and to provide evidences that Nectin is not only highly expressed in tube feet discs but is an actual component of the adhesive. These results give an unprecedented insight into the molecular mechanisms underlying sea urchin adhesion, and opening new doors to develop wet-reliable, reversible, and ecological biomimetic adhesives. Sea urchins attach strongly but in a reversible manner to substratum, being a valuable source of inspiration for industrial and biomedical applications. Yet, the molecular mechanisms governing reversible adhesion are still poorly studied delaying the engineering of biomimetic adhesives. We used the latest mass spectrometry techniques to analyze the differential proteome of an adhesive organ and the proteome of its secreted adhesive, allowing us to uncover the key players in sea urchin reversible adhesion. We demonstrate, that Nectin, a protein previously pointed out as potentially

Research for molecular magnetic theory

International Nuclear Information System (INIS)

Kuang Xiaoyu; Zhou Kangwei; Gou Qingquan

2002-01-01

Recently, the authors have established a DSF theoretical method suitable for researching molecular magnetism of the compounds consisting of transition group elements. By this method, the authors have revealed that the ferromagnetism of molecules is due to the cross-interaction between d orbitals of adjacent transition-metal ions, and that the antiferromagnetism is due to the parallel interactions. Further more, the authors have also established a magnetism theory for hetero-dinuclear molecular systems and covalent molecular systems, respectively. With these theoretical methods, a systematical studies are performed for the magnetism origin and the magnetism variation rule of transition metal complex molecules in various inorganic compounds, organic compounds and biologic proteins, and a reasonable explanation is presented for the strong antiferromagnetic coupling phenomenon in the catalysis active center of ribonucleotide reductase. This indicates that the main physical mechanisms are the combined effect of the direct-exchange, kinetic exchange and the molecular covalent property

Medulloblastoma in China: clinicopathologic analyses of SHH, WNT, and non-SHH/WNT molecular subgroups reveal different therapeutic responses to adjuvant chemotherapy.

Directory of Open Access Journals (Sweden)

Zhen-Yu Zhang

Full Text Available Medulloblastoma (MB is one of the most common primary central nervous system tumors in children. Data is lacking of a large cohort of medulloblastoma patients in China. Also, our knowledge on the sensitivity of different molecular subgroups of MB to adjuvant radiation therapy (RT or chemotherapy (CHT is still limited. The authors performed a retrospective study of 173 medulloblastoma patients treated at two institutions from 2002 to 2011. Formalin-fixed paraffin embedded (FFPE tissues were available in all the cases and sections were stained to classify histological and molecular subgroups. Univariate and multivariate analyses were used to investigate prognostic factors. Of 173 patients, there were 118 children and 55 adults, 112 males and 61 females. Estimated 5-year overall survival (OS rates for all patients, children and adults were 52%, 48% and 63%, respectively. After multivariate analysis, postoperative primary radiation therapy (RT and chemotherapy (CHT were revealed as favorable prognostic factors influencing OS and EFS. Postoperative primary chemotherapy (CHT was found significantly improving the survival of children (p<0.001 while it was not a significant prognostic factor for adult patients. Moreover, patients in WNT subtype had better OS (p = 0.028 than others (SHH and Non-SHH/WNT subtypes given postoperative adjuvant therapies. Postoperative primary RT was found to be a strong prognostic factor influencing the survival in all histological and molecular subgroups (p<0.001. Postoperative primary CHT was found significantly to influence the survival of classic medulloblastoma (CMB (OS p<0.001, EFS p<0.001, SHH subgroup (OS p = 0.020, EFS p = 0.049 and WNT subgroup (OS p = 0.003, EFS p = 0.016 but not in desmoplastic/nodular medulloblastoma (DMB (OS p = 0.361, EFS p = 0.834 and Non-SHH/WNT subgroup (OS p = 0.127, EFS p = 0.055. Our study showed postoperative primary CHT significantly influence the

Enhanced decomposition of dimethyl phthalate via molecular oxygen activated by Fe-Fe{sub 2}O{sub 3}/AC under microwave irradiation

Energy Technology Data Exchange (ETDEWEB)

Chen, Yiling [Key Laboratory of Pesticide and Chemical Biology of Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079 (China); Ai, Zhihui, E-mail: jennifer.ai@mail.ccnu.edu.cn [Key Laboratory of Pesticide and Chemical Biology of Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079 (China); Zhang, Lizhi [Key Laboratory of Pesticide and Chemical Biology of Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079 (China)

2012-10-15

Highlights: Black-Right-Pointing-Pointer Microwave irradiation induces the electrons transferring from AC to Fe-Fe{sub 2}O{sub 3} and reacts with molecular oxygen. Black-Right-Pointing-Pointer Microwave heating accelerates the electron transferring from AC to Fe-Fe{sub 2}O{sub 3} to generate reactive oxygen species. Black-Right-Pointing-Pointer This environmental remediation method is feasible for aqueous organic pollutants treatment. - Abstract: In this study, we demonstrate that the decomposition of dimethyl phthalate under microwave irradiation could be greatly enhanced over Fe-Fe{sub 2}O{sub 3} nanowires supported on activated carbon (Fe-Fe{sub 2}O{sub 3}/AC). The great enhanced decomposition of dimethyl phthalate could be attributed to a unique microwave induced molecular oxygen activation process. Upon microwave irradiation, electrons could be transferred from activated carbon to zero-valent iron, and then react with molecular oxygen to form O{sub 2}{center_dot}{sup -} and {center_dot}OH radicals for the decomposition of dimethyl phthalate. The deactivation and the regeneration of Fe-Fe{sub 2}O{sub 3}/AC catalyst were systematically studied. We also found that microwave heating could accelerate the electron transferring from AC to Fe-Fe{sub 2}O{sub 3} to generate more reactive oxygen species for the decomposition of DMP than conventional oil bath heating. This novel molecular oxygen activation approach may find applications for wastewater treatment and drinking water purification.

Molecular and Ultrastructural Mechanisms Underlying Yellow Dwarf Symptom Formation in Wheat after Infection of Barley Yellow Dwarf Virus.

Science.gov (United States)

Rong, Wei; Wang, Xindong; Wang, Xifeng; Massart, Sebastien; Zhang, Zengyan

2018-04-13

Wheat ( Tritium aestivum L.) production is essential for global food security. Infection of barley yellow dwarf virus-GAV (BYDV-GAV) results in wheat showing leaf yellowing and plant dwarfism symptom. To explore the molecular and ultrastructural mechanisms underlying yellow dwarf symptom formation in BYDV-GAV-infected wheat, we investigated the chloroplast ultrastructure via transmission electron microscopy (TEM), examined the contents of the virus, H₂O₂, and chlorophyll in Zhong8601, and studied the comparative transcriptome through microarray analyses in the susceptible wheat line Zhong8601 after virus infection. TEM images indicated that chloroplasts in BYDV-GAV-infected Zhong8601 leaf cells were fragmentized. Where thylakoids were not well developed, starch granules and plastoglobules were rare. Compared with mock-inoculated Zhong8601, chlorophyll content was markedly reduced, but the virus and H₂O₂ contents were significantly higher in BYDV-GAV-infected Zhong8601. The transcriptomic analyses revealed that chlorophyll biosynthesis and chloroplast related transcripts, encoding chlorophyll a/b binding protein, glucose-6-phosphate/phosphate translocator 2, and glutamyl-tRNA reductase 1, were down-regulated in BYDV-GAV-infected Zhong8601. Some phytohormone signaling-related transcripts, including abscisic acid (ABA) signaling factors (phospholipase D alpha 1 and calcineurin B-like protein 9) and nine ethylene response factors, were up-regulated. Additionally, reactive oxygen species (ROS)-related genes were transcriptionally regulated in BYDV-GAV infected Zhong8601, including three up-regulated transcripts encoding germin-like proteins (promoting ROS accumulation) and four down-regulated transcripts encoding peroxides (scavenging ROS). These results clearly suggest that the yellow dwarf symptom formation is mainly attributed to reduced chlorophyll content and fragmentized chloroplasts caused by down-regulation of the chlorophyll and chloroplast biosynthesis

Physiological and Proteomics Analyses Reveal Low-Phosphorus Stress Affected the Regulation of Photosynthesis in Soybean.

Science.gov (United States)

Chu, Shanshan; Li, Hongyan; Zhang, Xiangqian; Yu, Kaiye; Chao, Maoni; Han, Suoyi; Zhang, Dan

2018-06-06

Previous studies have revealed a significant genetic relationship between phosphorus (P)-efficiency and photosynthesis-related traits in soybean. In this study, we used proteome profiling in combination with expression analysis, biochemical investigations, and leaf ultrastructural analysis to identify the underlying physiological and molecular responses. The expression analysis and ultrastructural analysis showed that the photosynthesis key genes were decreased at transcript levels and the leaf mesophyll and chloroplast were severely damaged after low-P stress. Approximately 55 protein spots showed changes under low-P condition by mass spectrometry, of which 17 were involved in various photosynthetic processes. Further analysis revealed the depression of photosynthesis caused by low-P stress mainly involves the regulation of leaf structure, adenosine triphosphate (ATP) synthesis, absorption and transportation of CO₂, photosynthetic electron transport, production of assimilatory power, and levels of enzymes related to the Calvin cycle. In summary, our findings indicated that the existence of a stringent relationship between P supply and the genomic control of photosynthesis in soybean. As an important strategy to protect soybean photosynthesis, P could maintain the stability of cell structure, up-regulate the enzymes’ activities, recover the process of photosystem II (PSII), and induce the expression of low-P responsive genes and proteins.

Molecular subgroups of medulloblastoma identification using noninvasive magnetic resonance spectroscopy.

Science.gov (United States)

Blüml, Stefan; Margol, Ashley S; Sposto, Richard; Kennedy, Rebekah J; Robison, Nathan J; Vali, Marzieh; Hung, Long T; Muthugounder, Sakunthala; Finlay, Jonathan L; Erdreich-Epstein, Anat; Gilles, Floyd H; Judkins, Alexander R; Krieger, Mark D; Dhall, Girish; Nelson, Marvin D; Asgharzadeh, Shahab

2016-01-01

Medulloblastomas in children can be categorized into 4 molecular subgroups with differing clinical characteristics, such that subgroup determination aids in prognostication and risk-adaptive treatment strategies. Magnetic resonance spectroscopy (MRS) is a widely available, noninvasive tool that is used to determine the metabolic characteristics of tumors and provide diagnostic information without the need for tumor tissue. In this study, we investigated the hypothesis that metabolite concentrations measured by MRS would differ between molecular subgroups of medulloblastoma and allow accurate subgroup determination. MRS was used to measure metabolites in medulloblastomas across molecular subgroups (SHH = 12, Groups 3/4 = 17, WNT = 1). Levels of 14 metabolites were analyzed to determine those that were the most discriminant for medulloblastoma subgroups in order to construct a multivariable classifier for distinguishing between combined Group 3/4 and SHH tumors. Medulloblastomas across molecular subgroups revealed distinct spectral features. Group 3 and Group 4 tumors demonstrated metabolic profiles with readily detectable taurine, lower levels of lipids, and high levels of creatine. SHH tumors showed prominent choline and lipid with low levels of creatine and little or no evidence of taurine. A 5-metabolite subgroup classifier inclusive of creatine, myo-inositol, taurine, aspartate, and lipid 13a was developed that could discriminate between Group 3/4 and SHH medulloblastomas with excellent accuracy (cross-validated area under the curve [AUC] = 0.88). The data show that medulloblastomas of Group 3/4 differ metabolically as measured using MRS when compared with SHH molecular subgroups. MRS is a useful and accurate tool to determine medulloblastoma molecular subgroups. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Molecular genetic diversity of Punica granatum L. (pomegranate) as revealed by microsatellite DNA markers

Science.gov (United States)

Pomegranate (Punica granatum L.) is one of the oldest known edible fruits and more and more it arouse interest of scientific community given its numerous biological activities. However, information about its genetic resources and characterization using reliable molecular markers are still scarce. In...

Unifying hydrotropy under Gibbs phase rule.

