Thermostating extended Lagrangian Born-Oppenheimer molecular dynamics.

PubMed

Martínez, Enrique; Cawkwell, Marc J; Voter, Arthur F; Niklasson, Anders M N

2015-04-21

Extended Lagrangian Born-Oppenheimer molecular dynamics is developed and analyzed for applications in canonical (NVT) simulations. Three different approaches are considered: the Nosé and Andersen thermostats and Langevin dynamics. We have tested the temperature distribution under different conditions of self-consistent field (SCF) convergence and time step and compared the results to analytical predictions. We find that the simulations based on the extended Lagrangian Born-Oppenheimer framework provide accurate canonical distributions even under approximate SCF convergence, often requiring only a single diagonalization per time step, whereas regular Born-Oppenheimer formulations exhibit unphysical fluctuations unless a sufficiently high degree of convergence is reached at each time step. The thermostated extended Lagrangian framework thus offers an accurate approach to sample processes in the canonical ensemble at a fraction of the computational cost of regular Born-Oppenheimer molecular dynamics simulations.

Monogenic Mouse Models of Autism Spectrum Disorders: Common Mechanisms and Missing Links

PubMed Central

Hulbert, Samuel W.; Jiang, Yong-hui

2016-01-01

Autism Spectrum Disorders (ASDs) present unique challenges in the fields of genetics and neurobiology because of the clinical and molecular heterogeneity underlying these disorders. Genetic mutations found in ASD patients provide opportunities to dissect the molecular and circuit mechanisms underlying autistic behaviors using animal models. Ongoing studies of genetically modified models have offered critical insight into possible common mechanisms arising from different mutations, but links between molecular abnormalities and behavioral phenotypes remain elusive. The challenges encountered in modeling autism in mice demand a new analytic paradigm that integrates behavioral analysis with circuit-level analysis in genetically modified models with strong construct validity. PMID:26733386

Structural differences between native Hen egg white lysozyme and its fibrils under different environmental conditions

NASA Astrophysics Data System (ADS)

Bhattacharya, Susmita; Ghosh, Sudeshna; Dasgupta, Swagata; Roy, Anushree

2013-10-01

The difference in molecular structure of native HEWL and its fibrils, grown at a pH value near physiological pH 7.4 and at a pH value just above the pI, 10.7 in presence and absence of Cu(II) ions, is discussed. We focus on differences between the molecular structure of the native protein and fibrils using principal component analysis of their Raman spectra. The overlap areas of the scores of each species are used to quantify the difference in the structure of the native HEWL and fibrils in different environments. The overall molecular structures are significantly different for fibrils grown at two pH values. However, in presence of Cu(II) ions, the fibrils have similarities in their molecular structures at these pH environments. Spectral variation within each species, as obtained from the standard deviations of the scores in PCA plots, reveals the variability in the structure within a particular species.

Light absorption and plasmon – exciton interaction in three-layer nanorods with a gold core and outer shell composed of molecular J- and H-aggregates of dyes

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

Shapiro, B I; Tyshkunova, E S; Kondorskiy, A D

2015-12-31

Optical properties of hybrid rod-like nanoparticles, consisting of a gold core, an intermediate passive organic layer (spacer) and outer layer of ordered molecular cyanine dye aggregates, are experimentally and theoretically investigated. It is shown that these dyes can form not only ordered J-aggregates but also H-aggregates (differing by the packing angle of dye molecules in an aggregate and having other spectral characteristics) in the outer shell of the hybrid nanostructure. Absorption spectra of synthesised three-layer nanorods are recorded, and their sizes are determined. The optical properties of the composite nanostructures under study are found to differ significantly, depending on themore » type of the molecular aggregate formed in the outer shell. The experimental data are quantitatively explained based on computer simulation using the finite-difference time-domain (FDTD) method, and characteristic features of the plasmon – exciton interaction in the systems under study are revealed. (nanophotonics)« less

A Computational Study of the Rheology and Structure of Surfactant Covered Droplets

NASA Astrophysics Data System (ADS)

Maia, Joao; Boromand, Arman

Using different types of surface-active agents are ubiquitous in different industrial applications ranging from cosmetic and food industries to polymeric nano-composite and blends. This allows to produce stable multiphasic systems like foams and emulsions whose stability and shelf-life are directly determined by the efficiency and the type of the surfactant molecules. Moreover, presence and self-assembly of these species on an interface will display complex dynamics and structural evolution under different processing conditions. Analogous to bulk rheology of complex systems, surfactant covered interfaces will response to an external mechanical forces or deformation differently depends on the molecular configuration and topology of the system constituents. Although the effect of molecular configuration of the surface-active molecules on the planar interfaces has been studied both experimentally and computationally, it remains challenging from both experimental and computational aspects to track efficiency and effectiveness of different surfactant molecules with different molecular geometries on curved interfaces. Using Dissipative Particle Dynamics, we have studies effectiveness and efficiency of different surfactant molecules on a curved interface in equilibrium and far from equilibrium. Interfacial tension is calculated for linear and branched surfactant with different hydrophobic and hydrophilic tail and head groups with different branching densities. Deformation parameter and Taylor plots are obtained for individual surfactant molecules under shear flow.

Transcriptome analysis of two recombinant inbred lines of common bean contrasting for symbiotic nitrogen fixation

PubMed Central

Kamfwa, Kelvin; Zhao, Dongyan; Kelly, James D.

2017-01-01

Common bean (Phaseolus vulgaris L.) fixes atmospheric nitrogen (N2) through symbiotic nitrogen fixation (SNF) at levels lower than other grain legume crops. An understanding of the genes and molecular mechanisms underlying SNF will enable more effective strategies for the genetic improvement of SNF traits in common bean. In this study, transcriptome profiling was used to identify genes and molecular mechanisms underlying SNF differences between two common bean recombinant inbred lines that differed in their N-fixing abilities. Differential gene expression and functional enrichment analyses were performed on leaves, nodules and roots of the two lines when grown under N-fixing and non-fixing conditions. Receptor kinases, transmembrane transporters, and transcription factors were among the differentially expressed genes identified under N-fixing conditions, but not under non-fixing conditions. Genes up-regulated in the stronger nitrogen fixer, SA36, included those involved in molecular functions such as purine nucleoside binding, oxidoreductase and transmembrane receptor activities in nodules, and transport activity in roots. Transcription factors identified in this study are candidates for future work aimed at understanding the functional role of these genes in SNF. Information generated in this study will support the development of gene-based markers to accelerate genetic improvement of SNF in common bean. PMID:28192540

ASSESSING MOLECULAR MECHANISMS OF THREE TOXICOLOGICALLY DIFFERENT CONAZOLES BASED ON PATHWAY ANALYSIS OF MOUSE LIVER TRANSCRIPTOMES

EPA Science Inventory

The present study was designed to identify the underlying molecular mechanism for the induction of mouse liver tumors by structurally-related conazoles. CD-1 mice were treated with the tumor producing conazoles, triadimefon (1800, 500, or 100 ppm), or propiconazole (2500, 500, or...

Learning contextual gene set interaction networks of cancer with condition specificity

PubMed Central

2013-01-01

Background Identifying similarities and differences in the molecular constitutions of various types of cancer is one of the key challenges in cancer research. The appearances of a cancer depend on complex molecular interactions, including gene regulatory networks and gene-environment interactions. This complexity makes it challenging to decipher the molecular origin of the cancer. In recent years, many studies reported methods to uncover heterogeneous depictions of complex cancers, which are often categorized into different subtypes. The challenge is to identify diverse molecular contexts within a cancer, to relate them to different subtypes, and to learn underlying molecular interactions specific to molecular contexts so that we can recommend context-specific treatment to patients. Results In this study, we describe a novel method to discern molecular interactions specific to certain molecular contexts. Unlike conventional approaches to build modular networks of individual genes, our focus is to identify cancer-generic and subtype-specific interactions between contextual gene sets, of which each gene set share coherent transcriptional patterns across a subset of samples, termed contextual gene set. We then apply a novel formulation for quantitating the effect of the samples from each subtype on the calculated strength of interactions observed. Two cancer data sets were analyzed to support the validity of condition-specificity of identified interactions. When compared to an existing approach, the proposed method was much more sensitive in identifying condition-specific interactions even in heterogeneous data set. The results also revealed that network components specific to different types of cancer are related to different biological functions than cancer-generic network components. We found not only the results that are consistent with previous studies, but also new hypotheses on the biological mechanisms specific to certain cancer types that warrant further investigations. Conclusions The analysis on the contextual gene sets and characterization of networks of interaction composed of these sets discovered distinct functional differences underlying various types of cancer. The results show that our method successfully reveals many subtype-specific regions in the identified maps of biological contexts, which well represent biological functions that can be connected to specific subtypes. PMID:23418942

Thermostating extended Lagrangian Born-Oppenheimer molecular dynamics

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

Martínez, Enrique; Cawkwell, Marc J.; Voter, Arthur F.

Here, Extended Lagrangian Born-Oppenheimer molecular dynamics is developed and analyzed for applications in canonical (NVT) simulations. Three different approaches are considered: the Nosé and Andersen thermostats and Langevin dynamics. We have tested the temperature distribution under different conditions of self-consistent field (SCF) convergence and time step and compared the results to analytical predictions. We find that the simulations based on the extended Lagrangian Born-Oppenheimer framework provide accurate canonical distributions even under approximate SCF convergence, often requiring only a single diagonalization per time step, whereas regular Born-Oppenheimer formulations exhibit unphysical fluctuations unless a sufficiently high degree of convergence is reached atmore » each time step. Lastly, the thermostated extended Lagrangian framework thus offers an accurate approach to sample processes in the canonical ensemble at a fraction of the computational cost of regular Born-Oppenheimer molecular dynamics simulations.« less

Thermostating extended Lagrangian Born-Oppenheimer molecular dynamics

DOE PAGES

Martínez, Enrique; Cawkwell, Marc J.; Voter, Arthur F.; ...

2015-04-21

Here, Extended Lagrangian Born-Oppenheimer molecular dynamics is developed and analyzed for applications in canonical (NVT) simulations. Three different approaches are considered: the Nosé and Andersen thermostats and Langevin dynamics. We have tested the temperature distribution under different conditions of self-consistent field (SCF) convergence and time step and compared the results to analytical predictions. We find that the simulations based on the extended Lagrangian Born-Oppenheimer framework provide accurate canonical distributions even under approximate SCF convergence, often requiring only a single diagonalization per time step, whereas regular Born-Oppenheimer formulations exhibit unphysical fluctuations unless a sufficiently high degree of convergence is reached atmore » each time step. Lastly, the thermostated extended Lagrangian framework thus offers an accurate approach to sample processes in the canonical ensemble at a fraction of the computational cost of regular Born-Oppenheimer molecular dynamics simulations.« less

Thermal cracking of poly α-olefin aviation lubricating base oil

NASA Astrophysics Data System (ADS)

Fei, Yiwei; Wu, Nan; Ma, Jun; Hao, Jingtuan

2018-02-01

Thermal cracking of poly α-olefin (PAO) was conducted under different temperatures among 190 °C to 300 °C. The reacted mixtures were sequentially detected by gas chromatography-mass spectrometer (GC/MS). A series of small molecular normal alkanes, branched alkanes and olefins were identified. PAO perfect structure of aligned comb-likely side-chains has been seriously cracked under high temperatures. Property changes about kinematic viscosity and pour point of PAO samples reacted under high temperatures were also investigated. The appearance of small molecular compounds weakened the thermal stability, viscosity temperature performance and low temperature fluidity of PAO samples. Property of PAO samples was deteriorated due to thermal cracking under high temperatures.

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

PubMed

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.

Molecular dynamics study of radiation damage and microstructure evolution of zigzag single-walled carbon nanotubes under carbon ion incidence

NASA Astrophysics Data System (ADS)

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.

Enhancing GTEx by bridging the gaps between genotype, gene expression, and disease.

PubMed

2017-12-01

Genetic variants have been associated with myriad molecular phenotypes that provide new insight into the range of mechanisms underlying genetic traits and diseases. Identifying any particular genetic variant's cascade of effects, from molecule to individual, requires assaying multiple layers of molecular complexity. We introduce the Enhancing GTEx (eGTEx) project that extends the GTEx project to combine gene expression with additional intermediate molecular measurements on the same tissues to provide a resource for studying how genetic differences cascade through molecular phenotypes to impact human health.

Molecular imaging of tumor blood vessels in prostate cancer.

PubMed

Tilki, Derya; Seitz, Michael; Singer, Bernhard B; Irmak, Ster; Stief, Christian G; Reich, Oliver; Ergün, Süleyman

2009-05-01

In the past three decades many efforts have been undertaken to understand the mechanisms of tumor angiogenesis. The introduction of anti-angiogenic drugs in tumor therapy during the last few years necessitates the establishment of new techniques enabling molecular imaging of tumor vascular remodelling. The determination of tumor size as commonly used is not appropriate since the extended necrosis under anti-angiogenic therapy does not necessarily result in the reduction of tumor diameter. The basis for the molecular imaging of tumor blood vessels is the remodelling of the tumor vessels under anti-angiogenic therapy which obviously occurs at an early stage and seems to be a convincing parameter. Beside the enormous progress in this field during the last few years the resolution is still not high enough to evaluate the remodelling of the micro tumor vessels. New imaging approaches combining specific molecular markers for tumor vessels with the different imaging techniques are needed to overcome this issue as exemplarily discussed for prostate cancer in this review. Molecular contrast agents targeting the vasculature will allow clinicians the visualization of vascular remodelling processes taking place under anti-angiogenic therapy and improve tumor diagnosis and follow-up.

Drugs meeting the molecular basis of diabetic kidney disease: bridging from molecular mechanism to personalized medicine.

PubMed

Lambers Heerspink, Hiddo J; Oberbauer, Rainer; Perco, Paul; Heinzel, Andreas; Heinze, Georg; Mayer, Gert; Mayer, Bernd

2015-08-01

Diabetic kidney disease (DKD) is a complex, multifactorial disease and is associated with a high risk of renal and cardiovascular morbidity and mortality. Clinical practice guidelines for diabetes recommend essentially identical treatments for all patients without taking into account how the individual responds to the instituted therapy. Yet, individuals vary widely in how they respond to medications and therefore optimal therapy differs between individuals. Understanding the underlying molecular mechanisms of variability in drug response will help tailor optimal therapy. Polymorphisms in genes related to drug pharmacokinetics have been used to explore mechanisms of response variability in DKD, but with limited success. The complex interaction between genetic make-up and environmental factors on the abundance of proteins and metabolites renders pharmacogenomics alone insufficient to fully capture response variability. A complementary approach is to attribute drug response variability to individual variability in underlying molecular mechanisms involved in the progression of disease. The interplay of different processes (e.g. inflammation, fibrosis, angiogenesis, oxidative stress) appears to drive disease progression, but the individual contribution of each process varies. Drugs at the other hand address specific targets and thereby interfere in certain disease-associated processes. At this level, biomarkers may help to gain insight into which specific pathophysiological processes are involved in an individual followed by a rational assessment whether a specific drug's mode of action indeed targets the relevant process at hand. This article describes the conceptual background and data-driven workflow developed by the SysKid consortium aimed at improving characterization of the molecular mechanisms underlying DKD at the interference of the molecular impact of individual drugs in order to tailor optimal therapy to individual patients. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Secondary ion emission from phosphatidic acid sandwich films under atomic and molecular primary ion bombardment

NASA Astrophysics Data System (ADS)

Stapel, D.; Benninghoven, A.

2001-11-01

Secondary ion yields increase considerably when changing from atomic to molecular primary ions. Since secondary ion emission from deeper layers could result in a pronounced yield increase, the secondary ion emission depth of molecular fragments was investigated. A phosphatidic acid Langmuir-Blodgett (LB) sandwich system was applied. The well-defined layer structure of the applied sample allows the assignment of different depths of origin to the selected fragment ions. At least 93% of the detected characteristic molecular fragment ions originate from the first and second layers. This holds true for all applied atomic and molecular primary ions.

Molecular dynamics study of strengthening mechanism of nanolaminated graphene/Cu composites under compression.

PubMed

Weng, Shayuan; Ning, Huiming; Fu, Tao; Hu, Ning; Zhao, Yinbo; Huang, Cheng; Peng, Xianghe

2018-02-15

Molecular dynamics simulations of nanolaminated graphene/Cu (NGCu) and pure Cu under compression are conducted to investigate the underlying strengthening mechanism of graphene and the effect of lamella thickness. It is found that the stress-strain curves of NGCu undergo 3 regimes i.e. the elastic regime I, plastic strengthening regime II and plastic flow regime III. Incorporating graphene monolayer is proved to simultaneously contribute to the strength and ductility of the composites and the lamella thickness has a great effect on the mechanical properties of NGCu composites. Different strengthening mechanisms play main role in different regimes, the transition of mechanisms is found to be related to the deformation behavior. Graphene affected zone is developed and integrated with rule of mixtures and confined layer slip model to describe the elastic properties of NGCu and the strengthening effect of the incorporated graphene.

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

NASA Astrophysics Data System (ADS)

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.

Degradation mechanisms of bioresorbable polyesters. Part 2. Effects of initial molecular weight and residual monomer.

PubMed

Gleadall, Andrew; Pan, Jingzhe; Kruft, Marc-Anton; Kellomäki, Minna

2014-05-01

This paper presents an understanding of how initial molecular weight and initial monomer fraction affect the degradation of bioresorbable polymers in terms of the underlying hydrolysis mechanisms. A mathematical model was used to analyse the effects of initial molecular weight for various hydrolysis mechanisms including noncatalytic random scission, autocatalytic random scission, noncatalytic end scission or autocatalytic end scission. Different behaviours were identified to relate initial molecular weight to the molecular weight half-life and to the time until the onset of mass loss. The behaviours were validated by fitting the model to experimental data for molecular weight reduction and mass loss of samples with different initial molecular weights. Several publications that consider initial molecular weight were reviewed. The effect of residual monomer on degradation was also analysed, and shown to accelerate the reduction of molecular weight and mass loss. An inverse square root law relationship was found between molecular weight half-life and initial monomer fraction for autocatalytic hydrolysis. The relationship was tested by fitting the model to experimental data with various residual monomer contents. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Effect of molecular desorption on the electronic properties of self-assembled polarizable molecular monolayers.

PubMed

Wang, Gunuk; Jeong, Hyunhak; Ku, Jamin; Na, Seok-In; Kang, Hungu; Ito, Eisuke; Jang, Yun Hee; Noh, Jaegeun; Lee, Takhee

2014-04-01

We investigated the interfacial electronic properties of self-assembled monolayers (SAM)-modified Au metal surface at elevated temperatures. We observed that the work functions of the Au metal surfaces modified with SAMs changed differently under elevated-temperature conditions based on the type of SAMs categorized by three different features based on chemical anchoring group, molecular backbone structure, and the direction of the dipole moment. The temperature-dependent work function of the SAM-modified Au metal could be explained in terms of the molecular binding energy and the thermal stability of the SAMs, which were investigated with thermal desorption spectroscopic measurements and were explained with molecular modeling. Our study will aid in understanding the electronic properties at the interface between SAMs and metals in organic electronic devices if an annealing treatment is applied. Copyright © 2013 Elsevier Inc. All rights reserved.

Markov state models and molecular alchemy

NASA Astrophysics Data System (ADS)

Schütte, Christof; Nielsen, Adam; Weber, Marcus

2015-01-01

In recent years, Markov state models (MSMs) have attracted a considerable amount of attention with regard to modelling conformation changes and associated function of biomolecular systems. They have been used successfully, e.g. for peptides including time-resolved spectroscopic experiments, protein function and protein folding , DNA and RNA, and ligand-receptor interaction in drug design and more complicated multivalent scenarios. In this article, a novel reweighting scheme is introduced that allows to construct an MSM for certain molecular system out of an MSM for a similar system. This permits studying how molecular properties on long timescales differ between similar molecular systems without performing full molecular dynamics simulations for each system under consideration. The performance of the reweighting scheme is illustrated for simple test cases, including one where the main wells of the respective energy landscapes are located differently and an alchemical transformation of butane to pentane where the dimension of the state space is changed.

Network-based differential gene expression analysis suggests cell cycle related genes regulated by E2F1 underlie the molecular difference between smoker and non-smoker lung adenocarcinoma

PubMed Central

2013-01-01

Background Differential gene expression (DGE) analysis is commonly used to reveal the deregulated molecular mechanisms of complex diseases. However, traditional DGE analysis (e.g., the t test or the rank sum test) tests each gene independently without considering interactions between them. Top-ranked differentially regulated genes prioritized by the analysis may not directly relate to the coherent molecular changes underlying complex diseases. Joint analyses of co-expression and DGE have been applied to reveal the deregulated molecular modules underlying complex diseases. Most of these methods consist of separate steps: first to identify gene-gene relationships under the studied phenotype then to integrate them with gene expression changes for prioritizing signature genes, or vice versa. It is warrant a method that can simultaneously consider gene-gene co-expression strength and corresponding expression level changes so that both types of information can be leveraged optimally. Results In this paper, we develop a gene module based method for differential gene expression analysis, named network-based differential gene expression (nDGE) analysis, a one-step integrative process for prioritizing deregulated genes and grouping them into gene modules. We demonstrate that nDGE outperforms existing methods in prioritizing deregulated genes and discovering deregulated gene modules using simulated data sets. When tested on a series of smoker and non-smoker lung adenocarcinoma data sets, we show that top differentially regulated genes identified by the rank sum test in different sets are not consistent while top ranked genes defined by nDGE in different data sets significantly overlap. nDGE results suggest that a differentially regulated gene module, which is enriched for cell cycle related genes and E2F1 targeted genes, plays a role in the molecular differences between smoker and non-smoker lung adenocarcinoma. Conclusions In this paper, we develop nDGE to prioritize deregulated genes and group them into gene modules by simultaneously considering gene expression level changes and gene-gene co-regulations. When applied to both simulated and empirical data, nDGE outperforms the traditional DGE method. More specifically, when applied to smoker and non-smoker lung cancer sets, nDGE results illustrate the molecular differences between smoker and non-smoker lung cancer. PMID:24341432

Overlapping molecular pathological themes link Charcot-Marie-Tooth neuropathies and hereditary spastic paraplegias.

PubMed

Timmerman, Vincent; Clowes, Virginia E; Reid, Evan

2013-08-01

In this review we focus on Charcot-Marie-Tooth (CMT) neuropathies and hereditary spastic paraplegias (HSPs). Although these diseases differ in whether they primarily affect the peripheral or central nervous system, both are genetically determined, progressive, long axonopathies that affect motor and sensory pathways. This commonality suggests that there might be similarities in the molecular pathology underlying these conditions, and here we compare the molecular genetics and cellular pathology of the two groups. Copyright © 2012 Elsevier Inc. All rights reserved.

[Laser microdissection for biology and medicine].

PubMed

Podgornyĭ, O V; Lazarev, V N; Govorun, V M

2012-01-01

For routine extraction of DNA, RNA, proteins and metabolites, small tissue pieces are placed into lysing solution. These tissue pieces in general contain different cell types. For this reason, lysate contains components of different cell types, which complicates the interpretation of molecular analysis results. The laser microdissection allows overcoming this trouble. The laser microdissection is a method to procure tissue samples contained defined cell subpopulations, individual cells and even subsellular components under direct microscopic visualization. Collected samples can be undergone to different downstream molecular assays: DNA analysis, RNA transcript profiling, cDNA library generation and gene expression analysis, proteomic analysis and metabolite profiling. The laser microdissection has wide applications in oncology (research and routine), cellular and molecular biology, biochemistry and forensics. This paper reviews the principles of different laser microdissection instruments, examples of laser microdissection application and problems of sample preparation for laser microdissection.

Viscoelastic properties of dendrimers in the melt from nonequlibrium molecular dynamics

NASA Astrophysics Data System (ADS)

Bosko, Jaroslaw T.; Todd, B. D.; Sadus, Richard J.

2004-12-01

The viscoelastic properties of dendrimers of generation 1-4 are studied using nonequilibrium molecular dynamics. Flow properties of dendrimer melts under shear are compared to systems composed of linear chain polymers of the same molecular weight, and the influence of molecular architecture is discussed. Rheological material properties, such as the shear viscosity and normal stress coefficients, are calculated and compared for both systems. We also calculate and compare the microscopic properties of both linear chain and dendrimer molecules, such as their molecular alignment, order parameters and rotational velocities. We find that the highly symmetric shape of dendrimers and their highly constrained geometry allows for substantial differences in their material properties compared to traditional linear polymers of equivalent molecular weight.

QM/MM MD and Free Energy Simulation Study of Methyl Transfer Processes Catalyzed by PKMTs and PRMTs.

PubMed

Chu, Yuzhuo; Guo, Hong

2015-09-01

Methyl transfer processes catalyzed by protein lysine methyltransferases (PKMTs) and protein arginine methyltransferases (PRMTs) control important biological events including transcriptional regulation and cell signaling. One important property of these enzymes is that different PKMTs and PRMTs catalyze the formation of different methylated product (product specificity). These different methylation states lead to different biological outcomes. Here, we review the results of quantum mechanics/molecular mechanics molecular dynamics and free energy simulations that have been performed to study the reaction mechanism of PKMTs and PRMTs and the mechanism underlying the product specificity of the methyl transfer processes.

QM/MM MD and free energy simulation study of methyl transfer processes catalyzed by PKMTs and PRMTs.

PubMed

Chu, Yuzhuo; Guo, Hong

2015-01-16

Methyl transfer processes catalyzed by protein lysine methyltransferases (PKMTs) and protein arginine methyltransferases (PRMTs) control important biological events including transcriptional regulation and cell signaling. One important property of these enzymes is that different PKMTs and PRMTs catalyze the formation of different methylated product (product specificity). These different methylation states lead to different biological outcomes. Here we review the results of quantum mechanics/molecular mechanics (QM/MM) molecular dynamics (MD) and free energy simulations that have been performed to study the reaction mechanism of PKMTs and PRMTs and the mechanism underlying the product specificity of the methyl transfer processes.

Charge transport in molecular junctions: From tunneling to hopping with the probe technique

NASA Astrophysics Data System (ADS)

Kilgour, Michael; Segal, Dvira

2015-07-01

We demonstrate that a simple phenomenological approach can be used to simulate electronic conduction in molecular wires under thermal effects induced by the surrounding environment. This "Landauer-Büttiker's probe technique" can properly replicate different transport mechanisms, phase coherent nonresonant tunneling, ballistic behavior, and hopping conduction. Specifically, our simulations with the probe method recover the following central characteristics of charge transfer in molecular wires: (i) the electrical conductance of short wires falls off exponentially with molecular length, a manifestation of the tunneling (superexchange) mechanism. Hopping dynamics overtakes superexchange in long wires demonstrating an ohmic-like behavior. (ii) In off-resonance situations, weak dephasing effects facilitate charge transfer, but under large dephasing, the electrical conductance is suppressed. (iii) At high enough temperatures, kBT/ɛB > 1/25, with ɛB as the molecular-barrier height, the current is enhanced by a thermal activation (Arrhenius) factor. However, this enhancement takes place for both coherent and incoherent electrons and it does not readily indicate on the underlying mechanism. (iv) At finite-bias, dephasing effects may impede conduction in resonant situations. We further show that memory (non-Markovian) effects can be implemented within the Landauer-Büttiker's probe technique to model the interaction of electrons with a structured environment. Finally, we examine experimental results of electron transfer in conjugated molecular wires and show that our computational approach can reasonably reproduce reported values to provide mechanistic information.

Avoiding pitfalls in molecular genetic testing: case studies of high-resolution array comparative genomic hybridization testing in the definitive diagnosis of Mowat-Wilson syndrome.

PubMed

Kluk, Michael Joseph; An, Yu; James, Philip; Coulter, David; Harris, David; Wu, Bai-Lin; Shen, Yiping

2011-05-01

The molecular testing options available for the diagnosis of genetic disorders are numerous and include a variety of different assay platforms. The consultative input of molecular pathologists and cytogeneticists, working closely with the ordering clinicians, is often important for definitive diagnosis. Herein, we describe two patients who had long histories of unexplained signs and symptoms with a high clinical suspicion of an underlying genetic etiology. Initial molecular testing in both cases was negative, but the application of high-resolution array comparative genomic hybridization technology lead to definitive diagnosis in both cases. We summarize the clinical findings and molecular testing in each case, discuss the differential diagnoses, and review the clinical and pathological findings of Mowat-Wilson syndrome. This report highlights the importance for those involved in molecular testing to know the nature of the underlying genetic abnormalities associated with the suspected diagnosis, to recognize the limitations of each testing platform, and to persistently pursue repeat testing using high-resolution technologies when indicated. This concept is applicable to both germline and somatic molecular genetic testing. Copyright © 2011 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

The molecular mechanism studies of chirality effect of PHA-739358 on Aurora kinase A by molecular dynamics simulation and free energy calculations

NASA Astrophysics Data System (ADS)

Cheng, Yuanhua; Cui, Wei; Chen, Quan; Tung, Chen-Ho; Ji, Mingjuan; Zhang, Fushi

2011-02-01

Aurora kinase family is one of the emerging targets in oncology drug discovery and several small molecules targeting aurora kinases have been discovered and evaluated under early phase I/II trials. Among them, PHA-739358 (compound 1r) is a 3-aminopyrazole derivative with strong activity against Aurora A under early phase II trial. Inhibitory potency of compound 1r (the benzylic substituent at the pro-R position) is 30 times over that of compound 1s (the benzylic substituent at the pro-S position). In present study, the mechanism of how different configurations influence the binding affinity was investigated using molecular dynamics (MD) simulations, free energy calculations and free energy decomposition analysis. The predicted binding free energies of these two complexes are consistent with the experimental data. The analysis of the individual energy terms indicates that although the van der Waals contribution is important for distinguishing the binding affinities of these two inhibitors, the electrostatic contribution plays a more crucial role in that. Moreover, it is observed that different configurations of the benzylic substituent could form different binding patterns with protein, thus leading to variant inhibitory potency of compounds 1r and 1s. The combination of different molecular modeling techniques is an efficient way to interpret the chirality effects of inhibitors and our work gives valuable information for the chiral drug design in the near future.

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

PubMed

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).

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

PubMed

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 <0.0001. The mean values of the cross-validated proteomic score of normotensive and hypertensive patients were found to be -2.007±0.3568 and 3.383±0.2643, respectively, P <0.0001. The molecular determinants were successfully identified, and the proteomic model developed shows an excellent discriminatory ability between 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.

Influence of Molecular Structure on the Laser-Induced Plasma Emission of the Explosive RDX and Organic Polymers

NASA Astrophysics Data System (ADS)

De Lucia, Frank C.; Gottfried, Jennifer L.

2013-10-01

A series of organic polymers and the military explosive cyclotrimethylenetrinitramine (RDX) were studied using the light emission from a femtosecond laser-induced plasma under an argon atmosphere. The relationship between the molecular structure and plasma emission was established by using the percentages of the atomic species (C, H, N, O) and bond types (C-C, C═C, C-N, and C≡N) in combination with the atomic/molecular emission intensities and decay rates. In contrast to previous studies of organic explosives in which C2 was primarily formed by recombination, for the organic materials in this study the percentage of C-C (and C═C) bonds was strongly correlated to the molecular C2 emission. Time-resolved emission spectra were collected to determine the lifetimes of the atomic and molecular species in the plasma. Observed differences in decay rates were attributed to the differences in both the molecular structure of the organic polymers or RDX and the chemical reactions that occur within the plasma. These differences could potentially be exploited to improve the discrimination of explosive residues on organic substrates with laser-induced breakdown spectroscopy.

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

NASA Astrophysics Data System (ADS)

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.

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

PubMed Central

Sun, Xiaochuan; Wang, Yan; Xu, Liang; Li, Chao; Zhang, Wei; Luo, Xiaobo; Jiang, Haiyan; Liu, Liwang

2017-01-01

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. PMID:28769938

Characterization of asphaltene molecular structures by cracking under hydrogenation conditions and prediction of the viscosity reduction from visbreaking of heavy oils

NASA Astrophysics Data System (ADS)

Rueda Velasquez, Rosa Imelda

The chemical building blocks that comprise petroleum asphaltenes were determined by cracking samples under conditions that minimized alterations to aromatic and cycloalkyl groups. Hydrogenation conditions that used tetralin as hydrogen-donor solvent, with an iron-based catalyst, allowed asphaltenes from different geological regions to yield 50-60 wt% of distillates (<538°C fraction), with coke yields below 10 wt%. Control experiments with phenanthrene and 5alpha-cholestane confirmed low hydrogenation catalytic activity, and preservation of the cycloalkyl structures. Quantitative recovery of cracking products and characterization of the distillates, by gas chromatography-field ionization--time of flight high resolution mass spectrometry, displayed remarkable similarity in molecular composition for the different asphaltenes. Paraffins and 1-3 ring aromatics were the most abundant building blocks. The diversity of molecules identified, and the high yield of paraffins were consistent with high heterogeneity and complexity of molecules, built up by smaller fragments attached to each other by bridges. The sum of material remaining as vacuum residue and coke was in the range of 35-45 wt%; this total represents the maximum amount of large clusters in asphaltenes that could not be converted to lighter compounds under the evaluated cracking conditions. These analytical data for Cold Lake asphaltenes were transformed into probability density functions that described the molecular weight distributions of the building blocks. These distributions were input for a Monte Carlo approach that allowed stochastic construction of asphaltenes and simulation of their cracking reactions to examine differences in the distributions of products associated to the molecular topology. The construction algorithm evidenced that a significant amount of asphaltenes would consist of 3-5 building blocks. The results did not show significant differences between linear and dendritic molecular architectures, but suggested that dendritic molecules would experience slower reaction rates as they required more breakages to reach a given yield of distillates. Thermal cracking of asphaltenes in heavy oils and bitumens can dramatically reduce viscosity, enabling pipeline transportation with less solvent addition. The viscosities of the products from visbreaking reactions of two different heavy oils were modeled with lumped kinetics based on boiling point pseudo-components, and with the estimation of their individual fluid properties. The model was tuned with experimental viscosity data, and provided estimations of viscosities at different temperatures with absolute average deviations lower than 31%.

Chemical activation of bituminous coal for hampering oligomerization of organic contaminants.

PubMed

Yan, Liang; Sorial, George A

2011-12-15

Activated carbons prepared by KOH activation of bituminous coal were studied for hampering oligomerization of phenolic compounds on its surface. A total of 24 activated carbons with different microporosity and BET surface area were created. The effect of the different variables of the activation process (KOH/bituminous coal ratio, heating temperature, activation time, and flow rate of nitrogen gas) on critical carbon parameters was analyzed. The impact of activated carbon on oligomerization was examined by conducting isotherm experiments at a neutral pH on Carbon(exp) produced with optimal characteristics and granular activated carbon (GAC) F400 for phenol, 2-methylphenol and 2-ethylphenol. These isotherms were collected under anoxic (absence of molecular oxygen) and oxic (presence of molecular oxygen) conditions. The single solute adsorption of phenol, 2-methylphenol and 2-ethylphenol on Carbon(exp) showed no obvious differences between oxic and anoxic environment, which indicated that the Carbon(exp) sample is very effective in hampering the oligomerization of phenolic compounds under oxic conditions. On the other hand, F400, which have lower micropore percentage and BET surface area, significant increases in the adsorptive capacity had been observed when molecular oxygen was present. Copyright © 2011 Elsevier B.V. All rights reserved.

Subtype and pathway specific responses to anticancer compounds in breast cancer.

PubMed

Heiser, Laura M; Sadanandam, Anguraj; Kuo, Wen-Lin; Benz, Stephen C; Goldstein, Theodore C; Ng, Sam; Gibb, William J; Wang, Nicholas J; Ziyad, Safiyyah; Tong, Frances; Bayani, Nora; Hu, Zhi; Billig, Jessica I; Dueregger, Andrea; Lewis, Sophia; Jakkula, Lakshmi; Korkola, James E; Durinck, Steffen; Pepin, François; Guan, Yinghui; Purdom, Elizabeth; Neuvial, Pierre; Bengtsson, Henrik; Wood, Kenneth W; Smith, Peter G; Vassilev, Lyubomir T; Hennessy, Bryan T; Greshock, Joel; Bachman, Kurtis E; Hardwicke, Mary Ann; Park, John W; Marton, Laurence J; Wolf, Denise M; Collisson, Eric A; Neve, Richard M; Mills, Gordon B; Speed, Terence P; Feiler, Heidi S; Wooster, Richard F; Haussler, David; Stuart, Joshua M; Gray, Joe W; Spellman, Paul T

2012-02-21

Breast cancers are comprised of molecularly distinct subtypes that may respond differently to pathway-targeted therapies now under development. Collections of breast cancer cell lines mirror many of the molecular subtypes and pathways found in tumors, suggesting that treatment of cell lines with candidate therapeutic compounds can guide identification of associations between molecular subtypes, pathways, and drug response. In a test of 77 therapeutic compounds, nearly all drugs showed differential responses across these cell lines, and approximately one third showed subtype-, pathway-, and/or genomic aberration-specific responses. These observations suggest mechanisms of response and resistance and may inform efforts to develop molecular assays that predict clinical response.

Burning phylogenies: fire, molecular evolutionary rates, and diversification.

PubMed

Verdú, Miguel; Pausas, Juli G; Segarra-Moragues, José Gabriel; Ojeda, Fernando

2007-09-01

Mediterranean-type ecosystems are among the most remarkable plant biodiversity "hot spots" on the earth, and fire has traditionally been invoked as one of the evolutionary forces explaining this exceptional diversity. In these ecosystems, adult plants of some species are able to survive after fire (resprouters), whereas in other species fire kills the adults and populations are only maintained by an effective post-fire recruitment (seeders). Seeders tend to have shorter generation times than resprouters, particularly under short fire return intervals, thus potentially increasing their molecular evolutionary rates and, ultimately, their diversification. We explored whether seeder lineages actually have higher rates of molecular evolution and diversification than resprouters. Molecular evolutionary rates in different DNA regions were compared in 45 phylogenetically paired congeneric taxa from fire-prone Mediterranean-type ecosystems with contrasting seeder and resprouter life histories. Differential diversification was analyzed with both topological and chronological approaches in five genera (Banksia, Daviesia, Lachnaea, Leucadendron, and Thamnochortus) from two fire-prone regions (Australia and South Africa). We found that seeders had neither higher molecular rates nor higher diversification than resprouters. Such lack of differences in molecular rates between seeders and resprouters-which did not agree with theoretical predictions-may occur if (1) the timing of the switch from seeding to resprouting (or vice versa) occurs near the branch tip, so that most of the branch length evolves under the opposite life-history form; (2) resprouters suffer more somatic mutations and therefore counterbalancing the replication-induced mutations of seeders; and (3) the rate of mutations is not related to shorter generation times because plants do not undergo determinate germ-line replication. The absence of differential diversification is to be expected if seeders and resprouters do not differ from each other in their molecular evolutionary rate, which is the fuel for speciation. Although other factors such as the formation of isolated populations may trigger diversification, we can conclude that fire acting as a throttle for diversification is by no means the rule in fire-prone ecosystems.

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

NASA Astrophysics Data System (ADS)

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.

Modeling of crack growth under mixed-mode loading by a molecular dynamics method and a linear fracture mechanics approach

NASA Astrophysics Data System (ADS)

Stepanova, L. V.

2017-12-01

Atomistic simulations of the central crack growth process in an infinite plane medium under mixed-mode loading using Large-Scale Atomic/Molecular Massively Parallel Simulator (LAMMPS), a classical molecular dynamics code, are performed. The inter-atomic potential used in this investigation is the Embedded Atom Method (EAM) potential. Plane specimens with an initial central crack are subjected to mixed-mode loadings. The simulation cell contains 400,000 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 range of temperatures (from 0.1 K to 800 K) are obtained and analyzed. It is shown that the crack propagation direction angles obtained by molecular dynamics 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. The multi-parameter fracture criteria are based on the multi-parameter stress field description taking into account the higher order terms of the Williams series expansion of the crack tip fields.

The effect of solvent upon molecularly thin rotaxane film formation

NASA Astrophysics Data System (ADS)

Farrell, Alan A.; Kay, Euan R.; Bottari, Giovanni; Leigh, David A.; Jarvis, Suzanne P.

2007-05-01

We have investigated variations in molecularly thin rotaxane films deposited by solvent evaporation, using atomic force microscopy (AFM). Small changes in rotaxane structure result in significant differences in film morphology. The addition of exo-pyridyl moietes to the rotaxane macrocycle results in uniform domains having orientations corresponding to the underlying substrate lattice, while a larger, less symmetric molecule results in a greater lattice mismatch and smaller domain sizes. We have measured differences in film heights both as a function of the solvent of deposition and as a function of surface coverage of rotaxanes. Based on these observations we describe how the use of solvents with higher hydrogen-bond basicity results in films which are more likely to favour sub-molecular motion.

Optimum conditions for producing Cs2 molecular condensates by stimulated Raman adiabatic passage

NASA Astrophysics Data System (ADS)

Feng, Zhifang; Li, Weidong; Wang, Lirong; Xiao, Liantuan; Jia, Suotang

2009-10-01

The optimum conditions for producing Cs2 molecular condensates from Cs atomic condensates with high transfer efficiency by stimulated Raman adiabatic passage are presented. Under the extended “two-photon” resonance condition, including the two-photon process, the mean-field correction, and the tunneling coupling between two upper excited molecular levels, a high and stable conversion efficiency is realized. The high conversion efficiency could be achieved by following two methods under experimentally less demanding conditions (relatively small effective Rabi frequency for pump laser pulse). One is adjusting the detuning difference between two laser pulses for same effective Rabi frequencies with up to 87.2% transfer efficiency. Another one is adjusting the effective Rabi frequency, the detuning of dump laser for given effective Rabi frequency, and the detuning of pump laser with up to 80.7% transfer efficiency.

Poisson-Boltzmann versus Size-Modified Poisson-Boltzmann Electrostatics Applied to Lipid Bilayers.

PubMed

Wang, Nuo; Zhou, Shenggao; Kekenes-Huskey, Peter M; Li, Bo; McCammon, J Andrew

2014-12-26

Mean-field methods, such as the Poisson-Boltzmann equation (PBE), are often used to calculate the electrostatic properties of molecular systems. In the past two decades, an enhancement of the PBE, the size-modified Poisson-Boltzmann equation (SMPBE), has been reported. Here, the PBE and the SMPBE are reevaluated for realistic molecular systems, namely, lipid bilayers, under eight different sets of input parameters. The SMPBE appears to reproduce the molecular dynamics simulation results better than the PBE only under specific parameter sets, but in general, it performs no better than the Stern layer correction of the PBE. These results emphasize the need for careful discussions of the accuracy of mean-field calculations on realistic systems with respect to the choice of parameters and call for reconsideration of the cost-efficiency and the significance of the current SMPBE formulation.

ProbeZT: Simulation of transport coefficients of molecular electronic junctions under environmental effects using Büttiker's probes

NASA Astrophysics Data System (ADS)

Korol, Roman; Kilgour, Michael; Segal, Dvira

2018-03-01

We present our in-house quantum transport package, ProbeZT. This program provides linear response coefficients: electrical and electronic thermal conductances, as well as the thermopower of molecular junctions in which electrons interact with the surrounding thermal environment. Calculations are performed based on the Büttiker probe method, which introduces decoherence, energy exchange and dissipation effects phenomenologically using virtual electrode terminals called probes. The program can realize different types of probes, each introducing various environmental effects, including elastic and inelastic scattering of electrons. The molecular system is described by an arbitrary tight-binding Hamiltonian, allowing the study of different geometries beyond simple one-dimensional wires. Applications of the program to study the thermoelectric performance of molecular junctions are illustrated. The program also has a built-in functionality to simulate electron transport in double-stranded DNA molecules based on a tight-binding (ladder) description of the junction.

Atomic scale friction of molecular adsorbates during diffusion.

PubMed

Lechner, B A J; de Wijn, A S; Hedgeland, H; Jardine, A P; Hinch, B J; Allison, W; Ellis, J

2013-05-21

Experimental observations suggest that molecular adsorbates exhibit a larger friction coefficient than atomic species of comparable mass, yet the origin of this increased friction is not well understood. We present a study of the microscopic origins of friction experienced by molecular adsorbates during surface diffusion. Helium spin-echo measurements of a range of five-membered aromatic molecules, cyclopentadienyl, pyrrole, and thiophene, on a copper(111) surface are compared with molecular dynamics simulations of the respective systems. The adsorbates have different chemical interactions with the surface and differ in bonding geometry, yet the measurements show that the friction is greater than 2 ps(-1) for all these molecules. We demonstrate that the internal and external degrees of freedom of these adsorbate species are a key factor in the underlying microscopic processes and identify the rotation modes as the ones contributing most to the total measured friction coefficient.

Getting the Right Answers for the Right Reasons: Toward Predictive Molecular Simulations of Water with Many-Body Potential Energy Functions.