Science.gov (United States)

Shimizu, Seishi; Matubayasi, Nobuyuki

2017-09-13

The task of elucidating the mechanism of solubility enhancement using hydrotropes has been hampered by the wide variety of phase behaviour that hydrotropes can exhibit, encompassing near-ideal aqueous solution, self-association, micelle formation, and micro-emulsions. Instead of taking a field guide or encyclopedic approach to classify hydrotropes into different molecular classes, we take a rational approach aiming at constructing a unified theory of hydrotropy based upon the first principles of statistical thermodynamics. Achieving this aim can be facilitated by the two key concepts: (1) the Gibbs phase rule as the basis of classifying the hydrotropes in terms of the degrees of freedom and the number of variables to modulate the solvation free energy; (2) the Kirkwood-Buff integrals to quantify the interactions between the species and their relative contributions to the process of solubilization. We demonstrate that the application of the two key concepts can in principle be used to distinguish the different molecular scenarios at work under apparently similar solubility curves observed from experiments. In addition, a generalization of our previous approach to solutes beyond dilution reveals the unified mechanism of hydrotropy, driven by a strong solute-hydrotrope interaction which overcomes the apparent per-hydrotrope inefficiency due to hydrotrope self-clustering.

Metabolite analysis of Mycobacterium species under aerobic and hypoxic conditions reveals common metabolic traits.

Science.gov (United States)

Drapal, Margit; Wheeler, Paul R; Fraser, Paul D

2016-08-01

A metabolite profiling approach has been implemented to elucidate metabolic adaptation at set culture conditions in five Mycobacterium species (two fast- and three slow-growing) with the potential to act as model organisms for Mycobacterium tuberculosis (Mtb). Analysis has been performed over designated growth phases and under representative environments (nutrient and oxygen depletion) experienced by Mtb during infection. The procedure was useful in determining a range of metabolites (60-120 compounds) covering nucleotides, amino acids, organic acids, saccharides, fatty acids, glycerols, -esters, -phosphates and isoprenoids. Among these classes of compounds, key biomarker metabolites, which can act as indicators of pathway/process activity, were identified. In numerous cases, common metabolite traits were observed for all five species across the experimental conditions (e.g. uracil indicating DNA repair). Amino acid content, especially glutamic acid, highlighted the different properties between the fast- and slow-growing mycobacteria studied (e.g. nitrogen assimilation). The greatest similarities in metabolite composition between fast- and slow-growing mycobacteria were apparent under hypoxic conditions. A comparison to previously reported transcriptomic data revealed a strong correlation between changes in transcription and metabolite content. Collectively, these data validate the changes in the transcription at the metabolite level, suggesting transcription exists as one of the predominant modes of cellular regulation in Mycobacterium. Sectors with restricted correlation between metabolites and transcription (e.g. hypoxic cultivation) warrant further study to elucidate and exploit post-transcriptional modes of regulation. The strong correlation between the laboratory conditions used and data derived from in vivo conditions, indicate that the approach applied is a valuable addition to our understanding of cell regulation in these Mycobacterium species.

Counterion Association and Structural Conformation Change of Charged PAMAM Dendrimer in Aqueous Solutions Revealed by Small Angle Neutron Scattering

International Nuclear Information System (INIS)

Chen, Wei-Ren

2009-01-01

Our previous study of the structure change of poly(amidoamine) starburst dendrimers (PAMAM) dendrimer of generation 5 (G5) have demonstrated that although the overall molecular size is practically unaffected by increasing DCl concentration, a configurational transformation, from a diffusive density profile to a more uniform density distribution, is clearly observed. In the current paper, the focus is placed on understanding the effect of counterion identity on the inter-molecular structure and the conformational properties by studying the effect due to DBr using small angle neutron scattering (SANS) and integral equation theory. While the overall molecular size is found to be essentially unaffected by the change in the pD of solutions, it is surprising that the intra-molecular configurational transformation is not observed when DBr is used. The overall effective charge of a dendrimer is nearly the same for 1, the effect of counterion identity becomes significant, the effective charge carried by a charged G5 PAPAM protonated by DBr becomes smaller than that of solutions with DCl. As a consequence, a counterion identity dependence of counterion association is revealed: Under the same level of molecular protonation, the specific counterion association, which is defined as the ratio of bound chloride anions to positively charged amines per molecule, is larger for the G5 PAMAM dendrimer charged by DBr than the one by DCl.

Mitochondrial and nuclear DNA reveals a complete lineage sorti ng ...

African Journals Online (AJOL)

Glossogobius callidus exhibits broad salinity tolerance and is distributed in both estuarine and freshwater environments in southern Africa. Previous studies revealed substantial morphological and molecular variation among populations, suggesting they constitute a species complex. The present study utilised phylogenetic ...

Molecular dynamics simulations of ejecta production from sinusoidal tin surfaces under supported and unsupported shocks

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Bao Wu

2018-04-01

Full Text Available Micro-ejecta, an instability growth process, occurs at metal/vacuum or metal/gas interface when compressed shock wave releases from the free surface that contains surface defects. We present molecular dynamics (MD simulations to investigate the ejecta production from tin surface shocked by supported and unsupported waves with pressures ranging from 8.5 to 60.8 GPa. It is found that the loading waveforms have little effect on spike velocity while remarkably affect the bubble velocity. The bubble velocity of unsupported shock loading remains nonzero constant value at late time as observed in experiments. Besides, the time evolution of ejected mass in the simulations is compared with the recently developed ejecta source model, indicating the suppressed ejection of unmelted or partial melted materials. Moreover, different reference positions are chosen to characterize the amount of ejecta under different loading waveforms. Compared with supported shock case, the ejected mass of unsupported shock case saturates at lower pressure. Through the analysis on unloading path, we find that the temperature of tin sample increases quickly from tensile stress state to zero pressure state, resulting in the melting of bulk tin under decaying shock. Thus, the unsupported wave loading exhibits a lower threshold pressure causing the solid-liquid phase transition on shock release than the supported shock loading.

In situ monitoring of molecular changes during cell differentiation processes in marine macroalgae through mass spectrometric imaging.

Science.gov (United States)

Kessler, Ralf W; Crecelius, Anna C; Schubert, Ulrich S; Wichard, Thomas

2017-08-01

Matrix-assisted laser desorption/ionization mass spectrometric imaging (MALDI-MSI) was employed to discriminate between cell differentiation processes in macroalgae. One of the key developmental processes in the algal life cycle is the production of germ cells (gametes and zoids). The gametogenesis of the marine green macroalga Ulva mutabilis (Chlorophyta) was monitored by metabolomic snapshots of the surface, when blade cells differentiate synchronously into gametangia and giving rise to gametes. To establish MSI for macroalgae, dimethylsulfoniopropionate (DMSP), a known algal osmolyte, was determined. MSI of the surface of U. mutabilis followed by chemometric data analysis revealed dynamic metabolomic changes during cell differentiation. DMSP and a total of 55 specific molecular biomarkers, which could be assigned to important stages of the gametogenesis, were detected. Our research contributes to the understanding of molecular mechanisms underlying macroalgal cell differentiation. Graphical abstract Molecular changes during cell differentiation of the marine macroalga Ulva were visualized by matrix assisted laser desorption/ionization mass spectrometric imaging (MALDI-MSI).

Mixed-culture transcriptome analysis reveals the molecular basis of mixed-culture growth in Streptococcus thermophilus and Lactobacillus bulgaricus.

Science.gov (United States)

Sieuwerts, Sander; Molenaar, Douwe; van Hijum, Sacha A F T; Beerthuyzen, Marke; Stevens, Marc J A; Janssen, Patrick W M; Ingham, Colin J; de Bok, Frank A M; de Vos, Willem M; van Hylckama Vlieg, Johan E T

2010-12-01

Many food fermentations are performed using mixed cultures of lactic acid bacteria. Interactions between strains are of key importance for the performance of these fermentations. Yogurt fermentation by Streptococcus thermophilus and Lactobacillus bulgaricus (basonym, Lactobacillus delbrueckii subsp. bulgaricus) is one of the best-described mixed-culture fermentations. These species are believed to stimulate each other's growth by the exchange of metabolites such as folic acid and carbon dioxide. Recently, postgenomic studies revealed that an upregulation of biosynthesis pathways for nucleotides and sulfur-containing amino acids is part of the global physiological response to mixed-culture growth in S. thermophilus, but an in-depth molecular analysis of mixed-culture growth of both strains remains to be established. We report here the application of mixed-culture transcriptome profiling and a systematic analysis of the effect of interaction-related compounds on growth, which allowed us to unravel the molecular responses associated with batch mixed-culture growth in milk of S. thermophilus CNRZ1066 and L. bulgaricus ATCC BAA-365. The results indicate that interactions between these bacteria are primarily related to purine, amino acid, and long-chain fatty acid metabolism. The results support a model in which formic acid, folic acid, and fatty acids are provided by S. thermophilus. Proteolysis by L. bulgaricus supplies both strains with amino acids but is insufficient to meet the biosynthetic demands for sulfur and branched-chain amino acids, as becomes clear from the upregulation of genes associated with these amino acids in mixed culture. Moreover, genes involved in iron uptake in S. thermophilus are affected by mixed-culture growth, and genes coding for exopolysaccharide production were upregulated in both organisms in mixed culture compared to monocultures. The confirmation of previously identified responses in S. thermophilus using a different strain combination

Molecular mechanisms underlying the role of microRNAs in the chemoresistance of pancreatic cancer.

Science.gov (United States)

Garajová, Ingrid; Le Large, Tessa Y; Frampton, Adam E; Rolfo, Christian; Voortman, Johannes; Giovannetti, Elisa

2014-01-01

Pancreatic ductal adenocarcinoma (PDAC) is an extremely severe disease where the mortality and incidence rates are almost identical. This is mainly due to late diagnosis and limited response to current treatments. The tumor macroenvironment/microenvironment have been frequently reported as the major contributors to chemoresistance in PDAC, preventing the drugs from reaching their intended site of action (i.e., the malignant duct cells). However, the recent discovery of microRNAs (miRNAs) has provided new directions for research on mechanisms underlying response to chemotherapy. Due to their tissue-/disease-specific expression and high stability in tissues and biofluids, miRNAs represent new promising diagnostic and prognostic/predictive biomarkers and therapeutic targets. Furthermore, several studies have documented that selected miRNAs, such as miR-21 and miR-34a, may influence response to chemotherapy in several tumor types, including PDAC. In this review, we summarize the current knowledge on the role of miRNAs in PDAC and recent advances in understanding their role in chemoresistance through multiple molecular mechanisms.

Molecular Mechanisms Underlying the Role of MicroRNAs in the Chemoresistance of Pancreatic Cancer

Directory of Open Access Journals (Sweden)

Ingrid Garajová

2014-01-01

Full Text Available Pancreatic ductal adenocarcinoma (PDAC is an extremely severe disease where the mortality and incidence rates are almost identical. This is mainly due to late diagnosis and limited response to current treatments. The tumor macroenvironment/microenvironment have been frequently reported as the major contributors to chemoresistance in PDAC, preventing the drugs from reaching their intended site of action (i.e., the malignant duct cells. However, the recent discovery of microRNAs (miRNAs has provided new directions for research on mechanisms underlying response to chemotherapy. Due to their tissue-/disease-specific expression and high stability in tissues and biofluids, miRNAs represent new promising diagnostic and prognostic/predictive biomarkers and therapeutic targets. Furthermore, several studies have documented that selected miRNAs, such as miR-21 and miR-34a, may influence response to chemotherapy in several tumor types, including PDAC. In this review, we summarize the current knowledge on the role of miRNAs in PDAC and recent advances in understanding their role in chemoresistance through multiple molecular mechanisms.

Synthesis of one-dimensional metal-containing insulated molecular wire with versatile properties directed toward molecular electronics materials.

Science.gov (United States)

Masai, Hiroshi; Terao, Jun; Seki, Shu; Nakashima, Shigeto; Kiguchi, Manabu; Okoshi, Kento; Fujihara, Tetsuaki; Tsuji, Yasushi

2014-02-05

We report, herein, the design, synthesis, and properties of new materials directed toward molecular electronics. A transition metal-containing insulated molecular wire was synthesized through the coordination polymerization of a Ru(II) porphyrin with an insulated bridging ligand of well-defined structure. The wire displayed not only high linearity and rigidity, but also high intramolecular charge mobility. Owing to the unique properties of the coordination bond, the interconversion between the monomer and polymer states was realized under a carbon monoxide atmosphere or UV irradiation. The results demonstrated a high potential of the metal-containing insulated molecular wire for applications in molecular electronics.