PubMed

Paesani, Francesco

2016-09-20

The central role played by water in fundamental processes relevant to different disciplines, including chemistry, physics, biology, materials science, geology, and climate research, cannot be overemphasized. It is thus not surprising that, since the pioneering work by Stillinger and Rahman, many theoretical and computational studies have attempted to develop a microscopic description of the unique properties of water under different thermodynamic conditions. Consequently, numerous molecular models based on either molecular mechanics or ab initio approaches have been proposed over the years. However, despite continued progress, the correct prediction of the properties of water from small gas-phase clusters to the liquid phase and ice through a single molecular model remains challenging. To large extent, this is due to the difficulties encountered in the accurate modeling of the underlying hydrogen-bond network in which both number and strength of the hydrogen bonds vary continuously as a result of a subtle interplay between energetic, entropic, and nuclear quantum effects. In the past decade, the development of efficient algorithms for correlated electronic structure calculations of small molecular complexes, accompanied by tremendous progress in the analytical representation of multidimensional potential energy surfaces, opened the doors to the design of highly accurate potential energy functions built upon rigorous representations of the many-body expansion (MBE) of the interaction energies. This Account provides a critical overview of the performance of the MB-pol many-body potential energy function through a systematic analysis of energetic, structural, thermodynamic, and dynamical properties as well as of vibrational spectra of water from the gas to the condensed phase. It is shown that MB-pol achieves unprecedented accuracy across all phases of water through a quantitative description of each individual term of the MBE, with a physically correct representation of both short- and long-range many-body contributions. Comparisons with experimental data probing different regions of the water potential energy surface from clusters to bulk demonstrate that MB-pol represents a major step toward the long-sought-after "universal model" capable of accurately describing the molecular properties of water under different conditions and in different environments. Along this path, future challenges include the extension of the many-body scheme adopted by MB-pol to the description of generic solutes as well as the integration of MB-pol in an efficient theoretical and computational framework to model acid-base reactions in aqueous environments. In this context, given the nontraditional form of the MB-pol energy and force expressions, synergistic efforts by theoretical/computational chemists/physicists and computer scientists will be critical for the development of high-performance software for many-body molecular dynamics simulations.

Quantification of the inert chemical oxygen demand of raw wastewater and evaluation of soluble microbial product production in demo-scale upflow anaerobic sludge blanket reactors under different operational conditions.

PubMed

Aquino, Sergio F; Gloria, Roberto M; Silva, Silvana Q; Chernicharo, Carlos A L

2009-06-01

This paper investigates the production of soluble microbial products (SMPs) in demonstration-scale upflow anaerobic sludge blanket reactors operated under different conditions and fed with raw wastewater. The results showed that 9.2 +/- 1.3% of the influent soluble chemical oxygen demand (COD) could be considered inert to anaerobic treatment and that the amount of COD produced by biomass varied from 30 to 70 mg x L(-1), accounting for 45 to 63% of the soluble effluent COD. The accumulation of SMP appeared to be dependent on the hydraulic retention time (HRT) applied to the reactors, with a larger accumulation of SMP observed at the lowest HRT (5 hours); this may have been due to stress conditions caused by high upflow velocity (1.1 m x h(-1)). In terms of residual COD characterization, ultrafiltration results showed that higher amounts of high molecular weight compounds were found when HRT was the lowest (5 hours), and that the molecular weight distribution depended on the operational condition of the reactors. Biodegradability tests showed that the low and high molecular weight SMPs were only partially degraded anaerobically (10 to 60%) and that the high molecular weight SMPs were difficult to degrade aerobically.

Genes and (Common) Pathways Underlying Drug Addiction

PubMed Central

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

Arbuscular mycorrhiza of Arnica montana under field conditions--conventional and molecular studies.

PubMed

Ryszka, Przemysław; Błaszkowski, Janusz; Jurkiewicz, Anna; Turnau, Katarzyna

2010-11-01

Two distinct populations of Arnica montana, an endangered medicinal plant, were studied under field conditions. The material was investigated using microscopic and molecular methods. The analyzed plants were always found to be mycorrhizal. Nineteen arbuscular mycorrhizal fungal DNA sequences were obtained from the roots. They were related to Glomus Group A, but most did not match any known species. Some showed a degree of similarity to fungi colonizing liverworts. Conventional analysis of spores isolated from soil samples allowed to identify different fungal taxa: Glomus macrocarpum, Glomus mosseae, Acaulospora lacunosa, and Scutellospora dipurpurescens. Their spores were also isolated from trap cultures.

Mind the gap: glucocorticoids modulate hippocampal glutamate tone underlying individual differences in stress susceptibility.

PubMed

Nasca, C; Bigio, B; Zelli, D; Nicoletti, F; McEwen, B S

2015-06-01

Why do some individuals succumb to stress and develop debilitating psychiatric disorders, whereas others adapt well in the face of adversity? There is a gap in understanding the neural bases of individual differences in the responses to environmental factors on brain development and functions. Here, using a novel approach for screening an inbred population of laboratory animals, we identified two subpopulations of mice: susceptible mice that show mood-related abnormalities compared with resilient mice, which cope better with stress. This approach combined with molecular and behavioral analyses, led us to recognize, in hippocampus, presynaptic mGlu2 receptors, which inhibit glutamate release, as a stress-sensitive marker of individual differences to stress-induced mood disorders. Indeed, genetic mGlu2 deletion in mice results in a more severe susceptibility to stress, mimicking the susceptible mouse sub-population. Furthermore, we describe an underlying mechanism by which glucocorticoids, acting via mineralocorticoid receptors (MRs), decrease resilience to stress via downregulation of mGlu2 receptors. We also provide a mechanistic link between MRs and an epigenetic control of the glutamatergic synapse that underlies susceptibility to stressful experiences. The approach and the epigenetic allostasis concept introduced here serve as a model for identifying individual differences based upon biomarkers and underlying mechanisms and also provide molecular features that may be useful in translation to human behavior and psychopathology.

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

PubMed Central

Seiler, Franka; Soll, Jürgen; Bölter, Bettina

2017-01-01

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. PMID:28608805

Dissection of the genetic architecture underlying the plant density response by mapping plant height-related traits in maize (Zea mays L.).

PubMed

Ku, Lixia; Zhang, Liangkun; Tian, Zhiqiang; Guo, Shulei; Su, Huihui; Ren, Zhenzhen; Wang, Zhiyong; Li, Guohui; Wang, Xiaobo; Zhu, Yuguang; Zhou, Jinlong; Chen, Yanhui

2015-08-01

Plant height is one of the most heritable traits in maize (Zea mays L.). Understanding the genetic control of plant height is important for elucidating the molecular mechanisms that regulate maize development. To investigate the genetic basis of the plant height response to density in maize, we evaluated the effects of two different plant densities (60,000 and 120,000 plant/hm(2)) on three plant height-related traits (plant height, ear height, and ear height-to-plant height ratio) using four sets of recombinant inbred line populations. The phenotypes observed under the two-plant density treatments indicated that high plant density increased the phenotypic performance values of the three measured traits. Twenty-three quantitative trait loci (QTLs) were detected under the two-plant density treatments, and five QTL clusters were located. Nine QTLs were detected under the low plant density treatment, and seven QTLs were detected under the high plant density treatment. Our results suggested that plant height may be controlled mainly by a common set of genes that could be influenced by additional genetic mechanisms when the plants were grown under high plant density. Fine mapping for genetic regions of the stable QTLs across different plant density environments may provide additional information about their different responses to density. The results presented here provide useful information for further research and will help to reveal the molecular mechanisms related to plant height in response to density.

Early and long-standing rheumatoid arthritis: distinct molecular signatures identified by gene-expression profiling in synovia

PubMed Central

Lequerré, Thierry; Bansard, Carine; Vittecoq, Olivier; Derambure, Céline; Hiron, Martine; Daveau, Maryvonne; Tron, François; Ayral, Xavier; Biga, Norman; Auquit-Auckbur, Isabelle; Chiocchia, Gilles; Le Loët, Xavier; Salier, Jean-Philippe

2009-01-01

Introduction Rheumatoid arthritis (RA) is a heterogeneous disease and its underlying molecular mechanisms are still poorly understood. Because previous microarray studies have only focused on long-standing (LS) RA compared to osteoarthritis, we aimed to compare the molecular profiles of early and LS RA versus control synovia. Methods Synovial biopsies were obtained by arthroscopy from 15 patients (4 early untreated RA, 4 treated LS RA and 7 controls, who had traumatic or mechanical lesions). Extracted mRNAs were used for large-scale gene-expression profiling. The different gene-expression combinations identified by comparison of profiles of early, LS RA and healthy synovia were linked to the biological processes involved in each situation. Results Three combinations of 719, 116 and 52 transcripts discriminated, respectively, early from LS RA, and early or LS RA from healthy synovia. We identified several gene clusters and distinct molecular signatures specifically expressed during early or LS RA, thereby suggesting the involvement of different pathophysiological mechanisms during the course of RA. Conclusions Early and LS RA have distinct molecular signatures with different biological processes participating at different times during the course of the disease. These results suggest that better knowledge of the main biological processes involved at a given RA stage might help to choose the most appropriate treatment. PMID:19563633

The Combined Influence of Molecular Weight and Temperature on the Aging and Viscoelastic Response of a Glassy Thermoplastic Polyimide

NASA Technical Reports Server (NTRS)

Nicholson, Lee M.; Whitley, Karen S.; Gates, Thomas S.

2000-01-01

The effect of molecular weight on the viscoelastic performance of an advanced polymer (LaRC-SI) was investigated through the use of creep compliance tests. Testing consisted of short-term isothermal creep and recovery with the creep segments performed under constant load. The tests were conducted at three temperatures below the glass transition temperature of five materials of different molecular weight. Through the use of time-aging-time superposition procedures, the material constants, material master curves and aging-related parameters were evaluated at each temperature for a given molecular weight. The time-temperature superposition technique helped to describe the effect of temperature on the timescale of the viscoelastic response of each molecular weight. It was shown that the low molecular weight materials have higher creep compliance and creep rate, and are more sensitive to temperature than the high molecular weight materials. Furthermore, a critical molecular weight transition was observed to occur at a weight-average molecular weight of M (bar) (sub w) 25000 g/mol below which, the temperature sensitivity of the time-temperature superposition shift factor increases rapidly. The short-term creep compliance data were used in association with Struik's effective time theory to predict the long-term creep compliance behavior for the different molecular weights. At long timescales, physical aging serves to significantly decrease the creep compliance and creep rate of all the materials tested.

Spotting the difference in molecular dynamics simulations of biomolecules

NASA Astrophysics Data System (ADS)

Sakuraba, Shun; Kono, Hidetoshi

2016-08-01

Comparing two trajectories from molecular simulations conducted under different conditions is not a trivial task. In this study, we apply a method called Linear Discriminant Analysis with ITERative procedure (LDA-ITER) to compare two molecular simulation results by finding the appropriate projection vectors. Because LDA-ITER attempts to determine a projection such that the projections of the two trajectories do not overlap, the comparison does not suffer from a strong anisotropy, which is an issue in protein dynamics. LDA-ITER is applied to two test cases: the T4 lysozyme protein simulation with or without a point mutation and the allosteric protein PDZ2 domain of hPTP1E with or without a ligand. The projection determined by the method agrees with the experimental data and previous simulations. The proposed procedure, which complements existing methods, is a versatile analytical method that is specialized to find the "difference" between two trajectories.

Chilling and Drought Stresses in Crop Plants: Implications, Cross Talk, and Potential Management Opportunities

PubMed Central

Hussain, Hafiz A.; Hussain, Saddam; Khaliq, Abdul; Ashraf, Umair; Anjum, Shakeel A.; Men, Shengnan; Wang, Longchang

2018-01-01

Plants face a combination of different abiotic stresses under field conditions which are lethal to plant growth and production. Simultaneous occurrence of chilling and drought stresses in plants due to the drastic and rapid global climate changes, can alter the morphological, physiological and molecular responses. Both these stresses adversely affect the plant growth and yields due to physical damages, physiological and biochemical disruptions, and molecular changes. In general, the co-occurrence of chilling and drought combination is even worse for crop production rather than an individual stress condition. Plants attain various common and different physiological and molecular protective approaches for tolerance under chilling and drought stresses. Nevertheless, plant responses to a combination of chilling and drought stresses are unique from those to individual stress. In the present review, we summarized the recent evidence on plant responses to chilling and drought stresses on shared as well as unique basis and tried to find a common thread potentially underlying these responses. We addressed the possible cross talk between plant responses to these stresses and discussed the potential management strategies for regulating the mechanisms of plant tolerance to drought and/or chilling stresses. To date, various novel approaches have been tested in minimizing the negative effects of combine stresses. Despite of the main improvements there is still a big room for improvement in combination of drought and chilling tolerance. Thus, future researches particularly using biotechnological and molecular approaches should be carried out to develop genetically engineered plants with enhanced tolerance against these stress factors. PMID:29692787

Unexpected amino acid composition of modern Reptilia and its implications in molecular mechanisms of dinosaur extinction.

PubMed

Wang, Guang-Zhong; Ma, Bin-Guang; Yang, Yan; Zhang, Hong-Yu

2005-08-12

Dinosaur extinction is a great challenge to evolutionary biology. Although accumulating evidence suggests that an abrupt change of environment, such as a long period of low temperature induced by asteroid hit or other disasters, may be responsible for dinosaur extinction, little is known about the underlying molecular mechanisms. By analyzing the amino acid compositions of 13 biological classes, we found that the charged amino acid content of modern Reptilia, the sibling of dinosaur, is strikingly different from those of other classes, which inspires us to propose a possible molecular mechanism for dinosaur extinction.

Role of molecular properties of ulvans on their ability to elaborate antiadhesive surfaces.

PubMed

Gadenne, Virginie; Lebrun, Laurent; Jouenne, Thierry; Thebault, Pascal

2015-03-01

Antiadhesive properties of polysaccharides (such ulvans) once immobilized on a surface are described in the literature but the parameters governing their antifouling properties are not yet well identified. In the present study, the relationship between molecular parameters of ulvans and the inhibition of bacterial adhesion was investigated. To this aim, various ulvans were grafted on silicon wafers under two different experimental immobilization conditions. Results showed that the experimental immobilization conditions and the polysaccharides molecular weight led to specific layer conformations which exhibited a key role in the surface antiadhesive properties. © 2014 Wiley Periodicals, Inc.

Molecular profiles to biology and pathways: a systems biology approach.

PubMed

Van Laere, Steven; Dirix, Luc; Vermeulen, Peter

2016-06-16

Interpreting molecular profiles in a biological context requires specialized analysis strategies. Initially, lists of relevant genes were screened to identify enriched concepts associated with pathways or specific molecular processes. However, the shortcoming of interpreting gene lists by using predefined sets of genes has resulted in the development of novel methods that heavily rely on network-based concepts. These algorithms have the advantage that they allow a more holistic view of the signaling properties of the condition under study as well as that they are suitable for integrating different data types like gene expression, gene mutation, and even histological parameters.

Coupling molecular spin centers to microwave resonators: steps towards the implementation of molecular qubits for hybrid quantum circuits

NASA Astrophysics Data System (ADS)

Bonizzoni, Claudio; Ghirri, Alberto; Affronte, Marco

Hybrid spin-photons quantum bits can be obtained under strong coupling regime between microwave photons and a spin ensemble, where coherent exchange of photons is realized. Molecular spins systems, thanks to their tailorable magnetic properties, are retained promising candidates for hybrid qubits. We present an experimental study of the coupling regimes between a high critical temperature YBCO superconducting resonator and different molecular spin ensembles. Three mononuclear compounds, (PPh4)2[Cu(mnt)2], [ErPc2]-TBA+ , Dy(trensal) and two organic radicals, DPPH and PyBTM, are studied. Strong coupling is found in radicals thanks to exchange narrowing. Possible strategies to achieve strong coupling with mononuclear compounds are discussed, and several hints in the design of molecular spins are given.

Discotic columnar liquid crystal studied in the bulk and nanoconfined states by molecular dynamics simulation

NASA Astrophysics Data System (ADS)

Busselez, Rémi; Cerclier, Carole V.; Ndao, Makha; Ghoufi, Aziz; Lefort, Ronan; Morineau, Denis

2014-10-01

A prototypical Gay Berne discotic liquid crystal was studied by means of molecular dynamics simulations both in the bulk state and under confinement in a nanoporous channel. The phase behavior of the confined system strongly differs from its bulk counterpart: the bulk isotropic-to-columnar transition is replaced by a continuous ordering from a paranematic to a columnar phase. Moreover, a new transition is observed at a lower temperature in the confined state, which corresponds to a reorganization of the intercolumnar order. It reflects the competing effects of pore surface interaction and genuine hexagonal packing of the columns. The translational molecular dynamics in the different phases has been thoroughly studied and discussed in terms of collective relaxation modes, non-Gaussian behavior, and hopping processes.

Subsumed complexity: abiogenesis as a by-product of complex energy transduction.

PubMed

Adam, Z R; Zubarev, D; Aono, M; Cleaves, H James

2017-12-28

The origins of life bring into stark relief the inadequacy of our current synthesis of thermodynamic, chemical, physical and information theory to predict the conditions under which complex, living states of organic matter can arise. Origins research has traditionally proceeded under an array of implicit or explicit guiding principles in lieu of a universal formalism for abiogenesis. Within the framework of a new guiding principle for prebiotic chemistry called subsumed complexity , organic compounds are viewed as by-products of energy transduction phenomena at different scales (subatomic, atomic, molecular and polymeric) that retain energy in the form of bonds that inhibit energy from reaching the ground state. There is evidence for an emergent level of complexity that is overlooked in most conceptualizations of abiogenesis that arises from populations of compounds formed from atomic energy input. We posit that different forms of energy input can exhibit different degrees of dissipation complexity within an identical chemical medium. By extension, the maximum capacity for organic chemical complexification across molecular and macromolecular scales subsumes, rather than emerges from, the underlying complexity of energy transduction processes that drive their production and modification.This article is part of the themed issue 'Reconceptualizing the origins of life'. © 2017 The Author(s).

Subsumed complexity: abiogenesis as a by-product of complex energy transduction

NASA Astrophysics Data System (ADS)

Adam, Z. R.; Zubarev, D.; Aono, M.; Cleaves, H. James

2017-11-01

The origins of life bring into stark relief the inadequacy of our current synthesis of thermodynamic, chemical, physical and information theory to predict the conditions under which complex, living states of organic matter can arise. Origins research has traditionally proceeded under an array of implicit or explicit guiding principles in lieu of a universal formalism for abiogenesis. Within the framework of a new guiding principle for prebiotic chemistry called subsumed complexity, organic compounds are viewed as by-products of energy transduction phenomena at different scales (subatomic, atomic, molecular and polymeric) that retain energy in the form of bonds that inhibit energy from reaching the ground state. There is evidence for an emergent level of complexity that is overlooked in most conceptualizations of abiogenesis that arises from populations of compounds formed from atomic energy input. We posit that different forms of energy input can exhibit different degrees of dissipation complexity within an identical chemical medium. By extension, the maximum capacity for organic chemical complexification across molecular and macromolecular scales subsumes, rather than emerges from, the underlying complexity of energy transduction processes that drive their production and modification. This article is part of the themed issue 'Reconceptualizing the origins of life'.

Phase Transition of Single-Layer Molybdenum Disulfide Nanosheets under Mechanical Loading Based on Molecular Dynamics Simulations.

PubMed

Pang, Haosheng; Li, Minglin; Gao, Chenghui; Huang, Haili; Zhuo, Weirong; Hu, Jianyue; Wan, Yaling; Luo, Jing; Wang, Weidong

2018-03-27

The single-layer molybdenum disulfide (SLMoS2) nanosheets have been experimentally discovered to exist in two different polymorphs, which exhibit different electrical properties, metallic or semiconducting. Herein, molecular dynamics (MD) simulations of nanoindentation and uniaxial compression were conducted to investigate the phase transition of SLMoS2 nanosheets. Typical load-deflection curves, stress-strain curves, and local atomic structures were obtained. The loading force decreases sharply and then increases again at a critical deflection under the nanoindentation, which is inferred to the phase transition. In addition to the layer thickness, some related bond lengths and bond angles were also found to suddenly change as the phase transition occurs. A bell-like hollow, so-called residual deformation, was found to form, mainly due to the lattice distortion around the waist of the bell. The effect of indenter size on the residual hollow was also analyzed. Under the uniaxial compression along the armchair direction, a different phase transition, a uniformly quadrilateral structure, was observed when the strain is greater than 27.7%. The quadrilateral structure was found to be stable and exhibit metallic conductivity in view of the first-principle calculation.

Forty years of research on xeroderma pigmentosum at the US National Institutes of Health.

PubMed

Kraemer, Kenneth H; DiGiovanna, John J

2015-01-01

In 1968, Dr. James Cleaver reported defective DNA repair in cultured cells from patients with xeroderma pigmentosum. This link between clinical disease and molecular pathophysiology has sparked interest in understanding not only the clinical characteristics of sun sensitivity, damage and cancer that occurred in XP patients but also the mechanisms underlying the damage and repair. While affected patients are rare, their exaggerated UV damage provides a window into the workings of DNA repair. These studies have clarified the importance of a functioning DNA repair system to the maintenance of skin and neurologic health in the general population. Understanding the role of damage in causing cancer, neurologic degeneration, hearing loss and internal cancers provides an opportunity for prevention and treatment. Characterizing complementation groups pointed to the importance of different underlying genes. Studying differences in cancer age of onset and underlying molecular signatures in cancers occurring either in XP patients or the general population has led to insights into differences in carcinogenic mechanisms. The accelerated development of cancers in XP has been used as a model to discover new cancer chemopreventive agents. An astute insight can be a "tipping point" triggering decades of productive inquiry. © 2015 The American Society of Photobiology.

Forty Years of Research on Xeroderma Pigmentosum at the US National Institutes of Health†

PubMed Central

Kraemer, Kenneth H.; DiGiovanna, John J.

2014-01-01

In 1968, Dr. James Cleaver reported defective DNA repair in cultured cells from patients with xeroderma pigmentosum. This link between clinical disease and molecular pathophysiology has sparked interest in understanding not only the clinical characteristics of sun sensitivity, damage and cancer that occurred in XP patients but also the mechanisms underlying the damage and repair. While affected patients are rare, their exaggerated UV damage provides a window into the workings of DNA repair. These studies have clarified the importance of a functioning DNA repair system to the maintenance of skin and neurologic health in the general population. Understanding the role of damage in causing cancer, neurologic degeneration, hearing loss and internal cancers provides an opportunity for prevention and treatment. Characterizing complementation groups pointed to the importance of different underlying genes. Studying differences in cancer age of onset and underlying molecular signatures in cancers occurring either in XP patients or the general population has led to insights into differences in carcinogenic mechanisms. The accelerated development of cancers in XP has been used as a model to discover new cancer chemopreventive agents. An astute insight can be a “tipping point” triggering decades of productive inquiry. PMID:25220021

Molecular Origin of the Vibrational Structure of Ice Ih.

PubMed

Moberg, Daniel R; Straight, Shelby C; Knight, Christopher; Paesani, Francesco

2017-06-15

An unambiguous assignment of the vibrational spectra of ice I h remains a matter of debate. This study demonstrates that an accurate representation of many-body interactions between water molecules, combined with an explicit treatment of nuclear quantum effects through many-body molecular dynamics (MB-MD), leads to a unified interpretation of the vibrational spectra of ice I h in terms of the structure and dynamics of the underlying hydrogen-bond network. All features of the infrared and Raman spectra in the OH stretching region can be unambiguously assigned by taking into account both the symmetry and the delocalized nature of the lattice vibrations as well as the local electrostatic environment experienced by each water molecule within the crystal. The high level of agreement with experiment raises prospects for predictive MB-MD simulations that, complementing analogous measurements, will provide molecular-level insights into fundamental processes taking place in bulk ice and on ice surfaces under different thermodynamic conditions.

H2B ubiquitination: Conserved molecular mechanism, diverse physiologic functions of the E3 ligase during meiosis.

PubMed

Wang, Liying; Cao, Chunwei; Wang, Fang; Zhao, Jianguo; Li, Wei

2017-09-03

RNF20/Bre1 mediated H2B ubiquitination (H2Bub) has various physiologic functions. Recently, we found that H2Bub participates in meiotic recombination by promoting chromatin relaxation during meiosis. We then analyzed the phylogenetic relationships among the E3 ligase for H2Bub, its E2 Rad6 and their partner WW domain-containing adaptor with a coiled-coil (WAC) or Lge1, and found that the molecular mechanism underlying H2Bub is evolutionarily conserved from yeast to mammals. However, RNF20 has diverse physiologic functions in different organisms, which might be caused by the evolutionary divergency of their domain/motif architectures. In the current extra view, we not only elucidate the evolutionarily conserved molecular mechanism underlying H2Bub, but also discuss the diverse physiologic functions of RNF20 during meiosis.

Is pigment patterning in fish skin determined by the Turing mechanism?

PubMed

Watanabe, Masakatsu; Kondo, Shigeru

2015-02-01

More than half a century ago, Alan Turing postulated that pigment patterns may arise from a mechanism that could be mathematically modeled based on the diffusion of two substances that interact with each other. Over the past 15 years, the molecular and genetic tools to verify this prediction have become available. Here, we review experimental studies aimed at identifying the mechanism underlying pigment pattern formation in zebrafish. Extensive molecular genetic studies in this model organism have revealed the interactions between the pigment cells that are responsible for the patterns. The mechanism discovered is substantially different from that predicted by the mathematical model, but it retains the property of 'local activation and long-range inhibition', a necessary condition for Turing pattern formation. Although some of the molecular details of pattern formation remain to be elucidated, current evidence confirms that the underlying mechanism is mathematically equivalent to the Turing mechanism. Copyright © 2014 Elsevier Ltd. All rights reserved.

Dimeric [Mo₂S₁₂]²⁻ Cluster: A Molecular Analogue of MoS₂ Edges for Superior Hydrogen-Evolution Electrocatalysis

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

Huang, Zhongjie; Luo, Wenjia; Ma, Lu

2015-12-07

Proton reduction is one of the most fundamental and important reactions in nature. MoS2 edges have been identified as the active sites for hydrogen evolution reaction (HER) electrocatalysis. Designing molecular mimics of MoS2 edge sites is an attractive strategy to understand the underlying catalytic mechanism of different edge sites and improve their activities. Herein we report a dimeric molecular analogue [Mo₂S₁₂]²⁻, as the smallest unit possessing both the terminal and bridging disulfide ligands. Our electrochemical tests show that [Mo₂S₁₂]²⁻ is a superior heterogeneous HER catalyst under acidic conditions. Computations suggest that the bridging disulfide ligand of [Mo₂S₁₂]²⁻ exhibits a hydrogenmore » adsorption free energy near zero (-0.05eV). This work helps shed light on the rational design of HER catalysts and biomimetics of hydrogen-evolving enzymes.« less

[Genodiagnosis and molecular typing of the pathogens for plague, cholera, and anthrax].

PubMed

Kutyrev, V V; Smirnova, N I

2003-01-01

The paper contains a survey of published data about the use of DNA-diagnostics in indicating and identifying the causative agents of highly dangerous infections like plague, cholera and anthrax. A discussion of data about the genetic relationship between strains of the mentioned causative agents isolated from different sources by using the molecular-typing methods as well as about the evolution ties between strains of different origins is in the focus of attention. Results of comparative studies of nucleotide sequences of genomes or of individual genomes in different Yersinia pestis, Vibrio cholerae and Bacillus anthracis strains, which are indicative of the evolution of their pathogenicity, are also under discussion.

Understanding the effects of lignosulfonate on enzymatic saccharification of pure cellulose

Treesearch

Hongming Lou; Haifeng Zhou; Xiuli Li; Mengxia Wang; J.Y. Zhu; Xueqing Qiu

2014-01-01

The effects of lignosulfonate (LS) on enzymatic saccharification of pure cellulose were studied. Four fractions of LS with different molecular weight (MW) prepared by ultrafiltration of a commercial LS were applied at different loadings to enzymatic hydrolysis of Whatman paper under different pH. Using LS fractions with low MW and high degree of sulfonation can enhance...

Cellulose Aggregation under Hydrothermal Pretreatment Conditions.

PubMed

Silveira, Rodrigo L; Stoyanov, Stanislav R; Kovalenko, Andriy; Skaf, Munir S

2016-08-08

Cellulose, the most abundant biopolymer on Earth, represents a resource for sustainable production of biofuels. Thermochemical treatments make lignocellulosic biomaterials more amenable to depolymerization by exposing cellulose microfibrils to enzymatic or chemical attacks. In such treatments, the solvent plays fundamental roles in biomass modification, but the molecular events underlying these changes are still poorly understood. Here, the 3D-RISM-KH molecular theory of solvation has been employed to analyze the role of water in cellulose aggregation under different thermodynamic conditions. The results show that, under ambient conditions, highly structured hydration shells around cellulose create repulsive forces that protect cellulose microfibrils from aggregating. Under hydrothermal pretreatment conditions, however, the hydration shells lose structure, and cellulose aggregation is favored. These effects are largely due to a decrease in cellulose-water interactions relative to those at ambient conditions, so that cellulose-cellulose attractive interactions become prevalent. Our results provide an explanation to the observed increase in the lateral size of cellulose crystallites when biomass is subject to pretreatments and deepen the current understanding of the mechanisms of biomass modification.

Sodium chloride stress induced morphological and ultrastructural changes in Aspergillus repens.

PubMed

Kelavkar, U; Rao, K S; Ghhatpar, H S

1993-06-01

Halotolerant fungus, A. repens, showed a considerable difference in its growth rate, morphology, ultrastructural and molecular composition under NaCl stress as compared to control i.e. non-stressed condition. Light microscopic observations revealed significant differences in their mycelial thickness, their branching and septa. Transmission electron microscopic observations of both the conditions depicted significant differences in the qualitative and quantitative changes in mitochondria. Frequent pinocytotic vesiculation (vacuoles) of plasma membrane was observed in fungus under stress but no such vesiculation in control. The multivesiculate structures observed under stress with their origin from the cell membranes and subsequent release into vacuoles have not been reported in fungi under normal physiological conditions. The observations on pinocytosis are discussed in relation to ion compartmentation and salt tolerance in A. repens.

Patterning in time and space: HoxB cluster gene expression in the developing chick embryo.

PubMed

Gouveia, Analuce; Marcelino, Hugo M; Gonçalves, Lisa; Palmeirim, Isabel; Andrade, Raquel P

2015-01-01

The developing embryo is a paradigmatic model to study molecular mechanisms of time control in Biology. Hox genes are key players in the specification of tissue identity during embryo development and their expression is under strict temporal regulation. However, the molecular mechanisms underlying timely Hox activation in the early embryo remain unknown. This is hindered by the lack of a rigorous temporal framework of sequential Hox expression within a single cluster. Herein, a thorough characterization of HoxB cluster gene expression was performed over time and space in the early chick embryo. Clear temporal collinearity of HoxB cluster gene expression activation was observed. Spatial collinearity of HoxB expression was evidenced in different stages of development and in multiple tissues. Using embryo explant cultures we showed that HoxB2 is cyclically expressed in the rostral presomitic mesoderm with the same periodicity as somite formation, suggesting a link between timely tissue specification and somite formation. We foresee that the molecular framework herein provided will facilitate experimental approaches aimed at identifying the regulatory mechanisms underlying Hox expression in Time and Space.

Patterning in time and space: HoxB cluster gene expression in the developing chick embryo

PubMed Central

Gouveia, Analuce; Marcelino, Hugo M; Gonçalves, Lisa; Palmeirim, Isabel; Andrade, Raquel P

2015-01-01

The developing embryo is a paradigmatic model to study molecular mechanisms of time control in Biology. Hox genes are key players in the specification of tissue identity during embryo development and their expression is under strict temporal regulation. However, the molecular mechanisms underlying timely Hox activation in the early embryo remain unknown. This is hindered by the lack of a rigorous temporal framework of sequential Hox expression within a single cluster. Herein, a thorough characterization of HoxB cluster gene expression was performed over time and space in the early chick embryo. Clear temporal collinearity of HoxB cluster gene expression activation was observed. Spatial collinearity of HoxB expression was evidenced in different stages of development and in multiple tissues. Using embryo explant cultures we showed that HoxB2 is cyclically expressed in the rostral presomitic mesoderm with the same periodicity as somite formation, suggesting a link between timely tissue specification and somite formation. We foresee that the molecular framework herein provided will facilitate experimental approaches aimed at identifying the regulatory mechanisms underlying Hox expression in Time and Space. PMID:25602523

Canadian Association of Neurosciences Review: learning at a snail's pace.

PubMed

Parvez, Kashif; Rosenegger, David; Martens, Kara; Orr, Michael; Lukowiak, Ken

2006-11-01

While learning and memory are related, they are distinct processes each with different forms of expression and underlying molecular mechanisms. An invertebrate model system, Lymnaea stagnalis, is used to study memory formation of a non-declarative memory. We have done so because: (1) We have discovered the neural circuit that mediates an interesting and tractable behaviour; (2) This behaviour can be operantly conditioned and intermediate-term and long-term memory can be demonstrated; and (3) It is possible to demonstrate that a single neuron in the model system is a necessary site of memory formation. This article reviews how Lymnaea has been used in the study of behavioural and molecular mechanisms underlying consolidation, reconsolidation, extinction and forgetting.

Wall-collision line broadening of molecular oxygen within nanoporous materials

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

Xu, Can T.; Lewander, Maerta; Andersson-Engels, Stefan

2011-10-15

Wall-collision broadening of near-infrared absorption lines of molecular oxygen confined in nanoporous zirconia is studied by employing high-resolution diode-laser spectroscopy. The broadening is studied for pores of different sizes under a range of pressures, providing new insights on how wall collisions and intermolecular collisions influence the total spectroscopic line profile. The pressure series show that wall-collision broadening is relatively more prominent under reduced pressures, enabling sensitive means to probe pore sizes of porous materials. In addition, we show that the total wall-collision-broadened profile strongly deviates from a Voigt profile and that wall-collision broadening exhibits an additive-like behavior to the pressuremore » and Doppler broadening.« less

Modeling the effect of pathogenic mutations on the conformational landscape of protein kinases.

PubMed

Saladino, Giorgio; Gervasio, Francesco Luigi

2016-04-01

Most proteins assume different conformations to perform their cellular functions. This conformational dynamics is physiologically regulated by binding events and post-translational modifications, but can also be affected by pathogenic mutations. Atomistic molecular dynamics simulations complemented by enhanced sampling approaches are increasingly used to probe the effect of mutations on the conformational dynamics and on the underlying conformational free energy landscape of proteins. In this short review we discuss recent successful examples of simulations used to understand the molecular mechanism underlying the deregulation of physiological conformational dynamics due to non-synonymous single point mutations. Our examples are mostly drawn from the protein kinase family. Copyright © 2016 Elsevier Ltd. All rights reserved.

Bioinformatics Analysis Reveals Distinct Molecular Characteristics of Hepatitis B-Related Hepatocellular Carcinomas from Very Early to Advanced Barcelona Clinic Liver Cancer Stages.

PubMed

Kong, Fan-Yun; Wei, Xiao; Zhou, Kai; Hu, Wei; Kou, Yan-Bo; You, Hong-Juan; Liu, Xiao-Mei; Zheng, Kui-Yang; Tang, Ren-Xian

2016-01-01

Hepatocellular carcinoma (HCC)is the fifth most common malignancy associated with high mortality. One of the risk factors for HCC is chronic hepatitis B virus (HBV) infection. The treatment strategy for the disease is dependent on the stage of HCC, and the Barcelona clinic liver cancer (BCLC) staging system is used in most HCC cases. However, the molecular characteristics of HBV-related HCC in different BCLC stages are still unknown. Using GSE14520 microarray data from HBV-related HCC cases with BCLC stages from 0 (very early stage) to C (advanced stage) in the gene expression omnibus (GEO) database, differentially expressed genes (DEGs), including common DEGs and unique DEGs in different BCLC stages, were identified. These DEGs were located on different chromosomes. The molecular functions and biology pathways of DEGs were identified by gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and the interactome networks of DEGs were constructed using the NetVenn online tool. The results revealed that both common DEGs and stage-specific DEGs were associated with various molecular functions and were involved in special biological pathways. In addition, several hub genes were found in the interactome networks of DEGs. The identified DEGs and hub genes promote our understanding of the molecular mechanisms underlying the development of HBV-related HCC through the different BCLC stages, and might be used as staging biomarkers or molecular targets for the treatment of HCC with HBV infection.

Molecular mechanisms underlying the physiological responses of the cold-water coral Desmophyllum dianthus to ocean acidification

NASA Astrophysics Data System (ADS)

Carreiro-Silva, M.; Cerqueira, T.; Godinho, A.; Caetano, M.; Santos, R. S.; Bettencourt, R.

2014-06-01

Cold-water corals (CWCs) are thought to be particularly vulnerable to ocean acidification (OA) due to increased atmospheric pCO2, because they inhabit deep and cold waters where the aragonite saturation state is naturally low. Several recent studies have evaluated the impact of OA on organism-level physiological processes such as calcification and respiration. However, no studies to date have looked at the impact at the molecular level of gene expression. Here, we report results of a long-term, 8-month experiment to compare the physiological responses of the CWC Desmophyllum dianthus to OA at both the organismal and gene expression levels under two pCO2/pH treatments: ambient pCO2 (460 μatm, pHT = 8.01) and elevated pCO2 (997 μatm, pHT = 7.70). At the organismal level, no significant differences were detected in the calcification and respiration rates of D. dianthus. Conversely, significant differences were recorded in gene expression profiles, which showed an up-regulation of genes involved in cellular stress (HSP70) and immune defence (mannose-binding c-type lectin). Expression of alpha-carbonic anhydrase, a key enzyme involved in the synthesis of coral skeleton, was also significantly up-regulated in corals under elevated pCO2, indicating that D. dianthus was under physiological reconditioning to calcify under these conditions. Thus, gene expression profiles revealed physiological impacts that were not evident at the organismal level. Consequently, understanding the molecular mechanisms behind the physiological processes involved in a coral's response to elevated pCO2 is critical to assess the ability of CWCs to acclimate or adapt to future OA conditions.

Effect of the molecular weight of a neutral polysaccharide on soy protein gelation.

PubMed

Monteiro, Sónia R; Lopes-da-Silva, José A

2017-12-01

The effects of galactomannans with different molecular weights on the heat-induced gelation characteristics of soybean protein were investigated using dynamic small-strain rheometry, under conditions where the proteins carry a net negative charge (pH7). Microstructure of the resulting gels was investigated by confocal laser scanning microscopy. Phase-separated systems were obtained with different morphologies and degree of phase separation, depending on both biopolymer concentrations and polysaccharide molecular weight. In general, a gelling enhancing effect on soy proteins was verified, despite extensive phase-separation processes observed at the higher polysaccharide molecular weight. This effect was demonstrated by an increase of the gelation rate, a decrease in the temperature at the onset of gelation, and an increase of gel stiffness and elastic character, with the length of polysaccharide chains. Overall, the results obtained established that the judicious selection of the galactomannan molecular weight may be used to modify the structure and gelation properties of soy proteins, originating a diversity of rheological characteristics and microstructures that will impact on the design of novel food formulations. Copyright © 2017 Elsevier Ltd. All rights reserved.

Variations in the Composition of Gelling Agents Affect Morphophysiological and Molecular Responses to Deficiencies of Phosphate and Other Nutrients1[C][W][OA

PubMed Central

Jain, Ajay; Poling, Michael D.; Smith, Aaron P.; Nagarajan, Vinay K.; Lahner, Brett; Meagher, Richard B.; Raghothama, Kashchandra G.

2009-01-01

Low inorganic phosphate (Pi) availability triggers an array of spatiotemporal adaptive responses in Arabidopsis (Arabidopsis thaliana). There are several reports on the effects of Pi deprivation on the root system that have been attributed to different growth conditions and/or inherent genetic variability. Here we show that the gelling agents, largely treated as inert components, significantly affect morphophysiological and molecular responses of the seedlings to deficiencies of Pi and other nutrients. Inductively coupled plasma-mass spectroscopy analysis revealed variable levels of elemental contaminants not only in different types of agar but also in different batches of the same agar. Fluctuating levels of phosphorus (P) in different agar types affected the growth of the seedlings under Pi-deprivation condition. Since P interacts with other elements such as iron, potassium, and sulfur, contaminating effects of these elements in different agars were also evident in the Pi-deficiency-induced morphological and molecular responses. P by itself acted as a contaminant when studying the responses of Arabidopsis to micronutrient (iron and zinc) deficiencies. Together, these results highlighted the likelihood of erroneous interpretations that could be easily drawn from nutrition studies when different agars have been used. As an alternative, we demonstrate the efficacy of a sterile and contamination-free hydroponic system for dissecting morphophysiological and molecular responses of Arabidopsis to different nutrient deficiencies. PMID:19386810

Molecular Gibbs Surface Excess and CO2-Hydrate Density Determine the Strong Temperature- and Pressure-Dependent Supercritical CO2-Brine Interfacial Tension.

PubMed

Ji, Jiayuan; Zhao, Lingling; Tao, Lu; Lin, Shangchao

2017-06-29

In CO 2 geological storage, the interfacial tension (IFT) between supercritical CO 2 and brine is critical for the storage capacitance design to prevent CO 2 leakage. IFT relies not only on the interfacial molecule properties but also on the environmental conditions at different storage sites. In this paper, supercritical CO 2 -NaCl solution systems are modeled at 343-373 K and 6-35 MPa under the salinity of 1.89 mol/L using molecular dynamics simulations. After computing and comparing the molecular density profile across the interface, the atomic radial distribution function, the molecular orientation distribution, the molecular Gibbs surface excess (derived from the molecular density profile), and the CO 2 -hydrate number density under the above environmental conditions, we confirm that only the molecular Gibbs surface excess of CO 2 molecules and the CO 2 -hydrate number density correlate strongly with the temperature- and pressure-dependent IFTs. We also compute the populations of two distinct CO 2 -hydrate structures (T-type and H-type) and attribute the observed dependence of IFTs to the dominance of the more stable, surfactant-like T-type CO 2 -hydrates at the interface. On the basis of these new molecular mechanisms behind IFT variations, this study could guide the rational design of suitable injecting environmental pressure and temperature conditions. We believe that the above two molecular-level metrics (Gibbs surface excess and hydrate number density) are of great fundamental importance for understanding the supercritical CO 2 -water interface and engineering applications in geological CO 2 storage.

Cyclin-dependent kinase 4 signaling acts as a molecular switch between syngenic differentiation and neural transdifferentiation in human mesenchymal stem cells

PubMed Central

Lee, Janet; Baek, Jeong-Hwa; Choi, Kyu-Sil; Kim, Hyun-Soo; Park, Hye-Young; Ha, Geun-Hyoung; Park, Ho; Lee, Kyo-Won; Lee, Chang Geun; Yang, Dong-Yun; Moon, Hyo Eun; Paek, Sun Ha; Lee, Chang-Woo

2013-01-01

Multipotent mesenchymal stem/stromal cells (MSCs) are capable of differentiating into a variety of cell types from different germ layers. However, the molecular and biochemical mechanisms underlying the transdifferentiation of MSCs into specific cell types still need to be elucidated. In this study, we unexpectedly found that treatment of human adipose- and bone marrow-derived MSCs with cyclin-dependent kinase (CDK) inhibitor, in particular CDK4 inhibitor, selectively led to transdifferentiation into neural cells with a high frequency. Specifically, targeted inhibition of CDK4 expression using recombinant adenovial shRNA induced the neural transdifferentiation of human MSCs. However, the inhibition of CDK4 activity attenuated the syngenic differentiation of human adipose-derived MSCs. Importantly, the forced regulation of CDK4 activity showed reciprocal reversibility between neural differentiation and dedifferentiation of human MSCs. Together, these results provide novel molecular evidence underlying the neural transdifferentiation of human MSCs; in addition, CDK4 signaling appears to act as a molecular switch from syngenic differentiation to neural transdifferentiation of human MSCs. PMID:23324348

Impact of tree cutting on water-soluble organic compounds in podzolic soils of the European North-East

NASA Astrophysics Data System (ADS)

Lapteva, Elena; Bondarenko, Natalia; Shamrikova, Elena; Kubik, Olesya; Punegov, Vasili

2016-04-01

Water-soluble organic compounds (WOCs) and their single components, i.e. low-molecular organic acids, alcohols, and carbohydrates, attain a great deal of attention among soil scientists. WOCs are an important component of soil organic matter (SOM) and form as a results of different biological and chemical processes in soils. These processes are mainly responsible for formation and development of soils in aboveground ecosystems. The purpose of the work was identifying qualitative and quantitative composition of low-molecular organic substances which form in podzolic loamy soils against natural reforestation after spruce forest cutting. The studies were conducted on the territory of the European North-East of Russia, in the middle taiga subzone (Komi Republic, Ust-Kulom region). The study materials were soil of undisturbed bilberry spruce forest (Sample Plot 1 (SP1)) and soils of different-aged tree stands where cutting activities took place in winter 2001/2002 (SP2) and 1969/1970 (SP3). Description of soils and vegetation cover on the plots is given in [1]. Low-molecular organic compounds in soil water extracts were identified by the method of gas chromatography mass-spectrometry [2, 3]. Finally, reforestationafterspruceforestcutting was found to be accompanied by different changes in soil chemical composition. In contrast with soils under undisturbed spruce forest, organic soil horizons under different-aged cuts decreased in organic carbon reserves and production of low-molecular organic compounds, changed in soil acidity. Within the soil series of SP1→SP2→SP3, the highest content of WOCs was identified for undisturbed spruce forest (738 mg kg-1 soil). In soils of coniferous-deciduous forests on SP1 and SP3, WOC content was 294 and 441 mg kg-1 soil, correspondingly. Soils at cuts decreased in concentration of any water-soluble low-molecular SOM components as low-molecular acids, alcohols, and carbohydrates. Structure of low-molecular WOCs in the study podzolic soils was dominated by carbohydrates with ratio from 49% (SP1) to 63-66% (SP2, SP3) of total content of all identified compounds. The increase in relative content in carbohydrates observed for soils under cuts was possibly affected by vegetation cover change after clear-cutting and presence of birch and aspen leaves in plant waste composition (due to tree species change). At SP2 and SP3 cuts, content of alcohols and low-molecular carboxylic acids fell by almost twice as compared with SP1. Tree cuts changed not only in total content of water-soluble compounds but also in ratio of individual low-molecular compounds in water extracts composition. Totally, we identified 26 various compounds, including 12 low-molecular organic (carboxylic) acids, 10 carbohydrates, and 4 alcohols. Composition of carboxylic acids was dominated by aliphatic substituted acids (mainly 2-oxyacetic acid, 2-oxypropane, and 2,3-dioxypropane acids). Total number of aliphatic substituted acids, as well as aliphatic non-substituted and aromatic carboxylic acids, decreased in soils under cuts at initial reforestation stages (SP2). Content of all mentioned acids gradually rose with time (SP3). Soils under cut forests were observed for a decrease of erythrite ratio in composition of water-soluble alcohols (from 52 to 40% of total alcohols) and an increase of glycerin ratio (from 46 to 72%). 10 of identified mono- and disaccharides were dominated by mannose, galactopyranose, and D-ribose. Disturbed soils were identified for increased ratio of galactopyranose and D-ribose and for by almost twice as decreased ratio of mannose. References 1. Dymov, A. A. Changes in the organic matter of taiga soils during the natural reaforestation after cutting in the middle taigaof the Komi Republic / A. A. Dymov, E. Yu. Milanovskii // Eurasian Soil Science, 2013. Vol. 46. № 12. P. 1164-1171. 2. Shamrikova E.V., Punegov V.V., Gruzdev I.V., Vanchikova E.V., Vetoshkina A.A. Individual organic compounds in water extracts from podzolic soils of the Komi Republic // Eurasian Soil Science, 2012. T. 45. № 10. C. 939-946. 3. Shamrikova E.V., Gruzdev I.V., Punegov V.V., Khabibullina F.M., Kubik O.S. Water-soluble low-molecular-weight organic acids in automorphic loamy soils of the tundra and taiga zones // Eurasian Soil Science, 2013. T. 46.№ 6. C. 654-659.

Multiple determinants of transfer of evaluative function after conditioning with free-operant schedules of reinforcement.

PubMed

Dack, Charlotte; Reed, Phil; McHugh, Louise

2010-11-01

The aim of the four present experiments was to explore how different schedules of reinforcement influence schedule-induced behavior, their impact on evaluative ratings given to conditioned stimuli associated with each schedule through evaluative conditioning, and the transfer of these evaluations through derived stimulus networks. Experiment 1 compared two contrasting response reinforcement rules (variable ratio [VR], variable interval [VI]). Experiment 2 varied the response to reinforcement rule between two schedules but equated the outcome to response rate (differential reinforcement of high rate [DRH] vs. VR). Experiment 3 compared molar and molecular aspects of contingencies of reinforcement (tandem VIVR vs. tandem VRVI). Finally, Experiment 4 employed schedules that induced low rates of responding to determine whether, under these circumstances, responses were more sensitive to the molecular aspects of a schedule (differential reinforcement of low rate [DRL] vs. VI). The findings suggest that the transfer of evaluative functions is determined mainly by differences in response rate between the schedules and the molar aspects of the schedules. However, when neither schedule was based on a strong response reinforcement rule, the transfer of evaluative judgments came under the control of the molecular aspects of the schedule.

Structural Rearrangement of Au-Pd Nanoparticles under Reaction Conditions: An ab Initio Molecular Dynamics Study.

PubMed

Xu, Cong-Qiao; Lee, Mal-Soon; Wang, Yang-Gang; Cantu, David C; Li, Jun; Glezakou, Vassiliki-Alexandra; Rousseau, Roger

2017-02-28

The structure, composition, and atomic distribution of nanoalloys under operating conditions are of significant importance for their catalytic activity. In the present work, we use ab initio molecular dynamics simulations to understand the structural behavior of Au-Pd nanoalloys supported on rutile TiO 2 under different conditions. We find that the Au-Pd structure is strongly dependent on the redox properties of the support, originating from strong metal-support interactions. Under reducing conditions, Pd atoms are inclined to move toward the metal/oxide interface, as indicated by a significant increase of Pd-Ti bonds. This could be attributed to the charge localization at the interface that leads to Coulomb attractions to positively charged Pd atoms. In contrast, under oxidizing conditions, Pd atoms would rather stay inside or on the exterior of the nanoparticle. Moreover, Pd atoms on the alloy surface can be stabilized by hydrogen adsorption, forming Pd-H bonds, which are stronger than Au-H bonds. Our work offers critical insights into the structure and redox properties of Au-Pd nanoalloy catalysts under working conditions.

Concordance and discordance of sequence survey methods for molecular epidemiology

PubMed Central

Hasan, Nur A.; Cebula, Thomas A.; Colwell, Rita R.; Robison, Richard A.; Johnson, W. Evan; Crandall, Keith A.

2015-01-01

The post-genomic era is characterized by the direct acquisition and analysis of genomic data with many applications, including the enhancement of the understanding of microbial epidemiology and pathology. However, there are a number of molecular approaches to survey pathogen diversity, and the impact of these different approaches on parameter estimation and inference are not entirely clear. We sequenced whole genomes of bacterial pathogens, Burkholderia pseudomallei, Yersinia pestis, and Brucella spp. (60 new genomes), and combined them with 55 genomes from GenBank to address how different molecular survey approaches (whole genomes, SNPs, and MLST) impact downstream inferences on molecular evolutionary parameters, evolutionary relationships, and trait character associations. We selected isolates for sequencing to represent temporal, geographic origin, and host range variability. We found that substitution rate estimates vary widely among approaches, and that SNP and genomic datasets yielded different but strongly supported phylogenies. MLST yielded poorly supported phylogenies, especially in our low diversity dataset, i.e., Y. pestis. Trait associations showed that B. pseudomallei and Y. pestis phylogenies are significantly associated with geography, irrespective of the molecular survey approach used, while Brucella spp. phylogeny appears to be strongly associated with geography and host origin. We contrast inferences made among monomorphic (clonal) and non-monomorphic bacteria, and between intra- and inter-specific datasets. We also discuss our results in light of underlying assumptions of different approaches. PMID:25737810

High molecular diversity of extraterrestrial organic matter in Murchison meteorite revealed 40 years after its fall

PubMed Central

Schmitt-Kopplin, Philippe; Gabelica, Zelimir; Gougeon, Régis D.; Fekete, Agnes; Kanawati, Basem; Harir, Mourad; Gebefuegi, Istvan; Eckel, Gerhard; Hertkorn, Norbert

2010-01-01

Numerous descriptions of organic molecules present in the Murchison meteorite have improved our understanding of the early interstellar chemistry that operated at or just before the birth of our solar system. However, all molecular analyses were so far targeted toward selected classes of compounds with a particular emphasis on biologically active components in the context of prebiotic chemistry. Here we demonstrate that a nontargeted ultrahigh-resolution molecular analysis of the solvent-accessible organic fraction of Murchison extracted under mild conditions allows one to extend its indigenous chemical diversity to tens of thousands of different molecular compositions and likely millions of diverse structures. This molecular complexity, which provides hints on heteroatoms chronological assembly, suggests that the extraterrestrial chemodiversity is high compared to terrestrial relevant biological- and biogeochemical-driven chemical space. PMID:20160129

High molecular diversity of extraterrestrial organic matter in Murchison meteorite revealed 40 years after its fall.

PubMed

Schmitt-Kopplin, Philippe; Gabelica, Zelimir; Gougeon, Régis D; Fekete, Agnes; Kanawati, Basem; Harir, Mourad; Gebefuegi, Istvan; Eckel, Gerhard; Hertkorn, Norbert

2010-02-16

Numerous descriptions of organic molecules present in the Murchison meteorite have improved our understanding of the early interstellar chemistry that operated at or just before the birth of our solar system. However, all molecular analyses were so far targeted toward selected classes of compounds with a particular emphasis on biologically active components in the context of prebiotic chemistry. Here we demonstrate that a nontargeted ultrahigh-resolution molecular analysis of the solvent-accessible organic fraction of Murchison extracted under mild conditions allows one to extend its indigenous chemical diversity to tens of thousands of different molecular compositions and likely millions of diverse structures. This molecular complexity, which provides hints on heteroatoms chronological assembly, suggests that the extraterrestrial chemodiversity is high compared to terrestrial relevant biological- and biogeochemical-driven chemical space.

Behavioral and molecular studies of quantitative differences in hygienic behavior in honeybees.

PubMed

Gempe, Tanja; Stach, Silke; Bienefeld, Kaspar; Otte, Marianne; Beye, Martin

2016-10-21

Hygienic behavior (HB) enables honeybees to tolerate parasites, including infection with the parasitic mite Varroa destructor, and it is a well-known example of a quantitative genetic trait. The understanding of the molecular processes underpinning the quantitative differences in this behavior remains limited. We performed gene expression studies in worker bees that displayed quantitative genetic differences in HB. We established a high and low genetic source of HB performance and studied the engagements into HB of single worker bees under the same environmental conditions. We found that the percentage of worker bees that engaged in a hygienic behavioral task tripled in the high versus low HB sources, thus suggesting that genetic differences may mediate differences in stimulated states to perform HB. We found 501 differently expressed genes (DEGs) in the brains of hygienic and non-hygienic performing workers in the high HB source bees, and 342 DEGs in the brains of hygienic performing worker bees, relative to the gene expression in non-hygienic worker bees from the low HB source group. "Cell surface receptor ligand signal transduction" in the high and "negative regulation of cell communication" in the low HB source were overrepresented molecular processes, suggesting that these molecular processes in the brain may play a role in the regulation of quantitative differences in HB. Moreover, only 21 HB-associated DEGs were common between the high and low HB sources. The better HB colony performance is primarily achieved by a high number of bees engaging in the hygienic tasks that associate with distinct molecular processes in the brain. We propose that different gene products and pathways may mediate the quantitative genetic differences of HB.

Effects of elevated line sources on turbulent mixing in channel flow

NASA Astrophysics Data System (ADS)

Nguyen, Quoc; Papavassiliou, Dimitrios

2016-11-01

Fluids mixing in turbulent flows has been studied extensively, due to the importance of this phenomena in nature and engineering. Convection effects along with motion of three-dimensional coherent structures in turbulent flow disperse a substance more efficiently than molecular diffusion does on its own. We present here, however, a study that explores the conditions under which turbulent mixing does not happen, when different substances are released into the flow field from different vertical locations. The study uses a method which combines Direct Numerical Simulation (DNS) with Lagrangian Scalar Tracking (LST) to simulate a turbulent channel flow and track the motion of passive scalars with different Schmidt numbers (Sc). The particles are released from several instantaneous line sources, ranging from the wall to the center region of the channel. The combined effects of mean velocity difference, molecular diffusion and near-wall coherent structures lead to the observation of different concentrations of particles downstream from the source. We then explore in details the conditions under which particles mixing would not happen. Results from numerical simulation at friction Reynolds number of 300 and 600 will be discussed and for Sc ranging from 0.1 to 2,400.

Chiral expression from molecular to macroscopic level via pH modulation in terbium coordination polymers.

PubMed

Huang, Jian; Ding, Hong-Ming; Xu, Yan; Zeng, Dai; Zhu, Hui; Zang, Dong-Mian; Bao, Song-Song; Ma, Yu-Qiang; Zheng, Li-Min

2017-12-14

Chiral expression from the molecular to macroscopic level is common in biological systems, but is difficult to realise for coordination polymers (CPs). The assembly of homochiral CPs in both crystalline and helical forms can provide a bridge for understanding the relationship between the molecular and macroscopic scales of chirality. Herein, we report homochiral helices of [Tb(R- or S-pempH) 3 ]∙2H 2 O (R - or S -1) (pempH 2  = (1-phenylethylamino)methylphosphonic acid) and their crystalline counterparts (R - or S -3), which are formed at different pH of the reaction mixtures under hydrothermal conditions. By combining the experiments and molecular simulations, we propose that the formation of helices of R -1 or S -1 occurs via a hierarchical self-assembly route, which involves twisted packing due to the geometric incompatibility of the different types of chains. The observed chiral transcription from molecules to morphologies is significant for understanding bio-related self-assembly processes on the nano- to macro-scale.

Magnetic Response of Aromatic Rings Under Rotation: Aromatic Shielding Cone of Benzene Upon Different Orientations of the Magnetic Field.

PubMed

Papadopoulos, A G; Charistos, N D; Muñoz-Castro, A

2017-06-20

The induced shielding cone is one of the most characteristic aspects of aromatic species. Herein, we explore its behavior under different orientations of the applied magnetic field by evaluating the overall and dissected π- and σ-electron contributions. Our results shed light onto the orientation dependence behavior of the shielding cone, unraveling a characteristic pattern upon rotation of the aromatic ring. This pattern decreases the long range of the magnetic response, such that it resembles the behavior under constant molecular tumbling in solution. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Molecular Weight Effects on the Viscoelastic Response of a Polyimide

NASA Technical Reports Server (NTRS)

Nicholson, Lee M.; Whitley, Karen S.; Gates, Thomas S.

2000-01-01

The effect of molecular weight on the viscoelastic performance of an advanced polymer (LaRC -SI) was investigated through the use of creep compliance tests. Testing consisted of short-term isothermal creep and recovery with the creep segments performed under constant load. The tests were conducted at three temperatures below the glass transition temperature of each material with different molecular weight. Through the use of time-aging-time superposition procedures, the material constants, material master curves and aging-related parameters were evaluated at each temperature for a given molecular weight. The time-temperature superposition technique helped to describe the effect of temperature on the timescale of the viscoelastic response of each molecular weight. It was shown that the low molecular weight materials have increased creep compliance and creep compliance rate, and are more sensitive to temperature than the high molecular weight materials. Furthermore, a critical molecular weight transition was observed to occur at a weight-average molecular weight of approximately 25000 g/mol below which, the temperature sensitivity of the time-temperature superposition shift factor increases rapidly.

A Systems Biology Approach Reveals Converging Molecular Mechanisms that Link Different POPs to Common Metabolic Diseases.

PubMed

Ruiz, Patricia; Perlina, Ally; Mumtaz, Moiz; Fowler, Bruce A

2016-07-01

A number of epidemiological studies have identified statistical associations between persistent organic pollutants (POPs) and metabolic diseases, but testable hypotheses regarding underlying molecular mechanisms to explain these linkages have not been published. We assessed the underlying mechanisms of POPs that have been associated with metabolic diseases; three well-known POPs [2,3,7,8-tetrachlorodibenzodioxin (TCDD), 2,2´,4,4´,5,5´-hexachlorobiphenyl (PCB 153), and 4,4´-dichlorodiphenyldichloroethylene (p,p´-DDE)] were studied. We used advanced database search tools to delineate testable hypotheses and to guide laboratory-based research studies into underlying mechanisms by which this POP mixture could produce or exacerbate metabolic diseases. For our searches, we used proprietary systems biology software (MetaCore™/MetaDrug™) to conduct advanced search queries for the underlying interactions database, followed by directional network construction to identify common mechanisms for these POPs within two or fewer interaction steps downstream of their primary targets. These common downstream pathways belong to various cytokine and chemokine families with experimentally well-documented causal associations with type 2 diabetes. Our systems biology approach allowed identification of converging pathways leading to activation of common downstream targets. To our knowledge, this is the first study to propose an integrated global set of step-by-step molecular mechanisms for a combination of three common POPs using a systems biology approach, which may link POP exposure to diseases. Experimental evaluation of the proposed pathways may lead to development of predictive biomarkers of the effects of POPs, which could translate into disease prevention and effective clinical treatment strategies. Ruiz P, Perlina A, Mumtaz M, Fowler BA. 2016. A systems biology approach reveals converging molecular mechanisms that link different POPs to common metabolic diseases. Environ Health Perspect 124:1034-1041; http://dx.doi.org/10.1289/ehp.1510308.

The Interaction Properties of the Human Rab GTPase Family – A Comparative Analysis Reveals Determinants of Molecular Binding Selectivity

PubMed Central

Stein, Matthias; Pilli, Manohar; Bernauer, Sabine; Habermann, Bianca H.; Zerial, Marino; Wade, Rebecca C.

2012-01-01

Background 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. Methodology/Principal Findings 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. Conclusions/Significance 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. PMID:22523562

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

PubMed

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

2012-02-24

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

[The perichromatin compartment of the cell nucleus].

PubMed

Bogoliubov, D S

2014-01-01

In this review, the data on the structure and composition of the perichromatin compartment, a special border area between the condensed chromatin and the interchromatin space of the cell nucleus, are discussed in the light of the concept of nuclear functions in complex nuclear architectonics. Morphological features, molecular composition and functions of main extrachromosomal structures of the perichromatin compartment, perichromatin fibrils (PFs) and perichromatin granules (PGs) including nuclear stress-bodies (nSBs) that are derivates of the PGs under heat shock, are presented. A special attention was paid to the features of the molecular compositions of PFs and PGs in different cell types and at different physiological conditions.

Informed walks: whispering hints to gene hunters inside networks' jungle.

PubMed

Bourdakou, Marilena M; Spyrou, George M

2017-10-11

Systemic approaches offer a different point of view on the analysis of several types of molecular associations as well as on the identification of specific gene communities in several cancer types. However, due to lack of sufficient data needed to construct networks based on experimental evidence, statistical gene co-expression networks are widely used instead. Many efforts have been made to exploit the information hidden in these networks. However, these approaches still need to capitalize comprehensively the prior knowledge encrypted into molecular pathway associations and improve their efficiency regarding the discovery of both exclusive subnetworks as candidate biomarkers and conserved subnetworks that may uncover common origins of several cancer types. In this study we present the development of the Informed Walks model based on random walks that incorporate information from molecular pathways to mine candidate genes and gene-gene links. The proposed model has been applied to TCGA (The Cancer Genome Atlas) datasets from seven different cancer types, exploring the reconstructed co-expression networks of the whole set of genes and driving to highlighted sub-networks for each cancer type. In the sequel, we elucidated the impact of each subnetwork on the indication of underlying exclusive and common molecular mechanisms as well as on the short-listing of drugs that have the potential to suppress the corresponding cancer type through a drug-repurposing pipeline. We have developed a method of gene subnetwork highlighting based on prior knowledge, capable to give fruitful insights regarding the underlying molecular mechanisms and valuable input to drug-repurposing pipelines for a variety of cancer types.

Frontal Polymerization in Microgravity

NASA Technical Reports Server (NTRS)

Pojman, John A.

1999-01-01

Frontal polymerization systems, with their inherent large thermal and compositional gradients, are greatly affected by buoyancy-driven convection. Sounding rocket experiments allowed the preparation of benchmark materials and demonstrated that methods to suppress the Rayleigh-Taylor instability in ground-based research did not significantly affect the molecular weight of the polymer. Experiments under weightlessness show clearly that bubbles produced during the reaction interact very differently than under 1 g.

Separation of both fibrous and globular proteins on the basis of molecular weight using high-performance size exclusion chromatography.

PubMed

Barden, J A

1983-11-01

A high-performance size exclusion liquid chromatographic system has been used to separate proteins with different shapes solely on the basis of their molecular weights. After the effects of ionic and hydrophobic interactions with the stationary phase have been overcome, protein elution is normally governed by their effective size in solution. Conditions are described under which proteins, with isoelectric points within the normal operating pH range of the columns, are eluted independent of their Stokes' radii. Even fibrous proteins with axial ratios of 50 elute according to their known molecular weights over the range 2000-2,000,000.

Design theory and performance of cryogenic molecular adsorption refrigeration systems

NASA Technical Reports Server (NTRS)

Hartwig, W. H.; Woltman, A. W.; Masson, J. P.

1978-01-01

Closed-cycle operation of molecular adsorption refrigeration systems (MARS) has been demonstrated by using thermally cycled zeolites to adsorb and desorb various gases under pressures of 20-60 atm. This paper develops three aspects of the design theory: the physical theory of molecular adsorption of small molecules such as A, N2, N2O and NH3, the design relations for closed-cycle flow for three or more compressors, and the coefficient of performance. This work is intended to demonstrate nonmechanical gas compression for various cryogenic gases than can compete with mechanical systems with a different mix of advantages and disadvantages.

Comparative transcriptome analysis of Sogatella furcifera (Horváth) exposed to different insecticides.

PubMed

Zhou, Cao; Yang, Hong; Wang, Zhao; Long, Gui-Yun; Jin, Dao-Chao

2018-06-08

White-backed planthopper, Sogatella furcifera (Horváth) (Hemiptera: Delphacidae), one of the main agricultural insect pests in China, is resistant to a wide variety of insecticides. We used transcriptome analysis to compare the expression patterns of resistance- and stress-response genes in S. furcifera subjected to imidacloprid, deltamethrin, and triazophos stress, to determine the molecular mechanisms of resistance to these insecticides. A comparative analysis of gene expression under imidacloprid, deltamethrin, and triazophos stress revealed 1,123, 841, and 316 upregulated unigenes, respectively, compared to the control. These upregulated genes included seven P450s (two CYP2 clade, three CYP3 clade, and two CYP4 clade), one GST, one ABC transporter (ABCF), and seven Hsps (one 90 and six Hsp70s) under imidacloprid stress; one P450 (CYP3 clade), two ABC transporters (one ABCF and one ABCD), and one Hsp (Hsp90) under deltamethrin stress; one P450 (CYP3 clade) and one ABC transporter (ABCF) under triazophos stress. In addition, 80 genes were commonly upregulated in response to the three insecticide treatments, including laminin, larval cuticle protein, and fasciclin, which are associated with epidermal formation. These results provide a valuable resource for the molecular characterisation of insecticide action in S. furcifera, especially the molecular characteristics of insecticide cross resistance.

Effects of different enzymatic hydrolysis methods on the bioactivity of peptidoglycan in Litopenaeus vannamei

NASA Astrophysics Data System (ADS)

Song, Xiaoling; Zhang, Yue; Wei, Song; Huang, Jie

2013-03-01

The effects of different hydrolysis methods on peptidoglycan (PG) were assessed in terms of their impact on the innate immunity and disease resistance of Pacific white shrimp, Litop enaeus vannamei. PG derived from Bifidobacterium thermophilum was prepared in the laboratory and processed with lysozyme and protease under varying conditions to produce several different PG preparations. A standard shrimp feed was mixed with 0.05% PG preparations to produce a number of experimental diets for shrimp. The composition, concentration, and molecular weight ranges of the soluble PG were analyzed. Serum phenoloxidase and acid phosphatase activity in the shrimp were determined on Days 6—31 of the experiment. The protective activity of the PG preparations was evaluated by exposing shrimp to white spot syndrome virus (WSSV). Data on the composition of the PG preparations indicated that preparations hydrolyzed with lysozyme for 72 h had more low-molecular-weight PG than those treated for 24 h, and hydrolysis by protease enhanced efficiency of hydrolysis compared to lysozyme. SDS-PAGE showed changes in the molecular weight of the soluble PG produced by the different hydrolysis methods. Measurements of serum phenoloxidase and acid phosphatase activity levels in the shrimp indicated that the PG preparations processed with enzymes were superior to the preparation which had not undergone hydrolysis in enhancing the activity of the two serum enzymes. In addition, the preparation containing more low-molecular-weight PG enhanced the resistance of the shrimp to WSSV, whereas no increased resistance was observed for preparations containing less low-molecular-weight PG. These findings suggest that the immunity-enhancing activity of PG is related to its molecular weight and that increasing the quantity of low-molecular-weight PG can fortify the effect of immunity enhancement.

Increasing the wear resistance of ultra-high molecular weight polyethylene by adding solid lubricating fillers

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

Panin, S. V., E-mail: svp@ispms.tsc.ru; Kornienko, L. A.; Poltaranin, M. A.

2014-11-14

In order to compare effectiveness of adding solid lubricating fillers for polymeric composites based on ultra-high molecular weight polyethylene (UHMWPE) with graphite, molybdenum disulfide and polytetrafluoroethylene, their tribotechnical characteristics under dry friction, boundary lubrication and abrasive wearing were investigated. The optimal weight fractions of fillers in terms of improving wear resistance have been determined. The supramolecular structure and topography of wear track surfaces of UHMWPE-based composites with different content of fillers have been studied.

Diverse Molecular Targets for Chalcones with Varied Bioactivities

PubMed Central

Zhou, Bo; Xing, Chengguo

2015-01-01

Natural or synthetic chalcones with different substituents have revealed a variety of biological activities that may benefit human health. The underlying mechanisms of action, particularly with respect to the direct cellular targets and the modes of interaction with the targets, have not been rigorously characterized, which imposes challenges to structure-guided rational development of therapeutic agents or chemical probes with acceptable target-selectivity profile. This review summarizes literature evidence on chalcones’ direct molecular targets in the context of their biological activities. PMID:26798565

Molecular and cellular bases of adaptation to a changing environment in microorganisms.

PubMed

Bleuven, Clara; Landry, Christian R

2016-10-26

Environmental heterogeneity constitutes an evolutionary challenge for organisms. While evolutionary dynamics under variable conditions has been explored for decades, we still know relatively little about the cellular and molecular mechanisms involved. It is of paramount importance to examine these molecular bases because they may play an important role in shaping the course of evolution. In this review, we examine the diversity of adaptive mechanisms in the face of environmental changes. We exploit the recent literature on microbial systems because those have benefited the most from the recent emergence of genetic engineering and experimental evolution followed by genome sequencing. We identify four emerging trends: (i) an adaptive molecular change in a pathway often results in fitness trade-off in alternative environments but the effects are dependent on a mutation's genetic background; (ii) adaptive changes often modify transcriptional and signalling pathways; (iii) several adaptive changes may occur within the same molecular pathway but be associated with pleiotropy of different signs across environments; (iv) because of their large associated costs, macromolecular changes such as gene amplification and aneuploidy may be a rapid mechanism of adaptation in the short-term only. The course of adaptation in a variable environment, therefore, depends on the complexity of the environment but also on the molecular relationships among the genes involved and between the genes and the phenotypes under selection. © 2016 The Author(s).

How do molecular marker patterns of BC change at increasing age of chars?

NASA Astrophysics Data System (ADS)

Schneider, M. P. W.; Hilf, M.; Schmidt, M. W. I.

2009-04-01

Black carbon (BC) is considered to be a relatively stable form of organic carbon. However, previous results have shown that the physical and chemical properties of BC can vary considerably with formation temperature. Thus, to understand the long-term carbon sink potential of BC there is increasing interest to gain more information about i) the conditions under which BC was formed, and ii) the resulting degradability of BC under natural conditions. In a first step, we synthesised chars from two different sources of biomass (chestnut wood, rice straw) under well-defined conditions as model substances to analyse the changes in their molecular structure at increasing formation temperature. Results are presented obtained from a set of laboratory produced char samples pyrolysed at increasing temperatures with a high resolution between 200 and 1000 °C. The chars were characterized by a molecular marker method for pyrogenic carbon quantification, which additionally provides information about the degree of condensation of chars. At temperatures between 275 and 500°C, which typically are observed during wildfires and thus are relevant for natural char formation, the molecular marker pattern of the chars remains almost constant. In a next step, we analysed changes in the molecular marker patterns of chars from a chronosequence, with BC deposited between 0 and 100 years ago. Based on the data obtained from the laboratory char series, we compare changes in the molecular marker patterns of the chars from the chronosequence over time. These results show if less condensed forms of BC are degraded preferentially and more condensed, aromatic backbone of BC becomes enriched in the soils with time of degradation. Our results provide information about the fate of BC in the environment, which has important implications in the context of carbon sequestration strategies.

Comprehensive analysis of differentially expressed genes reveals the molecular response to elevated CO2 levels in two sea buckthorn cultivars.

PubMed

Zhang, Guoyun; Zhang, Tong; Liu, Juanjuan; Zhang, Jianguo; He, Caiyun

2018-06-20

Atmospheric carbon dioxide (CO 2 ) concentration increases every year. It is critical to understand the elevated CO 2 response molecular mechanisms of plants using genomic techniques. Hippophae rhamnoides L. is a high stress resistance plant species widely distributed in Europe and Asia. However, the molecular mechanism of elevated CO 2 response in H. rhamnoides has been limited. In this study, transcriptomic analysis of two sea buckthorn cultivars under different CO 2 concentrations was performed, based on the next-generation illumina sequencing platform and de novo assembly. We identified 4740 differentially expressed genes in sea buckthorn response to elevated CO 2 concentrations. According to the gene ontology (GO) results, photosystem I, photosynthesis and chloroplast thylakoid membrane were the main enriched terms in 'xiangyang' sea buckthorn. In 'zhongguo' sea buckthorn, photosynthesis was also the main significantly enriched term. However, the number of photosynthesis related differentially expressed genes were different between two sea buckthorn cultivars. Our GO and pathway analyses indicated that the expression levels of the transcription factors WRKY, MYB and NAC were significantly different between the two sea buckthorn cultivars. This study provides a reliable transcriptome sequence resource and is a valuable resource for genetic and genomic researches for plants under high CO 2 concentration in the future. Copyright © 2018 Elsevier B.V. All rights reserved.

Molecular dynamics study on the effect of boundary heating rate on the phase change characteristics of thin film liquid

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

Hasan, Mohammad Nasim, E-mail: nasim@me.buet.ac.bd.com; Morshed, A. K. M. Monjur, E-mail: shavik@me.buet.ac.bd.com; Rabbi, Kazi Fazle, E-mail: rabbi35.me10@gmail.com

2016-07-12

In this study, theoretical investigation of thin film liquid phase change phenomena under different boundary heating rates has been conducted with the help of molecular dynamics simulation. To do this, the case of argon boiling over a platinum surface has been considered. The study has been conducted to get a better understanding of the nano-scale physics of evaporation/boiling for a three phase system with particular emphasis on the effect of boundary heating rate. The simulation domain consisted of liquid and vapor argon atoms placed over a platinum wall. Initially the whole system was brought to an equilibrium state at 90more » K with the help of equilibrium molecular dynamics and then the temperature of the bottom wall was increased to a higher temperature (250 K/130 K) over a finite heating period. Depending on the heating period, the boundary heating rate has been varied in the range of 1600×10{sup 9} K/s to 8×10{sup 9} K/s. The variations of argon region temperature, pressure, net evaporation number with respect to time under different boundary heating rates have been determined and discussed. The heat fluxes normal to platinum wall for different cases were also calculated and compared with theoretical upper limit of maximum possible heat transfer to elucidate the effect of boundary heating rate.« less

Molecular response to water stress in two contrasting Mediterranean pines (Pinus pinaster and Pinus pinea).

PubMed

Perdiguero, Pedro; Barbero, María Del Carmen; Cervera, María Teresa; Collada, Carmen; Soto, Alvaro

2013-06-01

Adaptation to water stress has determined the evolution and diversification of vascular plants. Water stress is forecasted to increase drastically in the next decades in certain regions, such as in the Mediterranean basin. Consequently, a proper knowledge of the response and adaptations to drought stress is essential for the correct management of plant genetic resources. However, most of the advances in the understanding of the molecular response to water stress have been attained in angiosperms, and are not always applicable to gymnosperms. In this work we analyse the transcriptional response of two emblematic Mediterranean pines, Pinus pinaster and Pinus pinea, which show noticeable differences in their performance under water stress. Using microarray analysis, up to 113 genes have been detected as significantly induced by drought in both species. Reliability of expression patterns has been confirmed by RT-PCR. While induced genes with similar profiles in both species can be considered as general candidate genes for the study of drought response in conifers, genes with diverging expression patterns can underpin the differences displayed by these species under water stress. Most promising candidate genes for drought stress response include genes related to carbohydrate metabolism, such as glycosyltransferases or galactosidases, sugar transporters, dehydrins and transcription factors. Additionally, differences in the molecular response to drought and polyethylene-glycol-induced water stress are also discussed. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Sex differences in stress-related psychiatric disorders: neurobiological perspectives.

PubMed

Bangasser, Debra A; Valentino, Rita J

2014-08-01

Stress is associated with the onset and severity of several psychiatric disorders that occur more frequently in women than men, including posttraumatic stress disorder (PTSD) and depression. Patients with these disorders present with dysregulation of several stress response systems, including the neuroendocrine response to stress, corticolimbic responses to negatively valenced stimuli, and hyperarousal. Thus, sex differences within their underlying circuitry may explain sex biases in disease prevalence. This review describes clinical studies that identify sex differences within the activity of these circuits, as well as preclinical studies that demonstrate cellular and molecular sex differences in stress responses systems. These studies reveal sex differences from the molecular to the systems level that increase endocrine, emotional, and arousal responses to stress in females. Exploring these sex differences is critical because this research can reveal the neurobiological underpinnings of vulnerability to stress-related psychiatric disorders and guide the development of novel pharmacotherapies. Copyright © 2014 Elsevier Inc. All rights reserved.

Sex Differences in Stress-Related Psychiatric Disorders: Neurobiological Perspectives

PubMed Central

Bangasser, Debra A.; Valentino, Rita J.

2014-01-01

Stress is associated with the onset and severity of several psychiatric disorders that occur more frequently in women than men, including posttraumatic stress disorder (PTSD) and depression. Patients with these disorders present with dysregulation of several stress response systems, including the neuroendocrine response to stress, corticolimbic responses to negatively valenced stimuli, and hyperarousal. Thus, sex differences within their underlying circuitry may explain sex biases in disease prevalence. This review describes clinical studies that identify sex differences within the activity of these circuits, as well as preclinical studies that demonstrate cellular and molecular sex differences in stress responses systems. These studies reveal sex differences from the molecular to the systems level that increase endocrine, emotional, and arousal responses to stress in females. Exploring these sex differences is critical because this research can reveal the neurobiological underpinnings of vulnerability to stress-related psychiatric disorders and guide the development of novel pharmacotherapies. PMID:24726661

Geographic differences in the distribution of molecular subtypes of breast cancer in Brazil

PubMed Central

2014-01-01

Background To compare the distribution of the intrinsic molecular subtypes of breast cancer based on immunohistochemical profile in the five major geographic regions of Brazil, a country of continental dimension, with a wide racial variation of people. Methods The study was retrospective observational. We classified 5,687 invasive breast cancers by molecular subtype based on immunohistochemical expression of estrogen-receptor (ER), progesterone-receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67 proliferation index. Cases were classified as luminal A (ER and/or PR positive and HER2 negative, Ki-67 < 14%), luminal B (ER and/or PR positive, HER2 negative, and Ki-67 > 14%), triple-positive (ER and/or PR positive and HER2 positive), HER2-enriched (ER and PR negative, and HER2- positive), and triple-negative (TN) (ER negative, PR negative, and HER2- negative). Comparisons of the ages of patients and molecular subtypes between different geographic regions were performed. Results South and Southeast regions with a higher percentage of European ancestry and higher socioeconomic status presented with the highest proportion of luminal tumors. The North region presented with more aggressive subtypes (HER2-enriched and triple-negative), while the Central-West region predominated triple-positive carcinomas. The Northeast—a region with a high African influence—presented intermediate frequency of the different molecular subtypes. The differences persisted in subgroups of patients under and over 50 years. Conclusions The geographic regions differ according to the distribution of molecular subtypes of breast cancer. However, other differences, beside those related to African ancestry, such as socioeconomic, climatic, nutritional, and geographic, have to be considered to explain our results. The knowledge of the differences in breast cancer characteristics among the geographic regions may help to organize healthcare programs in large countries like Brazil with diverse economic and race composition among different geographic regions. PMID:25174527

Molecular responses of genetically modified maize to abiotic stresses as determined through proteomic and metabolomic analyses

PubMed Central

Benevenuto, Rafael Fonseca; Agapito-Tenfen, Sarah Zanon; Vilperte, Vinicius; Wikmark, Odd-Gunnar; van Rensburg, Peet Jansen; Nodari, Rubens Onofre

2017-01-01

Some genetically modified (GM) plants have transgenes that confer tolerance to abiotic stressors. Meanwhile, other transgenes may interact with abiotic stressors, causing pleiotropic effects that will affect the plant physiology. Thus, physiological alteration might have an impact on the product safety. However, routine risk assessment (RA) analyses do not evaluate the response of GM plants exposed to different environmental conditions. Therefore, we here present a proteome profile of herbicide-tolerant maize, including the levels of phytohormones and related compounds, compared to its near-isogenic non-GM variety under drought and herbicide stresses. Twenty differentially abundant proteins were detected between GM and non-GM hybrids under different water deficiency conditions and herbicide sprays. Pathway enrichment analysis showed that most of these proteins are assigned to energetic/carbohydrate metabolic processes. Among phytohormones and related compounds, different levels of ABA, CA, JA, MeJA and SA were detected in the maize varieties and stress conditions analysed. In pathway and proteome analyses, environment was found to be the major source of variation followed by the genetic transformation factor. Nonetheless, differences were detected in the levels of JA, MeJA and CA and in the abundance of 11 proteins when comparing the GM plant and its non-GM near-isogenic variety under the same environmental conditions. Thus, these findings do support molecular studies in GM plants Risk Assessment analyses. PMID:28245233

Probing numerical Laplace inversion methods for two and three-site molecular exchange between interconnected pore structures.

PubMed

Silletta, Emilia V; Franzoni, María B; Monti, Gustavo A; Acosta, Rodolfo H

2018-01-01

Two-dimension (2D) Nuclear Magnetic Resonance relaxometry experiments are a powerful tool extensively used to probe the interaction among different pore structures, mostly in inorganic systems. The analysis of the collected experimental data generally consists of a 2D numerical inversion of time-domain data where T 2 -T 2 maps are generated. Through the years, different algorithms for the numerical inversion have been proposed. In this paper, two different algorithms for numerical inversion are tested and compared under different conditions of exchange dynamics; the method based on Butler-Reeds-Dawson (BRD) algorithm and the fast-iterative shrinkage-thresholding algorithm (FISTA) method. By constructing a theoretical model, the algorithms were tested for a two- and three-site porous media, varying the exchange rates parameters, the pore sizes and the signal to noise ratio. In order to test the methods under realistic experimental conditions, a challenging organic system was chosen. The molecular exchange rates of water confined in hierarchical porous polymeric networks were obtained, for a two- and three-site porous media. Data processed with the BRD method was found to be accurate only under certain conditions of the exchange parameters, while data processed with the FISTA method is precise for all the studied parameters, except when SNR conditions are extreme. Copyright © 2017 Elsevier Inc. All rights reserved.

Neuronal cell fate specification by the molecular convergence of different spatio-temporal cues on a common initiator terminal selector gene

PubMed Central

Stratmann, Johannes

2017-01-01

The extensive genetic regulatory flows underlying specification of different neuronal subtypes are not well understood at the molecular level. The Nplp1 neuropeptide neurons in the developing Drosophila nerve cord belong to two sub-classes; Tv1 and dAp neurons, generated by two distinct progenitors. Nplp1 neurons are specified by spatial cues; the Hox homeotic network and GATA factor grn, and temporal cues; the hb -> Kr -> Pdm -> cas -> grh temporal cascade. These spatio-temporal cues combine into two distinct codes; one for Tv1 and one for dAp neurons that activate a common terminal selector feedforward cascade of col -> ap/eya -> dimm -> Nplp1. Here, we molecularly decode the specification of Nplp1 neurons, and find that the cis-regulatory organization of col functions as an integratory node for the different spatio-temporal combinatorial codes. These findings may provide a logical framework for addressing spatio-temporal control of neuronal sub-type specification in other systems. PMID:28414802

Spin-Filtering Rectifying and Negative Differential Resistance Behaviors in Co(dmit)2 Molecular Devices with Monatomic (C, Fe, Au) Electrodes

NASA Astrophysics Data System (ADS)

Yan, Shenlang; Long, Mengqiu; Zhang, Xiaojiao; He, Jun; Xu, Hui; Gao, Yongli

2014-09-01

Using nonequilibrium Green's functions (NEGFs) combined with the density functional theory (DFT), we study the electronic transport properties of a single molecule magnet Co(dmit)2, which is sandwiched between two monatomic chain electrodes, and the different electrode materials carbon, iron and gold, have been considered. The results show that the electrodes play a crucial role in the spin-dependent transport of the Co(dmit)2 molecular device, and some interesting phenomenon, such as perfect spin-filtering effect, rectifying and negative differential resistance (NDR) can be observed. We demonstrated that the magnetic Fe electrode can lead to high spin-flittering effect, and the different hybridization and alignment of energy levels between the molecule and the electrodes may be responsible for the rectification performance, and the distributions (delocalization or localization) of the frontier molecular orbitals under different bias result in the NDR behaviors. These characteristics could be used in the study of spin physics and the realization of nanospintronic devices.

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

NASA Astrophysics Data System (ADS)

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.

Investigating the Mechanisms Underlying Neuronal Death in Ischemia Using In Vitro Oxygen-Glucose Deprivation: Potential Involvement of Protein SUMOylation

PubMed Central

CIMAROSTI, HELENA; HENLEY, JEREMY M.

2012-01-01

It is well established that brain ischemia can cause neuronal death via different signaling cascades. The relative importance and interrelationships between these pathways, however, remain poorly understood. Here is presented an overview of studies using oxygen-glucose deprivation of organotypic hippocampal slice cultures to investigate the molecular mechanisms involved in ischemia. The culturing techniques, setup of the oxygen-glucose deprivation model, and analytical tools are reviewed. The authors focus on SUMOylation, a posttranslational protein modification that has recently been implicated in ischemia from whole animal studies as an example of how these powerful tools can be applied and could be of interest to investigate the molecular pathways underlying ischemic cell death. PMID:19029060

Changes in Soil Organic Matter Abundance, Molecular Composition, and Diversity in an Arid Ecosystem in Response to Long-term Elevated CO2 Manipulation.

NASA Astrophysics Data System (ADS)

Hess, N. J.; Tfaily, M.; Evans, R. D.; Koyama, A.

2017-12-01

Little is known about how soils in arid ecosystems will respond to rising atmospheric CO2 concentration yet arid and semi-arid ecosystems cover more than 40% of Earth's land surface. Previous work in the Mojave Desert (Evans et al., 2014 Nature Climate Change) reported higher soil organic carbon (SOC) and total nitrogen (N) concentrations following 10 years exposure to elevated atmospheric CO2 at the Nevada Desert Free-Air-Carbon dioxide-Enrichment (FACE) Facility (NDFF). In this study, we investigated potential mechanisms that resulted in increased SOC and total N accumulation and stabilization using high resolution mass spectrometry at the NDFF site. Samples were collected from soil profiles to 1 m in depth with a 0.2 m a increment under the dominant evergreen shrub Larrea tridentata. The differences in the molecular composition and diversity of soil organic matter (SOM) were more evident in surface soils and declined with depth, and were consistent with higher SOC and total N concentrations under elevated than ambient CO2. Our molecular analysis also suggested increased root exudation and/or microbial necromass from stabilization of labile C and N contributed to SOM and N stocks. Increased microbial activity and metabolism under elevated CO2 compared to ambient plots suggested that elevated CO2 altered microbial carbon (C) use patterns, reflecting changes in the quality and quantity of SOC inputs. We found that plant-derived compounds were primary substrates for microbial activity under elevated CO2 and microbial products were the main constituents of stabilized SOM. Our results suggest that arid ecosystems are a potential large C sink under elevated CO2, give the extensive coverage of the land surface, and that labile compounds are transformed to stable SOM via microbial processes. Arid systems are limited by water, and thus may have a different C storage potential under changing climates than other ecosystems that are limited by nitrogen or phosphorus.

Dynamics and kinetics of reversible homo-molecular dimerization of polycyclic aromatic hydrocarbons

NASA Astrophysics Data System (ADS)

Mao, Qian; Ren, Yihua; Luo, K. H.; van Duin, Adri C. T.

2017-12-01

Physical dimerization of polycyclic aromatic hydrocarbons (PAHs) has been investigated via molecular dynamics (MD) simulation with the ReaxFF reactive force field that is developed to bridge the gap between the quantum mechanism and classical MD. Dynamics and kinetics of homo-molecular PAH collision under different temperatures, impact parameters, and orientations are studied at an atomic level, which is of great value to understand and model the PAH dimerization. In the collision process, the enhancement factors of homo-molecular dimerizations are quantified and found to be larger at lower temperatures or with smaller PAH instead of size independent. Within the capture radius, the lifetime of the formed PAH dimer decreases as the impact parameter increases. Temperature and PAH characteristic dependent forward and reverse rate constants of homo-molecular PAH dimerization are derived from MD simulations, on the basis of which a reversible model is developed. This model can predict the tendency of PAH dimerization as validated by pyrene dimerization experiments [H. Sabbah et al., J. Phys. Chem. Lett. 1(19), 2962 (2010)]. Results from this study indicate that the physical dimerization cannot be an important source under the typical flame temperatures and PAH concentrations, which implies a more significant role played by the chemical route.

Measurement of incident molecular temperature in the formation of organic thin films

NASA Astrophysics Data System (ADS)

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.

Insight into the molecular genetics of myopia

PubMed Central

Li, Jiali

2017-01-01

Myopia is the most common cause of visual impairment worldwide. Genetic and environmental factors contribute to the development of myopia. Studies on the molecular genetics of myopia are well established and have implicated the important role of genetic factors. With linkage analysis, association studies, sequencing analysis, and experimental myopia studies, many of the loci and genes associated with myopia have been identified. Thus far, there has been no systemic review of the loci and genes related to non-syndromic and syndromic myopia based on the different approaches. Such a systemic review of the molecular genetics of myopia will provide clues to identify additional plausible genes for myopia and help us to understand the molecular mechanisms underlying myopia. This paper reviews recent genetic studies on myopia, summarizes all possible reported genes and loci related to myopia, and suggests implications for future studies on the molecular genetics of myopia. PMID:29386878

PMG: online generation of high-quality molecular pictures and storyboarded animations

PubMed Central

Autin, Ludovic; Tufféry, Pierre

2007-01-01

The Protein Movie Generator (PMG) is an online service able to generate high-quality pictures and animations for which one can then define simple storyboards. The PMG can therefore efficiently illustrate concepts such as molecular motion or formation/dissociation of complexes. Emphasis is put on the simplicity of animation generation. Rendering is achieved using Dino coupled to POV-Ray. In order to produce highly informative images, the PMG includes capabilities of using different molecular representations at the same time to highlight particular molecular features. Moreover, sophisticated rendering concepts including scene definition, as well as modeling light and materials are available. The PMG accepts Protein Data Bank (PDB) files as input, which may include series of models or molecular dynamics trajectories and produces images or movies under various formats. PMG can be accessed at http://bioserv.rpbs.jussieu.fr/PMG.html. PMID:17478496

Motion of Fullerenes around Topological Defects on Metals: Implications for the Progress of Molecular Scale Devices.