Low Molecular Weight Fucoidan Inhibits Tumor Angiogenesis through Downregulation of HIF-1/VEGF Signaling under Hypoxia

Directory of Open Access Journals (Sweden)

Meng-Chuan Chen

2015-07-01

Full Text Available Activation of hypoxia-induced hypoxia-inducible factors-1 (HIF-1 plays a critical role in promoting tumor angiogenesis, growth and metastasis. Low molecular weight fucoidan (LMWF is prepared from brown algae, and exhibits anticancer activity. However, whether LMWF attenuates hypoxia-induced angiogenesis in bladder cancer cells and the molecular mechanisms involved remain unclear. This is the first study to demonstrate that LMWF can inhibit hypoxia-stimulated H2O2 formation, HIF-1 accumulation and transcriptional activity vascular endothelial growth factor (VEGF secretion, and the migration and invasion in hypoxic human bladder cancer cells (T24 cells. LMWF also downregulated hypoxia-activated phosphorylation of PI3K/AKT/mTOR/p70S6K/4EBP-1 signaling in T24 cells. Blocking PI3K/AKT or mTOR activity strongly diminished hypoxia-induced HIF-1α expression and VEGF secretion in T24 cells, supporting the involvement of PI3K/AKT/mTOR in the induction of HIF-1α and VEGF. Additionally, LMWF significantly attenuated angiogenesis in vitro and in vivo evidenced by reduction of tube formation of hypoxic human umbilical vascular endothelial cells and blood capillary generation in the tumor. Similarly, administration of LMWF also inhibited the HIF-1α and VEGF expression in vivo, accompanied by a reduction of tumor growth. In summary, under hypoxia conditions, the antiangiogenic activity of LMWF in bladder cancer may be associated with suppressing HIF-1/VEGF-regulated signaling pathway.

[Advances of Molecular Diagnostic Techniques Application in Clinical Diagnosis.

Science.gov (United States)

Ying, Bin-Wu

2016-11-01

Over the past 20 years,clinical molecular diagnostic technology has made rapid development,and became the most promising field in clinical laboratory medicine.In particular,with the development of genomics,clinical molecular diagnostic methods will reveal the nature of clinical diseases in a deeper level,thus guiding the clinical diagnosis and treatments.Many molecular diagnostic projects have been routinely applied in clinical works.This paper reviews the advances on application of clinical diagnostic techniques in infectious disease,tumor and genetic disorders,including nucleic acid amplification,biochip,next-generation sequencing,and automation molecular system,and so on.

Characterization of small HSPs from Anemonia viridis reveals insights into molecular evolution of alpha crystallin genes among cnidarians.

Directory of Open Access Journals (Sweden)

Aldo Nicosia

Full Text Available Gene family encoding small Heat-Shock Proteins (sHSPs containing α-crystallin domain are found both in prokaryotic and eukaryotic organisms; however, there is limited knowledge of their evolution. In this study, two small HSP genes termed AvHSP28.6 and AvHSP27, both organized in one intron and two exons, were characterised in the Mediterranean snakelocks anemone Anemonia viridis. The release of the genome sequence of Hydra magnipapillata and Nematostella vectensis enabled a comprehensive study of the molecular evolution of α-crystallin gene family among cnidarians. Most of the H. magnipapillata sHSP genes share the same gene organization described for AvHSP28.6 and AvHSP27, differing from the sHSP genes of N. vectensis which mainly show an intronless architecture. The different genomic organization of sHSPs, the phylogenetic analyses based on protein sequences, and the relationships among Cnidarians, suggest that the A.viridis sHSPs represent the common ancestor from which H. magnipapillata genes directly evolved through segmental genome duplication. Additionally retroposition events may be considered responsible for the divergence of sHSP genes of N. vectensis from A. viridis. Analyses of transcriptional expression profile showed that AvHSP28.6 was constitutively expressed among different tissues from both ectodermal and endodermal layers of the adult sea anemones, under normal physiological conditions and also under different stress condition. Specifically, we profiled the transcriptional activation of AvHSP28.6 after challenges with different abiotic/biotic stresses showing induction by extreme temperatures, heavy metals exposure and immune stimulation. Conversely, no AvHSP27 transcript was detected in such dissected tissues, in adult whole body cDNA library or under stress conditions. Hence, the involvement of AvHSP28.6 gene in the sea anemone defensome is strongly suggested.

Characterization of small HSPs from Anemonia viridis reveals insights into molecular evolution of alpha crystallin genes among cnidarians.

Science.gov (United States)

Nicosia, Aldo; Maggio, Teresa; Mazzola, Salvatore; Gianguzza, Fabrizio; Cuttitta, Angela; Costa, Salvatore

2014-01-01

Gene family encoding small Heat-Shock Proteins (sHSPs containing α-crystallin domain) are found both in prokaryotic and eukaryotic organisms; however, there is limited knowledge of their evolution. In this study, two small HSP genes termed AvHSP28.6 and AvHSP27, both organized in one intron and two exons, were characterised in the Mediterranean snakelocks anemone Anemonia viridis. The release of the genome sequence of Hydra magnipapillata and Nematostella vectensis enabled a comprehensive study of the molecular evolution of α-crystallin gene family among cnidarians. Most of the H. magnipapillata sHSP genes share the same gene organization described for AvHSP28.6 and AvHSP27, differing from the sHSP genes of N. vectensis which mainly show an intronless architecture. The different genomic organization of sHSPs, the phylogenetic analyses based on protein sequences, and the relationships among Cnidarians, suggest that the A.viridis sHSPs represent the common ancestor from which H. magnipapillata genes directly evolved through segmental genome duplication. Additionally retroposition events may be considered responsible for the divergence of sHSP genes of N. vectensis from A. viridis. Analyses of transcriptional expression profile showed that AvHSP28.6 was constitutively expressed among different tissues from both ectodermal and endodermal layers of the adult sea anemones, under normal physiological conditions and also under different stress condition. Specifically, we profiled the transcriptional activation of AvHSP28.6 after challenges with different abiotic/biotic stresses showing induction by extreme temperatures, heavy metals exposure and immune stimulation. Conversely, no AvHSP27 transcript was detected in such dissected tissues, in adult whole body cDNA library or under stress conditions. Hence, the involvement of AvHSP28.6 gene in the sea anemone defensome is strongly suggested.

Molecular fingerprinting of complex grass allergoids: size assessments reveal new insights in epitope repertoires and functional capacities.

Science.gov (United States)

Starchenka, S; Bell, A J; Mwange, J; Skinner, M A; Heath, M D

2017-01-01

Subcutaneous allergen immunotherapy (SCIT) is a well-documented treatment for allergic disease which involves injections of native allergen or modified (allergoid) extracts. The use of allergoid vaccines is a growing sector of the allergy immunotherapy market, associated with shorter-course therapy. The aim of this study was the structural and immunological characterisation of group 1 (Lol p 1) IgG-binding epitopes within a complex mix grass allergoid formulation containing rye grass. HP-SEC was used to resolve a mix grass allergoid preparation of high molecular weight into several distinct fractions with defined molecular weight and elution profiles. Allergen verification of the HP-SEC allergoid fractions was confirmed by mass spectrometry analysis. IgE and IgG immunoreactivity of the allergoid preparations was explored and Lol p 1 specific IgG-binding epitopes mapped by SPOT synthesis technology (PepSpot™) with structural analysis based on a Lol p 1 homology model. Grass specific IgE reactivity of the mix grass modified extract (allergoid) was diminished in comparison with the mix grass native extract. A difference in IgG profiles was observed between an intact mix grass allergoid preparation and HP-SEC allergoid fractions, which indicated enhancement of accessible reactive IgG epitopes across size distribution profiles of the mix grass allergoid formulation. Detailed analysis of the epitope specificity showed retention of six Lol p 1 IgG-binding epitopes in the mix grass modified extract. The structural and immunological changes which take place following the grass allergen modification process was further unravelled revealing distinct IgG immunological profiles. All epitopes were mapped on the solvent exposed area of Lol p 1 homology model accessible for IgG binding. One of the epitopes was identified as an 'immunodominant' Lol p 1 IgG-binding epitope (62-IFKDGRGCGSCFEIK-76) and classified as a novel epitope. The results from this study support the concept

Mathematical modeling of the crack growth in linear elastic isotropic materials by conventional fracture mechanics approaches and by molecular dynamics method: crack propagation direction angle under mixed mode loading

Science.gov (United States)

Stepanova, Larisa; Bronnikov, Sergej

2018-03-01

The crack growth directional angles in the isotropic linear elastic plane with the central crack under mixed-mode loading conditions for the full range of the mixity parameter are found. Two fracture criteria of traditional linear fracture mechanics (maximum tangential stress and minimum strain energy density criteria) are used. Atomistic simulations of the central crack growth process in an infinite plane medium under mixed-mode loading using Large-scale Molecular Massively Parallel Simulator (LAMMPS), a classical molecular dynamics code, are performed. The inter-atomic potential used in this investigation is Embedded Atom Method (EAM) potential. The plane specimens with initial central crack were subjected to Mixed-Mode loadings. The simulation cell contains 400000 atoms. The crack propagation direction angles under different values of the mixity parameter in a wide range of values from pure tensile loading to pure shear loading in a wide diapason of temperatures (from 0.1 К to 800 К) are obtained and analyzed. It is shown that the crack propagation direction angles obtained by molecular dynamics method coincide with the crack propagation direction angles given by the multi-parameter fracture criteria based on the strain energy density and the multi-parameter description of the crack-tip fields.

Pressure and temperature phase diagram of Gd{sub 2}Ti{sub 2}O{sub 7} under irradiation

Energy Technology Data Exchange (ETDEWEB)

Catillon, G. [Université Paris-Est, G2I, EA4119, 5 Blvd. Descartes, F-77454 Marne la Vallée Cedex 2 (France); Chartier, A., E-mail: alain.chartier@cea.fr [CEA, DEN, DMN, SCCME, F-91191 Gif-Sur-Yvette Cedex (France)

2014-11-21

The pressure and temperature phase diagram of Gd{sub 2}Ti{sub 2}O{sub 7} under irradiation are calculated by means of molecular dynamics calculations. The critical temperature for amorphization obeys a linear law with pressure. Gd{sub 2}Ti{sub 2}O{sub 7} under irradiation transits towards the fluorite above this temperature and amorphizes below. The configuration of the Ti interstitial reveals to be the key of the amorphizability of Gd{sub 2}Ti{sub 2}O{sub 7}. Its stability depends upon disorder and pressure. Low pressure promotes the stabilization of Ti linked-polyhedra that drive the system to the amorphous state under irradiation. Conversely, high pressure activates its destabilization to interstitials that recombine with vacancies, driving the system to the fluorite structure under irradiation.

Deep phenotyping of 89 xeroderma pigmentosum patients reveals unexpected heterogeneity dependent on the precise molecular defect

Science.gov (United States)

Fassihi, Hiva; Sethi, Mieran; Fawcett, Heather; Wing, Jonathan; Chandler, Natalie; Mohammed, Shehla; Craythorne, Emma; Morley, Ana M. S.; Lim, Rongxuan; Turner, Sally; Henshaw, Tanya; Garrood, Isabel; Giunti, Paola; Hedderly, Tammy; Abiona, Adesoji; Naik, Harsha; Harrop, Gemma; McGibbon, David; Jaspers, Nicolaas G. J.; Botta, Elena; Nardo, Tiziana; Stefanini, Miria; Young, Antony R.; Sarkany, Robert P. E.; Lehmann, Alan R.

2016-01-01

Xeroderma pigmentosum (XP) is a rare DNA repair disorder characterized by increased susceptibility to UV radiation (UVR)-induced skin pigmentation, skin cancers, ocular surface disease, and, in some patients, sunburn and neurological degeneration. Genetically, it is assigned to eight complementation groups (XP-A to -G and variant). For the last 5 y, the UK national multidisciplinary XP service has provided follow-up for 89 XP patients, representing most of the XP patients in the United Kingdom. Causative mutations, DNA repair levels, and more than 60 clinical variables relating to dermatology, ophthalmology, and neurology have been measured, using scoring systems to categorize disease severity. This deep phenotyping has revealed unanticipated heterogeneity of clinical features, between and within complementation groups. Skin cancer is most common in XP-C, XP-E, and XP-V patients, previously considered to be the milder groups based on cellular analyses. These patients have normal sunburn reactions and are therefore diagnosed later and are less likely to adhere to UVR protection. XP-C patients are specifically hypersensitive to ocular damage, and XP-F and XP-G patients appear to be much less susceptible to skin cancer than other XP groups. Within XP groups, different mutations confer susceptibility or resistance to neurological damage. Our findings on this large cohort of XP patients under long-term follow-up reveal that XP is more heterogeneous than has previously been appreciated. Our data now enable provision of personalized prognostic information and management advice for each XP patient, as well as providing new insights into the functions of the XP proteins. PMID:26884178

The bladed Bangiales (Rhodophyta) of the South Eastern Pacific: Molecular species delimitation reveals extensive diversity.