PubMed

Nirmalraj, Peter; Daly, Ronan; Martin, Nazario; Thompson, Damien

2017-03-08

Research on motion of molecules in the presence of thermal noise is central for progress in two-terminal molecular scale electronic devices. However, it is still unclear what influence imperfections in bottom metal electrode surface can have on molecular motion. Here, we report a two-layer crowding study, detailing the early stages of surface motion of fullerene molecules on Au(111) with nanoscale pores in a n-tetradecane chemical environment. The motion of the fullerenes is directed by crowding of the underlying n-tetradecane molecules around the pore fringes at the liquid-solid interface. We observe in real-space the growth of molecular populations around different pore geometries. Supported by atomic-scale modeling, our findings extend the established picture of molecular crowding by revealing that trapped solvent molecules serve as prime nucleation sites at nanopore fringes.

Noncovalent Molecular Electronics.

PubMed

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.

Molecular ecology of aquatic communities: Reflections and future directions

USGS Publications Warehouse

Zehr, J.P.; Voytek, M.A.

1999-01-01

During the 1980s, many new molecular biology techniques were developed, providing new capabilities for studying the genetics and activities of organisms. Biologists and ecologists saw the promise that these techniques held for studying different aspects of organisms, both in culture and in the natural environment. In less than a decade, these techniques were adopted by a large number of researchers studying many types of organisms in diverse environments. Much of the molecular-level information acquired has been used to address questions of evolution, biogeography, population structure and biodiversity. At this juncture, molecular ecologists are poised to contribute to the study of the fundamental characteristics underlying aquatic community structure. The goal of this overview is to assess where we have been, where we are now and what the future holds for revealing the basis of community structure and function with molecular-level information.

Insight into the molecular genetics of myopia.

PubMed

Li, Jiali; Zhang, Qingjiong

2017-01-01

Myopia is the most common cause of visual impairment worldwide. Genetic and environmental factors contribute to the development of myopia. Studies on the molecular genetics of myopia are well established and have implicated the important role of genetic factors. With linkage analysis, association studies, sequencing analysis, and experimental myopia studies, many of the loci and genes associated with myopia have been identified. Thus far, there has been no systemic review of the loci and genes related to non-syndromic and syndromic myopia based on the different approaches. Such a systemic review of the molecular genetics of myopia will provide clues to identify additional plausible genes for myopia and help us to understand the molecular mechanisms underlying myopia. This paper reviews recent genetic studies on myopia, summarizes all possible reported genes and loci related to myopia, and suggests implications for future studies on the molecular genetics of myopia.

Structure and Orientation Behavior of Highly Oriented Polymers Under Tensile and Compressive Stresses

NASA Astrophysics Data System (ADS)

Garcia-Ramirez, Rafael

The birefringence of Kevlar 49^ circler fibers has been shown to decrease with compressive strain, suggesting that structure changes under compression involve decreasing crystallite orientation. This mechanism appears to be the inverse of that occurring under tension, for which increasing crystallite orientation has been reported to occur, leading to non-linear elasticity. A contrast between the effects of both stress modes on structure (orientation) response is presented. While birefringence presents itself as a technically convenient and economically attractive technique for this type of study, caution must be exercised when interpreting results from measurements under stress. For highly crystalline fibers, experiments have led to the attribution of the observed changes in birefringence almost entirely to crystallite orientation. This study presents an analysis of the different contributions to birefringence under stress. X-ray diffraction experiments have been performed for Kevlar 49^ circler fibers under tensile stress. Results from crystal orientation cannot account for changes observed in birefringence. Moreover, they appear to account only for a small fraction of the total change. These observations suggest significant contributions from other sources. Theoretical calculations have been carried out under simulated stress conditions to quantify the effect of molecular deformation on the observed birefringence of Kevlar 49^circler fibers. The results have been obtained using semi-empirical molecular orbital calculations with the AM1 Hamiltonian in MOPAC. This analysis has been applied to poly(p^' -phenylene terephthalamide) (PPTA) and polyethylene (PE) chains. For PE, stress-free computations were performed on segments of up to 50 -(CH_2-CH _2)- units. Strains up to 1% were applied on segments of up to 40 units. For PPTA, segments of up to 5 PTA units were analyzed. Strain-free results indicate a linear dependence of molecular polarizability on chain length. The treatment yields also a linear trend for the effect of strain on the polarizability of PE segments. Thus, the calculations predict a plane in 3-D space for the dependence of molecular polarizability on both chain size and strain. The predicted molecular polarizabilities are used to evaluate the effect of stress on birefringence of the idealized polymers, by applying existing internal-field theory. Results indicate significant effects from molecules deforming under the stress field.

N Termini of apPDE4 Isoforms Are Responsible for Targeting the Isoforms to Different Cellular Membranes

ERIC Educational Resources Information Center

Jang, Deok-Jin; Park, Soo-Won; Lee, Jin-A; Lee, Changhoon; Chae, Yeon-Su; Park, Hyungju; Kim, Min-Jeong; Choi, Sun-Lim; Lee, Nuribalhae; Kim, Hyoung; Kaang, Bong-Kiun

2010-01-01

Phosphodiesterases (PDEs) are known to play a key role in the compartmentalization of cAMP signaling; however, the molecular mechanisms underlying intracellular localization of different PDE isoforms are not understood. In this study, we have found that each of the supershort, short, and long forms of apPDE4 showed distinct localization in the…

Combining animal personalities with transcriptomics resolves individual variation within a wild-type zebrafish population and identifies underpinning molecular differences in brain function.

PubMed

Rey, S; Boltana, S; Vargas, R; Roher, N; Mackenzie, S

2013-12-01

Resolving phenotype variation within a population in response to environmental perturbation is central to understanding biological adaptation. Relating meaningful adaptive changes at the level of the transcriptome requires the identification of processes that have a functional significance for the individual. This remains a major objective towards understanding the complex interactions between environmental demand and an individual's capacity to respond to such demands. The interpretation of such interactions and the significance of biological variation between individuals from the same or different populations remain a difficult and under-addressed question. Here, we provide evidence that variation in gene expression between individuals in a zebrafish population can be partially resolved by a priori screening for animal personality and accounts for >9% of observed variation in the brain transcriptome. Proactive and reactive individuals within a wild-type population exhibit consistent behavioural responses over time and context that relates to underlying differences in regulated gene networks and predicted protein-protein interactions. These differences can be mapped to distinct regions of the brain and provide a foundation towards understanding the coordination of underpinning adaptive molecular events within populations. © 2013 John Wiley & Sons Ltd.

Molecular dynamics simulations indicate that deoxyhemoglobin, oxyhemoglobin, carboxyhemoglobin, and glycated hemoglobin under compression and shear exhibit an anisotropic mechanical behavior.

PubMed

Yesudasan, Sumith; Wang, Xianqiao; Averett, Rodney D

2018-05-01

We developed a new mechanical model for determining the compression and shear mechanical behavior of four different hemoglobin structures. Previous studies on hemoglobin structures have focused primarily on overall mechanical behavior; however, this study investigates the mechanical behavior of hemoglobin, a major constituent of red blood cells, using steered molecular dynamics (SMD) simulations to obtain anisotropic mechanical behavior under compression and shear loading conditions. Four different configurations of hemoglobin molecules were considered: deoxyhemoglobin (deoxyHb), oxyhemoglobin (HbO 2 ), carboxyhemoglobin (HbCO), and glycated hemoglobin (HbA 1C ). The SMD simulations were performed on the hemoglobin variants to estimate their unidirectional stiffness and shear stiffness. Although hemoglobin is structurally denoted as a globular protein due to its spherical shape and secondary structure, our simulation results show a significant variation in the mechanical strength in different directions (anisotropy) and also a strength variation among the four different hemoglobin configurations studied. The glycated hemoglobin molecule possesses an overall higher compressive mechanical stiffness and shear stiffness when compared to deoxyhemoglobin, oxyhemoglobin, and carboxyhemoglobin molecules. Further results from the models indicate that the hemoglobin structures studied possess a soft outer shell and a stiff core based on stiffness.

Molecular origin of the vibrational structure of ice I h

DOE PAGES

Moberg, Daniel R.; Straight, Shelby C.; Knight, Christopher; ...

2017-05-25

Here, an unambiguous assignment of the vibrational spectra of ice I h remains a matter of debate. This study demonstrates that an accurate representation of many-body interactions between water molecules, combined with an explicit treatment of nuclear quantum effects through many-body molecular dynamics (MB-MD), leads to a unified interpretation of the vibrational spectra of ice I h in terms of the structure and dynamics of the underlying hydrogen-bond network. All features of the infrared and Raman spectra in the OH stretching region can be unambiguously assigned by taking into account both the symmetry and the delocalized nature of the latticemore » vibrations as well as the local electrostatic environment experienced by each water molecule within the crystal. The high level of agreement with experiment raises prospects for predictive MB-MD simulations that, complementing analogous measurements, will provide molecular-level insights into fundamental processes taking place in bulk ice and on ice surfaces under different thermodynamic conditions.« less

Molecular Mechanisms Underlying Occult Hepatitis B Virus Infection

PubMed Central

Samal, Jasmine; Kandpal, Manish

2012-01-01

Summary: Chronic hepatitis B virus (HBV) infection is a complex clinical entity frequently associated with cirrhosis and hepatocellular carcinoma (HCC). The persistence of HBV genomes in the absence of detectable surface antigenemia is termed occult HBV infection. Mutations in the surface gene rendering HBsAg undetectable by commercial assays and inhibition of HBV by suppression of viral replication and viral proteins represent two fundamentally different mechanisms that lead to occult HBV infections. The molecular mechanisms underlying occult HBV infections, including recently identified mechanisms associated with the suppression of HBV replication and inhibition of HBV proteins, are reviewed in detail. The availability of highly sensitive molecular methods has led to increased detection of occult HBV infections in various clinical settings. The clinical relevance of occult HBV infection and the utility of appropriate diagnostic methods to detect occult HBV infection are discussed. The need for specific guidelines on the diagnosis and management of occult HBV infection is being increasingly recognized; the aspects of mechanistic studies that warrant further investigation are discussed in the final section. PMID:22232374

Heat stress-induced nuclear transport mediated by Hikeshi confers nuclear function of Hsp70s.

PubMed

Imamoto, Naoko

2018-06-01

The prime feature of eukaryotic cells is the separation of the intracellular space into two compartments, the nucleus and the cytoplasm. Active nuclear transport is crucial for the maintenance of this separation. In this report, we focus on a nuclear transport receptor named Hikeshi, which mediates the heat stress-induced nuclear import of 70-kDa heat shock proteins (Hsp70s), and discuss how the same protein can function differently depending on the cellular compartment in which it is localized. Hsp70 is a molecular chaperone that is predominantly localized in the cytoplasm under normal conditions but is known to accumulate in the nucleus under conditions of heat stress. Although the reported function of Hsp70 is mostly attributed to its molecular function in the cytoplasm, the functions of Hsp70 may extend beyond molecular chaperone activity in the nucleus. Copyright © 2018 The Author. Published by Elsevier Ltd.. All rights reserved.

Understanding the molecular signatures in leaves and flowers by desorption electrospray ionization mass spectrometry (DESI MS) imaging.

PubMed

Hemalatha, R G; Pradeep, T

2013-08-07

The difference in size, shape, and chemical cues of leaves and flowers display the underlying genetic makeup and their interactions with the environment. The need to understand the molecular signatures of these fragile plant surfaces is illustrated with a model plant, Madagascar periwinkle (Catharanthus roseus (L.) G. Don). Flat, thin layer chromatographic imprints of leaves/petals were imaged using desorption electrospray ionization mass spectrometry (DESI MS), and the results were compared with electrospray ionization mass spectrometry (ESI MS) of their extracts. Tandem mass spectrometry with DESI and ESI, in conjunction with database records, confirmed the molecular species. This protocol has been extended to other plants. Implications of this study in identifying varietal differences, toxic metabolite production, changes in metabolites during growth, pest/pathogen attack, and natural stresses are shown with illustrations. The possibility to image subtle features like eye color of petals, leaf vacuole, leaf margin, and veins is demonstrated.

Cellular and Molecular Mechanisms of Sexual Differentiation in the Mammalian Nervous System

PubMed Central

Forger, Nancy G.; Strahan, J. Alex; Castillo-Ruiz, Alexandra

2016-01-01

Neuroscientists are likely to discover new sex differences in the coming years, spurred by the National Institutes of Health initiative to include both sexes in preclinical studies. This review summarizes the current state of knowledge of the cellular and molecular mechanisms underlying sex differences in the mammalian nervous system, based primarily on work in rodents. Cellular mechanisms examined include neurogenesis, migration, the differentiation of neurochemical and morphological cell phenotype, and cell death. At the molecular level we discuss evolving roles for epigenetics, sex chromosome complement, the immune system, and newly identified cell signaling pathways. We review recent findings on the role of the environment, as well as genome-wide studies with some surprising results, causing us to rethink often-used models of sexual differentiation. We end by pointing to future directions, including an increased awareness of the important contributions of tissues outside of the nervous system to sexual differentiation of the brain. PMID:26790970

The evolutionary diversity of insect retinal mosaics: Common design principles and emerging molecular logic

PubMed Central

Wernet, Mathias F.; Perry, Michael W.; Desplan, Claude

2015-01-01

Independent evolution has resulted in a vast diversity of eyes. Despite the lack of a common Bauplan or ancestral structure, similar developmental strategies are used. For instance, different classes of photoreceptor cells (PRs) are distributed stochastically and/or localized in different regions of the retina. Here we focus on recent progress made towards understanding the molecular principles behind patterning retinal mosaics of insects, one of the most diverse groups of animals adapted to life on land, in the air, under water, or on the water surface. Morphological, physiological, and behavioral studies from many species provide detailed descriptions of the vast variation in retinal design and function. By integrating this knowledge with recent progress in the characterization of insect Rhodopsins as well as insight from the model organism Drosophila melanogaster, we seek to identify the molecular logic behind the adaptation of retinal mosaics to an animal’s habitat and way of life. PMID:26025917

Rigorous theory of molecular orientational nonlinear optics

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

Kwak, Chong Hoon, E-mail: chkwak@ynu.ac.kr; Kim, Gun Yeup

2015-01-15

Classical statistical mechanics of the molecular optics theory proposed by Buckingham [A. D. Buckingham and J. A. Pople, Proc. Phys. Soc. A 68, 905 (1955)] has been extended to describe the field induced molecular orientational polarization effects on nonlinear optics. In this paper, we present the generalized molecular orientational nonlinear optical processes (MONLO) through the calculation of the classical orientational averaging using the Boltzmann type time-averaged orientational interaction energy in the randomly oriented molecular system under the influence of applied electric fields. The focal points of the calculation are (1) the derivation of rigorous tensorial components of the effective molecularmore » hyperpolarizabilities, (2) the molecular orientational polarizations and the electronic polarizations including the well-known third-order dc polarization, dc electric field induced Kerr effect (dc Kerr effect), optical Kerr effect (OKE), dc electric field induced second harmonic generation (EFISH), degenerate four wave mixing (DFWM) and third harmonic generation (THG). We also present some of the new predictive MONLO processes. For second-order MONLO, second-order optical rectification (SOR), Pockels effect and difference frequency generation (DFG) are described in terms of the anisotropic coefficients of first hyperpolarizability. And, for third-order MONLO, third-order optical rectification (TOR), dc electric field induced difference frequency generation (EFIDFG) and pump-probe transmission are presented.« less

The Physics and Physical Chemistry of Molecular Machines.

PubMed

Astumian, R Dean; Mukherjee, Shayantani; Warshel, Arieh

2016-06-17

The concept of a "power stroke"-a free-energy releasing conformational change-appears in almost every textbook that deals with the molecular details of muscle, the flagellar rotor, and many other biomolecular machines. Here, it is shown by using the constraints of microscopic reversibility that the power stroke model is incorrect as an explanation of how chemical energy is used by a molecular machine to do mechanical work. Instead, chemically driven molecular machines operating under thermodynamic constraints imposed by the reactant and product concentrations in the bulk function as information ratchets in which the directionality and stopping torque or stopping force are controlled entirely by the gating of the chemical reaction that provides the fuel for the machine. The gating of the chemical free energy occurs through chemical state dependent conformational changes of the molecular machine that, in turn, are capable of generating directional mechanical motions. In strong contrast to this general conclusion for molecular machines driven by catalysis of a chemical reaction, a power stroke may be (and often is) an essential component for a molecular machine driven by external modulation of pH or redox potential or by light. This difference between optical and chemical driving properties arises from the fundamental symmetry difference between the physics of optical processes, governed by the Bose-Einstein relations, and the constraints of microscopic reversibility for thermally activated processes. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The use of genetic markers in the molecular epidemiology of histoplasmosis: a systematic review.

PubMed

Damasceno, L S; Leitão, T M J S; Taylor, M L; Muniz, M M; Zancopé-Oliveira, R M

2016-01-01

Histoplasmosis is a systemic mycosis caused by Histoplasma capsulatum, a dimorphic fungal pathogen that can infect both humans and animals. This disease has worldwide distribution and affects mainly immunocompromised individuals. In the environment, H. capsulatum grows as mold but undergoes a morphologic transition to the yeast morphotype under special conditions. Molecular techniques are important tools to conduct epidemiologic investigations for fungal detection, identification of infection sources, and determination of different fungal genotypes associated to a particular disease symptom. In this study, we performed a systematic review in the PubMed database to improve the understanding about the molecular epidemiology of histoplasmosis. This search was restricted to English and Spanish articles. We included a combination of specific keywords: molecular typing [OR] genetic diversity [OR] polymorphism [AND] H. capsulatum; molecular epidemiology [AND] histoplasmosis; and molecular epidemiology [AND] Histoplasma. In addition, we used the specific terms: histoplasmosis [AND] outbreaks. Non-English or non-Spanish articles, dead links, and duplicate results were excluded from the review. The results reached show that the main methods used for molecular typing of H. capsulatum were: restriction fragment length polymorphism, random amplified polymorphic DNA, microsatellites polymorphism, sequencing of internal transcribed spacers region, and multilocus sequence typing. Different genetic profiles were identified among H. capsulatum isolates, which can be grouped according to their source, geographical origin, and clinical manifestations.

Charge transport in organic multi-layer devices under electric and optical fields

NASA Astrophysics Data System (ADS)

Park, June Hyoung

2007-12-01

Charge transport in small organic molecules and conjugated conducting polymers under electric or optical fields is studied by using field effect transistors and photo-voltaic cells with multiple thin layers. With these devices, current under electric field, photo-current under optical field, and luminescence of optical materials are measured to characterize organic and polymeric materials. For electric transport studies, poly(3,4-ethylenedioxythiophene) doped by polystyrenesulfonic acid is used, which is conductive with conductivity of approximately 25 S/cm. Despite their high conductance, field effect transistors based on the films are successfully built and characterized by monitoring modulations of drain current by gate voltage and IV characteristic curves. Due to very thin insulating layers of poly(vinylphenol), the transistors are relative fast under small gate voltage variation although heavy ions are involved in charge transport. In IV characteristic curves, saturation effects can be observed. Analysis using conventional field effect transistor model indicates high mobility of charge carriers, 10 cm2/V·sec, which is not consistent with the mobility of the conducting polymer. It is proposed that the effect of a small density of ions injected via polymer dielectric upon application of gate voltage and the ion compensation of key hopping sites accounts for the operation of the field effect transistors. For the studies of transport under optical field, photovoltaic cells with 3 different dendrons, which are efficient to harvest photo-excited electrons, are used. These dendrons consist of two electron-donors (tetraphenylporphyrin) and one electron-accepter (naphthalenediimide). Steady-state fluorescence measurements show that inter-molecular interaction is dominant in solid dendron film, although intra-molecular interaction is still present. Intra-molecular interaction is suggested by different fluorescence lifetimes between solutions of donor and dendrons. This intra-molecular interaction has two processes, transport via pi-stackings and transport via linking functional groups in the dendrons. IV characteristic spectra of the photovoltaic cells suggest that the transport route of photo-excited charges depends on wavelength of incident light on the cells. For excitation by the Soret band and the lowest Q band, a photo-excited electron can transport directly to a neighbor dendron. For excitation by high-energy Q bands, a photo-excited electron transports via the electron-accepters.

Mesoscale Simulation and Machine Learning of Asphaltene Aggregation Phase Behavior and Molecular Assembly Landscapes.

PubMed

Wang, Jiang; Gayatri, Mohit A; Ferguson, Andrew L

2017-05-11

Asphaltenes constitute the heaviest fraction of the aromatic group in crude oil. Aggregation and precipitation of asphaltenes during petroleum processing costs the petroleum industry billions of dollars each year due to downtime and production inefficiencies. Asphaltene aggregation proceeds via a hierarchical self-assembly process that is well-described by the Yen-Mullins model. Nevertheless, the microscopic details of the emergent cluster morphologies and their relative stability under different processing conditions remain poorly understood. We perform coarse-grained molecular dynamics simulations of a prototypical asphaltene molecule to establish a phase diagram mapping the self-assembled morphologies as a function of temperature, pressure, and n-heptane:toluene solvent ratio informing how to control asphaltene aggregation by regulating external processing conditions. We then combine our simulations with graph matching and nonlinear manifold learning to determine low-dimensional free energy surfaces governing asphaltene self-assembly. In doing so, we introduce a variant of diffusion maps designed to handle data sets with large local density variations, and report the first application of many-body diffusion maps to molecular self-assembly to recover a pseudo-1D free energy landscape. Increasing pressure only weakly affects the landscape, serving only to destabilize the largest aggregates. Increasing temperature and toluene solvent fraction stabilizes small cluster sizes and loose bonding arrangements. Although the underlying molecular mechanisms differ, the strikingly similar effect of these variables on the free energy landscape suggests that toluene acts upon asphaltene self-assembly as an effective temperature.

Intestinal Insulin Signaling Encodes Two Different Molecular Mechanisms for the Shortened Longevity Induced by Graphene Oxide in Caenorhabditis elegans

NASA Astrophysics Data System (ADS)

Zhao, Yunli; Yang, Ruilong; Rui, Qi; Wang, Dayong

2016-04-01

Graphene oxide (GO) has been shown to cause multiple toxicities in various organisms. However, the underlying molecular mechanisms for GO-induced shortened longevity are still unclear. We employed Caenorhabditis elegans to investigate the possible involvement of insulin signaling pathway in the control of GO toxicity and its underlying molecular mechanisms. Mutation of daf-2, age-1, akt-1, or akt-2 gene induced a resistant property of nematodes to GO toxicity, while mutation of daf-16 gene led to a susceptible property of nematodes to GO toxicity, suggesting that GO may dysregulate the functions of DAF-2/IGF-1 receptor, AGE-1, AKT-1 and AKT-2-mediated kinase cascade, and DAF-16/FOXO transcription factor. Genetic interaction analysis suggested the involvement of signaling cascade of DAF-2-AGE-1-AKT-1/2-DAF-16 in the control of GO toxicity on longevity. Moreover, intestinal RNA interference (RNAi) analysis demonstrated that GO reduced longevity by affecting the functions of signaling cascade of DAF-2-AGE-1-AKT-1/2-DAF-16 in the intestine. DAF-16 could also regulate GO toxicity on longevity by functioning upstream of SOD-3, which encodes an antioxidation system that prevents the accumulation of oxidative stress. Therefore, intestinal insulin signaling may encode two different molecular mechanisms responsible for the GO toxicity in inducing the shortened longevity. Our results highlight the key role of insulin signaling pathway in the control of GO toxicity in organisms.

Features of Knowledge Building in Biology: Understanding Undergraduate Students' Ideas about Molecular Mechanisms.

PubMed

Southard, Katelyn; Wince, Tyler; Meddleton, Shanice; Bolger, Molly S

2016-01-01

Research has suggested that teaching and learning in molecular and cellular biology (MCB) is difficult. We used a new lens to understand undergraduate reasoning about molecular mechanisms: the knowledge-integration approach to conceptual change. Knowledge integration is the dynamic process by which learners acquire new ideas, develop connections between ideas, and reorganize and restructure prior knowledge. Semistructured, clinical think-aloud interviews were conducted with introductory and upper-division MCB students. Interviews included a written conceptual assessment, a concept-mapping activity, and an opportunity to explain the biomechanisms of DNA replication, transcription, and translation. Student reasoning patterns were explored through mixed-method analyses. Results suggested that students must sort mechanistic entities into appropriate mental categories that reflect the nature of MCB mechanisms and that conflation between these categories is common. We also showed how connections between molecular mechanisms and their biological roles are part of building an integrated knowledge network as students develop expertise. We observed differences in the nature of connections between ideas related to different forms of reasoning. Finally, we provide a tentative model for MCB knowledge integration and suggest its implications for undergraduate learning. © 2016 K. Southard et al. CBE—Life Sciences Education © 2016 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Degradation of 4-n-nonylphenol under nitrate reducing conditions

PubMed Central

Viñas, Marc; Grotenhuis, Tim; Rijnaarts, Huub H. M.; Langenhoff, Alette A. M.

2010-01-01

Nonylphenol (NP) is an endocrine disruptor present as a pollutant in river sediment. Biodegradation of NP can reduce its toxicological risk. As sediments are mainly anaerobic, degradation of linear (4-n-NP) and branched nonylphenol (tNP) was studied under methanogenic, sulphate reducing and denitrifying conditions in NP polluted river sediment. Anaerobic bioconversion was observed only for linear NP under denitrifying conditions. The microbial population involved herein was further studied by enrichment and molecular characterization. The largest change in diversity was observed between the enrichments of the third and fourth generation, and further enrichment did not affect the diversity. This implies that different microorganisms are involved in the degradation of 4-n-NP in the sediment. The major degrading bacteria were most closely related to denitrifying hexadecane degraders and linear alkyl benzene sulphonate (LAS) degraders. The molecular structures of alkanes and LAS are similar to the linear chain of 4-n-NP, this might indicate that the biodegradation of linear NP under denitrifying conditions starts at the nonyl chain. Initiation of anaerobic NP degradation was further tested using phenol as a structure analogue. Phenol was chosen instead of an aliphatic analogue, because phenol is the common structure present in all NP isomers while the structure of the aliphatic chain differs per isomer. Phenol was degraded in all cases, but did not affect the linear NP degradation under denitrifying conditions and did not initiate the degradation of tNP and linear NP under the other tested conditions. PMID:20640878

The shear response of copper bicrystals with Σ11 symmetric and asymmetric tilt grain boundaries by molecular dynamics simulation

NASA Astrophysics Data System (ADS)

Zhang, Liang; Lu, Cheng; Tieu, Kiet; Zhao, Xing; Pei, Linqing

2015-04-01

Grain boundaries (GBs) are important microstructure features and can significantly affect the properties of nanocrystalline materials. Molecular dynamics simulation was carried out in this study to investigate the shear response and deformation mechanisms of symmetric and asymmetric Σ11<1 1 0> tilt GBs in copper bicrystals. Different deformation mechanisms were reported, depending on GB inclination angles and equilibrium GB structures, including GB migration coupled to shear deformation, GB sliding caused by local atomic shuffling, and dislocation nucleation from GB. The simulation showed that migrating Σ11(1 1 3) GB under shear can be regarded as sliding of GB dislocations and their combination along the boundary plane. A non-planar structure with dissociated intrinsic stacking faults was prevalent in Σ11 asymmetric GBs of Cu. This type of structure can significantly increase the ductility of bicrystal models under shear deformation. A grain boundary can be a source of dislocation and migrate itself at different stress levels. The intrinsic free volume involved in the grain boundary area was correlated with dislocation nucleation and GB sliding, while the dislocation nucleation mechanism can be different for a grain boundary due to its different equilibrium structures.Grain boundaries (GBs) are important microstructure features and can significantly affect the properties of nanocrystalline materials. Molecular dynamics simulation was carried out in this study to investigate the shear response and deformation mechanisms of symmetric and asymmetric Σ11<1 1 0> tilt GBs in copper bicrystals. Different deformation mechanisms were reported, depending on GB inclination angles and equilibrium GB structures, including GB migration coupled to shear deformation, GB sliding caused by local atomic shuffling, and dislocation nucleation from GB. The simulation showed that migrating Σ11(1 1 3) GB under shear can be regarded as sliding of GB dislocations and their combination along the boundary plane. A non-planar structure with dissociated intrinsic stacking faults was prevalent in Σ11 asymmetric GBs of Cu. This type of structure can significantly increase the ductility of bicrystal models under shear deformation. A grain boundary can be a source of dislocation and migrate itself at different stress levels. The intrinsic free volume involved in the grain boundary area was correlated with dislocation nucleation and GB sliding, while the dislocation nucleation mechanism can be different for a grain boundary due to its different equilibrium structures. Electronic supplementary information (ESI) available: Movies show the evolution of different grain boundaries under shear deformation: S-0, S-54.74, S-70.53-A, S-70.53-B, S-90. See DOI: 10.1039/c4nr07496c

Interlocking Mechanism between Molecular Gears Attached to Surfaces.

PubMed

Zhao, Rundong; Zhao, Yan-Ling; Qi, Fei; Hermann, Klaus E; Zhang, Rui-Qin; Van Hove, Michel A

2018-03-27

While molecular machines play an increasingly significant role in nanoscience research and applications, there remains a shortage of investigations and understanding of the molecular gear (cogwheel), which is an indispensable and fundamental component to drive a larger correlated molecular machine system. Employing ab initio calculations, we investigate model systems consisting of molecules adsorbed on metal or graphene surfaces, ranging from very simple triple-arm gears such as PF 3 and NH 3 to larger multiarm gears based on carbon rings. We explore in detail the transmission of slow rotational motion from one gear to the next by these relatively simple molecules, so as to isolate and reveal the mechanisms of the relevant intermolecular interactions. Several characteristics of molecular gears are discussed, in particular the flexibility of the arms and the slipping and skipping between interlocking arms of adjacent gears, which differ from familiar macroscopic rigid gears. The underlying theoretical concepts suggest strongly that other analogous structures may also exhibit similar behavior which may inspire future exploration in designing large correlated molecular machines.

Molecular Ecological Basis of Grasshopper (Oedaleus asiaticus) Phenotypic Plasticity under Environmental Selection

PubMed Central

Qin, Xinghu; Hao, Kun; Ma, Jingchuan; Huang, Xunbing; Tu, Xiongbing; Ali, Md. Panna; Pittendrigh, Barry R.; Cao, Guangchun; Wang, Guangjun; Nong, Xiangqun; Whitman, Douglas W.; Zhang, Zehua

2017-01-01

While ecological adaptation in insects can be reflected by plasticity of phenotype, determining the causes and molecular mechanisms for phenotypic plasticity (PP) remains a crucial and still difficult question in ecology, especially where control of insect pests is involved. Oedaleus asiaticus is one of the most dominant pests in the Inner Mongolia steppe and represents an excellent system to study phenotypic plasticity. To better understand ecological factors affecting grasshopper phenotypic plasticity and its molecular control, we conducted a full transcriptional screening of O. asiaticus grasshoppers reared in four different grassland patches in Inner Mongolia. Grasshoppers showed different degrees of PP associated with unique gene expressions and different habitat plant community compositions. Grasshopper performance variables were susceptible to habitat environment conditions and closely associated with plant architectures. Intriguingly, eco-transcriptome analysis revealed five potential candidate genes playing important roles in grasshopper performance, with gene expression closely relating to PP and plant community factors. By linking the grasshopper performances to gene profiles and ecological factors using canonical regression, we first demonstrated the eco-transcriptomic architecture (ETA) of grasshopper phenotypic traits (ETAGPTs). ETAGPTs revealed plant food type, plant density, coverage, and height were the main ecological factors influencing PP, while insect cuticle protein (ICP), negative elongation factor A (NELFA), and lactase-phlorizin hydrolase (LCT) were the key genes associated with PP. Our study gives a clear picture of gene-environment interaction in the formation and maintenance of PP and enriches our understanding of the transcriptional events underlying molecular control of rapid phenotypic plasticity associated with environmental variability. The findings of this study may also provide new targets for pest control and highlight the significance of ecological management practice on grassland conservation. PMID:29066978

Can Molecular Hippocampal Alterations Explain Behavioral Differences in Prenatally Stressed Rats?

EPA Science Inventory

Studies in both humans and animals have shown that prenatal stress can alter cognitive function and other neurological behaviors in adult offspring. One possible underlying mechanism for this may lie with alterations in hippocampal gene expression. The present study examined geno...

Molecular Darwinism: The Contingency of Spontaneous Genetic Variation

PubMed Central

Arber, Werner

2011-01-01

The availability of spontaneously occurring genetic variants is an important driving force of biological evolution. Largely thanks to experimental investigations by microbial geneticists, we know today that several different molecular mechanisms contribute to the overall genetic variations. These mechanisms can be assigned to three natural strategies to generate genetic variants: 1) local sequence changes, 2) intragenomic reshuffling of DNA segments, and 3) acquisition of a segment of foreign DNA. In these processes, specific gene products are involved in cooperation with different nongenetic elements. Some genetic variations occur fully at random along the DNA filaments, others rather with a statistical reproducibility, although at many possible sites. We have to be aware that evolution in natural ecosystems is of higher complexity than under most laboratory conditions, not at least in view of symbiotic associations and the occurrence of horizontal gene transfer. The encountered contingency of genetic variation can possibly best ensure a long-term persistence of life under steadily changing living conditions. PMID:21979160

Emergence of robust growth laws from optimal regulation of ribosome synthesis.

PubMed

Scott, Matthew; Klumpp, Stefan; Mateescu, Eduard M; Hwa, Terence

2014-08-22

Bacteria must constantly adapt their growth to changes in nutrient availability; yet despite large-scale changes in protein expression associated with sensing, adaptation, and processing different environmental nutrients, simple growth laws connect the ribosome abundance and the growth rate. Here, we investigate the origin of these growth laws by analyzing the features of ribosomal regulation that coordinate proteome-wide expression changes with cell growth in a variety of nutrient conditions in the model organism Escherichia coli. We identify supply-driven feedforward activation of ribosomal protein synthesis as the key regulatory motif maximizing amino acid flux, and autonomously guiding a cell to achieve optimal growth in different environments. The growth laws emerge naturally from the robust regulatory strategy underlying growth rate control, irrespective of the details of the molecular implementation. The study highlights the interplay between phenomenological modeling and molecular mechanisms in uncovering fundamental operating constraints, with implications for endogenous and synthetic design of microorganisms. © 2014 The Authors. Published under the terms of the CC BY 4.0 license.

G12V Kras mutations in cervical cancer under virtual microscope of molecular dynamics simulations.

PubMed

Chen, X P; Xu, W H; Xu, D F; Fu, S M; Ma, Z C

2016-01-01

Kras mutations and cancers are common and their role in the progression of cancer is well known and elucidated. The present work is searching for the most deleterious mutation of the four found at codon 12 and 13 of Kras in cervical cancers using prediction servers; different servers were used to look into different factors that govern the protein function. The in silico results predicted G12V to be the most devastating; this particular mutation was then subjected to molecular dynamics simulation (MDS) for further analysis. The authors' approach of MDSs helped them to place the native and mutant structure under virtual microscope and observe their dynamics over time. The results generated are enlightening the effect of G12V variation on the dynamics of Kras. The structural variation between the native and mutant Kras over 50 nanoseconds (ns) run varied at every parameter checked and the results are in excellent agreement with the available experimental data.

Multiscale analysis of the correlation of processing parameters on viscidity of composites fabricated by automated fiber placement

NASA Astrophysics Data System (ADS)

Han, Zhenyu; Sun, Shouzheng; Fu, Yunzhong; Fu, Hongya

2017-10-01

Viscidity is an important physical indicator for assessing fluidity of resin that is beneficial to contact resin with the fibers effectively and reduce manufacturing defects during automated fiber placement (AFP) process. However, the effect of processing parameters on viscidity evolution is rarely studied during AFP process. In this paper, viscidities under different scales are analyzed based on multi-scale analysis method. Firstly, viscous dissipation energy (VDE) within meso-unit under different processing parameters is assessed by using finite element method (FEM). According to multi-scale energy transfer model, meso-unit energy is used as the boundary condition for microscopic analysis. Furthermore, molecular structure of micro-system is built by molecular dynamics (MD) method. And viscosity curves are then obtained by integrating stress autocorrelation function (SACF) with time. Finally, the correlation characteristics of processing parameters to viscosity are revealed by using gray relational analysis method (GRAM). A group of processing parameters is found out to achieve the stability of viscosity and better fluidity of resin.

Molecular Darwinism: the contingency of spontaneous genetic variation.

PubMed

Arber, Werner

2011-01-01

The availability of spontaneously occurring genetic variants is an important driving force of biological evolution. Largely thanks to experimental investigations by microbial geneticists, we know today that several different molecular mechanisms contribute to the overall genetic variations. These mechanisms can be assigned to three natural strategies to generate genetic variants: 1) local sequence changes, 2) intragenomic reshuffling of DNA segments, and 3) acquisition of a segment of foreign DNA. In these processes, specific gene products are involved in cooperation with different nongenetic elements. Some genetic variations occur fully at random along the DNA filaments, others rather with a statistical reproducibility, although at many possible sites. We have to be aware that evolution in natural ecosystems is of higher complexity than under most laboratory conditions, not at least in view of symbiotic associations and the occurrence of horizontal gene transfer. The encountered contingency of genetic variation can possibly best ensure a long-term persistence of life under steadily changing living conditions.

Erythropoietin regulations in humans under different environmental and experimental conditions.

PubMed

Gunga, H-C; Kirsch, K A; Roecker, L; Kohlberg, E; Tiedemann, J; Steinach, M; Schobersberger, W

2007-09-30

In the adult human, the kidney is the main organ for the production and release of erythropoietin (EPO). EPO is stimulating erythropoiesis by increasing the proliferation, differentiation and maturation of the erythroid precursors. In the last decades, enormous efforts were made in the purification, molecular encoding and description of the EPO gene. This led to an incredible increase in the understanding of the EPO-feedback-regulation loop at a molecular level, especially the oxygen-dependent EPO gene expression, a key function in the regulation loop. However, studies in humans at a systemic level are still very scanty. Therefore, it is the purpose of the present review to report on the main recent investigations on EPO production and release in humans under different environmental and experimental conditions, including: (i) studies on EPO circadian, monthly and even annual variations, (ii) studies in connection with short-, medium- and long-term exercise at sea-level which will be followed (iii) by studies performed at moderate and high altitude.

Right- and left-handed three-helix proteins. II. Similarity and differences in mechanical unfolding of proteins.

PubMed

Glyakina, Anna V; Likhachev, Ilya V; Balabaev, Nikolay K; Galzitskaya, Oxana V

2014-01-01

Here, we study mechanical properties of eight 3-helix proteins (four right-handed and four left-handed ones), which are similar in size under stretching at a constant speed and at a constant force on the atomic level using molecular dynamics simulations. The analysis of 256 trajectories from molecular dynamics simulations with explicit water showed that the right-handed three-helix domains are more mechanically resistant than the left-handed domains. Such results are observed at different extension velocities studied (192 trajectories obtained at the following conditions: v = 0.1, 0.05, and 0.01 Å ps(-1) , T = 300 K) and under constant stretching force (64 trajectories, F = 800 pN, T = 300 K). We can explain this by the fact, at least in part, that the right-handed domains have a larger number of contacts per residue and the radius of cross section than the left-handed domains. Copyright © 2013 Wiley Periodicals, Inc.

Wavelength dependence of biological damage induced by UV radiation on bacteria.

PubMed

Santos, Ana L; Oliveira, Vanessa; Baptista, Inês; Henriques, Isabel; Gomes, Newton C M; Almeida, Adelaide; Correia, António; Cunha, Ângela

2013-01-01

The biological effects of UV radiation of different wavelengths (UVA, UVB and UVC) were assessed in nine bacterial isolates displaying different UV sensitivities. Biological effects (survival and activity) and molecular markers of oxidative stress [DNA strand breakage (DSB), generation of reactive oxygen species (ROS), oxidative damage to proteins and lipids, and the activity of antioxidant enzymes catalase and superoxide dismutase] were quantified and statistically analyzed in order to identify the major determinants of cell inactivation under the different spectral regions. Survival and activity followed a clear wavelength dependence, being highest under UVA and lowest under UVC. The generation of ROS, as well as protein and lipid oxidation, followed the same pattern. DNA damage (DSB) showed the inverse trend. Multiple stepwise regression analysis revealed that survival under UVA, UVB and UVC wavelengths was best explained by DSB, oxidative damage to lipids, and intracellular ROS levels, respectively.

Breast cancer lung metastasis: Molecular biology and therapeutic implications.

PubMed

Jin, Liting; Han, Bingchen; Siegel, Emily; Cui, Yukun; Giuliano, Armando; Cui, Xiaojiang

2018-03-26

Distant metastasis accounts for the vast majority of deaths in patients with cancer. Breast cancer exhibits a distinct metastatic pattern commonly involving bone, liver, lung, and brain. Breast cancer can be divided into different subtypes based on gene expression profiles, and different breast cancer subtypes show preference to distinct organ sites of metastasis. Luminal breast tumors tend to metastasize to bone while basal-like breast cancer (BLBC) displays a lung tropism of metastasis. However, the mechanisms underlying this organ-specific pattern of metastasis still remain to be elucidated. In this review, we will summarize the recent advances regarding the molecular signaling pathways as well as the therapeutic strategies for treating breast cancer lung metastasis.

The role of molecular imaging in diagnosis of deep vein thrombosis

PubMed Central

Houshmand, Sina; Salavati, Ali; Hess, Søren; Ravina, Mudalsha; Alavi, Abass

2014-01-01

Venous thromboembolism (VTE) mostly presenting as deep venous thrombosis (DVT) and pulmonary embolism (PE) affects up to 600,000 individuals in United States each year. Clinical symptoms of VTE are nonspecific and sometimes misleading. Additionally, side effects of available treatment plans for DVT are significant. Therefore, medical imaging plays a crucial role in proper diagnosis and avoidance from over/under diagnosis, which exposes the patient to risk. In addition to conventional structural imaging modalities, such as ultrasonography and computed tomography, molecular imaging with different tracers have been studied for diagnosis of DVT. In this review we will discuss currently available and newly evolving targets and tracers for detection of DVT using molecular imaging methods. PMID:25143860

Cancer cachexia: understanding the molecular basis.

PubMed

Argilés, Josep M; Busquets, Sílvia; Stemmler, Britta; López-Soriano, Francisco J

2014-11-01

Cancer cachexia is a devastating, multifactorial and often irreversible syndrome that affects around 50-80% of cancer patients, depending on the tumour type, and that leads to substantial weight loss, primarily from loss of skeletal muscle and body fat. Since cachexia may account for up to 20% of cancer deaths, understanding the underlying molecular mechanisms is essential. The occurrence of cachexia in cancer patients is dependent on the patient response to tumour progression, including the activation of the inflammatory response and energetic inefficiency involving the mitochondria. Interestingly, crosstalk between different cell types ultimately seems to result in muscle wasting. Some of the recent progress in understanding the molecular mechanisms of cachexia may lead to new therapeutic approaches.

Acid-Labile Acyclic Cucurbit[n]uril Molecular Containers for Controlled Release.

PubMed

Mao, Dake; Liang, Yajun; Liu, Yamin; Zhou, Xianhao; Ma, Jiaqi; Jiang, Biao; Liu, Jia; Ma, Da

2017-10-02

Stimuli-responsive molecular containers are of great importance for controlled drug delivery and other biomedical applications. A new type of acid labile acyclic cucurbit[n]uril (CB[n]) molecular containers is presented that can degrade and release the encapsulated cargo at accelerated rates under mildly acidic conditions (pH 5.5-6.5). These containers retain the excellent recognition properties of CB[n]-type hosts. A cell culture study demonstrated that the cellular uptake of cargos could be fine-tuned by complexation with different containers. The release and cell uptake of cargo dye was promoted by acidic pH. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Molecular catalytic coal liquid conversion

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

Stock, L.M.; Yang, Shiyong

1995-12-31

This research, which is relevant to the development of new catalytic systems for the improvement of the quality of coal liquids by the addition of dihydrogen, is divided into two tasks. Task 1 centers on the activation of dihydrogen by molecular basic reagents such as hydroxide ion to convert it into a reactive adduct (OH{center_dot}H{sub 2}){sup {minus}} that can reduce organic molecules. Such species should be robust withstanding severe conditions and chemical poisons. Task 2 is focused on an entirely different approach that exploits molecular catalysts, derived from organometallic compounds that are capable of reducing monocyclic aromatic compounds under verymore » mild conditions. Accomplishments and conclusions are discussed.« less

Altered apolipoprotein C expression in association with cognition impairments and hippocampus volume in schizophrenia and bipolar disorder.

PubMed

Knöchel, Christian; Kniep, Jonathan; Cooper, Jason D; Stäblein, Michael; Wenzler, Sofia; Sarlon, Jan; Prvulovic, David; Linden, David E J; Bahn, Sabine; Stocki, Pawel; Ozcan, Sureyya; Alves, Gilberto; Carvalho, Andre F; Reif, Andreas; Oertel-Knöchel, Viola

2017-04-01

Proteomic analyses facilitate the interpretation of molecular biomarker probes which are very helpful in diagnosing schizophrenia (SZ). In the current study, we attempt to test whether potential differences in plasma protein expressions in SZ and bipolar disorder (BD) are associated with cognitive deficits and their underlying brain structures. Forty-two plasma proteins of 29 SZ patients, 25 BD patients and 93 non-clinical controls were quantified and analysed using multiple reaction monitoring-based triple quadrupole mass spectrometry approach. We also computed group comparisons of protein expressions between patients and controls, and between SZ and BD patients, as well. Potential associations of protein levels with cognitive functioning (psychomotor speed, executive functioning, crystallised intelligence) as well as underlying brain volume in the hippocampus were explored, using bivariate correlation analyses. The main finding of this study was that apolipoprotein expression differed between patients and controls and that these alterations in both disease groups were putatively related to cognitive impairments as well as to hippocampus volumes. However, none of the protein level differences were related to clinical symptom severity. In summary, altered apolipoprotein expression in BD and SZ was linked to cognitive decline and underlying morphological changes in both disorders. Our results suggest that the detection of molecular patterns in association with cognitive performance and its underlying brain morphology is of great importance for understanding of the pathological mechanisms of SZ and BD, as well as for supporting the diagnosis and treatment of both disorders.

Molecular mechanics of silk nanostructures under varied mechanical loading.

PubMed

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.

Molecular deformation mechanisms of the wood cell wall material.

PubMed

Jin, Kai; Qin, Zhao; Buehler, Markus J

2015-02-01

Wood is a biological material with outstanding mechanical properties resulting from its hierarchical structure across different scales. Although earlier work has shown that the cellular structure of wood is a key factor that renders it excellent mechanical properties at light weight, the mechanical properties of the wood cell wall material itself still needs to be understood comprehensively. The wood cell wall material features a fiber reinforced composite structure, where cellulose fibrils act as stiff fibers, and hemicellulose and lignin molecules act as soft matrix. The angle between the fiber direction and the loading direction has been found to be the key factor controlling the mechanical properties. However, how the interactions between theses constitutive molecules contribute to the overall properties is still unclear, although the shearing between fibers has been proposed as a primary deformation mechanism. Here we report a molecular model of the wood cell wall material with atomistic resolution, used to assess the mechanical behavior under shear loading in order to understand the deformation mechanisms at the molecular level. The model includes an explicit description of cellulose crystals, hemicellulose, as well as lignin molecules arranged in a layered nanocomposite. The results obtained using this model show that the wood cell wall material under shear loading deforms in an elastic and then plastic manner. The plastic regime can be divided into two parts according to the different deformation mechanisms: yielding of the matrix and sliding of matrix along the cellulose surface. Our molecular dynamics study provides insights of the mechanical behavior of wood cell wall material at the molecular level, and paves a way for the multi-scale understanding of the mechanical properties of wood. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effect of molecular shape on rotation under severe confinement

DOE PAGES

Dhiman, Indu; Bhowmik, Debsindhu; Shrestha, Utsab R.; ...

2018-01-31

Orientational structure and dynamics of molecules is known to be affected by confinement in space comparable in size to the molecule itself. ZSM-5 with porous channels of ≈0.55 nm is such a porous medium, which offers a strict spatial confinement on low molecular weight hydrocarbons. An important factor that determines these properties is the shape of the confined molecules. In this work, we employed molecular dynamics simulation to study the orientational structure and dynamics of four molecules that differ in shape but have similar kinetic diameters and moments of inertia, confined in ZSM-5. The effect of molecular shape on themore » orientational structure and dynamics of propane, acetonitrile, acetaldehyde and acetone in ZSM-5 is studied by means of probing the differences in the orientational distribution of molecules in the ZSM-5 channels, and extracting time scales of the decay of correlation functions related to rotational motion. Orientational correlation functions of all the four molecules exhibit two regimes of rotational motion. While the short time regime represents free rotation of the molecules before they collide with the pore walls, the long time orientational jumps driven by inter-channel migrations give rise to a very slow varying second regime. Of the molecules studied, orientational structure and dynamics of propane is found to be least affected by confinement under ZSM-5, whereas charge and shape asymmetry of other molecules makes their interchannel migration-driven rotation slow. The time scales involved in the rotational motion for the molecules studied are compared with similar studies reported in literature. Lastly, this study reveals the important role that molecular shape plays in the behavior of confined molecules.« less

Effect of molecular shape on rotation under severe confinement

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

Dhiman, Indu; Bhowmik, Debsindhu; Shrestha, Utsab R.

Orientational structure and dynamics of molecules is known to be affected by confinement in space comparable in size to the molecule itself. ZSM-5 with porous channels of ≈0.55 nm is such a porous medium, which offers a strict spatial confinement on low molecular weight hydrocarbons. An important factor that determines these properties is the shape of the confined molecules. In this work, we employed molecular dynamics simulation to study the orientational structure and dynamics of four molecules that differ in shape but have similar kinetic diameters and moments of inertia, confined in ZSM-5. The effect of molecular shape on themore » orientational structure and dynamics of propane, acetonitrile, acetaldehyde and acetone in ZSM-5 is studied by means of probing the differences in the orientational distribution of molecules in the ZSM-5 channels, and extracting time scales of the decay of correlation functions related to rotational motion. Orientational correlation functions of all the four molecules exhibit two regimes of rotational motion. While the short time regime represents free rotation of the molecules before they collide with the pore walls, the long time orientational jumps driven by inter-channel migrations give rise to a very slow varying second regime. Of the molecules studied, orientational structure and dynamics of propane is found to be least affected by confinement under ZSM-5, whereas charge and shape asymmetry of other molecules makes their interchannel migration-driven rotation slow. The time scales involved in the rotational motion for the molecules studied are compared with similar studies reported in literature. Lastly, this study reveals the important role that molecular shape plays in the behavior of confined molecules.« less

Differential expression of molecular markers of synaptic plasticity in the hippocampus, prefrontal cortex, and amygdala in response to spatial learning, predator exposure, and stress-induced amnesia.

PubMed

Zoladz, Phillip R; Park, Collin R; Halonen, Joshua D; Salim, Samina; Alzoubi, Karem H; Srivareerat, Marisa; Fleshner, Monika; Alkadhi, Karim A; Diamond, David M

2012-03-01

We have studied the effects of spatial learning and predator stress-induced amnesia on the expression of calcium/calmodulin-dependent protein kinase II (CaMKII), brain-derived neurotrophic factor (BDNF) and calcineurin in the hippocampus, basolateral amygdala (BLA), and medial prefrontal cortex (mPFC). Adult male rats were given a single training session in the radial-arm water maze (RAWM) composed of 12 trials followed by a 30-min delay period, during which rats were either returned to their home cages or given inescapable exposure to a cat. Immediately following the 30-min delay period, the rats were given a single test trial in the RAWM to assess their memory for the hidden platform location. Under control (no stress) conditions, rats exhibited intact spatial memory and an increase in phosphorylated CaMKII (p-CaMKII), total CaMKII, and BDNF in dorsal CA1. Under stress conditions, rats exhibited impaired spatial memory and a suppression of all measured markers of molecular plasticity in dorsal CA1. The molecular profiles observed in the BLA, mPFC, and ventral CA1 were markedly different from those observed in dorsal CA1. Stress exposure increased p-CaMKII in the BLA, decreased p-CaMKII in the mPFC, and had no effect on any of the markers of molecular plasticity in ventral CA1. These findings provide novel observations regarding rapidly induced changes in the expression of molecular plasticity in response to spatial learning, predator exposure, and stress-induced amnesia in brainregions involved in different aspects of memory processing. Copyright © 2011 Wiley Periodicals, Inc.

Usher syndrome (sensorineural deafness and retinitis pigmentosa): pathogenesis, molecular diagnosis and therapeutic approaches.

PubMed

Bonnet, Crystel; El-Amraoui, Aziz

2012-02-01

Usher syndrome (USH) is the most prevalent cause of hereditary deafness-blindness in humans. In this review, we pinpoint new insights regarding the molecular mechanisms defective in this syndrome, its molecular diagnosis and prospective therapies. Animal models wherein USH proteins were targeted at different maturation stages of the auditory hair cells have been engineered, shedding new light on the development and functioning of the hair bundle, the sound receptive structure. Improved protocols and guidelines for early molecular diagnosis of USH (USH genotyping microarrays, otochips and complete Sanger sequencing of the 366 coding exons of identified USH genes) have been developed. Approaches to alleviate or cure hearing and visual impairments have been initiated, leading to various degrees of functional rescuing. Whereas the mechanisms underlying hearing impairment in USH patients are being unraveled, showing in particular that USH1 proteins are involved in the shaping of the hair bundle and the functioning of the mechanoelectrical transduction machinery, the mechanisms underlying the retinal defects are still unclear. Efforts to improve clinical diagnosis have been successful. Yet, despite some encouraging results, further development of therapeutic approaches is necessary to ultimately treat this dual sensory defect.

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

PubMed

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.

Inferring diffusion in single live cells at the single-molecule level

PubMed Central

Robson, Alex; Burrage, Kevin; Leake, Mark C.

2013-01-01

The movement of molecules inside living cells is a fundamental feature of biological processes. The ability to both observe and analyse the details of molecular diffusion in vivo at the single-molecule and single-cell level can add significant insight into understanding molecular architectures of diffusing molecules and the nanoscale environment in which the molecules diffuse. The tool of choice for monitoring dynamic molecular localization in live cells is fluorescence microscopy, especially so combining total internal reflection fluorescence with the use of fluorescent protein (FP) reporters in offering exceptional imaging contrast for dynamic processes in the cell membrane under relatively physiological conditions compared with competing single-molecule techniques. There exist several different complex modes of diffusion, and discriminating these from each other is challenging at the molecular level owing to underlying stochastic behaviour. Analysis is traditionally performed using mean square displacements of tracked particles; however, this generally requires more data points than is typical for single FP tracks owing to photophysical instability. Presented here is a novel approach allowing robust Bayesian ranking of diffusion processes to discriminate multiple complex modes probabilistically. It is a computational approach that biologists can use to understand single-molecule features in live cells. PMID:23267182

Molecular Analysis of Mixed Endometrial Carcinomas Shows Clonality in Most Cases.

PubMed

Köbel, Martin; Meng, Bo; Hoang, Lien N; Almadani, Noorah; Li, Xiaodong; Soslow, Robert A; Gilks, C Blake; Lee, Cheng-Han

2016-02-01

Mixed endometrial carcinoma refers to a tumor that comprises 2 or more distinct histotypes. We studied 18 mixed-type endometrial carcinomas-11 mixed serous and low-grade endometrioid carcinomas (SC/EC), 5 mixed clear cell and low-grade ECs (CCC/EC), and 2 mixed CCC and SCs (CCC/SC), using targeted next-generation sequencing and immunohistochemistry to compare the molecular profiles of the different histotypes present in each case. In 16 of 18 cases there was molecular evidence that both components shared a clonal origin. Eight cases (6 EC/SC, 1 EC/CCC, and 1 SC/CCC) showed an SC molecular profile that was the same in both components. Five cases (3 CCC/EC and 2 SC/EC) showed a shared endometrioid molecular profile and identical mismatch-repair protein deficiency in both components. A single SC/EC case harbored the same POLE exonuclease domain mutation in both components. One SC/CCC and 1 EC/CCC case showed both shared and unique molecular features in the 2 histotype components, suggesting early molecular divergence from a common clonal origin. In 2 cases, there were no shared molecular features, and these appear to be biologically unrelated synchronous tumors. Overall, these results show that the different histologic components in mixed endometrial carcinomas typically share the same molecular aberrations. Mixed endometrial carcinomas most commonly occur through morphologic mimicry, whereby tumors with serous-type molecular profile show morphologic features of EC or CCC, or through underlying deficiency in DNA nucleotide repair, with resulting rapid accrual of mutations and intratumoral phenotypic heterogeneity. Less commonly, mixed endometrial carcinomas are the result of early molecular divergence from a common progenitor clone or are synchronous biologically unrelated tumors (collision tumors).

Molecular analysis of mixed endometrial carcinomas shows clonality in most cases

PubMed Central

Hoang, Lien N.; Almadani, Noorah; Li, Xiaodong; Soslow, Robert A; Gilks, C. Blake; Lee, Cheng-Han

2016-01-01

Mixed endometrial carcinoma refers to a tumor that is comprised of two or more distinct histotypes. We studied 18 mixed-type endometrial carcinomas - 11 mixed serous and low-grade endometrioid carcinomas (SC/EC), 5 mixed clear cell and low-grade endometrioid carcinomas (CCC/EC), and 2 mixed clear cell and serous carcinoma (CCC/SC), using targeted next generation sequencing and immunohistochemistry to compare the molecular profiles of the different histotypes present in each case. In 16 of 18 cases there was molecular evidence that both components shared a clonal origin. Eight cases (6 EC/SC, 1 EC/CCC and 1 SC/CCC) showed a serous carcinoma molecular profile that was the same in both components. Five cases (3 CCC/EC and 2 SC/EC) showed a shared endometrioid molecular profile and identical mismatch repair protein (MMR) deficiency in both components. A single SC/EC case harbored the same POLE exonuclease domain mutation in both components. One SC/CCC and one EC/CCC case showed both shared and unique molecular features in the two histotype components, suggesting early molecular divergence from a common clonal origin. In two cases, there were no shared molecular features and these appear to be biologically unrelated synchronous tumors. Overall, these results show that the different histologic components in mixed endometrial carcinomas typically share the same molecular aberrations. Mixed endometrial carcinomas most commonly occur through morphological mimicry, whereby tumors with serous-type molecular profile show morphological features of endometrioid or clear cell carcinoma, or through underlying deficiency in DNA nucleotide repair, with resulting rapid accrual of mutations and intratumoral phenotypic heterogeneity. Less commonly, mixed endometrial carcinomas are the result of early molecular divergence from a common progenitor clone or are synchronous biologically unrelated tumors (collision tumors). PMID:26492180

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

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

Huang, Q.; Tran, K. N.; Rodgers, J. M.

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. Furthermore, 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. But, thermodynamic arguments imply that the effects of pressure might lead to different organismal solutions than from the effects of temperature. Observationally,more » some of these solutions might be in the condensed matter properties of the intracellular milieu in addition to genetic modi1cations 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 ampli1ed by the results from molecular dynamics simulations. Our aim is to provide biological background for soft matter studies of these systems under pressure.« less

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

DOE PAGES

Huang, Q.; Tran, K. N.; Rodgers, J. M.; ...

2016-03-01

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. Furthermore, 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. But, thermodynamic arguments imply that the effects of pressure might lead to different organismal solutions than from the effects of temperature. Observationally,more » some of these solutions might be in the condensed matter properties of the intracellular milieu in addition to genetic modi1cations 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 ampli1ed by the results from molecular dynamics simulations. Our aim is to provide biological background for soft matter studies of these systems under pressure.« less

Background Nutrients Affect the Biotransformation of Tetracycline by Stenotrophomonas maltophilia as Revealed by Genomics and Proteomics.

PubMed

Leng, Yifei; Bao, Jianguo; Song, Dandan; Li, Jing; Ye, Mao; Li, Xu

2017-09-19

Certain bacteria are resistant to antibiotics and can even transform antibiotics in the environment. It is unclear how the molecular mechanisms underlying the resistance and biotransformation processes vary under different environmental conditions. The objective of this study is to investigate the molecular mechanisms of tetracycline resistance and biotransformation by Stenotrophomonas maltophilia strain DT1 under various background nutrient conditions. Strain DT1 was exposed to tetracycline for 7 days with four background nutrient conditions: no background (NB), peptone (P), peptone plus citrate (PC), and peptone plus glucose (PG). The biotransformation rate follows the order of PC > P > PG > NB ≈ 0. Genomic analysis showed that strain DT1 contained tet(X1), a gene encoding an FAD-binding monooxygenase, and eight peroxidase genes that could be relevant to tetracycline biotransformation. Quantitative proteomic analyses revealed that nodulation protein transported tetracycline outside of cells; hypoxanthine-guanine phosphoribosyltransferase facilitated the activation of the ribosomal protection proteins to prevent the binding of tetracycline to the ribosome and superoxide dismutase and peroxiredoxin-modified tetracycline molecules. Comparing different nutrient conditions showed that the biotransformation rates of tetracycline were positively correlated with the expression levels of superoxide dismutase.

Source-sink interaction: a century old concept under the light of modern molecular systems biology.

PubMed

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.

Integrating Evolutionary and Molecular Genetics of Aging

PubMed Central

Flatt, Thomas; Schmidt, Paul S.

2010-01-01

Aging or senescence is an age-dependent decline in physiological function, demographically manifest as decreased survival and fecundity with increasing age. Since aging is disadvantageous it should not evolve by natural selection. So why do organisms age and die? In the 1940’s and 1950’s evolutionary geneticists resolved this paradox by positing that aging evolves because selection is inefficient at maintaining function late in life. By the 1980’s and 1990’s this evolutionary theory of aging had received firm empirical support, but little was known about the mechanisms of aging. Around the same time biologists began to apply the tools of molecular genetics to aging and successfully identified mutations that affect longevity. Today, the molecular genetics of aging is a burgeoning field, but progress in evolutionary genetics of aging has largely stalled. Here we argue that some of the most exciting and unresolved questions about aging require an integration of molecular and evolutionary approaches. Is aging a universal process? Why do species age at different rates? Are the mechanisms of aging conserved or lineage-specific? Are longevity genes identified in the laboratory under selection in natural populations? What is the genetic basis of plasticity in aging in response to environmental cues and is this plasticity adaptive? What are the mechanisms underlying trade-offs between early fitness traits and life span? To answer these questions evolutionary biologists must adopt the tools of molecular biology, while molecular biologists must put their experiments into an evolutionary framework. The time is ripe for a synthesis of molecular biogerontology and the evolutionary biology of aging. PMID:19619612

Integrating evolutionary and molecular genetics of aging.

PubMed

Flatt, Thomas; Schmidt, Paul S

2009-10-01

Aging or senescence is an age-dependent decline in physiological function, demographically manifest as decreased survival and fecundity with increasing age. Since aging is disadvantageous it should not evolve by natural selection. So why do organisms age and die? In the 1940s and 1950s evolutionary geneticists resolved this paradox by positing that aging evolves because selection is inefficient at maintaining function late in life. By the 1980s and 1990s this evolutionary theory of aging had received firm empirical support, but little was known about the mechanisms of aging. Around the same time biologists began to apply the tools of molecular genetics to aging and successfully identified mutations that affect longevity. Today, the molecular genetics of aging is a burgeoning field, but progress in evolutionary genetics of aging has largely stalled. Here we argue that some of the most exciting and unresolved questions about aging require an integration of molecular and evolutionary approaches. Is aging a universal process? Why do species age at different rates? Are the mechanisms of aging conserved or lineage-specific? Are longevity genes identified in the laboratory under selection in natural populations? What is the genetic basis of plasticity in aging in response to environmental cues and is this plasticity adaptive? What are the mechanisms underlying trade-offs between early fitness traits and life span? To answer these questions evolutionary biologists must adopt the tools of molecular biology, while molecular biologists must put their experiments into an evolutionary framework. The time is ripe for a synthesis of molecular biogerontology and the evolutionary biology of aging.

Low-temperature adsorption of H2S on Ni(001) studied by near-edge- and surface-extended-x-ray-absorption fine structure

NASA Astrophysics Data System (ADS)

McGrath, R.; MacDowell, A. A.; Hashizume, T.; Sette, F.; Citrin, P. H.

1989-11-01

The adsorption of H2S on Ni(001) has been studied with surface-extended x-ray-absorption fine structure and near-edge x-ray-absorption fine structure (NEXAFS) using the AT&T Bell Laboratories X15B beamline at the National Synchrotron Light Source. At 95 K and full saturation coverage, ~0.45 monolayer (ML) of S atoms in fourfold-hollow sites are produced, characteristic of room-temperature adsorption, accompanied by ~0.05 ML of oriented molecular H2S. Both these atomic and molecular chemisorbed species are buried under ~0.9 ML of disordered physisorbed H2S. No evidence for HS is found. Above 190 K the two molecular H2S phases desorb, leaving only dissociated S. These findings differ from previously reported interpretations of data obtained with high-resolution electron-energy-loss spectroscopy. They also exemplify the utility of NEXAFS for identifying and quantifying atomic and molecular surface species even when their difference involves only H and the two species coexist.

Dynamics of Nanoscale Grain-Boundary Decohesion in Aluminum by Molecular-Dynamics Simulation

NASA Technical Reports Server (NTRS)

Yamakov, V.; Saether, E.; Phillips, D. R.; Glaessegen, E. H.

2007-01-01

The dynamics and energetics of intergranular crack growth along a flat grain boundary in aluminum is studied by a molecular-dynamics simulation model for crack propagation under steady-state conditions. Using the ability of the molecular-dynamics simulation to identify atoms involved in different atomistic mechanisms, it was possible to identify the energy contribution of different processes taking place during crack growth. The energy contributions were divided as: elastic energy, defined as the potential energy of the atoms in fcc crystallographic state; and plastically stored energy, the energy of stacking faults and twin boundaries; grain-boundary and surface energy. In addition, monitoring the amount of heat exchange with the molecular-dynamics thermostat gives the energy dissipated as heat in the system. The energetic analysis indicates that the majority of energy in a fast growing crack is dissipated as heat. This dissipation increases linearly at low speed, and faster than linear at speeds approaching 1/3 the Rayleigh wave speed when the crack tip becomes dynamically unstable producing periodic dislocation bursts until the crack is blunted.

Submicron particulate organic matter in the urban atmosphere: a new method for real-time measurement, molecular-level characterization and source apportionment

NASA Astrophysics Data System (ADS)

Müller, Markus; Eichler, Philipp; D'Anna, Barbara; Tan, Wen; Wisthaler, Armin

2017-04-01

We used a novel chemical analytical method for measuring submicron particulate organic matter in the atmosphere of three European cities (Innsbruck, Lyon, Valencia). Proton-Transfer-Reaction Time-of-Flight Mass Spectrometry (PTR-ToF-MS) was used in combination with the "chemical analysis of aerosol online" (CHARON) inlet for detecting particulate organic compounds on-line (i.e. without filter pre-collection), in real-time (1-min time resolution), at ng m-3 concentrations, with molecular-level resolution (i.e. obtaining molecular weight and elemental composition information). The CHARON-PTR-ToF-MS system monitored molecular tracers associated with different particle sources including levoglucosan from biomass combustion, PAHs from vehicular traffic, nicotine from cigarette smoking, and monoterpene oxidation products secondarily formed from biogenic emissions. The tracer information was used for interpreting positive matrix factorization (PMF) data which allowed us to apportion the sources of submicron particulate organic matter in the different urban environments. This work was funded through the PIMMS ITN, which was supported by the European Commission's 7th Framework Programme under grant agreement number 287382.

Technical Report: Serial collections of placentomes during parturition in cattle and subsequent reproductive performance

USDA-ARS?s Scientific Manuscript database

Placental separation is a complex physiological event in reproductive physiology and the underlying molecular mechanisms remain unclear. When comparing different experiments the timing of tissue collections is a significant consideration due to the variability in time between fetal expulsion and exp...

Controlling single-molecule junction conductance by molecular interactions

NASA Astrophysics Data System (ADS)

Kitaguchi, Y.; Habuka, S.; Okuyama, H.; Hatta, S.; Aruga, T.; Frederiksen, T.; Paulsson, M.; Ueba, H.

2015-07-01

For the rational design of single-molecular electronic devices, it is essential to understand environmental effects on the electronic properties of a working molecule. Here we investigate the impact of molecular interactions on the single-molecule conductance by accurately positioning individual molecules on the electrode. To achieve reproducible and precise conductivity measurements, we utilize relatively weak π-bonding between a phenoxy molecule and a STM-tip to form and cleave one contact to the molecule. The anchoring to the other electrode is kept stable using a chalcogen atom with strong bonding to a Cu(110) substrate. These non-destructive measurements permit us to investigate the variation in single-molecule conductance under different but controlled environmental conditions. Combined with density functional theory calculations, we clarify the role of the electrostatic field in the environmental effect that influences the molecular level alignment.

High-harmonic spectroscopy of aligned molecules

NASA Astrophysics Data System (ADS)

Yun, Hyeok; Yun, Sang Jae; Lee, Gae Hwang; Nam, Chang Hee

2017-01-01

High harmonics emitted from aligned molecules driven by intense femtosecond laser pulses provide the opportunity to explore the structural information of molecules. The field-free molecular alignment technique is an expedient tool for investigating the structural characteristics of linear molecules. The underlying physics of field-free alignment, showing the characteristic revival structure specific to molecular species, is clearly explained from the quantum-phase analysis of molecular rotational states. The anisotropic nature of molecules is shown from the harmonic polarization measurement performed with spatial interferometry. The multi-orbital characteristics of molecules are investigated using high-harmonic spectroscopy, applied to molecules of N2 and CO2. In the latter case the two-dimensional high-harmonic spectroscopy, implemented using a two-color laser field, is applied to distinguish harmonics from different orbitals. Molecular high-harmonic spectroscopy will open a new route to investigate ultrafast dynamics of molecules.

A Screening of UNF Targets Identifies Rnb, a Novel Regulator of Drosophila Circadian Rhythms.

PubMed

Kozlov, Anatoly; Jaumouillé, Edouard; Machado Almeida, Pedro; Koch, Rafael; Rodriguez, Joseph; Abruzzi, Katharine C; Nagoshi, Emi

2017-07-12

Behavioral circadian rhythms are controlled by multioscillator networks comprising functionally different subgroups of clock neurons. Studies have demonstrated that molecular clocks in the fruit fly Drosophila melanogaster are regulated differently in clock neuron subclasses to support their specific functions (Lee et al., 2016; Top et al., 2016). The nuclear receptor unfulfilled ( unf ) represents a regulatory node that provides the small ventral lateral neurons (s-LNvs) unique characteristics as the master pacemaker (Beuchle et al., 2012). We previously showed that UNF interacts with the s-LNv molecular clocks by regulating transcription of the core clock gene period ( per ) (Jaumouillé et al., 2015). To gain more insight into the mechanisms by which UNF contributes to the functioning of the circadian master pacemaker, we identified UNF target genes using chromatin immunoprecipitation. Our data demonstrate that a previously uncharacterized gene CG7837 , which we termed R and B ( Rnb ), acts downstream of UNF to regulate the function of the s-LNvs as the master circadian pacemaker. Mutations and LNv-targeted adult-restricted knockdown of Rnb impair locomotor rhythms. RNB localizes to the nucleus, and its loss-of-function blunts the molecular rhythms and output rhythms of the s-LNvs, particularly the circadian rhythms in PDF accumulation and axonal arbor remodeling. These results establish a second pathway by which UNF interacts with the molecular clocks in the s-LNvs and highlight the mechanistic differences in the molecular clockwork within the pacemaker circuit. SIGNIFICANCE STATEMENT Circadian behavior is generated by a pacemaker circuit comprising diverse classes of pacemaker neurons, each of which contains a molecular clock. In addition to the anatomical and functional diversity, recent studies have shown the mechanistic differences in the molecular clockwork among the pacemaker neurons in Drosophila Here, we identified the molecular characteristics distinguishing the s-LNvs, the master pacemaker of the locomotor rhythms, from other clock neuron subtypes. We demonstrated that a newly identified gene Rnb is an s-LNv-specific regulator of the molecular clock and essential for the generation of circadian locomotor behavior. Our results provide additional evidence to the emerging view that the differential regulation of the molecular clocks underlies the functional differences among the pacemaker neuron subgroups. Copyright © 2017 the authors 0270-6474/17/376673-13$15.00/0.

Biopython: freely available Python tools for computational molecular biology and bioinformatics.

PubMed

Cock, Peter J A; Antao, Tiago; Chang, Jeffrey T; Chapman, Brad A; Cox, Cymon J; Dalke, Andrew; Friedberg, Iddo; Hamelryck, Thomas; Kauff, Frank; Wilczynski, Bartek; de Hoon, Michiel J L

2009-06-01

The Biopython project is a mature open source international collaboration of volunteer developers, providing Python libraries for a wide range of bioinformatics problems. Biopython includes modules for reading and writing different sequence file formats and multiple sequence alignments, dealing with 3D macro molecular structures, interacting with common tools such as BLAST, ClustalW and EMBOSS, accessing key online databases, as well as providing numerical methods for statistical learning. Biopython is freely available, with documentation and source code at (www.biopython.org) under the Biopython license.

Investigations of the Formation of Molecular Hydrogen on Dust Grain Analogues

NASA Technical Reports Server (NTRS)

Vidali, Gianfranco; Roser, Joseph E.; Manico, Giulio; Pirronello, Valerio

2002-01-01

In the last four years we have been working to investigate the formation of molecular hydrogen on surfaces of materials of astrophysical interest, such as silicates, carbonaceous particles and ices, and in conditions approximating the ones present in a variety of astrophysical environments. Our experimental studies - the first of their kind and complemented with computer simulations and theoretical analyses - have given not only hydrogen recombination rates under different ISM conditions, but they have also offered new insights into this fundamental astrophysical problem. Here we summarize our experimental methods and most significant results.

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

PubMed

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

2016-08-30

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

Effect of Interfacial Molecular Orientation on Power Conversion Efficiency of Perovskite Solar Cells.

PubMed

Xiao, Minyu; Joglekar, Suneel; Zhang, Xiaoxian; Jasensky, Joshua; Ma, Jialiu; Cui, Qingyu; Guo, L Jay; Chen, Zhan

2017-03-08

A wide variety of charge carrier dynamics, such as transport, separation, and extraction, occur at the interfaces of planar heterojunction solar cells. Such factors can affect the overall device performance. Therefore, understanding the buried interfacial molecular structure in various devices and the correlation between interfacial structure and function has become increasingly important. Current characterization techniques for thin films such as X-ray diffraction, cross section scanning electronmicroscopy, and UV-visible absorption spectroscopy are unable to provide the needed molecular structural information at buried interfaces. In this study, by controlling the structure of the hole transport layer (HTL) in a perovskite solar cell and applying a surface/interface-sensitive nonlinear vibrational spectroscopic technique (sum frequency generation vibrational spectroscopy (SFG)), we successfully probed the molecular structure at the buried interface and correlated its structural characteristics to solar cell performance. Here, an edge-on (normal to the interface) polythiophene (PT) interfacial molecular orientation at the buried perovskite (photoactive layer)/PT (HTL) interface showed more than two times the power conversion efficiency (PCE) of a lying down (tangential) PT interfacial orientation. The difference in interfacial molecular structure was achieved by altering the alkyl side chain length of the PT derivatives, where PT with a shorter alkyl side chain showed an edge-on interfacial orientation with a higher PCE than that of PT with a longer alkyl side chain. With similar band gap alignment and bulk structure within the PT layer, it is believed that the interfacial molecular structural variation (i.e., the orientation difference) of the various PT derivatives is the underlying cause of the difference in perovskite solar cell PCE.

Molecular subgroups of medulloblastoma identification using noninvasive magnetic resonance spectroscopy.

PubMed

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.

A Review of the Molecular Mechanisms of Chemically-Induced Neoplasia in Rat and Mouse Models in National Toxicology Program Bioassays and Their Relevance to Human Cancer

PubMed Central

Hoenerhoff, Mark J.; Hong, Hue Hua; Ton, Tai-Vu; Lahousse, Stephanie A.; Sills, Robert C.

2012-01-01

Tumor response in the B6C3F1 mouse, F344 rat, and other animal models following exposure to various compounds provides evidence that people exposed to these or similar compounds may be at risk for developing cancer. Although tumors in rodents and humans are often morphologically similar, underlying mechanisms of tumorigenesis are often unknown and may be different between the species. Therefore, the relevance of an animal tumor response to human health would be better determined if the molecular pathogenesis were understood. The underlying molecular mechanisms leading to carcinogenesis are complex and involve multiple genetic and epigenetic events and other factors. To address the molecular pathogenesis of environmental carcinogens, we examine rodent tumors (e.g., lung, colon, mammary gland, skin, brain, mesothelioma) for alterations in cancer genes and epigenetic events that are associated with human cancer. Our NTP studies have identified several genetic alterations in chemically induced rodent neoplasms that are important in human cancer. Identification of such alterations in rodent models of chemical carcinogenesis caused by exposure to environmental contaminants, occupational chemicals, and other compounds lends further support that they are of potential human health risk. These studies also emphasize the importance of molecular evaluation of chemically induced rodent tumors for providing greater public health significance for NTP evaluated compounds. PMID:19846892

Molecular characterization and comparison of shale oils generated by different pyrolysis methods

USGS Publications Warehouse

Birdwell, Justin E.; Jin, Jang Mi; Kim, Sunghwan

2012-01-01

Shale oils generated using different laboratory pyrolysis methods have been studied using standard oil characterization methods as well as Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) with electrospray ionization (ESI) and atmospheric photoionization (APPI) to assess differences in molecular composition. The pyrolysis oils were generated from samples of the Mahogany zone oil shale of the Eocene Green River Formation collected from outcrops in the Piceance Basin, Colorado, using three pyrolysis systems under conditions relevant to surface and in situ retorting approaches. Significant variations were observed in the shale oils, particularly the degree of conjugation of the constituent molecules and the distribution of nitrogen-containing compound classes. Comparison of FT-ICR MS results to other oil characteristics, such as specific gravity; saturate, aromatic, resin, asphaltene (SARA) distribution; and carbon number distribution determined by gas chromatography, indicated correspondence between higher average double bond equivalence (DBE) values and increasing asphaltene content. The results show that, based on the shale oil DBE distributions, highly conjugated species are enriched in samples produced under low pressure, high temperature conditions, and under high pressure, moderate temperature conditions in the presence of water. We also report, for the first time in any petroleum-like substance, the presence of N4 class compounds based on FT-ICR MS data. Using double bond equivalence and carbon number distributions, structures for the N4 class and other nitrogen-containing compounds are proposed.

Study on different molecular weights of chitosan as an immobilization matrix for a glucose biosensor.

PubMed

Ang, Lee Fung; Por, Lip Yee; Yam, Mun Fei

2013-01-01

Two chitosan samples (medium molecular weight (MMCHI) and low molecular weight (LMCHI)) were investigated as an enzyme immobilization matrix for the fabrication of a glucose biosensor. Chitosan membranes prepared from acetic acid were flexible, transparent, smooth and quick-drying. The FTIR spectra showed the existence of intermolecular interactions between chitosan and glucose oxidase (GOD). Higher catalytic activities were observed on for GOD-MMCHI than GOD-LMCHI and for those crosslinked with glutaraldehyde than using the adsorption technique. Enzyme loading greater than 0.6 mg decreased the activity. Under optimum conditions (pH 6.0, 35°C and applied potential of 0.6 V) response times of 85 s and 65 s were observed for medium molecular weight chitosan glucose biosensor (GOD-MMCHI/PT) and low molecular weight chitosan glucose biosensor (GOD-LMCHI/PT), respectively. The apparent Michaelis-Menten constant ([Formula: see text]) was found to be 12.737 mM for GOD-MMCHI/PT and 17.692 mM for GOD-LMCHI/PT. This indicated that GOD-MMCHI/PT had greater affinity for the enzyme. Moreover, GOD-MMCHI/PT showed higher sensitivity (52.3666 nA/mM glucose) when compared with GOD-LMCHI/PT (9.8579 nA/mM glucose) at S/N>3. Better repeatability and reproducibility were achieved with GOD-MMCHI/PT than GOD-LMCHI/PT regarding glucose measurement. GOD-MMCHI/PT was found to give the highest enzymatic activity among the electrodes under investigation. The extent of interference encountered by GOD-MMCHI/PT and GOD-LMCHI/PT was not significantly different. Although the Nafion coated biosensor significantly reduced the signal due to the interferents under study, it also significantly reduced the response to glucose. The performance of the biosensors in the determination of glucose in rat serum was evaluated. Comparatively better accuracy and recovery results were obtained for GOD-MMCHI/PT. Hence, GOD-MMCHI/PT showed a better performance when compared with GOD-LMCHI/PT. In conclusion, chitosan membranes shave the potential to be a suitable matrix for the development of glucose biosensors.

Study on Different Molecular Weights of Chitosan as an Immobilization Matrix for a Glucose Biosensor

PubMed Central

Ang, Lee Fung; Por, Lip Yee; Yam, Mun Fei

2013-01-01

Two chitosan samples (medium molecular weight (MMCHI) and low molecular weight (LMCHI)) were investigated as an enzyme immobilization matrix for the fabrication of a glucose biosensor. Chitosan membranes prepared from acetic acid were flexible, transparent, smooth and quick-drying. The FTIR spectra showed the existence of intermolecular interactions between chitosan and glucose oxidase (GOD). Higher catalytic activities were observed on for GOD-MMCHI than GOD-LMCHI and for those crosslinked with glutaraldehyde than using the adsorption technique. Enzyme loading greater than 0.6 mg decreased the activity. Under optimum conditions (pH 6.0, 35°C and applied potential of 0.6 V) response times of 85 s and 65 s were observed for medium molecular weight chitosan glucose biosensor (GOD-MMCHI/PT) and low molecular weight chitosan glucose biosensor (GOD-LMCHI/PT), respectively. The apparent Michaelis-Menten constant () was found to be 12.737 mM for GOD-MMCHI/PT and 17.692 mM for GOD-LMCHI/PT. This indicated that GOD-MMCHI/PT had greater affinity for the enzyme. Moreover, GOD-MMCHI/PT showed higher sensitivity (52.3666 nA/mM glucose) when compared with GOD-LMCHI/PT (9.8579 nA/mM glucose) at S/N>3. Better repeatability and reproducibility were achieved with GOD-MMCHI/PT than GOD-LMCHI/PT regarding glucose measurement. GOD-MMCHI/PT was found to give the highest enzymatic activity among the electrodes under investigation. The extent of interference encountered by GOD-MMCHI/PT and GOD-LMCHI/PT was not significantly different. Although the Nafion coated biosensor significantly reduced the signal due to the interferents under study, it also significantly reduced the response to glucose. The performance of the biosensors in the determination of glucose in rat serum was evaluated. Comparatively better accuracy and recovery results were obtained for GOD-MMCHI/PT. Hence, GOD-MMCHI/PT showed a better performance when compared with GOD-LMCHI/PT. In conclusion, chitosan membranes shave the potential to be a suitable matrix for the development of glucose biosensors. PMID:23940599

Sex-specific movements in postfledging juvenile Ovenbirds (Seiurus aurocapilla)

Treesearch

Julianna M. A. Jenkins; Mikenzie Hart; Lori S. Eggert; John Faaborg

2017-01-01

Understanding sex-specific differences in behavior and survival is essential for informative population modeling and evolutionary biology in animal populations. Uneven sex ratios are common in many migrant passerine species; however, the underlying mechanisms remain unclear. We used molecular sex determination, nest monitoring, and radio telemetry of fledgling...

Evolution of the fruit endocarp: molecular mechanisms underlying adaptations in seed protection and dispersal strategies

USDA-ARS?s Scientific Manuscript database

Plant evolution is largely driven by adaptations in seed protection and dispersal strategies that allow diversification into new niches. This is evident by the tremendous variation in flowering and fruiting structures present both across and within different plant lineages. Within a single plant f...

Comparison of enterococci and cow-specific qPAR markers in streams impacted by farms under different management practices

EPA Science Inventory

Nonpoint Sources (NPS) of pollution (e.g., agriculture, wildlife, urban runoff) are major contributors of microbial contaminants to surface waters. However, little is known about the behavior and the effect of environmental determinants on molecular markers of fecal contamination...

Identification and characterization of large DNA deletions affecting oil quality traits in soybean seeds through transcriptome sequencing analysis

USDA-ARS?s Scientific Manuscript database

Understanding the molecular and genetic mechanisms underlying variation in seed composition and contents among different genotypes is important for soybean oil quality improvement. We designed a bioinformatics approach to compare seed transcriptomes of 9 soybean genotypes varying in oil composition ...

Association of plasma arginine with breast cancer molecular subtypes in women of Liaoning province.

PubMed

Hu, Lu; Gao, Yu; Cao, Yunfeng; Zhang, Yinxu; Xu, Minghao; Wang, Yuanyuan; Jing, Yu; Guo, Shengnan; Jing, Fangyu; Hu, Xiaodan; Zhu, Zhitu

2016-12-01

Arginine is one of the human nonessential amino acids critical for the growth of human cancers. The aim of this study is to investigate the variation of arginine between breast cancer (BC) patients and benign mammary gland disease (control) patients to determine its value in predicting the risk of BC. We also explore the associations between arginine levels and breast cancer subtypes. Preoperative blood samples were obtained from 267 patients (102 BC and 165 controls) in 2015. Plasma arginine values were determined for all preoperative blood samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to analyse differences in arginine levels between BC patients and control patients and the correlations between arginine and clinicopathologic parameters in BC. The arginine levels of BC patients were significantly lower than those of control patients (5.96 [3.76-12.47] vs. 12.54 [7.14-24.94], P = 0.000). The area under the curve (AUC) for arginine was 0.721 (95% CI, 0.660-0.782, P < 0.0001). The concentration of arginine was significantly different among different molecular BC subtypes (P = 0.030). Our results suggested that plasma arginine was associated with breast cancer molecular subtypes. © 2016 IUBMB Life, 68(12):980-984, 2016. © 2016 International Union of Biochemistry and Molecular Biology.

Molecular Identification of Ectomycorrhizal Mycelium in Soil Horizons

PubMed Central

Landeweert, Renske; Leeflang, Paula; Kuyper, Thom W.; Hoffland, Ellis; Rosling, Anna; Wernars, Karel; Smit, Eric

2003-01-01

Molecular identification techniques based on total DNA extraction provide a unique tool for identification of mycelium in soil. Using molecular identification techniques, the ectomycorrhizal (EM) fungal community under coniferous vegetation was analyzed. Soil samples were taken at different depths from four horizons of a podzol profile. A basidiomycete-specific primer pair (ITS1F-ITS4B) was used to amplify fungal internal transcribed spacer (ITS) sequences from total DNA extracts of the soil horizons. Amplified basidiomycete DNA was cloned and sequenced, and a selection of the obtained clones was analyzed phylogenetically. Based on sequence similarity, the fungal clone sequences were sorted into 25 different fungal groups, or operational taxonomic units (OTUs). Out of 25 basidiomycete OTUs, 7 OTUs showed high nucleotide homology (≥99%) with known EM fungal sequences and 16 were found exclusively in the mineral soil. The taxonomic positions of six OTUs remained unclear. OTU sequences were compared to sequences from morphotyped EM root tips collected from the same sites. Of the 25 OTUs, 10 OTUs had ≥98% sequence similarity with these EM root tip sequences. The present study demonstrates the use of molecular techniques to identify EM hyphae in various soil types. This approach differs from the conventional method of EM root tip identification and provides a novel approach to examine EM fungal communities in soil. PMID:12514012

Molecular Mechanisms of Right Ventricular Failure

PubMed Central

Reddy, Sushma; Bernstein, Daniel

2015-01-01

An abundance of data has provided insight into the mechanisms underlying the development of left ventricular (LV) hypertrophy and its progression to LV failure. In contrast, there is minimal data on the adaptation of the right ventricle (RV) to pressure and volume overload and the transition to RV failure. This is a critical clinical question, as the RV is uniquely at risk in many patients with repaired or palliated congenital heart disease and in those with pulmonary hypertension. Standard heart failure therapies have failed to improve function or survival in these patients, suggesting a divergence in the molecular mechanisms of RV vs. LV failure. Although, on the cellular level, the remodeling responses of the RV and LV to pressure overload are largely similar, there are several key differences: the stressed RV is more susceptible to oxidative stress, has a reduced angiogenic response, and is more likely to activate cell death pathways than the stressed LV. Together, these differences could explain the more rapid progression of the RV to failure vs. the LV. This review will highlight known molecular differences between the RV and LV responses to hemodynamic stress, the unique stressors on the RV associated with congenital heart disease, and the need to better understand these molecular mechanisms if we are to develop RV-specific heart failure therapeutics. PMID:26527692

Amyloid Oligomers and Protofibrils, but Not Filaments, Self-Replicate from Native Lysozyme

PubMed Central

2015-01-01

Self-assembly of amyloid fibrils is the molecular mechanism best known for its connection with debilitating human disorders such as Alzheimer’s disease but is also associated with various functional cellular responses. There is increasing evidence that amyloid formation proceeds along two distinct assembly pathways involving either globular oligomers and protofibrils or rigid monomeric filaments. Oligomers, in particular, have been implicated as the dominant molecular species responsible for pathogenesis. Yet the molecular mechanisms regulating their self-assembly have remained elusive. Here we show that oligomers/protofibrils and monomeric filaments, formed along distinct assembly pathways, display critical differences in their ability to template amyloid growth at physiological vs denaturing temperatures. At physiological temperatures, amyloid filaments remained stable but could not seed growth of native monomers. In contrast, oligomers and protofibrils not only remained intact but were capable of self-replication using native monomers as the substrate. Kinetic data further suggested that this prion-like growth mode of oligomers/protofibrils involved two distinct activities operating orthogonal from each other: autocatalytic self-replication of oligomers from native monomers and nucleated polymerization of oligomers into protofibrils. The environmental changes to stability and templating competence of these different amyloid species in different environments are likely to be important for understanding the molecular mechanisms underlying both pathogenic and functional amyloid self-assembly. PMID:24884889

Amyloid oligomers and protofibrils, but not filaments, self-replicate from native lysozyme.

PubMed

Mulaj, Mentor; Foley, Joseph; Muschol, Martin

2014-06-25

Self-assembly of amyloid fibrils is the molecular mechanism best known for its connection with debilitating human disorders such as Alzheimer's disease but is also associated with various functional cellular responses. There is increasing evidence that amyloid formation proceeds along two distinct assembly pathways involving either globular oligomers and protofibrils or rigid monomeric filaments. Oligomers, in particular, have been implicated as the dominant molecular species responsible for pathogenesis. Yet the molecular mechanisms regulating their self-assembly have remained elusive. Here we show that oligomers/protofibrils and monomeric filaments, formed along distinct assembly pathways, display critical differences in their ability to template amyloid growth at physiological vs denaturing temperatures. At physiological temperatures, amyloid filaments remained stable but could not seed growth of native monomers. In contrast, oligomers and protofibrils not only remained intact but were capable of self-replication using native monomers as the substrate. Kinetic data further suggested that this prion-like growth mode of oligomers/protofibrils involved two distinct activities operating orthogonal from each other: autocatalytic self-replication of oligomers from native monomers and nucleated polymerization of oligomers into protofibrils. The environmental changes to stability and templating competence of these different amyloid species in different environments are likely to be important for understanding the molecular mechanisms underlying both pathogenic and functional amyloid self-assembly.