Science.gov (United States)

Guillemin, Marie-Laure; Contreras-Porcia, Loretto; Ramírez, María Eliana; Macaya, Erasmo C; Contador, Cristian Bulboa; Woods, Helen; Wyatt, Christopher; Brodie, Juliet

2016-01-01

A molecular taxonomic study of the bladed Bangiales of the South Eastern Pacific (coast of Chile) was undertaken based on sequence data of the mitochondrial COI and chloroplast rbcL for 193 specimens collected from Arica (18°S) in the north to South Patagonia (53°S) in the south. The results revealed for the first time that four genera, Porphyra, Pyropia, Fuscifolium and Wildemania were present in the region. Species delimitation was determined based on a combination of a General Mixed Yule Coalescence model (GMYC) and Automatic Barcode Gap Discovery (ABGD) coupled with detection of monophyly in tree reconstruction. The overall incongruence between the species delimitation methods within each gene was 29%. The GMYC method led to over-splitting groups, whereas the ABGD method had a tendency to lump groups. Taking a conservative approach to the number of putative species, at least 18 were recognized and, with the exception of the recently described Pyropia orbicularis, all were new to the Chilean flora. Porphyra and Pyropia were the most diverse genera with eight 'species' each, whereas only a 'single' species each was found for Fuscifolium and Wildemania. There was also evidence of recently diverging groups: Wildemania sp. was distinct but very closely related to W. amplissima from the Northern Hemisphere and raises questions in relation to such disjunct distributions. Pyropia orbicularis was very closely related to two other species, making species delimitation very difficult but provides evidence of an incipient speciation. The difference between the 'species' discovered and those previously reported for the region is discussed in relation to the difficulty of distinguishing species based on morphological identification. Copyright © 2015 Elsevier Inc. All rights reserved.

Multishell structure formation in Ni nanowire under uniaxial strain along <0 0 1> crystallographic direction: A molecular dynamics simulation

Energy Technology Data Exchange (ETDEWEB)

Wang Li, E-mail: wanglihxf@sdu.edu.c [School of Mechanical and Electrical Engineering, Shandong University at Weihai, 180 Wenhuaxi Road, Weihai 264209 (China); Peng Chuanxiao [Key Laboratory of Liquid Structure and Heredity of Materials, Ministry of Education, Shandong University, Jinan 250061 (China); Gong Jianhong [School of Mechanical and Electrical Engineering, Shandong University at Weihai, 180 Wenhuaxi Road, Weihai 264209 (China)

2010-04-01

Molecular dynamics simulations based upon embedded-atom-method potential are employed to explore the fracture behavior of Ni nanowire along <0 0 1> crystallographic direction at temperature of 300 K. We find the formation of (5,5) multishell structure (MS), which is transformed from (6,5) MS at the necking region of nanowire under the strain rate of 0.02%ps{sup -1}. A reorientation transformation from <0 0 1> to <1 1 0> is first detected before formation of (6,5) MS. The formed (5,5) MS is more stable and can be tensioned longer as lower strain rate is loaded.

The one-sample PARAFAC approach reveals molecular size distributions of fluorescent components in dissolved organic matter

DEFF Research Database (Denmark)

Wünsch, Urban; Murphy, Kathleen R.; Stedmon, Colin

2017-01-01

Molecular size plays an important role in dissolved organic matter (DOM) biogeochemistry, but its relationship with the fluorescent fraction of DOM (FDOM) remains poorly resolved. Here high-performance size exclusion chromatography (HPSEC) was coupled to fluorescence emission-excitation (EEM...... but not their spectral properties. Thus, in contrast to absorption measurements, bulk fluorescence is unlikely to reliably indicate the average molecular size of DOM. The one-sample approach enables robust and independent cross-site comparisons without large-scale sampling efforts and introduces new analytical...... opportunities for elucidating the origins and biogeochemical properties of FDOM...

Clustering the Orion B giant molecular cloud based on its molecular emission

Science.gov (United States)

Bron, Emeric; Daudon, Chloé; Pety, Jérôme; Levrier, François; Gerin, Maryvonne; Gratier, Pierre; Orkisz, Jan H.; Guzman, Viviana; Bardeau, Sébastien; Goicoechea, Javier R.; Liszt, Harvey; Öberg, Karin; Peretto, Nicolas; Sievers, Albrecht; Tremblin, Pascal

2018-02-01

Context. Previous attempts at segmenting molecular line maps of molecular clouds have focused on using position-position-velocity data cubes of a single molecular line to separate the spatial components of the cloud. In contrast, wide field spectral imaging over a large spectral bandwidth in the (sub)mm domain now allows one to combine multiple molecular tracers to understand the different physical and chemical phases that constitute giant molecular clouds (GMCs). Aims: We aim at using multiple tracers (sensitive to different physical processes and conditions) to segment a molecular cloud into physically/chemically similar regions (rather than spatially connected components), thus disentangling the different physical/chemical phases present in the cloud. Methods: We use a machine learning clustering method, namely the Meanshift algorithm, to cluster pixels with similar molecular emission, ignoring spatial information. Clusters are defined around each maximum of the multidimensional probability density function (PDF) of the line integrated intensities. Simple radiative transfer models were used to interpret the astrophysical information uncovered by the clustering analysis. Results: A clustering analysis based only on the J = 1-0 lines of three isotopologues of CO proves sufficient to reveal distinct density/column density regimes (nH 100 cm-3, 500 cm-3, and >1000 cm-3), closely related to the usual definitions of diffuse, translucent and high-column-density regions. Adding two UV-sensitive tracers, the J = 1-0 line of HCO+ and the N = 1-0 line of CN, allows us to distinguish two clearly distinct chemical regimes, characteristic of UV-illuminated and UV-shielded gas. The UV-illuminated regime shows overbright HCO+ and CN emission, which we relate to a photochemical enrichment effect. We also find a tail of high CN/HCO+ intensity ratio in UV-illuminated regions. Finer distinctions in density classes (nH 7 × 103 cm-3, 4 × 104 cm-3) for the densest regions are also

Molecular Combing of DNA: Methods and Applications

DEFF Research Database (Denmark)

Nazari, Zeniab Esmail; Gurevich, Leonid

2013-01-01

studies to nanoelectronics. While molecular combing has been applied in a variety of DNA-related studies, no comprehensive review has been published on different combing methods proposed so far. In this review, the underlying mechanisms of molecular combing of DNA are described followed by discussion...

Transcriptome analysis reveals molecular anthelmintic effects of procyanidins in C. elegans.

Directory of Open Access Journals (Sweden)

Verena Spiegler

Full Text Available Worldwide, more than 1 billion people are affected by infestations with soil-transmitted helminths and also in veterinary medicine helminthiases are a severe threat to livestock due to emerging resistances against the common anthelmintics. Proanthocyanidins have been increasingly investigated for their anthelmintic properties, however, except for an interaction with certain proteins of the nematodes, not much is known about their mode of action. To investigate the anthelmintic activity on a molecular level, a transcriptome analysis was performed in Caenorhabditis elegans after treatment with purified and fully characterized oligomeric procyanidins (OPC. The OPCs had previously been obtained from a hydro-ethanolic (1:1 extract from the leaves of Combretum mucronatum, a plant which is traditionally used in West Africa for the treatment of helminthiasis, therefore, also the crude extract was included in the study. Significant changes in differential gene expression were observed mainly for proteins related to the intestine, many of which were located extracellularly or within cellular membranes. Among the up-regulated genes, several hitherto undescribed orthologues of structural proteins in humans were identified, but also genes that are potentially involved in the worms' defense against tannins. For example, T22D1.2, an orthologue of human basic salivary proline-rich protein (PRB 2, and numr-1 (nuclear localized metal responsive were found to be strongly up-regulated. Down-regulated genes were mainly associated with lysosomal activity, glycoside hydrolysis or the worms' innate immune response. No major differences were found between the groups treated with purified OPCs versus the crude extract. Investigations using GFP reporter gene constructs of T22D1.2 and numr-1 corroborated the intestine as the predominant site of the anthelmintic activity. The current findings support previous hypotheses of OPCs interacting with intestinal surface proteins

MOLECULAR GAS ALONG A BRIGHT H α FILAMENT IN 2A 0335+096 REVEALED BY ALMA

Energy Technology Data Exchange (ETDEWEB)

Vantyghem, A. N.; McNamara, B. R.; Hogan, M. T. [Department of Physics and Astronomy, University of Waterloo, Waterloo, ON N2L 3G1 (Canada); Russell, H. R.; Fabian, A. C. [Institute of Astronomy, Madingley Road, Cambridge CB3 0HA (United Kingdom); Edge, A. C. [Department of Physics, Durham University, Durham DH1 3LE (United Kingdom); Nulsen, P. E. J. [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Combes, F.; Salomé, P. [LERMA, Observatoire de Paris, CNRS, UPMC, PSL Univ., 61 avenue de l’Observatoire, 75014 Paris (France); Baum, S. A.; O’Dea, C. P. [Department of Physics and Astronomy, University of Manitoba, Winnipeg, MB R3T 2N2 (Canada); Donahue, M.; Voit, G. M. [Department of Physics and Astronomy, Michigan State University, 567 Wilson Road, East Lansing, MI 48824 (United States); Main, R. A.; Murray, N. W.; Parrish, I. J [Canadian Institute for Theoretical Astrophysics, University of Toronto, 60 St. George Street, Toronto, ON M5S 3H8 (Canada); O’Connell, R. W. [Department of Astronomy, University of Virginia, P.O. Box 400235, Charlottesville, VA 22904 (United States); Oonk, J. B. R. [ASTRON, the Netherlands Institute for Radio Astronomy, Postbus 2, NL-7990 AA Dwingeloo (Netherlands); Sanders, J. S. [Max-Planck-Institut für extraterrestrische Physik, Giessenbachstrasse 1, D-85748 Garching (Germany); Tremblay, G., E-mail: a2vantyg@uwaterloo.ca [Department of Physics and Yale Center for Astronomy and Astrophysics, Yale University, 217 Prospect Street, New Haven, CT 06511 (United States)

2016-12-01

We present ALMA CO(1–0) and CO(3–2) observations of the brightest cluster galaxy (BCG) in the 2A 0335+096 galaxy cluster ( z  = 0.0346). The total molecular gas mass of 1.13 ± 0.15 × 10{sup 9} M {sub ⊙} is divided into two components: a nuclear region and a 7 kpc long dusty filament. The central molecular gas component accounts for 3.2 ± 0.4 × 10{sup 8} M {sub ⊙} of the total supply of cold gas. Instead of forming a rotationally supported ring or disk, it is composed of two distinct, blueshifted clumps south of the nucleus and a series of low-significance redshifted clumps extending toward a nearby companion galaxy. The velocity of the redshifted clouds increases with radius to a value consistent with the companion galaxy, suggesting that an interaction between these galaxies <20 Myr ago disrupted a pre-existing molecular gas reservoir within the BCG. Most of the molecular gas, 7.8 ± 0.9 × 10{sup 8} M {sub ⊙}, is located in the filament. The CO emission is co-spatial with a 10{sup 4} K emission-line nebula and soft X-rays from 0.5 keV gas, indicating that the molecular gas has cooled out of the intracluster medium over a period of 25–100 Myr. The filament trails an X-ray cavity, suggesting that the gas has cooled from low-entropy gas that has been lifted out of the cluster core and become thermally unstable. We are unable to distinguish between inflow and outflow along the filament with the present data. Cloud velocities along the filament are consistent with gravitational free-fall near the plane of the sky, although their increasing blueshifts with radius are consistent with outflow.

Step-flow anisotropy of the m-plane GaN (1100) grown under nitrogen-rich conditions by plasma-assisted molecular beam epitaxy

International Nuclear Information System (INIS)

Sawicka, Marta; Siekacz, Marcin; Skierbiszewski, Czeslaw; Turski, Henryk; Krysko, Marcin; DziePcielewski, Igor; Grzegory, Izabella; Smalc-Koziorowska, Julita

2011-01-01

The homoepitaxial growth of m-plane (1100) GaN was investigated by plasma-assisted molecular beam epitaxy under nitrogen-rich conditions. The surface morphologies as a function of sample miscut were studied, providing evidence for a strong growth anisotropy that is a consequence of the anisotropy of Ga adatom diffusion barriers on the m-plane surface recently calculated ab initio[Lymperakis and Neugebauer, Phys. Rev. B 79, 241308(R) (2009)]. We found that substrate miscut toward [0001] implies a step flow toward while substrate miscut toward [0001] causes formation of atomic steps either perpendicular or parallel to the [0001] direction, under N-rich conditions at 730 deg C. We describe the growth conditions for achieving atomically flat m-plane GaN layers with parallel atomic steps.