A ligand-directed divergent catalytic approach to establish structural and functional scaffold diversity

NASA Astrophysics Data System (ADS)

Lee, Yen-Chun; Patil, Sumersing; Golz, Christopher; Strohmann, Carsten; Ziegler, Slava; Kumar, Kamal; Waldmann, Herbert

2017-02-01

The selective transformation of different starting materials by different metal catalysts under individually optimized reaction conditions to structurally different intermediates and products is a powerful approach to generate diverse molecular scaffolds. In a more unified albeit synthetically challenging strategy, common starting materials would be exposed to a common metal catalysis, leading to a common intermediate and giving rise to different scaffolds by tuning the reactivity of the metal catalyst through different ligands. Herein we present a ligand-directed synthesis approach for the gold(I)-catalysed cycloisomerization of oxindole-derived 1,6-enynes that affords distinct molecular scaffolds following different catalytic reaction pathways. Varying electronic properties and the steric demand of the gold(I) ligands steers the fate of a common intermediary gold carbene to selectively form spirooxindoles, quinolones or df-oxindoles. Investigation of a synthesized compound collection in cell-based assays delivers structurally novel, selective modulators of the Hedgehog and Wnt signalling pathways, autophagy and of cellular proliferation.

Molecular Genetic Analysis of Phototropism in Arabidopsis

PubMed Central

Sakai, Tatsuya; Haga, Ken

2012-01-01

Plant life is strongly dependent on the environment, and plants regulate their growth and development in response to many different environmental stimuli. One of the regulatory mechanisms involved in these responses is phototropism, which allows plants to change their growth direction in response to the location of the light source. Since the study of phototropism by Darwin, many physiological studies of this phenomenon have been published. Recently, molecular genetic analyses of Arabidopsis have begun to shed light on the molecular mechanisms underlying this response system, including phototropin blue light photoreceptors, phototropin signaling components, auxin transporters, auxin action mechanisms and others. This review highlights some of the recent progress that has been made in further elucidating the phototropic response, with particular emphasis on mutant phenotypes. PMID:22864452

Molecular genetic analysis of phototropism in Arabidopsis.

PubMed

Sakai, Tatsuya; Haga, Ken

2012-09-01

Plant life is strongly dependent on the environment, and plants regulate their growth and development in response to many different environmental stimuli. One of the regulatory mechanisms involved in these responses is phototropism, which allows plants to change their growth direction in response to the location of the light source. Since the study of phototropism by Darwin, many physiological studies of this phenomenon have been published. Recently, molecular genetic analyses of Arabidopsis have begun to shed light on the molecular mechanisms underlying this response system, including phototropin blue light photoreceptors, phototropin signaling components, auxin transporters, auxin action mechanisms and others. This review highlights some of the recent progress that has been made in further elucidating the phototropic response, with particular emphasis on mutant phenotypes.

Some Fundamental Molecular Mechanisms of Contractility in Fibrous Macromolecules

PubMed Central

Mandelkern, L.

1967-01-01

The fundamental molecular mechanisms of contractility and tension development in fibrous macromolecules are developed from the point of view of the principles of polymer physical chemistry. The problem is treated in a general manner to encompass the behavior of all macromolecular systems irrespective of their detailed chemical structure and particular function, if any. Primary attention is given to the contractile process which accompanies the crystal-liquid transition in axially oriented macromolecular systems. The theoretical nature of the process is discussed, and many experimental examples are given from the literature which demonstrate the expected behavior. Experimental attention is focused on the contraction of fibrous proteins, and the same underlying molecular mechanism is shown to be operative for a variety of different systems. PMID:6050598

Mitochondrial C4375T mutation might be a molecular risk factor in a maternal Chinese hypertensive family under haplotype C.

PubMed

Chen, Hong; Sun, Min; Fan, Zhen; Tong, Maoqing; Chen, Guodong; Li, Danhui; Ye, Jihui; Yang, Yumin; Zhu, Yongding; Zhu, Jianhua

2017-12-04

Here, we reported a Han Chinese essential hypertensive pedigree based on clinical hereditary and molecular data. To know the molecular basis on this family, mitochondrial genome of one proband from the family was identified through direct sequencing analysis. The age of onset year and affected degree of patients are different in this family. And matrilineal family members carrying C4375T mutation and belong to Eastern Asian halopgroup C. Phylogenetic analysis shows 4375C is highly conservative in 17 species. It is suggested that these mutations might participate in the development of hypertension in this family. And halopgroup C might play a modifying role on the phenotype in this Chinese hypertensive family.

MDWiZ: a platform for the automated translation of molecular dynamics simulations.

PubMed

Rusu, Victor H; Horta, Vitor A C; Horta, Bruno A C; Lins, Roberto D; Baron, Riccardo

2014-03-01

A variety of popular molecular dynamics (MD) simulation packages were independently developed in the last decades to reach diverse scientific goals. However, such non-coordinated development of software, force fields, and analysis tools for molecular simulations gave rise to an array of software formats and arbitrary conventions for routine preparation and analysis of simulation input and output data. Different formats and/or parameter definitions are used at each stage of the modeling process despite largely contain redundant information between alternative software tools. Such Babel of languages that cannot be easily and univocally translated one into another poses one of the major technical obstacles to the preparation, translation, and comparison of molecular simulation data that users face on a daily basis. Here, we present the MDWiZ platform, a freely accessed online portal designed to aid the fast and reliable preparation and conversion of file formats that allows researchers to reproduce or generate data from MD simulations using different setups, including force fields and models with different underlying potential forms. The general structure of MDWiZ is presented, the features of version 1.0 are detailed, and an extensive validation based on GROMACS to LAMMPS conversion is presented. We believe that MDWiZ will be largely useful to the molecular dynamics community. Such fast format and force field exchange for a given system allows tailoring the chosen system to a given computer platform and/or taking advantage of a specific capabilities offered by different software engines. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Epitaxially Grown Films of Standing and Lying Pentacene Molecules on Cu(110) Surfaces

PubMed Central

2011-01-01

Here, it is shown that pentacene thin films (30 nm) with distinctively different crystallographic structures and molecular orientations can be grown under essentially identical growth conditions in UHV on clean Cu(110) surfaces. By X-ray diffraction, we show that the epitaxially oriented pentacene films crystallize either in the “thin film” phase with standing molecules or in the “single crystal” structure with molecules lying with their long axes parallel to the substrate. The morphology of the samples observed by atomic force microscopy shows an epitaxial alignment of pentacene crystallites, which corroborates the molecular orientation observed by X-ray diffraction pole figures. Low energy electron diffraction measurements reveal that these dissimilar growth behaviors are induced by subtle differences in the monolayer structures formed by slightly different preparation procedures. PMID:21479111

Drastic stability change of X-X mismatch in d(CXG) trinucleotide repeat disorders under molecular crowding condition.

PubMed

Teng, Ye; Pramanik, Smritimoy; Tateishi-Karimata, Hisae; Ohyama, Tatsuya; Sugimoto, Naoki

2018-02-05

The trinucleotide repeat d(CXG) (X = A, C, G or T) is the most common sequence causing repeat expansion disorders. The formation of non-canonical structures, such as hairpin structures with X-X mismatches, has been proposed to affect gene expression and regulation, which are important in pathological studies of these devastating neurological diseases. However, little information is available regarding the thermodynamics of the repeat sequence under crowded cellular conditions where many non-canonical structures such as G-quadruplexes are highly stabilized, while duplexes are destabilised. In this study, we investigated the different stabilities of X-X mismatches in the context of internal d(CXG) self-complementary sequences in an environment with a high concentration of cosolutes to mimic the crowding conditions in cells. The stabilities of full-matched duplexes and duplexes with A-A, G-G, and T-T mismatched base pairs under molecular crowding conditions were notably decreased compared to under dilute conditions. However, the stability of the DNA duplex with a C-C mismatch base pair was only slightly destabilised. Investigating different stabilities of X-X mismatches in d(CXG) sequences is important for improving our understanding of the formation and transition of multiple non-canonical structures in trinucleotide repeat diseases, and may provide insights for pathological studies and drug development. Copyright © 2018 Elsevier Inc. All rights reserved.

A Neurogenetic Approach to Impulsivity

PubMed Central

Congdon, Eliza; Canli, Turhan

2008-01-01

Impulsivity is a complex and multidimensional trait that is of interest to both personality psychologists and to clinicians. For investigators seeking the biological basis of personality traits, the use of neuroimaging techniques such as positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) revolutionized personality psychology in less than a decade. Now, another revolution is under way, and it originates from molecular biology. Specifically, new findings in molecular genetics, the detailed mapping and the study of the function of genes, have shown that individual differences in personality traits can be related to individual differences within specific genes. In this article, we will review the current state of the field with respect to the neural and genetic basis of trait impulsivity. PMID:19012655

A model of how different biology experts explain molecular and cellular mechanisms.

PubMed

Trujillo, Caleb M; Anderson, Trevor R; Pelaez, Nancy J

2015-01-01

Constructing explanations is an essential skill for all science learners. The goal of this project was to model the key components of expert explanation of molecular and cellular mechanisms. As such, we asked: What is an appropriate model of the components of explanation used by biology experts to explain molecular and cellular mechanisms? Do explanations made by experts from different biology subdisciplines at a university support the validity of this model? Guided by the modeling framework of R. S. Justi and J. K. Gilbert, the validity of an initial model was tested by asking seven biologists to explain a molecular mechanism of their choice. Data were collected from interviews, artifacts, and drawings, and then subjected to thematic analysis. We found that biologists explained the specific activities and organization of entities of the mechanism. In addition, they contextualized explanations according to their biological and social significance; integrated explanations with methods, instruments, and measurements; and used analogies and narrated stories. The derived methods, analogies, context, and how themes informed the development of our final MACH model of mechanistic explanations. Future research will test the potential of the MACH model as a guiding framework for instruction to enhance the quality of student explanations. © 2015 C. M. Trujillo et al. CBE—Life Sciences Education © 2015 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Purification and characterization of vanillin dehydrogenases from alkaliphile Micrococcus sp. TA1 and neutrophile Burkholderia cepacia TM1.

PubMed

Mitsui, Ryoji; Hirota, Mizuho; Tsuno, Takuo; Tanaka, Mitsuo

2010-02-01

Vanillin dehydrogenases (VDHs) were purified and characterized from two bacterial strains that have different pH dependencies for growth. The alkaliphile Micrococcus sp. TA1, isolated from an alkaline spa, can grow on several aromatic compounds such as ferulic acid, vanillin, vanillic acid, and protocatechuic acid under alkaline conditions. The neutrophile Burkholderia cepacia TM1, which was isolated previously, also grew on the above-mentioned compounds because they functioned as the sole carbon source under neutral conditions. Purified VDHs showed activities toward some aromatic aldehydes. These enzymes have the same subunit molecular mass of about 57 kDa as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, but differed in some of their observed properties. Native molecular masses also differed between the purified enzymes. These were 250 kDa for the enzyme from alkaliphilic strain TA1 and 110 kDa for that from neutrophilic strain TM1, as determined by gel filtration. The enzyme from strain TA1 required NADP(+) as a coenzyme for its activity, but that from strain TM1 required NAD(+). These results are important because this is the first report of an alkaliphilic bacterium consuming lignin monomers.

Genetic and epigenetic factors underlying sex differences in the regulation of gene expression in the brain

PubMed Central

Ratnu, Vikram S.; Emami, Michael R.; Bredy, Timothy W.

2016-01-01

There are inherent biological differences between males and females that contribute to sex differences in brain function and to many sex-specific illnesses and disorders. Traditionally, it has been thought that such differences are largely due to hormonal regulation; however, there are also genetic and epigenetic effects caused by the inheritance and unequal dosage of genes located on the X- and Y-chromosomes. Here we discuss the evidence in favor of a genetic and epigenetic basis for sexually dimorphic behavior, as a consequence of underlying differences in the regulation of genes that drive brain function. A better understanding of sex-specific molecular processes in the brain will provide further insight for the development of novel therapeutic approaches for the treatment of neuropsychiatric disorders characterized by gender/sex differences. PMID:27870402

Multiscale Modeling of Primary Cilium Deformations Under Local Forces and Shear Flows

NASA Astrophysics Data System (ADS)

Peng, Zhangli; Feng, Zhe; Resnick, Andrew; Young, Yuan-Nan

2017-11-01

We study the detailed deformations of a primary cilium under local forces and shear flows by developing a multiscale model based on the state-of-the-art understanding of its molecular structure. Most eukaryotic cells are ciliated with primary cilia. Primary cilia play important roles in chemosensation, thermosensation, and mechanosensation, but the detailed mechanism for mechanosensation is not well understood. We apply the dissipative particle dynamics (DPD) to model an entire well with a primary cilium and consider its different components, including the basal body, microtubule doublets, actin cortex, and lipid bilayer. We calibrate the mechanical properties of individual components and their interactions from experimental measurements and molecular dynamics simulations. We validate the simulations by comparing the deformation profile of the cilium and the rotation of the basal body with optical trapping experiments. After validations, we investigate the deformation of the primary cilium under shear flows. Furthermore, we calculate the membrane tensions and cytoskeleton stresses, and use them to predict the activation of mechanosensitive channels.

Role of ergothioneine on S-nitrosoglutathione catabolism.

PubMed Central

Misiti, F; Castagnola, M; Zuppi, C; Giardina, B; Messana, I

2001-01-01

Ergothioneine (ESH) is a low-molecular-mass thiol present in millimolar concentrations in a limited number of tissues, including erythrocytes, kidney, seminal fluid and liver; however, its biological function is still unclear. In the present study we investigated the role of ESH in the catabolism of S-nitrosoglutathione (GSNO). The results show that: (1) GSNO decomposition is strongly influenced by ESH (k"=0.178+/-0.032 M(-1) x s(-1)); (2) ammonia is the main nitrogen-containing compound generated by the reaction; and (3) nitrite is practically absent under both aerobic and anaerobic conditions. These findings are markedly different from those reported for the GSH-induced decomposition of GSNO, in which the nitrogen-containing end products are nitrite, ammonia and nitrous oxide (N(2)O) under aerobic conditions but nitrite, ammonia, nitric oxide (NO) and small quantities of hydroxylamine under anaerobic conditions. Considering the high concentration of ESH in specific cells, the reaction with GSNO should be considered as an important molecular event occurring in the cell. PMID:11389687

Multi-Scale Molecular Deconstruction of the Serotonin Neuron System.

PubMed

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.

Multi-Scale Molecular Deconstruction of the Serotonin Neuron System

PubMed Central

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.

2016-01-01

Summary 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, novel 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 new subtypes, markers, organizing principles, and subtype-specific functions with potential disease relevance. PMID:26549332

Free energy surface of an intrinsically disordered protein: comparison between temperature replica exchange molecular dynamics and bias-exchange metadynamics.

PubMed

Zerze, Gül H; Miller, Cayla M; Granata, Daniele; Mittal, Jeetain

2015-06-09

Intrinsically disordered proteins (IDPs), which are expected to be largely unstructured under physiological conditions, make up a large fraction of eukaryotic proteins. Molecular dynamics simulations have been utilized to probe structural characteristics of these proteins, which are not always easily accessible to experiments. However, exploration of the conformational space by brute force molecular dynamics simulations is often limited by short time scales. Present literature provides a number of enhanced sampling methods to explore protein conformational space in molecular simulations more efficiently. In this work, we present a comparison of two enhanced sampling methods: temperature replica exchange molecular dynamics and bias exchange metadynamics. By investigating both the free energy landscape as a function of pertinent order parameters and the per-residue secondary structures of an IDP, namely, human islet amyloid polypeptide, we found that the two methods yield similar results as expected. We also highlight the practical difference between the two methods by describing the path that we followed to obtain both sets of data.

Molecular evolution of type 2 porcine reproductive and respiratory syndrome viruses circulating in Vietnam from 2007 to 2015.

PubMed

Do, Hai Quynh; Trinh, Dinh Thau; Nguyen, Thi Lan; Vu, Thi Thu Hang; Than, Duc Duong; Van Lo, Thi; Yeom, Minjoo; Song, Daesub; Choe, SeEun; An, Dong-Jun; Le, Van Phan

2016-11-17

Porcine respiratory and reproductive syndrome (PRRS) virus is one of the most economically significant pathogens in the Vietnamese swine industry. ORF5, which participates in many functional processes, including virion assembly, entry of the virus into the host cell, and viral adaptation to the host immune response, has been widely used in molecular evolution and phylogeny studies. Knowing of molecular evolution of PRRSV fields strains might contribute to PRRS control in Vietnam. The results showed that phylogenetic analysis indicated that all strains belonged to sub-lineages 8.7 and 5.1. The nucleotide and amino acid identities between strains were 84.5-100% and 82-100%, respectively. Furthermore, the results revealed differences in nucleotide and amino acid identities between the 2 sub-lineage groups. N-glycosylation prediction identified 7 potential N-glycosylation sites and 11 glycotypes. Analyses of the GP5 sequences, revealed 7 sites under positive selective pressure and 25 under negative selective pressure. Phylogenetic analysis based on ORF5 sequence indicated the diversity of PRRSV in Vietnam. Furthermore, the variance of N-glycosylation sites and position under selective pressure were demonstrated. This study expands existing knowledge on the genetic diversity and evolution of PRRSV in Vietnam and assists the effective strategies for PRRS vaccine development in Vietnam.

Pectinase hydrolysis of Dendrobium huoshanense polysaccharide and its effect on protein nonenzymatic glycation.

PubMed

Zha, Xue-Qiang; Li, Xiao-Long; Zhang, Hai-Lin; Cui, Shao-Hua; Liu, Jian; Wang, Jun-Hui; Pan, Li-Hua; Luo, Jian-Ping

2013-10-01

The aim of this study was to investigate the inhibitory effects of molecular weight alteration of Dendrobium huoshanense polysaccharide on protein nonenzymatic glycation. For this purpose, one homogeneous active polysaccharide DHPD1 with molecular weight 3.2 kDa was extracted from D. huoshanense. GC analysis showed that DHPD1 was mainly composed of glucose, arabinose, galactose in a molar ratio of 0.023:1.023:0.021 with a trace of mannose and xylose. In order to get DHPD1-derived fragments with different molecular weight, response surface methodology was employed to optimize the enzymatic degradation conditions. The maximum reducing sugar production (0.399 mg/mL) was obtained under an optimal condition including pectinase dosage 126 U/mL, reaction pH 4.46 and reaction temperature 48 °C. By applying this condition, three DHPD1-derived fragments with different molecular weights were obtained through changing the hydrolysis time. Infrared spectroscopy analysis indicated that the backbone structure of DHPD1 was not destroyed by pectinase hydrolysis. Monosaccharide composition analysis showed that pectinase preferred to liberate glucose from DHPD1. The inhibitory action of DHPD1 on protein nonenzymatic glycation reduced with the decrease of molecular weight. Copyright © 2013 Elsevier B.V. All rights reserved.

Germline Transgenic Methods for Tracking Cells and Testing Gene Function during Regeneration in the Axolotl

PubMed Central

Khattak, Shahryar; Schuez, Maritta; Richter, Tobias; Knapp, Dunja; Haigo, Saori L.; Sandoval-Guzmán, Tatiana; Hradlikova, Kristyna; Duemmler, Annett; Kerney, Ryan; Tanaka, Elly M.

2013-01-01

The salamander is the only tetrapod that regenerates complex body structures throughout life. Deciphering the underlying molecular processes of regeneration is fundamental for regenerative medicine and developmental biology, but the model organism had limited tools for molecular analysis. We describe a comprehensive set of germline transgenic strains in the laboratory-bred salamander Ambystoma mexicanum (axolotl) that open up the cellular and molecular genetic dissection of regeneration. We demonstrate tissue-dependent control of gene expression in nerve, Schwann cells, oligodendrocytes, muscle, epidermis, and cartilage. Furthermore, we demonstrate the use of tamoxifen-induced Cre/loxP-mediated recombination to indelibly mark different cell types. Finally, we inducibly overexpress the cell-cycle inhibitor p16INK4a, which negatively regulates spinal cord regeneration. These tissue-specific germline axolotl lines and tightly inducible Cre drivers and LoxP reporter lines render this classical regeneration model molecularly accessible. PMID:24052945

Nanoscale swimmers: hydrodynamic interactions and propulsion of molecular machines

NASA Astrophysics Data System (ADS)

Sakaue, T.; Kapral, R.; Mikhailov, A. S.

2010-06-01

Molecular machines execute nearly regular cyclic conformational changes as a result of ligand binding and product release. This cyclic conformational dynamics is generally non-reciprocal so that under time reversal a different sequence of machine conformations is visited. Since such changes occur in a solvent, coupling to solvent hydrodynamic modes will generally result in self-propulsion of the molecular machine. These effects are investigated for a class of coarse grained models of protein machines consisting of a set of beads interacting through pair-wise additive potentials. Hydrodynamic effects are incorporated through a configuration-dependent mobility tensor, and expressions for the propulsion linear and angular velocities, as well as the stall force, are obtained. In the limit where conformational changes are small so that linear response theory is applicable, it is shown that propulsion is exponentially small; thus, propulsion is nonlinear phenomenon. The results are illustrated by computations on a simple model molecular machine.

[Molecular biology of renal cancer: bases for genetic directed therapy in advanced disease].

PubMed

Maroto Rey, José Pablo; Cillán Narvaez, Elena

2013-06-01

There has been expansion of therapeutic options in the management of metastatic renal cell carcinoma due to a better knowledge of the molecular biology of kidney cancers. There are different tumors grouped under the term renal cell carcinoma, being clear cell cancer the most frequent and accounting for 80% of kidney tumors. Mutations in the Von Hippel-Lindau gene can be identified in up to 80% of sporadic clear cell cancer, linking a genetically inheritable disease where vascular tumors are frequent, with renal cell cancer. Other histologic types present specific alterations in molecular pathways, like c-MET in papillary type I tumors, and Fumarase Hydratase in papillary type II tumors. Identification of the molecular alteration for a specific tumor may offer an opportunity for treatment selection based on biomarkers, and, in the future, for developing an engineering designed genetic treatment.

Controlled Sol-Gel Transitions of a Thermoresponsive Polymer in a Photoswitchable Azobenzene Ionic Liquid as a Molecular Trigger.

PubMed

Wang, Caihong; Hashimoto, Kei; Tamate, Ryota; Kokubo, Hisashi; Watanabe, Masayoshi

2018-01-02

Producing ionic liquids (ILs) that function as molecular trigger for macroscopic change is a challenging issue. Photoisomerization of an azobenzene IL at the molecular level evokes a macroscopic response (light-controlled mechanical sol-gel transitions) for ABA triblock copolymer solutions. The A endblocks, poly(2-phenylethyl methacrylate), show a lower critical solution temperature in the IL mixture containing azobenzene, while the B midblock, poly(methyl methacrylate), is compatible with the mixture. In a concentrated polymer solution, different gelation temperatures were observed in it under dark and UV conditions. Light-controlled sol-gel transitions were achieved by a photoresponsive solubility change of the A endblocks upon photoisomerization of the azobenzene IL. Therefore, an azobenzene IL as a molecular switch can tune the self-assembly of a thermoresponsive polymer, leading to macroscopic light-controlled sol-gel transitions. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Molecular and Cellular Mechanisms of Axonal Regeneration After Spinal Cord Injury.

PubMed

van Niekerk, Erna A; Tuszynski, Mark H; Lu, Paul; Dulin, Jennifer N

2016-02-01

Following axotomy, a complex temporal and spatial coordination of molecular events enables regeneration of the peripheral nerve. In contrast, multiple intrinsic and extrinsic factors contribute to the general failure of axonal regeneration in the central nervous system. In this review, we examine the current understanding of differences in protein expression and post-translational modifications, activation of signaling networks, and environmental cues that may underlie the divergent regenerative capacity of central and peripheral axons. We also highlight key experimental strategies to enhance axonal regeneration via modulation of intraneuronal signaling networks and the extracellular milieu. Finally, we explore potential applications of proteomics to fill gaps in the current understanding of molecular mechanisms underlying regeneration, and to provide insight into the development of more effective approaches to promote axonal regeneration following injury to the nervous system. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Heat Shock Proteins: A Review of the Molecular Chaperones for Plant Immunity.

PubMed

Park, Chang-Jin; Seo, Young-Su

2015-12-01

As sessile organisms, plants are exposed to persistently changing stresses and have to be able to interpret and respond to them. The stresses, drought, salinity, chemicals, cold and hot temperatures, and various pathogen attacks have interconnected effects on plants, resulting in the disruption of protein homeostasis. Maintenance of proteins in their functional native conformations and preventing aggregation of non-native proteins are important for cell survival under stress. Heat shock proteins (HSPs) functioning as molecular chaperones are the key components responsible for protein folding, assembly, translocation, and degradation under stress conditions and in many normal cellular processes. Plants respond to pathogen invasion using two different innate immune responses mediated by pattern recognition receptors (PRRs) or resistance (R) proteins. HSPs play an indispensable role as molecular chaperones in the quality control of plasma membrane-resident PRRs and intracellular R proteins against potential invaders. Here, we specifically discuss the functional involvement of cytosolic and endoplasmic reticulum (ER) HSPs/chaperones in plant immunity to obtain an integrated understanding of the immune responses in plant cells.

Spontaneous polarization and dielectric relaxation dynamics of ferroelectric liquid crystals derived from 2(S)-[2(S)-ethylhexyolxy] propionic acid and its (S, R)-diastereomer

NASA Astrophysics Data System (ADS)

Huang, Lei-Ching; Fu, Chao-Ming

2015-09-01

The spontaneous polarization and molecular dynamics of four ferroelectric liquid crystals (FLCs) with two different kinds of core rings and two types of diastereomeric structures were investigated in this study. The FLCs with a biphenyl ring core structure showed higher spontaneous polarization than the FLCs with a naphthalene ring core structure. The complex dielectric spectra exhibited the Goldstone mode in the ferroelectric (SmC*) phase for all FLCs. The complex dielectric spectra of the four FLCs can be optimally fitted by the Debye model and the Cole-Cole model. Moreover, the Goldstone mode was enhanced under low DC bias fields for the FLCs with the (S, R)- diastereomeric structure, whereas the mode was suppressed for the FLCs with the (S, S)- diastereomeric structure. A microscopic molecular dynamic model is proposed to describe the underlying mechanism of the particular enhancement of the Goldstone mode. The experimental results of dielectric spectra and spontaneous polarization are explained in the discussion of the mesomorphic properties related to the FLC molecular structure.

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

PubMed

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.

RAFT-Polymerization-Induced Self-Assembly and Reorganizations: Ultrahigh-Molecular-Weight Polymer and Morphology-Tunable Micro-/Nanoparticles in One Pot.

PubMed

Zhang, Xiao-Yun; Liu, Dong-Ming; Lv, Xin-Hu; Sun, Miao; Sun, Xiao-Li; Wan, Wen-Ming

2016-11-01

A one-pot method is introduced for the successful synthesis of narrow-distributed (Đ = 1.22) vinyl polymer with both ultrahigh molecular weight (UHMW) (M w = 1.31 × 10 6 g mol -1 ) and micro-/nanomorphology under mild conditions. The method involves the following four stages: homogeneous polymerization, polymerization-induced self-assembly (PISA), PISA and reorganization, and PISA and multiple reorganizations. The key points to the production of UHMW polystyrene are to minimize radical termination by segregating radicals in different nanoreactors and to ensure sufficient chain propagation by promoting further reorganizations of these reactors in situ. This method therefore endows polymeric materials with the outstanding properties of both UHMW and tunable micro-/nanoparticles under mild conditions in one pot. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Temperature modulates the cell wall mechanical properties of rice coleoptiles by altering the molecular mass of hemicellulosic polysaccharides

NASA Technical Reports Server (NTRS)

Nakamura, Yukiko; Wakabayashi, Kazuyuki; Hoson, Takayuki

2003-01-01

The present study was conducted to investigate the mechanism inducing the difference in the cell wall extensibility of rice (Oryza sativa L. cv. Koshihikari) coleoptiles grown under various temperature (10-50 degrees C) conditions. The growth rate and the cell wall extensibility of rice coleoptiles exhibited the maximum value at 30-40 degrees C, and became smaller as the growth temperature rose or dropped from this temperature range. The amounts of cell wall polysaccharides per unit length of coleoptile increased in coleoptiles grown at 40 degrees C, but not at other temperature conditions. On the other hand, the molecular size of hemicellulosic polysaccharides was small at temperatures where the cell wall extensibility was high (30-40 degrees C). The autolytic activities of cell walls obtained from coleoptiles grown at 30 and 40 degrees C were substantially higher than those grown at 10, 20 and 50 degrees C. Furthermore, the activities of (1-->3),(1-->4)-beta-glucanases extracted from coleoptile cell walls showed a similar tendency. When oat (1-->3),(1-->4)-beta-glucans with high molecular mass were incubated with the cell wall enzyme preparations from coleoptiles grown at various temperature conditions, the extensive molecular mass downshifts were brought about only by the cell wall enzymes obtained from coleoptiles grown at 30-40 degrees C. There were close correlations between the cell wall extensibility and the molecular mass of hemicellulosic polysaccharides or the activity of beta -glucanases. These results suggest that the environmental temperature regulates the cell wall extensibility of rice coleoptiles by modifying mainly the molecular mass of hemicellulosic polysaccharides. Modulation of the activity of beta-glucanases under various temperature conditions may be involved in the alteration of the molecular size of hemicellulosic polysaccharides.

JAMI: a Java library for molecular interactions and data interoperability.

PubMed

Sivade Dumousseau, M; Koch, M; Shrivastava, A; Alonso-López, D; De Las Rivas, J; Del-Toro, N; Combe, C W; Meldal, B H M; Heimbach, J; Rappsilber, J; Sullivan, J; Yehudi, Y; Orchard, S

2018-04-11

A number of different molecular interactions data download formats now exist, designed to allow access to these valuable data by diverse user groups. These formats include the PSI-XML and MITAB standard interchange formats developed by Molecular Interaction workgroup of the HUPO-PSI in addition to other, use-specific downloads produced by other resources. The onus is currently on the user to ensure that a piece of software is capable of read/writing all necessary versions of each format. This problem may increase, as data providers strive to meet ever more sophisticated user demands and data types. A collaboration between EMBL-EBI and the University of Cambridge has produced JAMI, a single library to unify standard molecular interaction data formats such as PSI-MI XML and PSI-MITAB. The JAMI free, open-source library enables the development of molecular interaction computational tools and pipelines without the need to produce different versions of software to read different versions of the data formats. Software and tools developed on top of the JAMI framework are able to integrate and support both PSI-MI XML and PSI-MITAB. The use of JAMI avoids the requirement to chain conversions between formats in order to reach a desired output format and prevents code and unit test duplication as the code becomes more modular. JAMI's model interfaces are abstracted from the underlying format, hiding the complexity and requirements of each data format from developers using JAMI as a library.

Direct measurement of photomechanical switching cross-sections of single-molecules on a surface

NASA Astrophysics Data System (ADS)

Cho, Jongweon; Comstock, Matthew J.; Levy, Niv; Berbil-Bautista, Luis; Lauterwasser, Frank; Frechet, Jean M. J.; Crommie, Michael F.

2008-03-01

The photomechanical switching of photoactive molecules in solution strongly depends on the wavelength of light. This dependence is crucial to reliably control the photomechanical state of target molecules. Recently, reversible photomechanical switching of individual azobenzene molecular derivatives on the Au(111) surface has been reported for one particular wavelength of UV illumination [1]. To further understand this process and its possible applications in future nanotechnologies, we have investigated photomechanical switching rates and saturation behavior for azobenzene molecular derivatives at a surface under optical stimulation at different wavelengths. Using single-molecule-resolved scanning tunneling microscopy, we have determined both the forward and reverse photomechanical molecular switching cross-sections at different wavelengths. In a dramatic departure from solution-based environments, visible light does not efficiently reverse the photoreaction. [1] Matthew J. Comstock, Niv Levy, Armen Kirakosian, Jongweon Cho, Frank Lauterwasser, Jessica H. Harvey, David A. Strubbe, Jean M. J. Fr'echet, Dirk Trauner, Steven G. Louie, and Michael F. Crommie, Phys. Rev. Lett. 99, 038301 (2007)

[Pathophysiological mechanisms underlying cryopyrin-associated periodic syndromes: genetic and molecular basis and the inflammasome].

PubMed

Aróstegui, Juan I

2011-01-01

NLRP3 gene (formerly known as CIAS1) encodes for cryopyrin (Nalp3) protein, which belongs to the Nod-like family of innate immune receptors. Cryopyrin recruits different adaptor and effectors proteins into a cytosolic macromolecular complex termed Nalp3-inflammasome, which senses both several pathogen-associated and damage-associated molecular patterns as well as inorganic particles (asbestos, silica), and triggers innate immune and inflammatory responses. Gain-of-function NLRP3 mutations are the common molecular basis of cryopyrin-associated periodic syndromes (CAPS), which encompasses three clinical entities along a spectrum of disease severity (familial cold autoinflammatory syndrome, Muckle-Wells syndrome and CINCA-NOMID syndrome). This hypermorphic cryopyrin provokes an increased, unregulated secretion of different inflammatory cytokines (IL-1β, IL-18, IL-33) in patients with CAPS, and in vivo administration of IL-1 blocking agents results in excellent therapeutic responses in these patients. Copyright © 2011 Elsevier España S.L. All rights reserved.

Molecular mechanisms involved in Bacillus subtilis biofilm formation

PubMed Central

Mielich-Süss, Benjamin; Lopez, Daniel

2014-01-01

Summary Biofilms are the predominant lifestyle of bacteria in natural environments, and they severely impact our societies in many different fashions. Therefore, biofilm formation is a topic of growing interest in microbiology, and different bacterial models are currently studied to better understand the molecular strategies that bacteria undergo to build biofilms. Among those, biofilms of the soil-dwelling bacterium Bacillus subtilis are commonly used for this purpose. Bacillus subtilis biofilms show remarkable architectural features that are a consequence of sophisticated programs of cellular specialization and cell-cell communication within the community. Many laboratories are trying to unravel the biological role of the morphological features of biofilms, as well as exploring the molecular basis underlying cellular differentiation. In this review, we present a general perspective of the current state of knowledge of biofilm formation in B. subtilis. In particular, a special emphasis is placed on summarizing the most recent discoveries in the field and integrating them into the general view of these truly sophisticated microbial communities. PMID:24909922

The evolutionary diversity of insect retinal mosaics: common design principles and emerging molecular logic.

PubMed

Wernet, Mathias F; Perry, Michael W; Desplan, Claude

2015-06-01

Independent evolution has resulted in a vast diversity of eyes. Despite the lack of a common Bauplan or ancestral structure, similar developmental strategies are used. For instance, different classes of photoreceptor cells (PRs) are distributed stochastically and/or localized in different regions of the retina. Here, we focus on recent progress made towards understanding the molecular principles behind patterning retinal mosaics of insects, one of the most diverse groups of animals adapted to life on land, in the air, under water, or on the water surface. Morphological, physiological, and behavioral studies from many species provide detailed descriptions of the vast variation in retinal design and function. By integrating this knowledge with recent progress in the characterization of insect Rhodopsins as well as insight from the model organism Drosophila melanogaster, we seek to identify the molecular logic behind the adaptation of retinal mosaics to the habitat and way of life of an animal. Copyright © 2015 Elsevier Ltd. All rights reserved.

Self-organizing layers from complex molecular anions

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

Warneke, Jonas; McBriarty, Martin E.; Riechers, Shawn L.

Ions are promising building blocks for tunable self-organizing materials with advanced technological applications. However, because of strong Coulomb attraction with counterions, the intrinsic properties of ions are difficult to exploit for preparation of bulk materials. Here, we report the precisely-controlled preparation of macroscopic surface layers by soft landing of mass selected complex anions which determine the self organization of the layers with their molecular properties. The family of halogenated dodecaborates [B12X12]2- (X = F, Cl, Br, I), in which the internal charge distribution between core and shell regions of the molecular ions systematically vary, was deposited on different self assembledmore » monolayer surfaces (SAMs) on gold at high coverage. Layers of anions were found to be stabilized by accumulation of neutral molecules. Different phases, self-organization mechanisms and optical properties were observed to depend upon the internal charge distribution of the deposited anions, the underlying surface and the coadsorbed molecules. This demonstrates rational control of the properties of anion based layers.« less

Photo-responsive surface topology in chiral nematic media

NASA Astrophysics Data System (ADS)

Liu, Danqing; Bastiaansen, Cees W. M.; Toonder, Jaap. M. J.; Broer, Dirk J.

2012-03-01

We report on the design and fabrication of 'smart surfaces' that exhibit dynamic changes in their surface topology in response to exposure to light. The principle is based on anisotropic geometric changes of a liquid crystal network upon a change of the molecular order parameter. The photomechanical property of the coating is induced by incorporating an azobenzene moiety into the liquid crystal network. The responsive surface topology consists of regions with two different types of molecular order: planar chiral-nematic areas and homeotropic. Under flood exposure with 365 nm light the surfaces deform from flat to one with a surface relief. The height of the relief structures is of the order of 1 um corresponding to strain difference of around 20%. Furthermore, we demonstrate surface reliefs can form either convex or concave structures upon exposure to UV light corresponding to the decrease or increase molecular order parameter, respectively, related to the isomeric state of the azobenzene crosslinker. The reversible deformation to the initial flat state occurs rapidly after removing the light source.

Mastocytosis: current treatment concepts.

PubMed

Worobec, Alexandra S; Metcalfe, Dean D

2002-02-01

An explosion of research on mastocytosis in the last decade has witnessed a greater understanding of the molecular basis of this heterogeneous group of disorders and the conclusion that similar disease phenotypes may indeed be the result of different underlying genotypes. Along with our growing knowledge base of mastocytosis, newer approaches of treating these disorders are becoming available, all under investigational use at this time. This short review highlights the state of the art of current treatment strategies for the different categories of mastocytosis. The future will undoubtedly witness an even greater array of therapeutic options, as we continue to learn more about this enigmatic disease. Copyright 2002 S. Karger AG, Basel

The Quest for Molecular Regulation Underlying Unisexual Flower Development

PubMed Central

Sobral, Rómulo; Silva, Helena G.; Morais-Cecílio, Leonor; Costa, Maria M. R.

2016-01-01

The understanding of the molecular mechanisms responsible for the making of a unisexual flower has been a long-standing quest in plant biology. Plants with male and female flowers can be divided mainly into two categories: dioecious and monoecious, and both sexual systems co-exist in nature in ca of 10% of the angiosperms. The establishment of male and female traits has been extensively described in a hermaphroditic flower and requires the interplay of networks, directly and indirectly related to the floral organ identity genes including hormonal regulators, transcription factors, microRNAs, and chromatin-modifying proteins. Recent transcriptomic studies have been uncovering the molecular processes underlying the establishment of unisexual flowers and there are many parallelisms between monoecious, dioecious, and hermaphroditic individuals. Here, we review the paper entitled “Comparative transcriptomic analysis of male and female flowers of monoecious Quercus suber” published in 2014 in the Frontiers of Plant Science (volume 5 |Article 599) and discussed it in the context of recent studies with other dioecious and monoecious plants that utilized high-throughput platforms to obtain transcriptomic profiles of male and female unisexual flowers. In some unisexual flowers, the developmental programs that control organ initiation fail and male or female organs do not form, whereas in other species, organ initiation and development occur but they abort or arrest during different species-specific stages of differentiation. Therefore, a direct comparison of the pathways responsible for the establishment of unisexual flowers in different species are likely to reveal conserved modules of gene regulatory hubs involved in stamen or carpel development, as well as differences that reflect the different stages of development in which male and/or female organ arrest or loss-of-function occurs. PMID:26925078

By how much do we underestimate species diversity of liverworts using morphological evidence? An example from Australasian Plagiochila (Plagiochilaceae: Jungermanniopsida).

PubMed

Renner, Matt A M; Heslewood, Margaret M; Patzak, Simon D F; Schäfer-Verwimp, Alfons; Heinrichs, Jochen

2017-02-01

As a framework for revisionary study of the leafy liverwort Plagiochila in Australia, two methods for species delimitation on molecular sequence data, General Mixed Yule Coalescence model (GMYC) and Automatic Barcode Gap Discovery (ABGD) were applied to a dataset including 265 individuals from Australia, New Zealand, and the Pacific. Groups returned by GMYC and ABGD were incongruent in some lineages, and ABGD tended to lump groups. This may reflect underlying heterogeneity in the history of diversification within different lineages of Plagiochila. GMYC from trees calculated using three different molecular clocks were compared, in some lineages different primary species hypotheses were returned by analyses of trees estimated under different clock models, suggesting clock model selection should be a routine component of phylogeny reconstruction for tree-based species delimitation methods, such as GMYC. Our results suggest that a minimum of 71 Plagiochilaceae species occur in Australasia, 16 more than currently accepted for the region, comprising 8 undetermined species and 8 synonyms requiring reinstatement. Despite modern taxonomic investigation over a four decade period, (1) real diversity is 29% higher than currently recognized; and (2) 12 of 33, or 36%, of currently accepted and previously untested Australasian species have circumscription issues, including polyphyly, paraphyly, internal phylogenetic structure, or combinations of two or more of these issues. These both reflect the many challenges associated with grouping decisions based solely on morphological data in morphologically simple yet polymorphic plant lineages. Our results highlight again the critical need for combined molecular-morphological datasets as a basis for resolving robust species hypotheses in species-rich bryophyte lineages. Copyright © 2016 Elsevier Inc. All rights reserved.

BHD-associated kidney cancer exhibits unique molecular characteristics and a wide variety of variants in chromatin remodeling genes.

PubMed

Hasumi, Hisashi; Furuya, Mitsuko; Tatsuno, Kenji; Yamamoto, Shogo; Baba, Masaya; Hasumi, Yukiko; Isono, Yasuhiro; Suzuki, Kae; Jikuya, Ryosuke; Otake, Shinji; Muraoka, Kentaro; Osaka, Kimito; Hayashi, Narihiko; Makiyama, Kazuhide; Miyoshi, Yasuhide; Kondo, Keiichi; Nakaigawa, Noboru; Kawahara, Takashi; Izumi, Koji; Teranishi, Junichi; Yumura, Yasushi; Uemura, Hiroji; Nagashima, Yoji; Metwalli, Adam R; Schmidt, Laura S; Aburatani, Hiroyuki; Linehan, W Marston; Yao, Masahiro

2018-05-14

Birt-Hogg-Dubé (BHD) syndrome is a hereditary kidney cancer syndrome, which predisposes patients to develop kidney cancer, cutaneous fibrofolliculomas and pulmonary cysts. The responsible gene FLCN is a tumor suppressor for kidney cancer which plays an important role in energy homeostasis through the regulation of mitochondrial oxidative metabolism. However, the process by which FLCN-deficiency leads to renal tumorigenesis is unclear. In order to clarify molecular pathogenesis of BHD-associated kidney cancer, we conducted whole-exome sequencing analysis using next-generation sequencing technology as well as metabolite analysis using LC/MS and GC/MS. Whole-exome sequencing analysis of BHD-associated kidney cancer revealed that copy number variations (CNV) of BHD-associated kidney cancer are considerably different from those already reported in sporadic cases. In somatic variant analysis, very few variants were commonly observed in BHD-associated kidney cancer; however, variants in chromatin remodeling genes were frequently observed in BHD-associated kidney cancer (17/29 tumors, 59%). Metabolite analysis of BHD-associated kidney cancer revealed metabolic reprogramming towards upregulated redox regulation which may neutralize reactive oxygen species potentially produced from mitochondria with increased respiratory capacity under FLCN-deficiency. BHD-associated kidney cancer displays unique molecular characteristics which are completely different from sporadic kidney cancer, providing mechanistic insight into tumorigenesis under FLCN-deficiency as well as a foundation for development of novel therapeutics for kidney cancer.

Molecular dynamics simulations of ejecta production from sinusoidal tin surfaces under supported and unsupported shocks

NASA Astrophysics Data System (ADS)

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.

Molecular Mechanisms Underlying Individual Differences in Response to Stress in a Previously Validated Animal Model of PTSD

DTIC Science & Technology

2012-04-01

CONTRACTING ORGANIZATION: Bronx Veterans Medical Research Foundation, Inc... Bronx , NY 10468-3904 REPORT DATE: April 2012 TYPE OF REPORT: Final PREPARED FOR: U.S. Army...WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBER Bronx Veterans Medical Research

COMPARISON OF GENE EXPRESSION PROFILES FROM MICE FED THREE TOXICOLOGICALLY DIFFERENT TRIAZOLE-BASED CONAZOLES

EPA Science Inventory

The present study was designed to identify the underlying molecular mechanism for the induction of mouse liver tumors by conazoles. CD-1 mice were treated with the tumor producing conazoles, triadimefon (1800, 500, or 100 ppm), or propiconazole (2500, 500, or 100 ppm), or the non...

Modulation of microrna in two genetically disparate chicken lines showing different necrotic enteritis disease susceptibility

USDA-ARS?s Scientific Manuscript database

Necrotic enteritis (NE) is a re-emerging disease as a result of an increased restriction on the use of antibiotics in poultry. However, the molecular mechanisms underlying the pathology of NE are unclear. Therefore, we carried out small RNA transcriptome analysis in an experimentally induced NE m...