Ultrastructural and Molecular Analyses Reveal Enhanced Nucleolar Activity in Medicago truncatula Cells Overexpressing the MtTdp2α Gene

Science.gov (United States)

Macovei, Anca; Faè, Matteo; Biggiogera, Marco; de Sousa Araújo, Susana; Carbonera, Daniela; Balestrazzi, Alma

2018-01-01

The role of tyrosyl-DNA phosphodiesterase 2 (Tdp2) involved in the repair of 5′-end-blocking DNA lesions is still poorly explored in plants. To gain novel insights, Medicago truncatula suspension cultures overexpressing the MtTdp2α gene (Tdp2α-13C and Tdp2α-28 lines, respectively) and a control (CTRL) line carrying the empty vector were investigated. Transmission electron microscopy (TEM) revealed enlarged nucleoli (up to 44% expansion of the area, compared to CTRL), the presence of nucleolar vacuoles, increased frequency of multinucleolate cells (up to 4.3-fold compared to CTRL) and reduced number of ring-shaped nucleoli in Tdp2α-13C and Tdp2α-28 lines. Ultrastructural data suggesting for enhanced nucleolar activity in MtTdp2α-overexpressing lines were integrated with results from bromouridine incorporation. The latter revealed an increase of labeled transcripts in both Tdp2α-13C and Tdp2α-28 cells, within the nucleolus and in the extra-nucleolar region. MtTdp2α-overexpressing cells showed tolerance to etoposide, a selective inhibitor of DNA topoisomerase II, as evidenced by DNA diffusion assay. TEM analysis revealed etoposide-induced rearrangements within the nucleolus, resembling the nucleolar caps observed in animal cells under transcription impairment. Based on these findings it is evident that MtTdp2α-overexpression enhances nucleolar activity in plant cells. PMID:29868059

Ultrastructural and Molecular Analyses Reveal Enhanced Nucleolar Activity in Medicago truncatula Cells Overexpressing the MtTdp2α Gene

Directory of Open Access Journals (Sweden)

Anca Macovei

2018-05-01

Full Text Available The role of tyrosyl-DNA phosphodiesterase 2 (Tdp2 involved in the repair of 5′-end-blocking DNA lesions is still poorly explored in plants. To gain novel insights, Medicago truncatula suspension cultures overexpressing the MtTdp2α gene (Tdp2α-13C and Tdp2α-28 lines, respectively and a control (CTRL line carrying the empty vector were investigated. Transmission electron microscopy (TEM revealed enlarged nucleoli (up to 44% expansion of the area, compared to CTRL, the presence of nucleolar vacuoles, increased frequency of multinucleolate cells (up to 4.3-fold compared to CTRL and reduced number of ring-shaped nucleoli in Tdp2α-13C and Tdp2α-28 lines. Ultrastructural data suggesting for enhanced nucleolar activity in MtTdp2α-overexpressing lines were integrated with results from bromouridine incorporation. The latter revealed an increase of labeled transcripts in both Tdp2α-13C and Tdp2α-28 cells, within the nucleolus and in the extra-nucleolar region. MtTdp2α-overexpressing cells showed tolerance to etoposide, a selective inhibitor of DNA topoisomerase II, as evidenced by DNA diffusion assay. TEM analysis revealed etoposide-induced rearrangements within the nucleolus, resembling the nucleolar caps observed in animal cells under transcription impairment. Based on these findings it is evident that MtTdp2α-overexpression enhances nucleolar activity in plant cells.

Molecular profiling of interspecific lowland rice populations derived ...

African Journals Online (AJOL)

STORAGESEVER

2008-12-03

Dec 3, 2008 ... Molecular profiling of interspecific lowland rice populations ... Both cluster and principal component analyses revealed two major groups ...... simulations. Theor ... inheritance, chromosomal location, and population dynamics.

The Brassica oleracea genome reveals the asymmetrical evolution of polyploid genomes

Science.gov (United States)

Liu, Shengyi; Liu, Yumei; Yang, Xinhua; Tong, Chaobo; Edwards, David; Parkin, Isobel A. P.; Zhao, Meixia; Ma, Jianxin; Yu, Jingyin; Huang, Shunmou; Wang, Xiyin; Wang, Junyi; Lu, Kun; Fang, Zhiyuan; Bancroft, Ian; Yang, Tae-Jin; Hu, Qiong; Wang, Xinfa; Yue, Zhen; Li, Haojie; Yang, Linfeng; Wu, Jian; Zhou, Qing; Wang, Wanxin; King, Graham J; Pires, J. Chris; Lu, Changxin; Wu, Zhangyan; Sampath, Perumal; Wang, Zhuo; Guo, Hui; Pan, Shengkai; Yang, Limei; Min, Jiumeng; Zhang, Dong; Jin, Dianchuan; Li, Wanshun; Belcram, Harry; Tu, Jinxing; Guan, Mei; Qi, Cunkou; Du, Dezhi; Li, Jiana; Jiang, Liangcai; Batley, Jacqueline; Sharpe, Andrew G; Park, Beom-Seok; Ruperao, Pradeep; Cheng, Feng; Waminal, Nomar Espinosa; Huang, Yin; Dong, Caihua; Wang, Li; Li, Jingping; Hu, Zhiyong; Zhuang, Mu; Huang, Yi; Huang, Junyan; Shi, Jiaqin; Mei, Desheng; Liu, Jing; Lee, Tae-Ho; Wang, Jinpeng; Jin, Huizhe; Li, Zaiyun; Li, Xun; Zhang, Jiefu; Xiao, Lu; Zhou, Yongming; Liu, Zhongsong; Liu, Xuequn; Qin, Rui; Tang, Xu; Liu, Wenbin; Wang, Yupeng; Zhang, Yangyong; Lee, Jonghoon; Kim, Hyun Hee; Denoeud, France; Xu, Xun; Liang, Xinming; Hua, Wei; Wang, Xiaowu; Wang, Jun; Chalhoub, Boulos; Paterson, Andrew H

2014-01-01

Polyploidization has provided much genetic variation for plant adaptive evolution, but the mechanisms by which the molecular evolution of polyploid genomes establishes genetic architecture underlying species differentiation are unclear. Brassica is an ideal model to increase knowledge of polyploid evolution. Here we describe a draft genome sequence of Brassica oleracea, comparing it with that of its sister species B. rapa to reveal numerous chromosome rearrangements and asymmetrical gene loss in duplicated genomic blocks, asymmetrical amplification of transposable elements, differential gene co-retention for specific pathways and variation in gene expression, including alternative splicing, among a large number of paralogous and orthologous genes. Genes related to the production of anticancer phytochemicals and morphological variations illustrate consequences of genome duplication and gene divergence, imparting biochemical and morphological variation to B. oleracea. This study provides insights into Brassica genome evolution and will underpin research into the many important crops in this genus. PMID:24852848

Molecular processes of transgenerational acclimation to a warming ocean

KAUST Repository

Veilleux, Heather D.; Ryu, Tae Woo; Donelson, Jennifer M.; van Herwerden, Lynne; Seridi, Loqmane; Ghosheh, Yanal; Berumen, Michael L.; Leggat, William; Ravasi, Timothy; Munday, Philip L.

2015-01-01

Some animals have the remarkable capacity to acclimate across generations to projected future climate change1, 2, 3, 4; however, the underlying molecular processes are unknown. We sequenced and assembled de novo transcriptomes of adult tropical reef fish exposed developmentally or transgenerationally to projected future ocean temperatures and correlated the resulting expression profiles with acclimated metabolic traits from the same fish. We identified 69 contigs representing 53 key genes involved in thermal acclimation of aerobic capacity. Metabolic genes were among the most upregulated transgenerationally, suggesting shifts in energy production for maintaining performance at elevated temperatures. Furthermore, immune- and stress-responsive genes were upregulated transgenerationally, indicating a new complement of genes allowing the second generation of fish to better cope with elevated temperatures. Other differentially expressed genes were involved with tissue development and transcriptional regulation. Overall, we found a similar suite of differentially expressed genes among developmental and transgenerational treatments. Heat-shock protein genes were surprisingly unresponsive, indicating that short-term heat-stress responses may not be a good indicator of long-term acclimation capacity. Our results are the first to reveal the molecular processes that may enable marine fishes to adjust to a future warmer environment over multiple generations.

Molecular processes of transgenerational acclimation to a warming ocean

KAUST Repository

Veilleux, Heather D.

2015-07-20

Some animals have the remarkable capacity to acclimate across generations to projected future climate change1, 2, 3, 4; however, the underlying molecular processes are unknown. We sequenced and assembled de novo transcriptomes of adult tropical reef fish exposed developmentally or transgenerationally to projected future ocean temperatures and correlated the resulting expression profiles with acclimated metabolic traits from the same fish. We identified 69 contigs representing 53 key genes involved in thermal acclimation of aerobic capacity. Metabolic genes were among the most upregulated transgenerationally, suggesting shifts in energy production for maintaining performance at elevated temperatures. Furthermore, immune- and stress-responsive genes were upregulated transgenerationally, indicating a new complement of genes allowing the second generation of fish to better cope with elevated temperatures. Other differentially expressed genes were involved with tissue development and transcriptional regulation. Overall, we found a similar suite of differentially expressed genes among developmental and transgenerational treatments. Heat-shock protein genes were surprisingly unresponsive, indicating that short-term heat-stress responses may not be a good indicator of long-term acclimation capacity. Our results are the first to reveal the molecular processes that may enable marine fishes to adjust to a future warmer environment over multiple generations.

The coherence lifetime-borrowing effect in vibronically coupled molecular aggregates under non-perturbative system-environment interactions.

Science.gov (United States)

Yeh, Shu-Hao; Engel, Gregory S.; Kais, Sabre

Recently it has been suggested that the long-lived coherences in some photosynthetic pigment-protein systems, such as the Fenna-Matthews-Olson complex, could be attributed to the mixing of the pigments' electronic and vibrational degrees of freedom. In order to verify whether this is the case and to understand its underlying mechanism, a theoretical model capable of including both the electronic excitations and intramolecular vibrational modes of the pigments is necessary. Our model simultaneously considers the electronic and vibrational degrees of freedom, treating the system-environment interactions non-perturbatively by implementing the hierarchical equations of motion approach. Here we report the simulated two-dimensional electronic spectra of vibronically coupled molecular dimers to demonstrate how the electronic coherence lifetimes can be extended by borrowing the lifetime from the vibrational coherences. Funded by Qatar National Research Fund and Qatar Environment and Energy Research Institute.

Efficient Characterization of Protein Cavities within Molecular Simulation Trajectories: trj_cavity.

Science.gov (United States)

Paramo, Teresa; East, Alexandra; Garzón, Diana; Ulmschneider, Martin B; Bond, Peter J

2014-05-13

Protein cavities and tunnels are critical in determining phenomena such as ligand binding, molecular transport, and enzyme catalysis. Molecular dynamics (MD) simulations enable the exploration of the flexibility and conformational plasticity of protein cavities, extending the information available from static experimental structures relevant to, for example, drug design. Here, we present a new tool (trj_cavity) implemented within the GROMACS ( www.gromacs.org ) framework for the rapid identification and characterization of cavities detected within MD trajectories. trj_cavity is optimized for usability and computational efficiency and is applicable to the time-dependent analysis of any cavity topology, and optional specialized descriptors can be used to characterize, for example, protein channels. Its novel grid-based algorithm performs an efficient neighbor search whose calculation time is linear with system size, and a comparison of performance with other widely used cavity analysis programs reveals an orders-of-magnitude improvement in the computational cost. To demonstrate its potential for revealing novel mechanistic insights, trj_cavity has been used to analyze long-time scale simulation trajectories for three diverse protein cavity systems. This has helped to reveal, respectively, the lipid binding mechanism in the deep hydrophobic cavity of a soluble mite-allergen protein, Der p 2; a means for shuttling carbohydrates between the surface-exposed substrate-binding and catalytic pockets of a multidomain, membrane-proximal pullulanase, PulA; and the structural basis for selectivity in the transmembrane pore of a voltage-gated sodium channel (NavMs), embedded within a lipid bilayer environment. trj_cavity is available for download under an open-source license ( http://sourceforge.net/projects/trjcavity ). A simplified, GROMACS-independent version may also be compiled.

Revealing metabolite biomarkers for acupuncture treatment by linear programming based feature selection.

Science.gov (United States)

Wang, Yong; Wu, Qiao-Feng; Chen, Chen; Wu, Ling-Yun; Yan, Xian-Zhong; Yu, Shu-Guang; Zhang, Xiang-Sun; Liang, Fan-Rong

2012-01-01

Acupuncture has been practiced in China for thousands of years as part of the Traditional Chinese Medicine (TCM) and has gradually accepted in western countries as an alternative or complementary treatment. However, the underlying mechanism of acupuncture, especially whether there exists any difference between varies acupoints, remains largely unknown, which hinders its widespread use. In this study, we develop a novel Linear Programming based Feature Selection method (LPFS) to understand the mechanism of acupuncture effect, at molecular level, by revealing the metabolite biomarkers for acupuncture treatment. Specifically, we generate and investigate the high-throughput metabolic profiles of acupuncture treatment at several acupoints in human. To select the subsets of metabolites that best characterize the acupuncture effect for each meridian point, an optimization model is proposed to identify biomarkers from high-dimensional metabolic data from case and control samples. Importantly, we use nearest centroid as the prototype to simultaneously minimize the number of selected features and the leave-one-out cross validation error of classifier. We compared the performance of LPFS to several state-of-the-art methods, such as SVM recursive feature elimination (SVM-RFE) and sparse multinomial logistic regression approach (SMLR). We find that our LPFS method tends to reveal a small set of metabolites with small standard deviation and large shifts, which exactly serves our requirement for good biomarker. Biologically, several metabolite biomarkers for acupuncture treatment are revealed and serve as the candidates for further mechanism investigation. Also biomakers derived from five meridian points, Zusanli (ST36), Liangmen (ST21), Juliao (ST3), Yanglingquan (GB34), and Weizhong (BL40), are compared for their similarity and difference, which provide evidence for the specificity of acupoints. Our result demonstrates that metabolic profiling might be a promising method to

Cardiovascular molecular imaging of apoptosis

International Nuclear Information System (INIS)

Wolters, S.L.; Reutelingsperger, C.P.M.; Corsten, M.F.; Hofstra, L.; Narula, J.

2007-01-01

Molecular imaging strives to visualise processes at the molecular and cellular level in vivo. Understanding these processes supports diagnosis and evaluation of therapeutic efficacy on an individual basis and thereby makes personalised medicine possible. Apoptosis is a well-organised mode of cell suicide that plays a role in cardiovascular diseases (CVD). Apoptosis is associated with loss of cardiomyocytes following myocardial infarction, atherosclerotic plaque instability, congestive heart failure and allograft rejection of the transplanted heart. Thus, apoptosis constitutes an attractive target for molecular imaging of CVD. Our current knowledge about the molecular players and mechanisms underlying apoptosis offers a rich palette of potential molecular targets for molecular imaging. However, only a few have been successfully developed so far. This review highlights aspects of the molecular machinery and biochemistry of apoptosis relevant to the development of molecular imaging probes. It surveys the role of apoptosis in four major areas of CVD and portrays the importance and future perspectives of apoptosis imaging. The annexin A5 imaging protocol is emphasised since it is the most advanced protocol to measure apoptosis in both preclinical and clinical studies. (orig.)

Cardiovascular molecular imaging of apoptosis

Energy Technology Data Exchange (ETDEWEB)

Wolters, S.L.; Reutelingsperger, C.P.M. [Maastricht University, Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht (Netherlands); Corsten, M.F.; Hofstra, L. [Maastricht University, Department of Cardiology, Cardiovascular Research Institute Maastricht, P.O. Box 616, Maastricht (Netherlands); Narula, J. [University of California Irvine, Department of Cardiology, Irvine (United States)

2007-06-15

Molecular imaging strives to visualise processes at the molecular and cellular level in vivo. Understanding these processes supports diagnosis and evaluation of therapeutic efficacy on an individual basis and thereby makes personalised medicine possible. Apoptosis is a well-organised mode of cell suicide that plays a role in cardiovascular diseases (CVD). Apoptosis is associated with loss of cardiomyocytes following myocardial infarction, atherosclerotic plaque instability, congestive heart failure and allograft rejection of the transplanted heart. Thus, apoptosis constitutes an attractive target for molecular imaging of CVD. Our current knowledge about the molecular players and mechanisms underlying apoptosis offers a rich palette of potential molecular targets for molecular imaging. However, only a few have been successfully developed so far. This review highlights aspects of the molecular machinery and biochemistry of apoptosis relevant to the development of molecular imaging probes. It surveys the role of apoptosis in four major areas of CVD and portrays the importance and future perspectives of apoptosis imaging. The annexin A5 imaging protocol is emphasised since it is the most advanced protocol to measure apoptosis in both preclinical and clinical studies. (orig.)

Evolutionary history of genus Macrobrachium inferred from mitochondrial markers: a molecular clock approach.

Science.gov (United States)

Jose, Deepak; Harikrishnan, Mahadevan

2018-04-17

Caridea, an infraorder of shrimps coming under Pleocyemata was first reported from the oceans before 417 million years followed by their radiation recorded during the Permian period. Hitherto, about 3877 extant caridean species were accounted within which one quarter constitute freshwater species. Freshwater prawns of genus Macrobrachium (Infraorder Caridea; Family Palaemonidae), with more than 240 species are inhabitants of diverse aquatic habitats like coastal lagoons, lakes, tropical streams, ponds and rivers. Previous studies on Macrobrachium relied on the highly variable morphological characters which were insufficient for accurate diagnosis of natural species groups. Present study focuses on the utility of molecular markers (viz. COI and 16S rRNA) for resolving the evolutionary history of genus Macrobrachium using a combination of phylogeny and timescale components. It is for the first time a molecular clock approach had been carried out towards genus Macrobrachium in a broad aspect with the incorporation of congeners inhabiting diverse geographical realms including endemic species M. striatum from South West coast of India. Molecular results obtained revealed the phylogenetic relationships between congeners of genus Macrobrachium at intra/inter-continental level along with the corresponding evolutionary time estimates.

Prospects of molecular markers in Fusarium species diversity

DEFF Research Database (Denmark)

Nayaka, S. Chandra; Wulff, Ednar Gadelha; Udayashankar, A.C.

2011-01-01

focuses of various molecular-based techniques employed to study the diversity of Fusarium species causing diseases in major food crops. An introduction of fusarial diseases and their mycotoxins and molecular-marker-based methods for detection introduce the concept of marker application. Various well...... for generation of probes and their use in phylogeny of Fusarium spp. are also presented. The concluding part emphasizes the value of molecular markers for assessing genetic variability and reveals that molecular tools are indispensable for providing information not only of one Fusarium species but on whole......-known molecular techniques such as random amplified polymorphic DNA, amplification fragment length polymorphism, etc. to more modern ones such as DNA microarrays, DNA barcoding, and pyrosequencing and their application form the core of the review. Target regions in the genome which can be potential candidates...

Molecular scale

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Christopher H. Childers

2016-03-01

Full Text Available This manuscript demonstrates the molecular scale cure rate dependence of di-functional epoxide based thermoset polymers cured with amines. A series of cure heating ramp rates were used to determine the influence of ramp rate on the glass transition temperature (Tg and sub-Tg transitions and the average free volume hole size in these systems. The networks were comprised of 3,3′-diaminodiphenyl sulfone (33DDS and diglycidyl ether of bisphenol F (DGEBF and were cured at ramp rates ranging from 0.5 to 20 °C/min. Differential scanning calorimetry (DSC and NIR spectroscopy were used to explore the cure ramp rate dependence of the polymer network growth, whereas broadband dielectric spectroscopy (BDS and free volume hole size measurements were used to interrogate networks’ molecular level structural variations upon curing at variable heating ramp rates. It was found that although the Tg of the polymer matrices was similar, the NIR and DSC measurements revealed a strong correlation for how these networks grow in relation to the cure heating ramp rate. The free volume analysis and BDS results for the cured samples suggest differences in the molecular architecture of the matrix polymers due to cure heating rate dependence.

Molecular mechanism underlying juvenile hormone-mediated repression of precocious larval-adult metamorphosis.

Science.gov (United States)

Kayukawa, Takumi; Jouraku, Akiya; Ito, Yuka; Shinoda, Tetsuro

2017-01-31

Juvenile hormone (JH) represses precocious metamorphosis of larval to pupal and adult transitions in holometabolous insects. The early JH-inducible gene Krüppel homolog 1 (Kr-h1) plays a key role in the repression of metamorphosis as a mediator of JH action. Previous studies demonstrated that Kr-h1 inhibits precocious larval-pupal transition in immature larva via direct transcriptional repression of the pupal specifier Broad-Complex (BR-C). JH was recently reported to repress the adult specifier gene Ecdysone-induced protein 93F (E93); however, its mechanism of action remains unclear. Here, we found that JH suppressed ecdysone-inducible E93 expression in the epidermis of the silkworm Bombyx mori and in a B. mori cell line. Reporter assays in the cell line revealed that the JH-dependent suppression was mediated by Kr-h1. Genome-wide ChIP-seq analysis identified a consensus Kr-h1 binding site (KBS, 14 bp) located in the E93 promoter region, and EMSA confirmed that Kr-h1 directly binds to the KBS. Moreover, we identified a C-terminal conserved domain in Kr-h1 essential for the transcriptional repression of E93 Based on these results, we propose a mechanism in which JH-inducible Kr-h1 directly binds to the KBS site upstream of the E93 locus to repress its transcription in a cell-autonomous manner, thereby preventing larva from bypassing the pupal stage and progressing to precocious adult development. These findings help to elucidate the molecular mechanisms regulating the metamorphic genetic network, including the functional significance of Kr-h1, BR-C, and E93 in holometabolous insect metamorphosis.

Oxytetracycline recovery from aqueous media using computationally designed molecularly imprinted polymers.

Science.gov (United States)

Rodríguez-Dorado, Rosalía; Carro, Antonia M; Chianella, Iva; Karim, Kal; Concheiro, Angel; Lorenzo, Rosa A; Piletsky, Sergey; Alvarez-Lorenzo, Carmen

2016-09-01

Polymers for recovery/removal of the antimicrobial agent oxytetracycline (OTC) from aqueous media were developed with use of computational design and molecular imprinting. 2-Hydroxyethyl methacrylate, 2-acrylamide-2-methylpropane sulfonic acid (AMPS), and mixtures of the two were chosen according to their predicted affinity for OTC and evaluated as functional monomers in molecularly imprinted polymers and nonimprinted polymers. Two levels of AMPS were tested. After bulk polymerization, the polymers were crushed into particles (200-1000 μm). Pressurized liquid extraction was implemented for template removal with a low amount of methanol (less than 20 mL in each extraction) and a few extractions (12-18 for each polymer) in a short period (20 min per extraction). Particle size distribution, microporous structure, and capacity to rebind OTC from aqueous media were evaluated. Adsorption isotherms obtained from OTC solutions (30-110 mg L(-1)) revealed that the polymers prepared with AMPS had the highest affinity for OTC. The uptake capacity depended on the ionic strength as follows: purified water > saline solution (0.9 % NaCl) > seawater (3.5 % NaCl). Polymer particles containing AMPS as a functional monomer showed a remarkable ability to clean water contaminated with OTC. The usefulness of the stationary phase developed for molecularly imprinted solid-phase extraction was also demonstrated. Graphical Abstract Selection of functional monomers by molecular modeling renders polymer networks suitable for removal of pollutants from contaminated aqueous environments, under either dynamic or static conditions.

Site-discrimination by molecular imposters at dissymmetric molecular crystal surfaces

Science.gov (United States)

Poloni, Laura N.