Effects of various conditions in cold-welding of copper nanowires: A molecular dynamics study

NASA Astrophysics Data System (ADS)

Zhou, Hongjian; Wu, Wen-ping; Wu, Runni; Hu, Guoming; Xia, Re

2017-11-01

Cold-welding possesses such desirable environment as low temperature and low applied stress, thus becoming the prime candidate for nanojointing and nanoassembly techniques. To explore the welding mechanism of nanoscale structures, here, molecular dynamics was performed on copper nanowires under different welding conditions and various original characteristics to obtain an atomic-level depiction of their cold-welding behavior. By analyzing the mechanical properties of as-welded nanowires, the relations between welding quality and welding variables are revealed and identified. This comparison study will be of great importance to future mechanical processing and structural assembly of metallic nanowires.

Brain transcriptome atlases: a computational perspective.

PubMed

Mahfouz, Ahmed; Huisman, Sjoerd M H; Lelieveldt, Boudewijn P F; Reinders, Marcel J T

2017-05-01

The immense complexity of the mammalian brain is largely reflected in the underlying molecular signatures of its billions of cells. Brain transcriptome atlases provide valuable insights into gene expression patterns across different brain areas throughout the course of development. Such atlases allow researchers to probe the molecular mechanisms which define neuronal identities, neuroanatomy, and patterns of connectivity. Despite the immense effort put into generating such atlases, to answer fundamental questions in neuroscience, an even greater effort is needed to develop methods to probe the resulting high-dimensional multivariate data. We provide a comprehensive overview of the various computational methods used to analyze brain transcriptome atlases.

Edge cracks in nickel and aluminium single crystals: A molecular dynamics study

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

Chandra, Sagar, E-mail: sagarc@barc.gov.in; Chavan, V. M.; Patel, R. J.

A molecular dynamics study of edge cracks in Ni and Al single crystals under mode-I loading conditions is presented. Simulations are performed using embedded-atom method potentials for Ni and Al at a temperature of 0.5 K. The results reveal that Ni and Al show different fracture mechanisms. Overall failure behavior of Ni is brittle, while fracture in Al proceeds through void nucleation and coalescence with a zig-zag pattern of crack growth. The qualitative nature of results is discussed in the context of vacancy-formation energies and surface energies of the two FCC metals.

Symptomatic and asymptomatic benign prostatic hyperplasia: Molecular differentiation by using microarrays

NASA Astrophysics Data System (ADS)

Prakash, Kulkarni; Pirozzi, Gregorio; Elashoff, Michael; Munger, William; Waga, Iwao; Dhir, Rajiv; Kakehi, Yoshiyuki; Getzenberg, Robert H.

2002-05-01

Benign prostatic hyperplasia (BPH) is a disease of unknown etiology that significantly affects the quality of life in aging men. Histologic BPH may present itself either as symptomatic or asymptomatic in nature. To elucidate the molecular differences underlying BPH, gene expression profiles from the prostate transition zone tissue have been analyzed by using microarrays. A set of 511 differentially expressed genes distinguished symptomatic and asymptomatic BPH. This genetic signature separates BPH from normal tissue but does not seem to change with age. These data could provide novel approaches for alleviating symptoms and hyperplasia in BPH.

X-Ray Reflectometry of DMPS Monolayers on a Water Substrate

NASA Astrophysics Data System (ADS)

Tikhonov, A. M.; Asadchikov, V. E.; Volkov, Yu. O.; Roshchin, B. S.; Ermakov, Yu. A.

2017-12-01

The molecular structure of dimyristoyl phosphatidylserine (DMPS) monolayers on a water substrate in different phase states has been investigated by X-ray reflectometry with a photon energy of 8 keV. According to the experimental data, the transition from a two-dimensional expanded liquid state to a solid gel state (liquid crystal) accompanied by the ordering of the hydrocarbon tails C14H27 of the DMPS molecule occurs in the monolayer as the surface pressure rises. The monolayer thickness is 20 ± 3 and 28 ± 2 Å in the liquid and solid phases, respectively, with the deflection angle of the molecular tail axis from the normal to the surface in the gel phase being 26° ± 8°. At least a twofold decrease in the degree of hydration of the polar lipid groups also occurs under two-dimensional monolayer compression. The reflectometry data have been analyzed using two approaches: under the assumption about the presence of two layers with different electron densities in the monolayer and without any assumptions about the transverse surface structure. Both approaches demonstrate satisfactory agreement between themselves in describing the experimental results.

Predicting activation energy of thermolysis of polynitro arenes through molecular structure.

PubMed

Keshavarz, Mohammad Hossein; Pouretedal, Hamid Reza; Shokrolahi, Arash; Zali, Abbas; Semnani, Abolfazl

2008-12-15

The paper presents a new method for activation energy or the Arrhenius parameter E(a) of the thermolysis in the condensed state for different polynitro arenes as an important class of energetic molecules. The methodology assumes that E(a) of a polynitro arene with general formula C(a)H(b)N(c)O(d) can be expressed as a function of optimized elemental composition as well as the contribution of specific molecular structural parameters. The new method can predict E(a) of the thermolysis under conditions of Soviet Manometric Method (SMM), which can be related to the other convenient methods. The new correlation has the root mean square (rms) and the average deviations of 13.79 and 11.94kJ/mol, respectively, for 20 polynitro arenes with different molecular structures. The proposed new method can also be used to predict E(a) of three polynitro arenes, i.e. 2,2',2'',4,4',4'',6,6',6''-nonanitro-1,1':3',1''-terphenyl (NONA), 3,3'-diamino-2,2',4,4',6,6'-hexanitro-1,1'-biphenyl-3,3'-diamine (DIPAM) and N,N-bis(2,4-dinitrophenyl)-2,4,6-trinitroaniline (NTFA), which have complex molecular structures.

Spectrally resolved single-molecule electrometry

NASA Astrophysics Data System (ADS)

Ruggeri, F.; Krishnan, M.

2018-03-01

Escape-time electrometry is a recently developed experimental technique that offers the ability to measure the effective electrical charge of a single biomolecule in solution with sub-elementary charge precision. The approach relies on measuring the average escape-time of a single charged macromolecule or molecular species transiently confined in an electrostatic fluidic trap. Comparing the experiments with the predictions of a mean-field model of molecular electrostatics, we have found that the measured effective charge even reports on molecular conformation, e.g., folded or disordered state, and non-uniform charge distribution in disordered proteins or polyelectrolytes. Here we demonstrate the ability to use the spectral dimension to distinguish minute differences in electrical charge between individual molecules or molecular species in a single simultaneous measurement, under identical experimental conditions. Using one spectral channel for referenced measurement, this kind of photophysical distinguishability essentially eliminates the need for accurate knowledge of key experimental parameters, otherwise obtained through intensive characterization of the experimental setup. As examples, we demonstrate the ability to detect small differences (˜5%) in the length of double-stranded DNA fragments as well as single amino acid exchange in an intrinsically disordered protein, prothymosin α.

Molecular docking of superantigens with class II major histocompatibility complex proteins.

PubMed

Olson, M A; Cuff, L

1997-01-01

The molecular recognition of two superantigens with class II major histocompatibility complex molecules was simulated by using protein-protein docking. Superantigens studied were staphylococcal enterotoxin B (SEB) and toxic shock syndrome toxin-1 (TSST-1) in their crystallographic assemblies with HLA-DR1. Rigid-body docking was performed sampling configurational space of the interfacial surfaces by employing a strategy of partitioning the contact regions on HLA-DR1 into separate molecular recognition units. Scoring of docked conformations was based on an electrostatic continuum model evaluated with the finite-difference Poisson-Boltzmann method. Estimates of nonpolar contributions were derived from the buried molecular surface areas. We found for both superantigens that docking the HLA-DR1 surface complementary with the SEB and TSST-1 contact regions containing a homologous hydrophobic surface loop provided sufficient recognition for the reconstitution of native-like conformers exhibiting the highest-scoring free energies. For the SEB complex, the calculations were successful in reproducing the total association free energy. A comparison of the free-energy determinants of the conserved hydrophobic contact residue indicates functional similarity between the two proteins for this interface. Though both superantigens share a common global association mode, differences in binding topology distinguish the conformational specificities underlying recognition.

Adaptive molecular evolution of the two-pore channel 1 gene TPC1 in the karst-adapted genus Primulina (Gesneriaceae)

PubMed Central

Tao, Junjie; Feng, Chao; Ai, Bin; Kang, Ming

2016-01-01

Background and Aims Limestone karst areas possess high floral diversity and endemism. The genus Primulina, which contributes to the unique calcicole flora, has high species richness and exhibit specific soil-based habitat associations that are mainly distributed on calcareous karst soils. The adaptive molecular evolutionary mechanism of the genus to karst calcium-rich environments is still not well understood. The Ca2+-permeable channel TPC1 was used in this study to test whether its gene is involved in the local adaptation of Primulina to karst high-calcium soil environments. Methods Specific amplification and sequencing primers were designed and used to amplify the full-length coding sequences of TPC1 from cDNA of 76 Primulina species. The sequence alignment without recombination and the corresponding reconstructed phylogeny tree were used in molecular evolutionary analyses at the nucleic acid level and amino acid level, respectively. Finally, the identified sites under positive selection were labelled on the predicted secondary structure of TPC1. Key Results Seventy-six full-length coding sequences of Primulina TPC1 were obtained. The length of the sequences varied between 2220 and 2286 bp and the insertion/deletion was located at the 5′ end of the sequences. No signal of substitution saturation was detected in the sequences, while significant recombination breakpoints were detected. The molecular evolutionary analyses showed that TPC1 was dominated by purifying selection and the selective pressures were not significantly different among species lineages. However, significant signals of positive selection were detected at both TPC1 codon level and amino acid level, and five sites under positive selective pressure were identified by at least three different methods. Conclusions The Ca2+-permeable channel TPC1 may be involved in the local adaptation of Primulina to karst Ca2+-rich environments. Different species lineages suffered similar selective pressure associated with calcium in karst environments, and episodic diversifying selection at a few sites may play a major role in the molecular evolution of Primulina TPC1. PMID:27582362

Abnormal characteristics of binary molecular clusters in DMSO–ethanol mixtures under external electric fields

NASA Astrophysics Data System (ADS)

Wu, Zhiyan; Huang, Kama

2018-05-01

For the nonlinearly phenomena on the dielectric properties of dimethyl sulfoxide (DMSO)-ethanol mixtures under a low intensity microwave field, we propose a conjecture that there exist some abnormal molecular clusters. To interpret the mechanism of abnormal phenomena and confirm our conjecture about the existence of abnormal molecular clusters, an in-depth investigation about the structure evolutions of (DMSO)m(C2H5OH)n (m = 0-4; n = 0-4; m + n ≤ 4) molecular clusters induced by external electric fields has been given by using density functional theory. The results show that there exist some binary molecular clusters with large cluster radii in mixtures, and some of them are unstable under exposure of electric fields. It implies that the existence of certain abnormal molecular clusters in DMSO-ethanol mixtures results in their abnormality of dielectric properties.

Effects of temperature on anaerobic decomposition of high-molecular weight organic matter under sulfate-reducing conditions

NASA Astrophysics Data System (ADS)

Matsui, Takato; Kojima, Hisaya; Fukui, Manabu

2013-03-01

Most sedimentary mineralization occurs along coasts under anaerobic conditions. In the absence of oxygen, high-molecular weight organic matter in marine sediments is gradually decomposed by hydrolysis, fermentation and sulfate reduction. Because of the different responses of the respective steps to temperature, degradation may be specifically slowed or stopped in certain step. To evaluate the effect of temperature on cellobiose degradation, culture experiments were performed at six different temperatures (3 °C, 8 °C, 13 °C, 18 °C, 23 °C, and 28 °C) under sulfate-reducing conditions. This study measured the concentrations of sulfide, dissolved organic carbon (DOC), and organic acids during that degradation. Degradation patterns were divided into three temperature groups: 3 °C, 8/13 °C, and 18/23/28 °C. The decrease in DOC proceeded in two steps, except at 3 °C. The length of the stagnant phase separating these two steps differed greatly between temperatures of 8/13 °C and 18/23/28 °C. In the first step, organic carbon was consumed by hydrolysis, fermentation and sulfate reduction. In the second step, acetate accumulated during the first step was oxidized by sulfate reduction. Bacterial communities in the cultures were analyzed by denaturing gradient gel electrophoresis (DGGE); the major differences among the three temperature groups were attributed to shifts in acetate-using sulfate reducers of the genus Desulfobacter. This suggests that temperature characteristics of dominant acetate oxidizers are important factors in determining the response of carbon flow in coastal marine sediments in relation to the changes in temperature.

Incorporation of omics analyses into artificial gravity research for space exploration countermeasure development.

PubMed

Schmidt, Michael A; Goodwin, Thomas J; Pelligra, Ralph

The next major steps in human spaceflight include flyby, orbital, and landing missions to the Moon, Mars, and near earth asteroids. The first crewed deep space mission is expected to launch in 2022, which affords less than 7 years to address the complex question of whether and how to apply artificial gravity to counter the effects of prolonged weightlessness. Various phenotypic changes are demonstrated during artificial gravity experiments. However, the molecular dynamics (genotype and molecular phenotypes) that underlie these morphological, physiological, and behavioral phenotypes are far more complex than previously understood. Thus, targeted molecular assessment of subjects under various G conditions can be expected to miss important patterns of molecular variance that inform the more general phenotypes typically being measured. Use of omics methods can help detect changes across broad molecular networks, as various G-loading paradigms are applied. This will be useful in detecting off-target, or unanticipated effects of the different gravity paradigms applied to humans or animals. Insights gained from these approaches may eventually be used to inform countermeasure development or refine the deployment of existing countermeasures. This convergence of the omics and artificial gravity research communities may be critical if we are to develop the proper artificial gravity solutions under the severely compressed timelines currently established. Thus, the omics community may offer a unique ability to accelerate discovery, provide new insights, and benefit deep space missions in ways that have not been previously considered.

Molecular and functional characterization of cry1Ac transgenic pea lines.

PubMed

Teressa Negawo, Alemayehu; Baranek, Linda; Jacobsen, Hans-Jörg; Hassan, Fathi

2016-10-01

Transgenic pea lines transformed with the cry1Ac gene were characterized at molecular (PCR, RT-PCR, qRT-PCR and immunostrip assay) and functional levels (leaf paint and insect feeding bioassays). The results showed the presence, expression, inheritance and functionality of the introduced transgene at different progeny levels. Variation in the expression of the cry1Ac gene was observed among the different transgenic lines. In the insect bioassay studies using the larvae of Heliothis virescens, both larval survival and plant damage were highly affected on the different transgenic plants. Up to 100 % larval mortality was observed on the transgenic plants compared to 17.42 % on control plants. Most of the challenged transgenic plants showed very negligible to substantially reduced feeding damage indicating the insect resistance of the developed transgenic lines. Further analysis under field condition will be required to select promising lines for future uses.

Candidate genes implicated in type 1 diabetes susceptibility.

PubMed

Aribi, Mourad

2008-05-01

Type 1 diabetes (T1D) is an autoimmune disease resulting from pancreatic beta-cells destruction, often appearing on a genetic ground susceptibility under the influence of one or more environmental factors. Multiplex families studies, using genetic markers allowed the identification of various genes, including HLA, insulin, SUMO-4 and CTLA-4 all being linked with different degrees to disease risk. The MIF gene was also suggested, although its role has yet to be established on family or twin studies. The difference in susceptibility among T1D patients suggest the development of the disease as resulting from the interaction between genetic and environmental factors. This review emphasizes the importance of identifying the genes that have a direct impact on the autoimmune process, while recalling the different strategies that are followed. The style of writing should appeal to those with strong interests in molecular biology with an equal balance of immunology and molecular epidemiology.

Molecular and functional characterization of cry1Ac transgenic pea lines

PubMed Central

Teressa Negawo, Alemayehu; Baranek, Linda; Jacobsen, Hans-Jörg; Hassan, Fathi

2016-01-01

ABSTRACT Transgenic pea lines transformed with the cry1Ac gene were characterized at molecular (PCR, RT-PCR, qRT-PCR and immunostrip assay) and functional levels (leaf paint and insect feeding bioassays). The results showed the presence, expression, inheritance and functionality of the introduced transgene at different progeny levels. Variation in the expression of the cry1Ac gene was observed among the different transgenic lines. In the insect bioassay studies using the larvae of Heliothis virescens, both larval survival and plant damage were highly affected on the different transgenic plants. Up to 100 % larval mortality was observed on the transgenic plants compared to 17.42 % on control plants. Most of the challenged transgenic plants showed very negligible to substantially reduced feeding damage indicating the insect resistance of the developed transgenic lines. Further analysis under field condition will be required to select promising lines for future uses. PMID:27764552

Structure of New Zealand sweetpotato starch.

PubMed

Zhu, Fan; Xie, Qian

2018-05-15

New Zealand sweetpotatoes (kumara) (Ipomoea batatas) represent unique genetic resources for sweetpotato diversity, though they are much under-studied. In this study, 7 New Zealand sweetpotato varieties with commercial significance were collected for the characterization of the molecular and granular structure of the starches. In particular, the internal molecular structure of the amylopectins was detailed by chromatographic and enzymatic techniques. Maize and potato starches with normal amylose contents, which are among the most important commercial starch sources, were employed for comparison. The results revealed a degree of diversity in amylose composition, unit and internal chain composition, granule size distribution, and degree of crystallinity among the 7 sweetpotato starches. All the sweetpotato starches showed C A -type polymorph. The sweetpotato amylopectins have intermediate amounts of both short and long internal unit chains among amylopectins of different botanical sources. The differences in the structure of sweetpotato starches suggest differences in physicochemical properties. Copyright © 2018 Elsevier Ltd. All rights reserved.

Electrolyte Structure near Electrode Interfaces in Lithium-Ion Batteries

NASA Astrophysics Data System (ADS)

Lordi, Vincenzo; Ong, Mitchell; Verners, Osvalds; van Duin, Adri; Draeger, Erik; Pask, John

2014-03-01

The performance of lithium-ion secondary batteries (LIBs) is strongly tied to electrochemistry and ionic transport near the electrode-electrolyte interface. Changes in ion solvation near the interface affect ion conductivity and also are associated with the formation and evolution of solid-electrolyte interphase (SEI) layers, which impede transport but also passivate the interface. Thus, understanding these effects is critical to optimizing battery performance. Here we present molecular dynamics (MD) simulations of typical organic liquid LIB electrolytes in contact with graphite electrodes to understand differences in molecular structure and solvation near the interface compared to the bulk electrolyte. Results for different graphite terminations are presented. We compare the results of density-functional based MD to the empirical reactive forcefield ReaxFF and the non-reactive, non-polarizable COMPASS forcefield. Notable differences in the predictive power of each of these techniques are discussed. Prepared by LLNL under Contract DE-AC52-07NA27344.

The shift of harmonics with different initial vibrational states in the H{}_{2}^{+} molecular ion

NASA Astrophysics Data System (ADS)

Zhang, Jun; Pan, Xue-Fei; Xu, Tong-Tong; Liu, Xue-Shen

2017-05-01

Molecular high-order harmonic generation of H{}2+ and its isotopes is investigated by numerical simulations of the non-Born-Oppenheimer time-dependent Schrödinger equations. The general characteristic of the typical high-order harmonic generation (HHG) spectra for the H{}2+ molecule indicates that only the odd harmonics can be generated. Here we show that how the initial vibrational states and nuclear dynamics break down this standard characteristic, i.e. a redshift or blueshift of the harmonics appears. We investigate the effect of the initial vibrational states on the redshift or blueshift of the HHG spectrum under trapezoidal laser pulses. The ionization probability and time-frequency analysis are used to illustrate the physical mechanism of the shift of the harmonics. We also show the HHG spectra from the different isotopes of H2+ molecule with different initial vibrational states.

Separation of saccharides derivatized with 2-aminobenzoic acid by capillary electrophoresis and their structural consideration by nuclear magnetic resonance.

PubMed

He, Liping; Sato, Kae; Abo, Mitsuru; Okubo, Akira; Yamazaki, Sunao

2003-03-01

Saccharides including mono- and disaccharides were quantitatively derivatized with 2-aminobenzoic acid (2-AA). These derivatives were then separated by capillary zone electrophoresis with UV detection using 50mM sodium phosphate buffer as the running electrolyte solution. In particular, the saccharide derivatives with the same molecular weight as 2-AA aldohexoses (mannose and glucose) and 2-AA aldopentoses (ribose and xylose) were well separated. The underlying reasons for separation were explored by studying their structural data using 1H and 13C NMR. It was found that the configurational difference between their hydroxyl group at C2 or C3 could cause the difference in Stokes' radii between their molecules and thus lead to different electrophoretic mobilities. The correlation between the electrophoretic behavior of these carbohydrate derivatives and their structures was studied utilizing the calculated molecular models of the 2-AA-labeled mannose, glucose, ribose, and xylose.

Root gravitropism: an experimental tool to investigate basic cellular and molecular processes underlying mechanosensing and signal transmission in plants

NASA Technical Reports Server (NTRS)

Boonsirichai, K.; Guan, C.; Chen, R.; Masson, P. H.

2002-01-01

The ability of plant organs to use gravity as a guide for growth, named gravitropism, has been recognized for over two centuries. This growth response to the environment contributes significantly to the upward growth of shoots and the downward growth of roots commonly observed throughout the plant kingdom. Root gravitropism has received a great deal of attention because there is a physical separation between the primary site for gravity sensing, located in the root cap, and the site of differential growth response, located in the elongation zones (EZs). Hence, this system allows identification and characterization of different phases of gravitropism, including gravity perception, signal transduction, signal transmission, and curvature response. Recent studies support some aspects of an old model for gravity sensing, which postulates that root-cap columellar amyloplasts constitute the susceptors for gravity perception. Such studies have also allowed the identification of several molecules that appear to function as second messengers in gravity signal transduction and of potential signal transducers. Auxin has been implicated as a probable component of the signal that carries the gravitropic information between the gravity-sensing cap and the gravity-responding EZs. This has allowed the identification and characterization of important molecular processes underlying auxin transport and response in plants. New molecular models can be elaborated to explain how the gravity signal transduction pathway might regulate the polarity of auxin transport in roots. Further studies are required to test these models, as well as to study the molecular mechanisms underlying a poorly characterized phase of gravitropism that is independent of an auxin gradient.

Solid-State Solvation and Enhanced Exciton Diffusion in Doped Organic Thin Films under Mechanical Pressure.

PubMed

Chang, Wendi; Akselrod, Gleb M; Bulović, Vladimir

2015-04-28

Direct modification of exciton energy has been previously used to optimize the operation of organic optoelectronic devices. One demonstrated method for exciton energy modification is through the use of the solvent dielectric effects in doped molecular films. To gain a deeper appreciation of the underlying physical mechanisms, in this work we test the solid-state solvation effect in molecular thin films under applied external pressure. We observe that external mechanical pressure increases dipole-dipole interactions, leading to shifts in the Frenkel exciton energy and enhancement of the time-resolved spectral red shift associated with the energy-transfer-mediated exciton diffusion. Measurements are performed on host:dopant molecular thin films, which show bathochromic shifts in photoluminescence (PL) under increasing pressure. This is in agreement with a simple solvation theory model of exciton energetics with a fitting parameter based on the mechanical properties of the host matrix material. We measure no significant change in exciton lifetime with increasing pressure, consistent with unchanged aggregation in molecular films under compression. However, we do observe an increase in exciton spectral thermalization rate for compressed molecular films, indicating enhanced exciton diffusion for increased dipole-dipole interactions under pressure. The results highlight the contrast between molecular energy landscapes obtained when dipole-dipole interactions are increased by the pressure technique versus the conventional dopant concentration variation methods, which can lead to extraneous effects such as aggregation at higher doping concentrations. The present work demonstrates the use of pressure-probing techniques in studying energy disorder and exciton dynamics in amorphous molecular thin films.

Solid-State Solvation and Enhanced Exciton Diffusion in Doped Organic Thin Films under Mechanical Pressure

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

Chang, Wendi; Akselrod, Gleb M.; Bulović, Vladimir

2015-04-28

Direct modification of exciton energy has been previously used to optimize the operation of organic optoelectronic devices. One demonstrated method for exciton energy modification is through the use of the solvent dielectric effects in doped molecular films. To gain a deeper appreciation of the underlying physical mechanisms, in this work we test the solid-state solvation effect in molecular thin films under applied external pressure. We observe that external mechanical pressure increases dipole–dipole interactions, leading to shifts in the Frenkel exciton energy and enhancement of the time-resolved spectral red shift associated with the energy-transfer-mediated exciton diffusion. Measurements are performed on host:dopantmore » molecular thin films, which show bathochromic shifts in photoluminescence (PL) under increasing pressure. This is in agreement with a simple solvation theory model of exciton energetics with a fitting parameter based on the mechanical properties of the host matrix material. We measure no significant change in exciton lifetime with increasing pressure, consistent with unchanged aggregation in molecular films under compression. However, we do observe an increase in exciton spectral thermalization rate for compressed molecular films, indicating enhanced exciton diffusion for increased dipole–dipole interactions under pressure. The results highlight the contrast between molecular energy landscapes obtained when dipole–dipole interactions are increased by the pressure technique versus the conventional dopant concentration variation methods, which can lead to extraneous effects such as aggregation at higher doping concentrations. The present work demonstrates the use of pressure-probing techniques in studying energy disorder and exciton dynamics in amorphous molecular thin films.« less

MITOCHONDRIAL DISEASES PART III: THERAPEUTIC INTERVENTIONS IN MOUSE MODELS OF OXPHOS DEFICIENCIES

PubMed Central

Peralta, Susana; Torraco, Alessandra; Iommarini, Luisa; Diaz, Francisca

2015-01-01

Mitochondrial defects are the cause of numerous disorders affecting the oxidative phosphorylation system (OXPHOS) in humans leading predominantly to neurological and muscular degeneration. The molecular origin, manifestations, and progression of mitochondrial diseases have a broad spectrum, which makes very challenging to find a globally effective therapy. The study of the molecular mechanisms underlying the mitochondrial dysfunction indicates that there is a wide range of pathways, enzymes and molecules that could be potentially targeted for therapeutic purpose. Therefore, focusing on the pathology of the disease is essential to design new treatments. In this review, we will summarize and discuss the different therapeutic interventions tested in some mouse models of mitochondrial diseases laying emphasis on the molecular mechanisms of action and their potential applications. PMID:25638392

Information Theory Broadens the Spectrum of Molecular Ecology and Evolution.

PubMed

Sherwin, W B; Chao, A; Jost, L; Smouse, P E

2017-12-01

Information or entropy analysis of diversity is used extensively in community ecology, and has recently been exploited for prediction and analysis in molecular ecology and evolution. Information measures belong to a spectrum (or q profile) of measures whose contrasting properties provide a rich summary of diversity, including allelic richness (q=0), Shannon information (q=1), and heterozygosity (q=2). We present the merits of information measures for describing and forecasting molecular variation within and among groups, comparing forecasts with data, and evaluating underlying processes such as dispersal. Importantly, information measures directly link causal processes and divergence outcomes, have straightforward relationship to allele frequency differences (including monotonicity that q=2 lacks), and show additivity across hierarchical layers such as ecology, behaviour, cellular processes, and nongenetic inheritance. Copyright © 2017 Elsevier Ltd. All rights reserved.

The past and the future of Alzheimer's disease CSF biomarkers-a journey toward validated biochemical tests covering the whole spectrum of molecular events.

PubMed

Blennow, Kaj; Zetterberg, Henrik

2015-01-01

This paper gives a short review on cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD), from early developments to high-precision validated assays on fully automated lab analyzers. We also discuss developments on novel biomarkers, such as synaptic proteins and Aβ oligomers. Our vision for the future is that assaying a set of biomarkers in a single CSF tube can monitor the whole spectrum of AD molecular pathogenic events. CSF biomarkers will have a central position not only for clinical diagnosis, but also for the understanding of the sequence of molecular events in the pathogenic process underlying AD and as tools to monitor the effects of novel drug candidates targeting these different mechanisms.

Molecular Insight into Gut Microbiota and Rheumatoid Arthritis.

PubMed

Wu, Xiaohao; He, Bing; Liu, Jin; Feng, Hui; Ma, Yinghui; Li, Defang; Guo, Baosheng; Liang, Chao; Dang, Lei; Wang, Luyao; Tian, Jing; Zhu, Hailong; Xiao, Lianbo; Lu, Cheng; Lu, Aiping; Zhang, Ge

2016-03-22

Rheumatoid arthritis (RA) is a systemic, inflammatory, and autoimmune disorder. Gut microbiota play an important role in the etiology of RA. With the considerable progress made in next-generation sequencing techniques, the identified gut microbiota difference between RA patients and healthy individuals provides an updated overview of the association between gut microbiota and RA. We reviewed the reported correlation and underlying molecular mechanisms among gut microbiota, the immune system, and RA. It has become known that gut microbiota contribute to the pathogenesis of RA via multiple molecular mechanisms. The progressive understanding of the dynamic interaction between gut microbiota and their host will help in establishing a highly individualized management for each RA patient, and achieve a better efficacy in clinical practice, or even discovering new drugs for RA.

Molecular characterization of organic matter in converted forests in Western Europe; disentangling the effects of edaphic factors and input differences on SOM composition

NASA Astrophysics Data System (ADS)

Brock, Olaf; Kooijman, Annemieke; Vancampenhout, Karen; Muys, Bart; Jansen, Boris

2017-04-01

By storing carbon in the soil, forests can play an important role in climate mitigation. We studied how the SOM composition was affected by conversion of deciduous stands to mono-culture spruce plantations in the Mullerthal in Luxembourg and the Gaume in south-east Belgium. Both regions have a known and similar vegetation history on different lithologies, ranging from carcareous marls to decalcified sands. Lignin and cutin/suberin biomarkers were identified by using thermally assisted hydrolysis and methylation (THM) with unlabelled tetra methyl ammonium hydroxide (TMAH). Lignin was used to distinguish deciduous and coniferous litter sources, whereas cutin and suberin indicated the respective input of above- and belowground litter input. A twinplot setup was used to be able to independently evaluate the effect of edaphic factors versus input differences on SOM composition. pH values and SOC stocks reflected the lithological gradients in both study areas. The difference was more subtle in the Gaume where the gradient is much narrower. The existence of pedogenic thresholds explains why significant differences in lignin yield and SOC stocks between plots with different lithology were also found along the subtle gradient in the Gaume. Secondly, we observed differences in molecular composition and also in decomposition state of lignin that were caused solely by input differences between adjacent deciduous and coniferous forest plots. Furthermore, we found a legacy effect, a signal of former deciduous forest in the deeper soil layers (15-20 cm) under the current spruce plantations, in the loamy substrate plots of the Gaume, which was not observed in the Mullerthal, despite the similar vegetation history of both regions. This can be explained by differences in environmental conditions between both areas. Higher pH values resulting in a higher biological activity could explain the absence of a legacy effect in the Mullerthal plots. Therefore, an important conclusion of this work is that the presence of a legacy effect depends on local soil conditions and soil process domains. Lignin decomposition was found to be higher under more acid conditions, as present in spruce soils compared with the soils under deciduous trees. Moreover, the observance that in the Mullerthal the amount of lignin relative to TOC decreased with increasing depth from the surface, indicates preferential decomposition of lignin with depth. This is in line with the new paradigm that the (soil) environment rather than molecular composition is in many situations a dominant factor in determining the lignin turnover rate. Lastly, in both study areas within most twin plots SOC stocks were similar for both forest types, while SOC stocks were higher on a marl or limestone substrate than on a sandy substrate. We therefore argue that edapthic factors are of vital importance when considering forests to effectively mitigate climate change and that litter quality,and therefore the molecular composition of the organic matter, cannot be ignored when discussing organic matter persistence and carbon sequestration.

Comparison of extracellular protein profiles of seven serotypes of mutans streptococci grown under controlled conditions.

PubMed

Hardy, L N; Knox, K W; Brown, R A; Wicken, A J; Fitzgerald, R J

1986-05-01

Extracellular proteins produced by the four human commensal species of mutans streptococci were analysed. The organisms used were Streptococcus mutans, serotypes c, e and f, Streptococcus cricetus, serotype a, Streptococcus rattus, serotype b, and Streptococcus sobrinus, serotypes d and g. They were grown in continuous culture at different generation times and pH values in media containing either glucose or fructose to determine the extent of variation in extracellular protein production that could occur for an individual strain. The results for different organisms grown under the same conditions were then compared. The total amount of protein of molecular mass greater than or equal to 60 kDa varied considerably with the growth conditions and with the strain. Generally more protein was present at a higher pH, conditions under which the organisms also form more lipoteichoic acid. With respect to individual protein components SDS-PAGE proved better than isoelectric focusing for detecting phenotypic responses by a particular strain to environmental changes and differences between the different strains. Differences in the molecular masses of protein components were particularly pronounced in the regions designated P1 (185-200 kDa), P2 (130-155 kDa) and P3 (60-95 kDa). Every strain produced at least one component in the P1 region that cross-reacted with antiserum to the purified protein from S. mutans serotype c, a protein which is indistinguishable from antigens B and I/II. Two components in the P2 region were dominant in the case of S. cricetus and S. sobrinus strains and showed glucosyltransferase (GTF) activity. GTF activity was also detected in the P3 region, particularly with S. mutans strains.

A systems biology strategy to identify molecular mechanisms of action and protein indicators of traumatic brain injury.

PubMed

Yu, Chenggang; Boutté, Angela; Yu, Xueping; Dutta, Bhaskar; Feala, Jacob D; Schmid, Kara; Dave, Jitendra; Tawa, Gregory J; Wallqvist, Anders; Reifman, Jaques

2015-02-01

The multifactorial nature of traumatic brain injury (TBI), especially the complex secondary tissue injury involving intertwined networks of molecular pathways that mediate cellular behavior, has confounded attempts to elucidate the pathology underlying the progression of TBI. Here, systems biology strategies are exploited to identify novel molecular mechanisms and protein indicators of brain injury. To this end, we performed a meta-analysis of four distinct high-throughput gene expression studies involving different animal models of TBI. By using canonical pathways and a large human protein-interaction network as a scaffold, we separately overlaid the gene expression data from each study to identify molecular signatures that were conserved across the different studies. At 24 hr after injury, the significantly activated molecular signatures were nonspecific to TBI, whereas the significantly suppressed molecular signatures were specific to the nervous system. In particular, we identified a suppressed subnetwork consisting of 58 highly interacting, coregulated proteins associated with synaptic function. We selected three proteins from this subnetwork, postsynaptic density protein 95, nitric oxide synthase 1, and disrupted in schizophrenia 1, and hypothesized that their abundance would be significantly reduced after TBI. In a penetrating ballistic-like brain injury rat model of severe TBI, Western blot analysis confirmed our hypothesis. In addition, our analysis recovered 12 previously identified protein biomarkers of TBI. The results suggest that systems biology may provide an efficient, high-yield approach to generate testable hypotheses that can be experimentally validated to identify novel mechanisms of action and molecular indicators of TBI. © 2014 The Authors. Journal of Neuroscience Research Published by Wiley Periodicals, Inc.

Theoretical study on the rectifying performance of organoimido derivatives of hexamolybdates.

PubMed

Wen, Shizheng; Yang, Guochun; Yan, Likai; Li, Haibin; Su, Zhongmin

2013-02-25

We design a new type of molecular diode, based on the organoimido derivatives of hexamolybdates, by exploring the rectifying performances using density functional theory combined with the non-equilibrium Green's function. Asymmetric current-voltage characteristics were obtained for the models with an unexpected large rectification ratio. The rectifying behavior can be understood by the asymmetrical shift of the transmission peak observed under different polarities. It is interesting to find that the preferred electron-transport direction in our studied system is different from that of the organic D-bridge-A system. The results show that the studied organic-inorganic hybrid systems have an intrinsically robust rectifying ratio, which should be taken into consideration in the design of the molecular diodes. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Molecular aspects of stress-gene regulation during spaceflight

NASA Technical Reports Server (NTRS)

Paul, Anna-Lisa; Ferl, Robert J.

2002-01-01

Spaceflight-associated stress has been the topic of investigation since the first terrestrial organisms were exposed to this unique environment. Organisms that evolved under the selection pressures of earth-normal environments can perceive spaceflight as a stress, either directly because gravity influences an intrinsic biological process, or indirectly because of secondary effects imparted by spaceflight upon environmental conditions. Different organisms and even different organs within an organism adapt to a spaceflight environment with a diversity of tactics. Plants are keenly sensitive to gravity for directed development, and are also sensitive to other stresses associated with closed-system spaceflight environments. Within the past decade, the tools of molecular biology have begun to provide a sophisticated evaluation of spaceflight-associated stress and the genetic responses that accompany metabolic adaptation to spaceflight.

Disruption of adherens junction and alterations in YAP-related proliferation behavior as part of the underlying cell transformation process of alcohol-induced oral carcinogenesis.

PubMed

Husari, Ayman; Hülter-Hassler, Diana; Steinberg, Thorsten; Schulz, Simon Daniel; Tomakidi, Pascal

2018-01-01

Accumulating evidences indicate that alcohol might play a causative in oral cancer. Unfortunately, in vitro cell systems, uncovering the molecular background of the underlying cell transformation process, are rare. Therefore, this study was conducted, to identify molecular changes and characterize their putative cell behavioral consequences in epitheloid (EPI) and fibroblastoid (FIB) oral keratinocyte phenotypes, arising from chronical alcohol treatment. Concerning adherens junctions (AJs), both EPI and FIB showed membrane-bound β-catenin, but exhibited differences for E-cadherin and zyxin. While EPI revealed E-cadherin/β-catenin membrane co-localization, which in parts also applied for zyxin, FIB membranes were devoid of E-cadherin and exhibited marginal zyxin expression. Fetal calf serum (FCS) administration in starved cells promoted proliferation in both keratinocyte phenotypes, whereat EPI and FIB yielded a strikingly modified FCS sensitivity on the temporal scale. Impedance measurement-based cell index detection yielded proliferation stimulation occurring much earlier in FIB (<20h) compared to EPI (>45h). Nuclear preference of the proliferation-associated YAP co-transcription factor in FIB was FCS independent, while it required FCS in EPI. Taken together, the lack of membrane-inherent E-cadherin/β-catenin co-localization together with low zyxin - reveals perturbation of AJ integrity in FIB. Regarding cell behavior, perturbed AJs in FIB correlate with temporal proliferation sensitivity towards FCS. CYF of 5.6 strongly suggests involvement of chromatin-bound YAP in FIB's proliferation temperosensitivity. These molecular differences detected for EPI and FIB are part of the underlying cell transformation process of alcohol-induced oral carcinogenesis, and indicate FIB being in a more advanced transformation stage. Copyright © 2017 Elsevier B.V. All rights reserved.

Characterization of molecular disorder in vapor-deposited thin films of aluminum tris(quinoline-8-olate) by one-dimensional 27Al NMR under magic angle spinning.

PubMed

Utz, Marcel; Nandagopal, Magesh; Mathai, Mathew; Papadimitrakopoulos, Fotios

2006-01-21

Aluminum tris (quinoline-8-olate) (Alq3) is used as an electron-transport layer in organic light-emitting diodes. The material can be obtained in a wide range of different solid phases, both crystalline and amorphous, by deposition from the vapor phase or from solution under controlled conditions. While the structure of the crystalline polymorphs of Alq3 has been investigated thoroughly by x-ray diffraction as well as solid-state NMR, very little information is currently available on the amount of structural disorder in the amorphous forms of Alq3. In the present contribution, we report the use of 27Al NMR spectroscopy in the solid state under magic angle spinning to extract such information from amorphous vapor deposits of Alq3. The NMR spectra obtained from these samples exhibit different degrees of broadening, reflecting distributions of the electric-field gradient tensor at the site of the aluminum ion. These distributions can be obtained from the NMR spectra by solving the corresponding inverse problem. From these results, the magnitude of structural disorder in terms of molecular geometry has been estimated by density-functional theory calculations. It was found that the electric-field gradient anisotropy delta follows a bimodal distribution. Its majority component is centered around delta values comparable to the meridianal alpha crystal polymorph and has a width of about 10%, corresponding to distortions of the molecular geometry of a few degrees in the orientation of the ligands. Alq3 samples obtained at higher deposition rates exhibit higher degrees of disorder. The minor component, present at about 7%, has a much smaller anisotropy, suggesting that it may be due to the facial isomer of Alq3.

Seed maturation associated transcriptional programs and regulatory networks underlying genotypic difference in seed dormancy and size/weight in wheat (Triticum aestivum L.).

PubMed

Yamasaki, Yuji; Gao, Feng; Jordan, Mark C; Ayele, Belay T

2017-09-16

Maturation forms one of the critical seed developmental phases and it is characterized mainly by programmed cell death, dormancy and desiccation, however, the transcriptional programs and regulatory networks underlying acquisition of dormancy and deposition of storage reserves during the maturation phase of seed development are poorly understood in wheat. The present study performed comparative spatiotemporal transcriptomic analysis of seed maturation in two wheat genotypes with contrasting seed weight/size and dormancy phenotype. The embryo and endosperm tissues of maturing seeds appeared to exhibit genotype-specific temporal shifts in gene expression profile that might contribute to the seed phenotypic variations. Functional annotations of gene clusters suggest that the two tissues exhibit distinct but genotypically overlapping molecular functions. Motif enrichment predicts genotypically distinct abscisic acid (ABA) and gibberellin (GA) regulated transcriptional networks contribute to the contrasting seed weight/size and dormancy phenotypes between the two genotypes. While other ABA responsive element (ABRE) motifs are enriched in both genotypes, the prevalence of G-box-like motif specifically in tissues of the dormant genotype suggests distinct ABA mediated transcriptional mechanisms control the establishment of dormancy during seed maturation. In agreement with this, the bZIP transcription factors that co-express with ABRE enriched embryonic genes differ with genotype. The enrichment of SITEIIATCYTC motif specifically in embryo clusters of maturing seeds irrespective of genotype predicts a tissue specific role for the respective TCP transcription factors with no or minimal contribution to the variations in seed dormancy. The results of this study advance our understanding of the seed maturation associated molecular mechanisms underlying variation in dormancy and weight/size in wheat seeds, which is a critical step towards the designing of molecular strategies for enhancing seed yield and quality.

Functionalized Ergot-alkaloids as potential dopamine D3 receptor agonists for treatment of schizophrenia

NASA Astrophysics Data System (ADS)

Ivanova, Bojidarka; Spiteller, Michael

2012-12-01

The relationship between the molecular structure and physical properties of functionalized naturally occurred Ergot-alkaloids as potential dopamine D3 receptor agonists is presented. The molecular modeling of the ergoline-skeleton is based on the comprehensive theoretical study of the binding affinity of the isolated chemicals towards the active sites of the D3 sub-type receptor (D3R) loops. The studied proton accepting ability under physiological conditions allows classifying four types of monocationics, characterizing with the different binding modes to D3R involving selected amino acid residues to the active sites. These results marked the pharmaceutical potential and clinical usage of the reported compounds as antipsychotic drugs for Schizophrenia treatment, since they allowed evaluating the highlights of the different hypothesizes of the biochemical causes the illness. The applied complex approach for theoretical and experimental elucidation, including quantum chemistry method, electrospray ionization (ESI) and matrix assisted laser desorption/ionization (MALDI) mass spectrometric (MS) methods, nuclear magnetic resonance and vibrational IR and Raman spectroscopy on the isolated fifteen novel derivatives (1)-(15) and their different protonated forms (1a)-(15a) evidenced a strong dependence of molecular conformation, physical properties and binding affinity. Thus, the semi-synthetic functionalization of the naturally occurred products (NPs), provided significant possibilities to further molecular drugs-design and development of novel derivatives with wanted biological function, using the established profile of selected classes/families of NPs. The work described chiefly the non-linear (NL) approach for the interpretation of the mass chromatograms on the performed hybrid high performance liquid chromatography (HPLC) tandem MS/MS and MS/MS/MS experiments, discussing the merits and great diversity of instrumentation flexibility, thus achieving fundamental structural information, indispensable for the analysis of Ergot-alkaloid derivatives, which under the physiological conditions easily converted to d-lysergic acid (LSD).

Single molecular force across single integrins dictates cell spreading.

PubMed

Chowdhury, Farhan; Li, Isaac T S; Leslie, Benjamin J; Doğanay, Sultan; Singh, Rishi; Wang, Xuefeng; Seong, Jihye; Lee, Sang-Hak; Park, Seongjin; Wang, Ning; Ha, Taekjip

2015-10-01

Cells' ability to sense and interpret mechanical signals from the extracellular milieu modulates the degree of cell spreading. Yet how cells detect such signals and activate downstream signaling at the molecular level remain elusive. Herein, we utilize tension gauge tether (TGT) platform to investigate the underlying molecular mechanism of cell spreading. Our data from both differentiated cells of cancerous and non-cancerous origin show that for the same stiff underlying glass substrates and for same ligand density it is the molecular forces across single integrins that ultimately determine cell spreading responses. Furthermore, by decoupling molecular stiffness and molecular tension we demonstrate that molecular stiffness has little influence on cell spreading. Our data provide strong evidence that links molecular forces at the cell-substrate interface to the degree of cell spreading.

Organic matter characteristics in boreal forest soils under stands of silver birch, Norway spruce, and Norway spruce with a mixture of silver birch

NASA Astrophysics Data System (ADS)

Smolander, A.; Kitunen, V.