The organization of atoms and molecules into crystalline forms is ubiquitous in nature and has been critical to the development of many technologies on which modern society relies. Classical crystal growth theory can describe atomic crystal growth, however, a description of molecular crystal growth is lacking. Molecular crystals are often characterized by anisotropic intermolecular interactions and dissymmetric crystal surfaces with anisotropic growth rates along different crystallographic directions. This thesis describes combination of experimental and computational techniques to relate crystal structure to surface structure and observed growth rates. Molecular imposters, also known as tailor-made impurities, can be used to control crystal growth for practical applications such as inhibition of pathological crystals, but can also be used to understand site specificity at crystal growth surfaces. The first part of this thesis builds on previous real-time in situ atomic force microscopy (AFM) observations of dislocation-actuated growth on the morphologically significant face of hexagonal L-cystine crystals, which aggregate in vivo to form kidney stones in patients suffering from cystinuria. The inhibitory effect of various L-cystine structural mimics (a.k.a. molecular imposters) was investigated through experimental and computational methods to identify the key structural factors responsible for molecular recognition between molecular imposters and L-cystine crystal surface sites. The investigation of L-cystine crystal growth in the presence of molecular imposters through a combination of kinetic analysis using in situ AFM, morphology analysis and birefringence measurements of bulk crystals, and molecular modeling of imposter binding to energetically inequivalent surface sites revealed that different molecular imposters inhibited crystal growth by a Cabrera-Vermilyea pinning mechanism and that imposters bind to a single binding site on the dissymmetric {1000} L

Toward tunable doping in graphene FETs by molecular self-assembled monolayers

Science.gov (United States)

Li, Bing; Klekachev, Alexander V.; Cantoro, Mirco; Huyghebaert, Cedric; Stesmans, André; Asselberghs, Inge; de Gendt, Stefan; de Feyter, Steven

2013-09-01

In this paper, we report the formation of self-assembled monolayers (SAMs) of oleylamine (OA) on highly oriented pyrolytic graphite (HOPG) and graphene surfaces and demonstrate the potential of using such organic SAMs to tailor the electronic properties of graphene. Molecular resolution Atomic Force Microscopy (AFM) and Scanning Tunneling Microscopy (STM) images reveal the detailed molecular ordering. The electrical measurements show that OA strongly interacts with graphene leading to n-doping effects in graphene devices. The doping levels are tunable by varying the OA deposition conditions. Importantly, neither hole nor electron mobilities are decreased by the OA modification. As a benefit from this noncovalent modification strategy, the pristine characteristics of the device are recoverable upon OA removal. From this study, one can envision the possibility to correlate the graphene-based device performance with the molecular structure and supramolecular ordering of the organic dopant.In this paper, we report the formation of self-assembled monolayers (SAMs) of oleylamine (OA) on highly oriented pyrolytic graphite (HOPG) and graphene surfaces and demonstrate the potential of using such organic SAMs to tailor the electronic properties of graphene. Molecular resolution Atomic Force Microscopy (AFM) and Scanning Tunneling Microscopy (STM) images reveal the detailed molecular ordering. The electrical measurements show that OA strongly interacts with graphene leading to n-doping effects in graphene devices. The doping levels are tunable by varying the OA deposition conditions. Importantly, neither hole nor electron mobilities are decreased by the OA modification. As a benefit from this noncovalent modification strategy, the pristine characteristics of the device are recoverable upon OA removal. From this study, one can envision the possibility to correlate the graphene-based device performance with the molecular structure and supramolecular ordering of the organic

Signalling pathways involved in adult heart formation revealed by gene expression profiling in Drosophila.

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Bruno Zeitouni

2007-10-01

Full Text Available Drosophila provides a powerful system for defining the complex genetic programs that drive organogenesis. Under control of the steroid hormone ecdysone, the adult heart in Drosophila forms during metamorphosis by a remodelling of the larval cardiac organ. Here, we evaluated the extent to which transcriptional signatures revealed by genomic approaches can provide new insights into the molecular pathways that underlie heart organogenesis. Whole-genome expression profiling at eight successive time-points covering adult heart formation revealed a highly dynamic temporal map of gene expression through 13 transcript clusters with distinct expression kinetics. A functional atlas of the transcriptome profile strikingly points to the genomic transcriptional response of the ecdysone cascade, and a sharp regulation of key components belonging to a few evolutionarily conserved signalling pathways. A reverse genetic analysis provided evidence that these specific signalling pathways are involved in discrete steps of adult heart formation. In particular, the Wnt signalling pathway is shown to participate in inflow tract and cardiomyocyte differentiation, while activation of the PDGF-VEGF pathway is required for cardiac valve formation. Thus, a detailed temporal map of gene expression can reveal signalling pathways responsible for specific developmental programs and provides here substantial grasp into heart formation.

Azadirachtin(A) distinctively modulates subdomain 2 of actin - novel mechanism to induce depolymerization revealed by molecular dynamics study.

Science.gov (United States)

Pravin Kumar, R; Roopa, L; Sudheer Mohammed, M M; Kulkarni, Naveen

2016-12-01

Azadirachtin(A) (AZA), a potential insecticide from neem, binds to actin and induces depolymerization in Drosophila. AZA binds to the pocket same as that of Latrunculin A (LAT), but LAT inhibits actin polymerization by stiffening the actin structure and affects the ADP-ATP exchange. The mechanism by which AZA induces actin depolymerization is not clearly understood. Therefore, different computational experiments were conducted to delineate the precise mechanism of AZA-induced actin depolymerization. Molecular dynamics studies showed that AZA strongly interacted with subdomain 2 and destabilized the interactions between subdomain 2 of one actin and subdomains 1 and 4 of the adjacent actin, causing the separation of actin subunits. The separation was observed between subdomain 3 of subunit n and subdomain 4 of subunit n + 2. However, the specific triggering point for the separation of the subunits was the destabilization of direct interactions between subdomain 2 of subunit n (Arg39, Val45, Gly46 and Arg62) and subdomain 4 of subunit n + 2 (Asp286, Ile287, Asp288, Ile289, Asp244 and Lys291). These results reveal a unique mechanism of an actin filament modulator that induces depolymerization. This mechanism of AZA can be used to design similar molecules against mammalian actins for cancer therapy.

Host and Non-Host roots in rice: cellular and molecular approaches reveal differential responses to arbuscular mycorrhizal fungi.

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Valentina eFiorilli

2015-08-01

Full Text Available Oryza sativa, a model plant for Arbuscular Mycorrhizal (AM symbiosis, has both host and non-host roots. Large lateral (LLR and fine lateral (FLR roots display opposite responses: LLR support AM colonization, but FLR do not. Our research aimed to study the molecular, morphological and physiological aspects related to the non-host behavior of FLR. RNA-seq analysis revealed that LLR and FLR displayed divergent expression profiles, including changes in many metabolic pathways. Compared with LLR, FLR showed down-regulation of genes instrumental for AM establishment and gibberellin signaling, and a higher expression of nutrient transporters. Consistent with the transcriptomic data, FLR had higher phosphorus content. Light and electron microscopy demonstrated that, surprisingly, in the Selenio cultivar, FLR have a two-layered cortex, which is theoretically compatible with AM colonization. According to RNA-seq, a gibberellin inhibitor treatment increased anticlinal divisions leading to a higher number of cortex cells in FLR.We propose that some of the differentially regulated genes that lead to the anatomical and physiological properties of the two root types also function as genetic factors regulating fungal colonization. The rice root apparatus offers a unique tool to study AM symbiosis, allowing direct comparisons of host and non-host roots in the same individual plant.

A Novel Drug-Mouse Phenotypic Similarity Method Detects Molecular Determinants of Drug Effects.

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Jeanette Prinz

2016-09-01

Full Text Available The molecular mechanisms that translate drug treatment into beneficial and unwanted effects are largely unknown. We present here a novel approach to detect gene-drug and gene-side effect associations based on the phenotypic similarity of drugs and single gene perturbations in mice that account for the polypharmacological property of drugs. We scored the phenotypic similarity of human side effect profiles of 1,667 small molecules and biologicals to profiles of phenotypic traits of 5,384 mouse genes. The benchmarking with known relationships revealed a strong enrichment of physical and indirect drug-target connections, causative drug target-side effect links as well as gene-drug links involved in pharmacogenetic associations among phenotypically similar gene-drug pairs. The validation by in vitro assays and the experimental verification of an unknown connection between oxandrolone and prokineticin receptor 2 reinforces the ability of this method to provide new molecular insights underlying drug treatment. Thus, this approach may aid in the proposal of novel and personalized treatments.

Molecularly targeted therapeutic radiopharmaceuticals

International Nuclear Information System (INIS)

Saw, M.M.

2007-01-01

Full text: It is generally agreed that current focus of nuclear medicine development should be on molecular imaging and therapy. Though, the widespread use of the terminology 'molecular imaging' is quite recent, nuclear medicine has used molecular imaging techniques for more than 20 years ago. A variety of radiopharmaceuticals have been introduced for the internal therapy of malignant and inflammatory lesions in nuclear medicine. In the field of bio/medical imaging, nuclear medicine is one of the disciplines which has the privilege of organized and well developed chemistry/ pharmacy section; radio-chemistry/radiopharmacy. Fundamental principles have been developed more than 40 years ago and advanced research is going well into postgenomic era. The genomic revolution and dramatically increased insight in the molecular mechanisms underlying pathology have led to paradigm shift in drug development. Likewise does in the nuclear medicine. Here, the author will present current clinical and pre-clinical therapeutic radiopharmaceuticals based on molecular targets such as membrane-bound receptors, enzymes, nucleic acids, sodium iodide symporter, etc, in correlation with fundamentals of radiopharmacy. (author)

Mass transport thermodynamics in nonisothermal molecular liquid mixtures

Energy Technology Data Exchange (ETDEWEB)

Semenov, Semen N [Institute for Biochemical Physics, Russian Academy of Sciences, Moscow (Russian Federation); Schimpf, M E [Department of Chemistry and Biochemistry, Boise State University, Boise, ID (United States)

2009-10-31

Mass transport in a nonisothermal binary molecular mixture is systematically discussed in terms of nonequilibrium thermodynamics, which for the first time allows a consistent and unambiguous description of the process. The thermodynamic and hydrodynamic approaches are compared, revealing that nonequilibrium thermodynamics and physicochemical hydrodynamics yield essentially the same results for molecular systems. The applicability limits for the proposed version of the thermodynamic approach are determined for large particles. (methodological notes)

ORIGIN AND KINEMATICS OF THE ERUPTIVE FLOW FROM XZ TAU REVEALED BY ALMA

Energy Technology Data Exchange (ETDEWEB)

Zapata, Luis A.; Galván-Madrid, Roberto; Carrasco-González, Carlos; Palau, Aina; Rodríguez, Luis F.; Kurtz, Stan E.; Tafoya, Daniel; Loinard, Laurent [Centro de Radioastronomía y Astrofísica, UNAM, Apdo. Postal 3-72 (Xangari), 58089 Morelia, Michoacán, México (Mexico); Curiel, Salvador [Instituto de Astronomía, Universidad Nacional Autónoma de México, Ap. 70-264, 04510 DF, México (Mexico)

2015-09-20

We present high angular resolution (∼0.″94) {sup 12}CO(1-0) Atacama Large Millimeter/submillimeter Array (ALMA) observations obtained during the 2014 long baseline campaign from the eruptive bipolar flow from the multiple XZ Tau stellar system discovered by the Hubble Space Telescope (HST). These observations reveal, for the first time, the kinematics of the molecular flow. The kinematics of the different ejections close to XZ Tau reveal a rotating and expanding structure with a southeast–northwest velocity gradient. The youngest eruptive bubbles unveiled in the optical HST images are inside of this molecular expanding structure. Additionally, we report a very compact and collimated bipolar outflow emanating from XZ Tau A, which indicates that the eruptive outflow is indeed originating from this object. The mass (3 × 10{sup −7} M{sub ⊙}) and energetics (E{sub kin} = 3 × 10{sup 37} erg) for the collimated outflow are comparable to those found in molecular outflows associated with young brown dwarfs.

Pressure effects on martensitic transformation under quenching process in a molecular dynamics model of NiAl alloy

International Nuclear Information System (INIS)

Kazanc, S.; Ozgen, S.; Adiguzel, O.

2003-01-01

The solid-solid phase transitions in NiAl alloys occur by the temperature changes and application of a pressure on the system. Both types of transitions are called martensitic transformation and have displacive and thermoelastic characters. Pressure effects on thermoelastic transformation in Ni 62.5 Al 37.5 alloy model have been studied by means of molecular dynamics method proposed by Parrinello-Rahman. Interaction forces between atoms in the model system were calculated by Lennard-Jones potential energy function. Thermodynamics and structural analysis of the martensitic transformations under hydrostatic pressure during the quenching processes have been performed. The simulation runs have been carried out in different hydrostatic pressures changing from zero to 40.65 GPa during the quenching process of the model alloy. At the zero and nonzero pressures, the system with B2-type ordered structure undergoes the product phase with L1 0 -type ordered structure by Bain distortion in the first step of martensitic transformation under the quenching process. The increase in hydrostatic pressure causes decrease in the formation time of the product phase, and twin-like lattice distortion is observed in low temperature L1 0 phase

Molecular characterization of Acanthamoeba strains isolated from domestic dogs in Tenerife, Canary Islands, Spain.

Science.gov (United States)

Valladares, María; Reyes-Batlle, María; Martín-Navarro, Carmen M; López-Arencibia, Atteneri; Dorta-Gorrín, Alexis; Wagner, Carolina; Martínez-Carretero, Enrique; Piñero, José E; Valladares, Basilio; Lorenzo-Morales, Jacob

2015-06-01

The present study describes two cases of Acanthamoeba infections (keratitis and ascites/peritonitis) in small breed domestic dogs in Tenerife, Canary Islands, Spain. In both cases, amoebic trophozoites were observed under the inverted microscope and isolated from the infected tissues and/or fluids, without detecting the presence of other viral, fungal or bacterial pathogens. Amoebae were isolated using 2 % non-nutrient agar plates and axenified for further biochemical and molecular analyses. Osmotolerance and thermotolerance assays revealed that both isolates were able to grow up to 37 °C and 1 M of mannitol and were thus considered as potentially pathogenic. Moreover, the strains were classified as highly cytotoxic as they cause more than 75 % of toxicity when incubated with two eukaryotic cell lines. In order to classify the strains at the molecular level, the diagnostic fragment 3 (DF3) region of the 18S rDNA of Acanthamoeba was amplified and sequenced, revealing that both isolates belonged to genotype T4. In both cases, owners of the animals did not allow any further studies or follow-up and therefore the current status of these animals is unknown. Furthermore, the isolation of these pathogenic amoebae should raise awareness with the veterinary community locally and worldwide.

Riboflavin ameliorates cisplatin induced toxicities under photoillumination.

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Iftekhar Hassan

Full Text Available BACKGROUND: Cisplatin is an effective anticancer drug that elicits many side effects mainly due to induction of oxidative and nitrosative stresses during prolonged chemotherapy. The severity of these side effects consequently restricts its clinical use under long term treatment. Riboflavin is an essential vitamin used in various metabolic redox reactions in the form of flavin adenine dinucleotide and flavin mononucleotide. Besides, it has excellent photosensitizing property that can be used to ameliorate these toxicities in mice under photodynamic therapy. METHODS AND FINDINGS: Riboflavin, cisplatin and their combinations were given to the separate groups of mice under photoilluminated condition under specific treatment regime. Their kidney and liver were excised for comet assay and histopathological studies. Furthermore, Fourier Transform Infrared Spectroscopy of riboflavin-cisplatin combination in vitro was also conducted to investigate any possible interaction between the two compounds. Their comet assay and histopathological examination revealed that riboflavin in combination with cisplatin was able to protect the tissues from cisplatin induced toxicities and damages. Moreover, Fourier Transform Infrared Spectroscopy analysis of the combination indicated a strong molecular interaction among their constituent groups that may be assigned for the protective effect of the combination in the treated animals. CONCLUSION: Inclusion of riboflavin diminishes cisplatin induced toxicities which may possibly make the cisplatin-riboflavin combination, an effective treatment strategy under chemoradiotherapy in pronouncing its antineoplastic activity and sensitivity towards the cancer cells as compared to cisplatin alone.

Molecular dynamics simulations of the melting curve of NiAl alloy under pressure

International Nuclear Information System (INIS)

Zhang, Wenjin; Peng, Yufeng; Liu, Zhongli

2014-01-01

The melting curve of B2-NiAl alloy under pressure has been investigated using molecular dynamics technique and the embedded atom method (EAM) potential. The melting temperatures were determined with two approaches, the one-phase and the two-phase methods. The first one simulates a homogeneous melting, while the second one involves a heterogeneous melting of materials. Both approaches reduce the superheating effectively and their results are close to each other at the applied pressures. By fitting the well-known Simon equation to our melting data, we yielded the melting curves for NiAl: 1783(1 + P/9.801) 0.298 (one-phase approach), 1850(1 + P/12.806) 0.357 (two-phase approach). The good agreement of the resulting equation of states and the zero-pressure melting point (calc., 1850 ± 25 K, exp., 1911 K) with experiment proved the correctness of these results. These melting data complemented the absence of experimental high-pressure melting of NiAl. To check the transferability of this EAM potential, we have also predicted the melting curves of pure nickel and pure aluminum. Results show the calculated melting point of Nickel agrees well with experiment at zero pressure, while the melting point of aluminum is slightly higher than experiment

Probing flexible conformations in molecular junctions by inelastic electron tunneling spectroscopy

Energy Technology Data Exchange (ETDEWEB)

Deng, Mingsen [Department of Physics, Guizhou University, Guiyang, 550025 (China); Guizhou Provincial Key Laboratory of Computational Nano-Material Science, Institute of Applied Physics, Guizhou Normal College, Guiyang, 550018 (China); Ye, Gui; Jiang, Jun, E-mail: jiangj1@ustc.edu.cn [Department of Chemical Physics, School of Chemistry and Materials Science, University of Science and Technology of China, Hefei, 230026 (China); Cai, Shaohong, E-mail: caish@mail.gufe.edu.cn [Department of Physics, Guizhou University, Guiyang, 550025 (China); Guizhou Key Laboratory of Economic System Simulation, Guizhou University of Finance and Economics, Guiyang, 550004 (China); Sun, Guangyu [Guizhou Provincial Key Laboratory of Computational Nano-Material Science, Institute of Applied Physics, Guizhou Normal College, Guiyang, 550018 (China)

2015-01-15

The probe of flexible molecular conformation is crucial for the electric application of molecular systems. We have developed a theoretical procedure to analyze the couplings of molecular local vibrations with the electron transportation process, which enables us to evaluate the structural fingerprints of some vibrational modes in the inelastic electron tunneling spectroscopy (IETS). Based on a model molecule of Bis-(4-mercaptophenyl)-ether with a flexible center angle, we have revealed and validated a simple mathematical relationship between IETS signals and molecular angles. Our results might open a route to quantitatively measure key geometrical parameters of molecular junctions, which helps to achieve precise control of molecular devices.

Reversal to air-driven sound production revealed by a molecular phylogeny of tongueless frogs, family Pipidae

Directory of Open Access Journals (Sweden)

Glaw Frank

2011-04-01

Full Text Available Abstract Background Evolutionary novelties often appear by conferring completely new functions to pre-existing structures or by innovating the mechanism through which a particular function is performed. Sound production plays a central role in the behavior of frogs, which use their calls to delimit territories and attract mates. Therefore, frogs have evolved complex vocal structures capable of producing a wide variety of advertising sounds. It is generally acknowledged that most frogs call by moving an air column from the lungs through the glottis with the remarkable exception of the family Pipidae, whose members share a highly specialized sound production mechanism independent of air movement. Results Here, we performed behavioral observations in the poorly known African pipid genus Pseudhymenochirus and document that the sound production in this aquatic frog is almost certainly air-driven. However, morphological comparisons revealed an indisputable pipid nature of Pseudhymenochirus larynx. To place this paradoxical pattern into an evolutionary framework, we reconstructed robust molecular phylogenies of pipids based on complete mitochondrial genomes and nine nuclear protein-coding genes that coincided in placing Pseudhymenochirus nested among other pipids. Conclusions We conclude that although Pseudhymenochirus probably has evolved a reversal to the ancestral non-pipid condition of air-driven sound production, the mechanism through which it occurs is an evolutionary innovation based on the derived larynx of pipids. This strengthens the idea that evolutionary solutions to functional problems often emerge based on previous structures, and for this reason, innovations largely depend on possibilities and constraints predefined by the particular history of each lineage.

Transcriptional profiling of sugarcane leaves and roots under progressive osmotic stress reveals a regulated coordination of gene expression in a spatiotemporal manner.

Directory of Open Access Journals (Sweden)

Alejandro Pereira-Santana

Full Text Available Sugarcane is one of the most important crops worldwide and is a key plant for the global production of sucrose. Sugarcane cultivation is severely affected by drought stress and it is considered as the major limiting factor for their productivity. In recent years, this plant has been subjected to intensive research focused on improving its resilience against water scarcity; particularly the molecular mechanisms in response to drought stress have become an underlying issue for its improvement. To better understand water stress and the molecular mechanisms we performed a de novo transcriptomic assembly of sugarcane (var. Mex 69-290. A total of 16 libraries were sequenced in a 2x100 bp configuration on a HiSeq-Illumina platform. A total of 536 and 750 genes were differentially up-regulated along with the stress treatments for leave and root tissues respectively, while 1093 and 531 genes were differentially down-regulated in leaves and roots respectively. Gene Ontology functional analysis showed that genes related to response of water deprivation, heat, abscisic acid, and flavonoid biosynthesis were enriched during stress treatment in our study. The reliability of the observed expression patterns was confirmed by RT-qPCR. Additionally, several physiological parameters of sugarcane were significantly affected due to stress imposition. The results of this study may help identify useful target genes and provide tissue-specific data set of genes that are differentially expressed in response to osmotic stress, as well as a complete analysis of the main groups is significantly enriched under this condition. This study provides a useful benchmark for improving drought tolerance in sugarcane and other economically important grass species.

Genome sequencing reveals metabolic and cellular interdependence in an amoeba-kinetoplastid symbiosis

Czech Academy of Sciences Publication Activity Database

Tanifuji, G.; Cenci, U.; Moog, D.; Dean, S.; Nakayama, T.; David, Vojtěch; Fiala, Ivan; Curtis, B.A.; Sibbald, S. J.; Onodera, N. T.; Colp, M.; Flegontov, Pavel; Johnson-MacKinnon, J.; McPhee, M.; Inagaki, Y.; Hashimoto, T.; Kelly, S.; Gull, K.; Lukeš, Julius; Archibald, J.M.

2017-01-01

Roč. 7, SEP 15 (2017), č. článku 11688. ISSN 2045-2322 R&D Projects: GA ČR(CZ) GA14-23986S; GA MŠk LL1601 Institutional support: RVO:60077344 Keywords : trypanosoma-brucei reveals * hidden markov model * neoparamoeba-pemaquidensis * gill disease * phylogenetic analyses * ichthyobodo-necator * gene prediction * host control * evolution * proteomics Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Biochemistry and molecular biology Impact factor: 4.259, year: 2016

Carbon Nanotubes: Molecular Electronic Components

Science.gov (United States)

Srivastava, Deepak; Saini, Subhash; Menon, Madhu

1997-01-01

The carbon Nanotube junctions have recently emerged as excellent candidates for use as the building blocks in the formation of nanoscale molecular electronic networks. While the simple joint of two dissimilar tubes can be generated by the introduction of a pair of heptagon-pentagon defects in an otherwise perfect hexagonal graphene sheet, more complex joints require other mechanisms. In this work we explore structural characteristics of complex 3-point junctions of carbon nanotubes using a generalized tight-binding molecular-dynamics scheme. The study of pi-electron local densities of states (LDOS) of these junctions reveal many interesting features, most prominent among them being the defect-induced states in the gap.

Thymic function in the regulation of T cells, and molecular mechanisms underlying the modulation of cytokines and stress signaling (Review).

Science.gov (United States)

Yan, Fenggen; Mo, Xiumei; Liu, Junfeng; Ye, Siqi; Zeng, Xing; Chen, Dacan

2017-11-01

The thymus is critical in establishing and maintaining the appropriate microenvironment for promoting the development and selection of T cells. The function and structure of the thymus gland has been extensively studied, particularly as the thymus serves an important physiological role in the lymphatic system. Numerous studies have investigated the morphological features of thymic involution. Recently, research attention has increasingly been focused on thymic proteins as targets for drug intervention. Omics approaches have yielded novel insights into the thymus and possible drug targets. The present review addresses the signaling and transcriptional functions of the thymus, including the molecular mechanisms underlying the regulatory functions of T cells and their role in the immune system. In addition, the levels of cytokines secreted in the thymus have a significant effect on thymic functions, including thymocyte migration and development, thymic atrophy and thymic recovery. Furthermore, the regulation and molecular mechanisms of stress‑mediated thymic atrophy and involution were investigated, with particular emphasis on thymic function as a potential target for drug development and discovery using proteomics.

Featured Image: A Molecular Cloud Outside Our Galaxy

Science.gov (United States)

Kohler, Susanna