2012-04-01

The aim was to study how tree species and a tree species mixture affect microbial C and N transformations and two major plant secondary compound groups, terpenes and phenolic compounds in soil. The study site was a tree-species experiment in middle-eastern part of Finland containing plots of 43-year-old silver birch, Norway spruce and Norway spruce with a mixture of silver birch (22 and 37 % birch of the total stem number). Soil was podzol and humus type mor. Samples were taken from the organic layer. C and N in the microbial biomass, rates of C mineralization (CO2 evolution), net N mineralization and nitrification, and concentrations of total water-soluble phenolic compounds, condensed tannins and different kind of terpenes were measured. Amounts of C and N in the microbial biomass and the rates of C mineralization and net N mineralization were all lower under spruce than birch, and particularly net N mineralization was stimulated by birch mixture. Concentrations of total water-soluble phenolic compounds were on a similar level, irrespective of tree species. However, there were less low-molecular-weight phenolics and more high-molecular-weight phenolics under spruce than birch. Concentrations of condensed tannins and both sesqui- and diterpenes were all higher under spruce than birch but the concentrations of triterpenes were similar in all soils. The difference between tree species was greatest with monoterpenes which were measured from both organic layer and soil atmosphere: high concentrations under spruce and negligible under birch. Birch mixture tended to decrease the concentrations of condensed tannins and mono-, sesqui- and diterpenes.

How the Molecular Packing Affects the Room Temperature Phosphorescence in Pure Organic Compounds: Ingenious Molecular Design, Detailed Crystal Analysis, and Rational Theoretical Calculations.

PubMed

Xie, Yujun; Ge, Yuwei; Peng, Qian; Li, Conggang; Li, Qianqian; Li, Zhen

2017-05-01

Long-lived phosphorescence at room temperature (RTP) from pure organic molecules is rare. Recent research reveals various crystalline organic molecules can realize RTP with lifetimes extending to the magnitude of second. There is little research on how molecular packing affecting RTP. Three compounds are designed with similar optical properties in solution, but tremendously different solid emission characteristics. By investigating the molecular packing arrangement in single crystals, it is found that the packing style of the compact face to face favors of long phosphorescence lifetime and high photoluminescence efficiency, with the lifetime up to 748 ms observed in the crystal of CPM ((9H-carbazol-9-yl)(phenyl)methanone). Theoretical calculation analysis also reveals this kind of packing style can remarkably reduce the singlet excited energy level and prompt electron communication between dimers. Surprisingly, CPM has two very similar single crystals, labeled as CPM and CPM-A, with almost identical crystal data, and the only difference is that molecules in CPM-A crystal take a little looser packing arrangement. X-ray diffraction and cross-polarization under magic spinning 13 C NMR spectra double confirm that they are different crystals. Interestingly, CPM-A crystal shows negligible RTP compared to the CPM crystal, once again proving that the packing style is critical to the RTP property. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Morphological Study of Langmuir Polymer Films by means of Atomic Force Microscopy and MD Simulations

NASA Astrophysics Data System (ADS)

Reiter, Renate; Knecht, Volker; Chandran, Sivasurender; Reiter, Günter

In general it is difficult to reproduce well defined morphologies of Langmuir polymer films (LPFs) because they have a high propensity to form non-equilibrium states. We present a systematic study based on different compression protocols designed to allow for relaxations of LPFs under well defined conditions. The homo peptide poly-?-benzyl-L-glutamate (PBLG) was chosen for this study because it is a well investigated system that represents the relaxational behaviour of rod-like molecules which is expected to show less complexity than coiled polymer molecules. Our results demonstrate that experimentally manipulating the course of relaxations in LPFs has tremendous impact on the ordering of the molecules. Coarse grain molecular dynamics simulations were performed under comparable conditions. The results match the experimental observations reasonably well and allow to zoom into molecular details which are not resolved experimentally.

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

Moberg, Daniel R.; Straight, Shelby C.; Knight, Christopher

Here, an unambiguous assignment of the vibrational spectra of ice I h remains a matter of debate. This study demonstrates that an accurate representation of many-body interactions between water molecules, combined with an explicit treatment of nuclear quantum effects through many-body molecular dynamics (MB-MD), leads to a unified interpretation of the vibrational spectra of ice I h in terms of the structure and dynamics of the underlying hydrogen-bond network. All features of the infrared and Raman spectra in the OH stretching region can be unambiguously assigned by taking into account both the symmetry and the delocalized nature of the latticemore » vibrations as well as the local electrostatic environment experienced by each water molecule within the crystal. The high level of agreement with experiment raises prospects for predictive MB-MD simulations that, complementing analogous measurements, will provide molecular-level insights into fundamental processes taking place in bulk ice and on ice surfaces under different thermodynamic conditions.« less

Nitrate reductase and nitrous oxide production by Fusarium oxysporum 11dn1 under aerobic and anaerobic conditions.

PubMed

Kurakov, A V; Nosikov, A N; Skrynnikova, E V; L'vov, N P

2000-08-01

The fungus Fusarium oxysporum 11dn1 was found to be able to grow and produce nitrous oxide on nitrate-containing medium in anaerobic conditions. The rate of nitrous oxide formation was three to six orders of magnitude lower than the rates of molecular nitrogen production by common denitrifying bacteria. Acetylene and ammonia did not affect the release of nitrous oxide release. It was shown that under anaerobic conditions fast increase of nitrate reductase activity occurred, caused by the synthesis of enzyme de novo and protein dephosphorylation. Reverse transfer of the mycelium to aerobic conditions led to a decline in nitrate reductase activity and stopped nitrous oxide production. The presence of two nitrate reductases was shown, which differed in molecular mass, location, temperature optima, and activity in nitrate- and ammonium-containing media. Two enzymes represent assimilatory and dissimilatory nitrate reductases, which are active in aerobic and anaerobic conditions, respectively.

An ab initio molecular dynamics and density functional theory study of the formation of phosphate chains from metathiophosphates.

PubMed

Mosey, Nicholas J; Woo, Tom K

2006-09-04

The reactions that occur between metathiophosphate (MTP) molecules are identified and examined through ab initio molecular dynamics simulations and static quantum chemical calculations at the density functional level of theory. The simulations show that certain types of MTPs can react to yield phosphate chains, while others only dimerize. These differences are rationalized in terms of reaction energies and the electronic structures of these molecules. In the reaction leading to the formation of phosphate chains, the reactive center, a tri-coordinate phosphorus atom, is continually regenerated. A polymerization mechanism linking MTPs to phosphate chains is developed on the basis of these results. This information sheds light on the underlying processes that may be responsible for the formation of phosphates under high-temperature conditions and may prove useful in the development of protocols for the rational synthesis of complex phosphate structures.

Fibroblast growth factor receptors in breast cancer: expression, downstream effects, and possible drug targets.

PubMed

Tenhagen, M; van Diest, P J; Ivanova, I A; van der Wall, E; van der Groep, P

2012-08-01

Cancer treatments are increasingly focusing on the molecular mechanisms underlying the oncogenic processes present in tumors of individual patients. Fibroblast growth factor receptors (FGFRs) are among the many molecules that are involved in oncogenesis and are currently under investigation for their potential as drug targets in breast cancer patients. These receptor tyrosine kinases play a role in several processes including proliferation, angiogenesis, and migration. Alterations in these basal processes can contribute to the development and progression of tumors. Among breast cancer patients, several subgroups have been shown to harbor genetic aberrations in FGFRs, including amplifications of FGFR1, FGFR2, and FGFR4 and mutations in FGFR2 and FGFR4. Here, we review in vitro and in vivo models that have partly elucidated the molecular implications of these different genetic aberrations, the resulting tumor characteristics, and the potential of FGFRs as therapeutic targets for breast cancer treatment.

Similar folds with different stabilization mechanisms: the cases of prion and doppel proteins

PubMed Central

Colacino, Stefano; Tiana, Guido; Colombo, Giorgio

2006-01-01

Background Protein misfolding is the main cause of a group of fatal neurodegenerative diseases in humans and animals. In particular, in Prion-related diseases the normal cellular form of the Prion Protein PrP (PrPC) is converted into the infectious PrPSc through a conformational process during which it acquires a high β-sheet content. Doppel is a protein that shares a similar native fold, but lacks the scrapie isoform. Understanding the molecular determinants of these different behaviours is important both for biomedical and biophysical research. Results In this paper, the dynamical and energetic properties of the two proteins in solution is comparatively analyzed by means of long time scale explicit solvent, all-atom molecular dynamics in different temperature conditions. The trajectories are analyzed by means of a recently introduced energy decomposition approach (Tiana et al, Prot. Sci. 2004) aimed at identifying the key residues for the stabilization and folding of the protein. Our analysis shows that Prion and Doppel have two different cores stabilizing the native state and that the relative contribution of the nucleus to the global stability of the protein for Doppel is sensitively higher than for PrP. Moreover, under misfolding conditions the Doppel core is conserved, while the energy stabilization network of PrP is disrupted. Conclusion These observations suggest that different sequences can share similar native topology with different stabilizing interactions and that the sequences of the Prion and Doppel proteins may have diverged under different evolutionary constraints resulting in different folding and stabilization mechanisms. PMID:16857062

Mechanism of Urea Crystal Dissolution in Water from Molecular Dynamics Simulation.

PubMed

Anand, Abhinav; Patey, G N

2018-01-25

Molecular dynamics simulations are used to determine the mechanism of urea crystal dissolution in water under sink conditions. Crystals of cubic and tablet shapes are considered, and results are reported for four commonly used water models. The dissolution rates for different water models can differ considerably, but the overall dissolution mechanism remains the same. Urea dissolution occurs in three stages: a relatively fast initial stage, a slower intermediate stage, and a final stage. We show that the long intermediate stage is well described by classical rate laws, which assume that the dissolution rate is proportional to the active surface area. By carrying out simulations at different temperatures, we show that urea dissolution is an activated process, with an activation energy of ∼32 kJ mol -1 . Our simulations give no indication of a significant diffusion layer, and we conclude that the detachment of molecules from the crystal is the rate-determining step for dissolution. The results we report for urea are consistent with earlier observations for the dissolution of NaCl crystals. This suggests that the three-stage mechanism and classical rate laws might apply to the dissolution of other ionic and molecular crystals.

A Computational Study of the Rheology and Structure of Surfactant Covered Droplets

NASA Astrophysics Data System (ADS)

Maia, Joao; Boromand, Arman; Jamali, Safa

2015-11-01

The use of different types of surface-active agents is ubiquitous practice in different industrial applications ranging from cosmetic and food industries to polymeric nano-composite and blends. This allows stable multiphasic systems like foams and emulsions to be produced. Stability and shelf-life of those products are directly determined by the efficiency of the surfactant molecules. Although the effect of molecular configuration of the surface-active molecules on the planar interfaces has been studied both experimentally and computationally, it remains challenging to track the efficiency and effectiveness of different surfactant molecules on curved interfaces. In this study we address this gap by using Dissipative Particle Dynamics, to study the effectiveness and efficiency of different surfactant molecules (linear vs. branched) on a curved interface in equilibrium and far from equilibrium. In particular, we are interested to relate interfacial properties of the surface covered droplets and its dynamics to the molecular configuration of the surface active molecules under equilibrium and far from equilibrium condition.

Microbial production of polyhydroxybutyrate with tailor-made properties: an integrated modelling approach and experimental validation.

PubMed

Penloglou, Giannis; Chatzidoukas, Christos; Kiparissides, Costas

2012-01-01

The microbial production of polyhydroxybutyrate (PHB) is a complex process in which the final quantity and quality of the PHB depend on a large number of process operating variables. Consequently, the design and optimal dynamic operation of a microbial process for the efficient production of PHB with tailor-made molecular properties is an extremely interesting problem. The present study investigates how key process operating variables (i.e., nutritional and aeration conditions) affect the biomass production rate and the PHB accumulation in the cells and its associated molecular weight distribution. A combined metabolic/polymerization/macroscopic modelling approach, relating the process performance and product quality with the process variables, was developed and validated using an extensive series of experiments and measurements. The model predicts the dynamic evolution of the biomass growth, the polymer accumulation, the consumption of carbon and nitrogen sources and the average molecular weights of the PHB in a bioreactor, under batch and fed-batch operating conditions. The proposed integrated model was used for the model-based optimization of the production of PHB with tailor-made molecular properties in Azohydromonas lata bacteria. The process optimization led to a high intracellular PHB accumulation (up to 95% g of PHB per g of DCW) and the production of different grades (i.e., different molecular weight distributions) of PHB. Copyright © 2011 Elsevier Inc. All rights reserved.

Efficient removal of methyl orange using Cu2O as a dual function catalyst

NASA Astrophysics Data System (ADS)

Zhang, Fan; Dong, Guohui; Wang, Mian; Zeng, Yubin; Wang, Chuanyi

2018-06-01

In this study, we synthesized Cu2O particles with rough surfaces by a facile solvothermal method as a dual-function material that can degrade contaminants not only under light irradiation but also in dark circumstance. Both the as-prepared Cu2O and commercial Cu2O exhibited excellent performance for the removal of methyl orange under visible light irradiation through a photocatalysis-based strategy. However, the former was found to show remarkable capability under dark circumstances by means of molecular oxygen activation, while the latter performed poor efficiently under the same condition. This significant difference of performances under dark circumstances was related to rich oxygen vacancies existed on the as-prepared Cu2O surfaces that are associated with the single-electron reduction of O2 to generate radO2-, which play a dominant role in the generation of Cu+. In addition, Cu+ was identified to play key roles in the broken of azo bond. Then, the generated intermediates were mineralized by radOH generated through molecular oxygen activation process. This study could not only deep the understanding of the MO removal mechanism by Cu2O but also show a novel direction of amphibious application for photocatalytic materials.

Molecular recognition of naphthalene diimide ligands by telomeric quadruplex-DNA: the importance of the protonation state and mediated hydrogen bonds.

PubMed

Spinello, A; Barone, G; Grunenberg, J

2016-01-28

In depth Monte Carlo conformational scans in combination with molecular dynamics (MD) simulations and electronic structure calculations were applied in order to study the molecular recognition process between tetrasubstituted naphthalene diimide (ND) guests and G-quadruplex (G4) DNA receptors. ND guests are a promising class of telomere stabilizers due to which they are used in novel anticancer therapeutics. Though several ND guests have been studied experimentally in the past, the protonation state under physiological conditions is still unclear. Based on chemical intuition, in the case of N-methyl-piperazine substitution, different protonation states are possible and might play a crucial role in the molecular recognition process by G4-DNA. Depending on the proton concentration, different nitrogen atoms of the N-methyl-piperazine might (or might not) be protonated. This fact was considered in our simulation in terms of a case by case analysis, since the process of molecular recognition is determined by possible donor or acceptor positions. The results of our simulations show that the electrostatic interactions between the ND ligands and the G4 receptor are maximized in the case of the protonation of the terminal nitrogen atoms, forming compact ND G4 complexes inside the grooves. The influence of different protonation states in terms of the ability to form hydrogen bonds with the sugar-phosphate backbone, as well as the importance of mediated vs. direct hydrogen bonding, was analyzed in detail by MD and relaxed force constant (compliance constant) simulations.

Rapid three-dimensional microfluidic mixer for high viscosity solutions to unravel earlier folding kinetics of G-quadruplex under molecular crowding conditions.

PubMed

Liu, Chao; Li, Ying; Li, Yiwei; Chen, Peng; Feng, Xiaojun; Du, Wei; Liu, Bi-Feng

2016-01-01

Rapid mixing of highly viscous solutions is a great challenge, which helps to analyze the reaction kinetics in viscous liquid phase, particularly to discover the folding kinetics of macromolecules under molecular crowding conditions mimicking the conditions inside cells. Here, we demonstrated a novel microfluidic mixer based on Dean flows with three-dimensional (3D) microchannel configuration for fast mixing of high-viscosity fluids. The main structure contained three consecutive subunits, each consisting of a "U"-type channel followed by a chamber with different width and height. Thus, the two solutions injected from the two inlets would undergo a mixing in the first "U"-type channel due to the Dean flow effect, and simultaneous vortices expansions in both horizontal and vertical directions in the following chamber. Numerical simulations and experimental characterizations confirmed that the micromixer could achieve a mixing time of 122.4μs for solutions with viscosities about 33.6 times that of pure water. It was the fastest micromixer for high viscosity solutions compared with previous reports. With this highly efficient 3D microfluidic mixer, we further characterized the early folding kinetics of human telomere G-quadruplex under molecular crowding conditions, and unravelled a new folding process within 550μs. Copyright © 2015 Elsevier B.V. All rights reserved.

A consolidated analysis of the physiologic and molecular responses induced under acid stress in the legume-symbiont model-soil bacterium Sinorhizobium meliloti.

PubMed

Draghi, W O; Del Papa, M F; Hellweg, C; Watt, S A; Watt, T F; Barsch, A; Lozano, M J; Lagares, A; Salas, M E; López, J L; Albicoro, F J; Nilsson, J F; Torres Tejerizo, G A; Luna, M F; Pistorio, M; Boiardi, J L; Pühler, A; Weidner, S; Niehaus, K; Lagares, A

2016-07-11

Abiotic stresses in general and extracellular acidity in particular disturb and limit nitrogen-fixing symbioses between rhizobia and their host legumes. Except for valuable molecular-biological studies on different rhizobia, no consolidated models have been formulated to describe the central physiologic changes that occur in acid-stressed bacteria. We present here an integrated analysis entailing the main cultural, metabolic, and molecular responses of the model bacterium Sinorhizobium meliloti growing under controlled acid stress in a chemostat. A stepwise extracellular acidification of the culture medium had indicated that S. meliloti stopped growing at ca. pH 6.0-6.1. Under such stress the rhizobia increased the O2 consumption per cell by more than 5-fold. This phenotype, together with an increase in the transcripts for several membrane cytochromes, entails a higher aerobic-respiration rate in the acid-stressed rhizobia. Multivariate analysis of global metabolome data served to unequivocally correlate specific-metabolite profiles with the extracellular pH, showing that at low pH the pentose-phosphate pathway exhibited increases in several transcripts, enzymes, and metabolites. Further analyses should be focused on the time course of the observed changes, its associated intracellular signaling, and on the comparison with the changes that operate during the sub lethal acid-adaptive response (ATR) in rhizobia.

A consolidated analysis of the physiologic and molecular responses induced under acid stress in the legume-symbiont model-soil bacterium Sinorhizobium meliloti

PubMed Central

Draghi, W. O.; Del Papa, M. F.; Hellweg, C.; Watt, S. A.; Watt, T. F.; Barsch, A.; Lozano, M. J.; Lagares, A.; Salas, M. E.; López, J. L.; Albicoro, F. J.; Nilsson, J. F.; Torres Tejerizo, G. A.; Luna, M. F.; Pistorio, M.; Boiardi, J. L.; Pühler, A.; Weidner, S.; Niehaus, K.; Lagares, A.

2016-01-01

Abiotic stresses in general and extracellular acidity in particular disturb and limit nitrogen-fixing symbioses between rhizobia and their host legumes. Except for valuable molecular-biological studies on different rhizobia, no consolidated models have been formulated to describe the central physiologic changes that occur in acid-stressed bacteria. We present here an integrated analysis entailing the main cultural, metabolic, and molecular responses of the model bacterium Sinorhizobium meliloti growing under controlled acid stress in a chemostat. A stepwise extracellular acidification of the culture medium had indicated that S. meliloti stopped growing at ca. pH 6.0–6.1. Under such stress the rhizobia increased the O2 consumption per cell by more than 5-fold. This phenotype, together with an increase in the transcripts for several membrane cytochromes, entails a higher aerobic-respiration rate in the acid-stressed rhizobia. Multivariate analysis of global metabolome data served to unequivocally correlate specific-metabolite profiles with the extracellular pH, showing that at low pH the pentose-phosphate pathway exhibited increases in several transcripts, enzymes, and metabolites. Further analyses should be focused on the time course of the observed changes, its associated intracellular signaling, and on the comparison with the changes that operate during the sub lethal acid-adaptive response (ATR) in rhizobia. PMID:27404346

Quasi-bound states in strained graphene

NASA Astrophysics Data System (ADS)

Bahamon, Dario; Qi, Zenan; Park, Harold; Pareira, Vitor; Campbell, David

In this work, we explore the possibility of manipulating electronic states in graphene nanostructures by mechanical means. Specifically, we use molecular dynamics and tight-binding models to access the electronic and transport properties of strained graphene nanobubbles and graphene kirigami. We establish that low energy electrons can be confined in the arms of the kirigami and within the nanobubbles; under different load conditions the coupling between confined states and continuous states is modified creating different conductance line-shapes.

The alteration of mRNA expression of SOD and GPX genes, and proteins in tomato (Lycopersicon esculentum Mill) under stress of NaCl and/or ZnO nanoparticles.

PubMed

Alharby, Hesham F; Metwali, Ehab M R; Fuller, Michael P; Aldhebiani, Amal Y

2016-11-01

Five cultivars of tomato having different levels of salt stress tolerance were exposed to different treatments of NaCl (0, 3 and 6 g L -1 ) and ZnO-NPs (0, 15 and 30 mg L -1 ). Treatments with NaCl at both 3 and 6 g L -1 suppressed the mRNA levels of superoxide dismutase (SOD) and glutathione peroxidase (GPX) genes in all cultivars while plants treated with ZnO-NPs in the presence of NaCl, showed increments in the mRNA expression levels. This indicated that ZnO-NPs had a positive response on plant metabolism under salt stress. Superior expression levels of mRNA were observed in the salt tolerant cultivars, Sandpoint and Edkawy while the lowest level was detected in the salt sensitive cultivar, Anna Aasa. SDS-PAGE showed clear differences in patterns of protein expression among the cultivars. A negative protein marker for salt sensitivity and ZnO-NPs was detected in cv. Anna Aasa at a molecular weight of 19.162 kDa, while the tolerant cultivar Edkawy had two positive markers at molecular weights of 74.991 and 79.735 kDa.

Theoretical molecular studies of astrophysical interest

NASA Technical Reports Server (NTRS)

Flynn, George

1991-01-01

When work under this grant began in 1974 there was a great need for state-to-state collisional excitation rates for interstellar molecules observed by radio astronomers. These were required to interpret observed line intensities in terms of local temperatures and densities, but, owing to lack of experimental or theoretical values, estimates then being used for this purpose ranged over several orders of magnitude. A problem of particular interest was collisional excitation of formaldehyde; Townes and Cheung had suggested that the relative size of different state-to-state rates (propensity rules) was responsible for the anomalous absorption observed for this species. We believed that numerical molecular scattering techniques (in particular the close coupling or coupled channel method) could be used to obtain accurate results, and that these would be computationally feasible since only a few molecular rotational levels are populated at the low temperatures thought to prevail in the observed regions. Such calculations also require detailed knowledge of the intermolecular forces, but we thought that those could also be obtained with sufficient accuracy by theoretical (quantum chemical) techniques. Others, notably Roy Gordon at Harvard, had made progress in solving the molecular scattering equations, generally using semi-empirical intermolecular potentials. Work done under this grant generalized Gordon's scattering code, and introduced the use of theoretical interaction potentials obtained by solving the molecular Schroedinger equation. Earlier work had considered only the excitation of a diatomic molecule by collisions with an atom, and we extended the formalism to include excitation of more general molecular rotors (e.g., H2CO, NH2, and H2O) and also collisions of two rotors (e.g., H2-H2).

Molecular structural property and potential energy dependence on nonequilibrium-thermodynamic state point of liquid n-hexadecane under shear.

PubMed

Tseng, Huan-Chang; Chang, Rong-Yeu; Wu, Jiann-Shing

2011-01-28

Extensive computer experiments have been conducted in order to shed light on the macroscopic shear flow behavior of liquid n-hexadecane fluid under isobaric-isothermal conditions through the nonequilibrium molecular dynamic methodology. With respect to shear rates, the accompanying variations in structural properties of the fluid span the microscopic range of understanding from the intrinsic to extrinsic characteristics. As drawn from the average value of bond length and bond angle, the distribution of dihedral angle, and the radius distribution function of intramolecular and intermolecular van der Waals distances, these intrinsic structures change with hardness, except in the situation of extreme shear rates. The shear-induced variation of thermodynamic state curve along with the shear rate studied is shown to consist of both the quasiequilibrium state plateau and the nonequilibrium-thermodynamic state slope. Significantly, the occurrence of nonequilibrium-thermodynamic state behavior is attributed to variations in molecular potential energies, which include bond stretching, bond bending, bond torsion, and intra- and intermolecular van der Waals interactions. To unfold the physical representation of extrinsic structural deformation, under the aggressive influence of a shear flow field, the molecular dimension and appearance can be directly described via the squared radius of gyration and the sphericity angle, R(g)(2) and ϕ, respectively. In addition, a specific orientational order S(x) defines the alignment of the molecules with the flow direction of the x-axis. As a result, at low shear rates, the overall molecules are slightly stretched and shaped in a manner that is increasingly ellipsoidal. Simultaneously, there is an obvious enhancement in the order. In contrast to high shear rates, the molecules spontaneously shrink themselves with a decreased value of R(g)(2), while their shape and order barely vary with an infinite value of ϕ and S(x). It is important to note that under different temperatures and pressures, these three parameters are integrated within a molecular description in response to thermodynamic state variable of density and rheological material function of shear viscosity.

DNA under Force: Mechanics, Electrostatics, and Hydration.

PubMed

Li, Jingqiang; Wijeratne, Sithara S; Qiu, Xiangyun; Kiang, Ching-Hwa

2015-02-25

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.

Microscopic Structure and Solubility Predictions of Multifunctional Solids in Supercritical Carbon Dioxide: A Molecular Simulation Study.

PubMed

Noroozi, Javad; Paluch, Andrew S

2017-02-23

Molecular dynamics simulations were employed to both estimate the solubility of nonelectrolyte solids, such as acetanilide, acetaminophen, phenacetin, methylparaben, and lidocaine, in supercritical carbon dioxide and understand the underlying molecular-level driving forces. The solubility calculations involve the estimation of the solute's limiting activity coefficient, which may be computed using conventional staged free-energy calculations. For the case of lidocaine, wherein the infinite dilution approximation is not appropriate, we demonstrate how the activity coefficient at finite concentrations may be estimated without additional effort using the dilute solution approximation and how this may be used to further understand the solvation process. Combining with experimental pure-solid properties, namely, the normal melting point and enthalpy of fusion, solubilities were estimated. The results are in good quantitative agreement with available experimental data, suggesting that molecular simulations may be a powerful tool for understanding supercritical processes and the design of carbon dioxide-philic molecular systems. Structural analyses were performed to shed light on the microscopic details of the solvation of different functional groups by carbon dioxide and the observed solubility trends.

Molecular model for the diffusion of associating telechelic polymer networks

NASA Astrophysics Data System (ADS)

Ramirez, Jorge; Dursch, Thomas; Olsen, Bradley

Understanding the mechanisms of motion and stress relaxation of associating polymers at the molecular level is critical for advanced technological applications such as enhanced oil-recovery, self-healing materials or drug delivery. In associating polymers, the strength and rates of association/dissociation of the reversible physical crosslinks govern the dynamics of the network and therefore all the macroscopic properties, like self-diffusion and rheology. Recently, by means of forced Rayleigh scattering experiments, we have proved that associating polymers of different architectures show super-diffusive behavior when the free motion of single molecular species is slowed down by association/dissociation kinetics. Here we discuss a new molecular picture for unentangled associating telechelic polymers that considers concentration, molecular weight, number of arms of the molecules and equilibrium and rate constants of association/dissociation. The model predicts super-diffusive behavior under the right combination of values of the parameters. We discuss some of the predictions of the model using scaling arguments, show detailed results from Brownian dynamics simulations of the FRS experiments, and attempt to compare the predictions of the model to experimental data.

Two-center interference effects in (e, 2e) ionization of H2 and CO2 at large momentum transfer

NASA Astrophysics Data System (ADS)

Yamazaki, Masakazu; Nakajima, Isao; Satoh, Hironori; Watanabe, Noboru; Jones, Darryl; Takahashi, Masahiko

2015-09-01

In recent years, there has been considerable interest in understanding quantum mechanical interference effects in molecular ionization. Since this interference appears as a consequence of coherent electron emission from the different molecular centers, it should depend strongly on the nature of the ionized molecular orbital. Such molecular orbital patterns can be investigated by means of binary (e, 2e) spectroscopy, which is a kinematically-complete electron-impact ionization experiment performed under the high-energy Bethe ridge conditions. In this study, two-center interference effects in the (e, 2e) cross sections of H2 and CO2 at large momentum transfer are demonstrated with a high-statistics experiment, in order to elucidate the relationship between molecular orbital patterns and the interference structure. It is shown that the two-center interference is highly sensitive to the phase, spatial pattern, symmetry of constituent atomic orbital, and chemical bonding nature of the molecular orbital. This work was partially supported by Grant-in-Aids for Scientific Research (S) (No. 20225001) and for Young Scientists (B) (No. 21750005) from the Ministry of Education, Culture, Sports, Science and Technology.

MoleculeNet: a benchmark for molecular machine learning† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c7sc02664a

PubMed Central

Wu, Zhenqin; Ramsundar, Bharath; Feinberg, Evan N.; Gomes, Joseph; Geniesse, Caleb; Pappu, Aneesh S.; Leswing, Karl

2017-01-01

Molecular machine learning has been maturing rapidly over the last few years. Improved methods and the presence of larger datasets have enabled machine learning algorithms to make increasingly accurate predictions about molecular properties. However, algorithmic progress has been limited due to the lack of a standard benchmark to compare the efficacy of proposed methods; most new algorithms are benchmarked on different datasets making it challenging to gauge the quality of proposed methods. This work introduces MoleculeNet, a large scale benchmark for molecular machine learning. MoleculeNet curates multiple public datasets, establishes metrics for evaluation, and offers high quality open-source implementations of multiple previously proposed molecular featurization and learning algorithms (released as part of the DeepChem open source library). MoleculeNet benchmarks demonstrate that learnable representations are powerful tools for molecular machine learning and broadly offer the best performance. However, this result comes with caveats. Learnable representations still struggle to deal with complex tasks under data scarcity and highly imbalanced classification. For quantum mechanical and biophysical datasets, the use of physics-aware featurizations can be more important than choice of particular learning algorithm. PMID:29629118

Operation of micro and molecular machines: a new concept with its origins in interface science.

PubMed

Ariga, Katsuhiko; Ishihara, Shinsuke; Izawa, Hironori; Xia, Hong; Hill, Jonathan P

2011-03-21

A landmark accomplishment of nanotechnology would be successful fabrication of ultrasmall machines that can work like tweezers, motors, or even computing devices. Now we must consider how operation of micro- and molecular machines might be implemented for a wide range of applications. If these machines function only under limited conditions and/or require specialized apparatus then they are useless for practical applications. Therefore, it is important to carefully consider the access of functionality of the molecular or nanoscale systems by conventional stimuli at the macroscopic level. In this perspective, we will outline the position of micro- and molecular machines in current science and technology. Most of these machines are operated by light irradiation, application of electrical or magnetic fields, chemical reactions, and thermal fluctuations, which cannot always be applied in remote machine operation. We also propose strategies for molecular machine operation using the most conventional of stimuli, that of macroscopic mechanical force, achieved through mechanical operation of molecular machines located at an air-water interface. The crucial roles of the characteristics of an interfacial environment, i.e. connection between macroscopic dimension and nanoscopic function, and contact of media with different dielectric natures, are also described.

Error Sensitivity to Environmental Noise in Quantum Circuits for Chemical State Preparation.

PubMed

Sawaya, Nicolas P D; Smelyanskiy, Mikhail; McClean, Jarrod R; Aspuru-Guzik, Alán

2016-07-12

Calculating molecular energies is likely to be one of the first useful applications to achieve quantum supremacy, performing faster on a quantum than a classical computer. However, if future quantum devices are to produce accurate calculations, errors due to environmental noise and algorithmic approximations need to be characterized and reduced. In this study, we use the high performance qHiPSTER software to investigate the effects of environmental noise on the preparation of quantum chemistry states. We simulated 18 16-qubit quantum circuits under environmental noise, each corresponding to a unitary coupled cluster state preparation of a different molecule or molecular configuration. Additionally, we analyze the nature of simple gate errors in noise-free circuits of up to 40 qubits. We find that, in most cases, the Jordan-Wigner (JW) encoding produces smaller errors under a noisy environment as compared to the Bravyi-Kitaev (BK) encoding. For the JW encoding, pure dephasing noise is shown to produce substantially smaller errors than pure relaxation noise of the same magnitude. We report error trends in both molecular energy and electron particle number within a unitary coupled cluster state preparation scheme, against changes in nuclear charge, bond length, number of electrons, noise types, and noise magnitude. These trends may prove to be useful in making algorithmic and hardware-related choices for quantum simulation of molecular energies.

Importance of anisotropy in detachment rates for force production and cargo transport by a team of motor proteins.

PubMed

Takshak, Anjneya; Kunwar, Ambarish

2016-05-01

Many cellular processes are driven by collective forces generated by a team consisting of multiple molecular motor proteins. One aspect that has received less attention is the detachment rate of molecular motors under mechanical force/load. While detachment rate of kinesin motors measured under backward force increases rapidly for forces beyond stall-force; this scenario is just reversed for non-yeast dynein motors where detachment rate from microtubule decreases, exhibiting a catch-bond type behavior. It has been shown recently that yeast dynein responds anisotropically to applied load, i.e. detachment rates are different under forward and backward pulling. Here, we use computational modeling to show that these anisotropic detachment rates might help yeast dynein motors to improve their collective force generation in the absence of catch-bond behavior. We further show that the travel distance of cargos would be longer if detachment rates are anisotropic. Our results suggest that anisotropic detachment rates could be an alternative strategy for motors to improve the transport properties and force production by the team. © 2016 The Protein Society.

Molecular-dynamics simulation of Richtmyer-Meshkov instability on a Li-H2 interface at extreme compressing conditions

NASA Astrophysics Data System (ADS)

Huang, Shenghong; Wang, Weirong; Luo, Xisheng

2018-06-01

The new characteristics of Richtmyer-Meshkov instability (RMI) under extreme shock conditions are numerically studied by using molecular dynamics simulation incorporated with the electron force field model. The emphasis is placed on the ionization effects caused by different impacting speeds (6-30 km/s) on the microscale RMI on a Li-H2 interface. The linear region of the amplitude growth rate of the shocked interface under extreme shock conditions is observed to be much longer than that at the ordinary impact, which is in good accord with experimental results obtained with a Nova laser. It is also found that the amplitude of the nonlinear region is larger than the ordinary counterpart or the prediction by theory without considering the ionization effect. The two new characteristics are attributed to the ambipolar acceleration induced by the extra electric field due to the electron/ion separation under extreme shock conditions. These new findings may shed new light on the very complex physical process of the inertial confinement fusion on nanoscales.

Molecular dynamics simulation of shock induced ejection on fused silica surface

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

Su, Rui; Xiang, Meizhen; Jiang, Shengli

2014-05-21

Shock response and surface ejection behaviors of fused silica are studied by using non-equilibrium molecular dynamics combining with the Tersoff potential. First, bulk structure and Hugoniot curves of fused silica are calculated and compared with experimental results. Then, the dynamical process of surface ejection behavior is simulated under different loading velocities ranging from 3.5 to 5.0 km∕s, corresponding to shock wave velocities from 7.1 to 8.8 km∕s. The local atomistic shear strain parameter is used to describe the local plastic deformation under conditions of shock compression or releasing. Our result shows that the shear strain is localized in the bottom area ofmore » groove under the shock compression. Surface ejection is observed when the loading velocity exceeds 4.0 km∕s. Meanwhile, the temperature of the micro-jet is ∼5574.7 K, which is close to experiment measurement. Several kinds of structural defects including non-bridging oxygen are found in the bulk area of the sample after ejection.« less

Molecular systematics of terraranas (Anura: Brachycephaloidea) with an assessment of the effects of alignment and optimality criteria.

PubMed

Padial, José M; Grant, Taran; Frost, Darrel R

2014-06-26

Brachycephaloidea is a monophyletic group of frogs with more than 1000 species distributed throughout the New World tropics, subtropics, and Andean regions. Recently, the group has been the target of multiple molecular phylogenetic analyses, resulting in extensive changes in its taxonomy. Here, we test previous hypotheses of phylogenetic relationships for the group by combining available molecular evidence (sequences of 22 genes representing 431 ingroup and 25 outgroup terminals) and performing a tree-alignment analysis under the parsimony optimality criterion using the program POY. To elucidate the effects of alignment and optimality criterion on phylogenetic inferences, we also used the program MAFFT to obtain a similarity-alignment for analysis under both parsimony and maximum likelihood using the programs TNT and GARLI, respectively. Although all three analytical approaches agreed on numerous points, there was also extensive disagreement. Tree-alignment under parsimony supported the monophyly of the ingroup and the sister group relationship of the monophyletic marsupial frogs (Hemiphractidae), while maximum likelihood and parsimony analyses of the MAFFT similarity-alignment did not. All three methods differed with respect to the position of Ceuthomantis smaragdinus (Ceuthomantidae), with tree-alignment using parsimony recovering this species as the sister of Pristimantis + Yunganastes. All analyses rejected the monophyly of Strabomantidae and Strabomantinae as originally defined, and the tree-alignment analysis under parsimony further rejected the recently redefined Craugastoridae and Pristimantinae. Despite the greater emphasis in the systematics literature placed on the choice of optimality criterion for evaluating trees than on the choice of method for aligning DNA sequences, we found that the topological differences attributable to the alignment method were as great as those caused by the optimality criterion. Further, the optimal tree-alignment indicates that insertions and deletions occurred in twice as many aligned positions as implied by the optimal similarity-alignment, confirming previous findings that sequence turnover through insertion and deletion events plays a greater role in molecular evolution than indicated by similarity-alignments. Our results also provide a clear empirical demonstration of the different effects of wildcard taxa produced by missing data in parsimony and maximum likelihood analyses. Specifically, maximum likelihood analyses consistently (81% bootstrap frequency) provided spurious resolution despite a lack of evidence, whereas parsimony correctly depicted the ambiguity due to missing data by collapsing unsupported nodes. We provide a new taxonomy for the group that retains previously recognized Linnaean taxa except for Ceuthomantidae, Strabomantidae, and Strabomantinae. A phenotypically diagnosable superfamily is recognized formally as Brachycephaloidea, with the informal, unranked name terrarana retained as the standard common name for these frogs. We recognize three families within Brachycephaloidea that are currently diagnosable solely on molecular grounds (Brachycephalidae, Craugastoridae, and Eleutherodactylidae), as well as five subfamilies (Craugastorinae, Eleutherodactylinae, Holoadeninae, Phyzelaphryninae, and Pristimantinae) corresponding in large part to previous families and subfamilies. Our analyses upheld the monophyly of all tested genera, but we found numerous subgeneric taxa to be non-monophyletic and modified the taxonomy accordingly.

Synthesis and DFT calculations of some 2-aminothiazoles

NASA Astrophysics Data System (ADS)

Rezania, Jafar; Behzadi, Hadi; Shockravi, Abbas; Ehsani, Morteza; Akbarzadeh, Elahe

2018-04-01

A series of 2-aminothiazole derivatives have been synthesized by the reaction of acetyl compounds with thiourea and iodine as catalyst under solvent-free condition, a green chemistry method. The quantum chemical calculations at the DFT/B3LYP level of theory in gas phase were carried out for starting acetyl derivatives. The highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) and related reactivity descriptor of acetyl derivatives, as well as, enthalpy of reactions are calculated in order to investigate the reaction properties of acetyl compounds and yields of the reactions. The calculated reactivity descriptors are well correlated to activity of different acetyl derivatives.

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

Wallace, Bram; Atzberger, Paul J.; D’Auria, Sabato

Forster resonance energy transfer (FRET) is a widely used single-molecule technique for measuring nanoscale distances from changes in the non-radiative transfer of energy between donor and acceptor fluorophores. For macromolecules and complexes this observed transfer efficiency is used to infer changes in molecular conformation under differing experimental conditions. But, sometimes shifts are observed in the FRET efficiency even when there is strong experimental evidence that the molecular conformational state is unchanged. Here, we investigate ways in which such discrepancies can arise from kinetic effects. We show that significant shifts can arise from the interplay between excitation kinetics, orientation diffusion ofmore » fluorophores, separation diffusion of fluorophores, and non-emitting quenching.« less

Building muscle: molecular regulation of myogenesis.

PubMed

Bentzinger, C Florian; Wang, Yu Xin; Rudnicki, Michael A

2012-02-01

The genesis of skeletal muscle during embryonic development and postnatal life serves as a paradigm for stem and progenitor cell maintenance, lineage specification, and terminal differentiation. An elaborate interplay of extrinsic and intrinsic regulatory mechanisms controls myogenesis at all stages of development. Many aspects of adult myogenesis resemble or reiterate embryonic morphogenetic episodes, and related signaling mechanisms control the genetic networks that determine cell fate during these processes. An integrative view of all aspects of myogenesis is imperative for a comprehensive understanding of muscle formation. This article provides a holistic overview of the different stages and modes of myogenesis with an emphasis on the underlying signals, molecular switches, and genetic networks.

Determination of the molecular weight of low-molecular-weight heparins by using high-pressure size exclusion chromatography on line with a triple detector array and conventional methods.

PubMed

Bisio, Antonella; Mantegazza, Alessandra; Vecchietti, Davide; Bensi, Donata; Coppa, Alessia; Torri, Giangiacomo; Bertini, Sabrina

2015-03-19

The evaluation of weight average molecular weight (Mw) and molecular weight distribution represents one of the most controversial aspects concerning the characterization of low molecular weight heparins (LMWHs). As the most commonly used method for the measurement of such parameters is high performance size exclusion chromatography (HP-SEC), the soundness of results mainly depends on the appropriate calibration of the chromatographic columns used. With the aim of meeting the requirement of proper Mw standards for LMWHs, in the present work the determination of molecular weight parameters (Mw and Mn) by HP-SEC combined with a triple detector array (TDA) was performed. The HP-SEC/TDA technique permits the evaluation of polymeric samples by exploiting the combined and simultaneous action of three on-line detectors: light scattering detectors (LALLS/RALLS); refractometer and viscometer. Three commercial LMWH samples, enoxaparin, tinzaparin and dalteparin, a γ-ray depolymerized heparin (γ-Hep) and its chromatographic fractions, and a synthetic pentasaccharide were analysed by HP-SEC/TDA. The same samples were analysed also with a conventional HP-SEC method employing refractive index (RI) and UV detectors and two different chromatographic column set, silica gel and polymeric gel columns. In both chromatographic systems, two different calibration curves were built up by using (i) γ-Hep chromatographic fractions and the corresponding Mw parameters obtained via HP-SEC/TDA; (ii) the whole γ-Hep preparation with broad Mw dispersion and the corresponding cumulative distribution function calculated via HP-SEC/TDA. In addition, also a chromatographic column calibration according to European Pharmacopoeia indication was built up. By comparing all the obtained results, some important differences among Mw and size distribution values of the three LMWHs were found with the five different calibration methods and with HP-SEC/TDA method. In particular, the detection of the lower molecular weight components turned out to be the most critical aspect. Whereas HP-SEC/TDA may underestimate species under 2 KDa when present in low concentration, other methods appeared to emphasize their content.

Exploring the role of molecular biomarkers as a potential weapon against gastric cancer: A review of the literature.

PubMed

Matboli, Marwa; El-Nakeep, Sarah; Hossam, Nourhan; Habieb, Alaa; Azazy, Ahmed E M; Ebrahim, Ali E; Nagy, Ziad; Abdel-Rahman, Omar

2016-07-14

Gastric cancer (GC) is a global health problem and a major cause of cancer-related death with high recurrence rates ranging from 25% to 40% for GC patients staging II-IV. Unfortunately, while the majority of GC patients usually present with advanced tumor stage; there is still limited evidence-based therapeutic options. Current approach to GC management consists mainly of; endoscopy followed by, gastrectomy and chemotherapy or chemo-radiotherapy. Recent studies in GC have confirmed that it is a heterogeneous disease. Many molecular characterization studies have been performed in GC. Recent discoveries of the molecular pathways underlying the disease have opened the door to more personalized treatment and better predictable outcome. The identification of molecular markers is a useful tool for clinical managementin GC patients, assisting in diagnosis, evaluation of response to treatment and development of novel therapeutic modalities. While chemotherapeutic agents have certain physiological effects on the tumor cells, the prediction of the response is different from one type of tumor to the other. The specificity of molecular biomarkers is a principal feature driving their application in anticancer therapies. Here we are trying to focus on the role of molecular pathways of GC and well-established molecular markers that can guide the therapeutic management.

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

PubMed

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 magnetic resonance imaging of atherosclerotic vessel wall disease.

PubMed

Nörenberg, Dominik; Ebersberger, Hans U; Diederichs, Gerd; Hamm, Bernd; Botnar, René M; Makowski, Marcus R

2016-03-01

Molecular imaging aims to improve the identification and characterization of pathological processes in vivo by visualizing the underlying biological mechanisms. Molecular imaging techniques are increasingly used to assess vascular inflammation, remodeling, cell migration, angioneogenesis and apoptosis. In cardiovascular diseases, molecular magnetic resonance imaging (MRI) offers new insights into the in vivo biology of pathological vessel wall processes of the coronary and carotid arteries and the aorta. This includes detection of early vascular changes preceding plaque development, visualization of unstable plaques and assessment of response to therapy. The current review focuses on recent developments in the field of molecular MRI to characterise different stages of atherosclerotic vessel wall disease. A variety of molecular MR-probes have been developed to improve the non-invasive detection and characterization of atherosclerotic plaques. Specifically targeted molecular probes allow for the visualization of key biological steps in the cascade leading to the development of arterial vessel wall lesions. Early detection of processes which lead to the development of atherosclerosis and the identification of vulnerable atherosclerotic plaques may enable the early assessment of response to therapy, improve therapy planning, foster the prevention of cardiovascular events and may open the door for the development of patient-specific treatment strategies. Targeted MR-probes allow the characterization of atherosclerosis on a molecular level. Molecular MRI can identify in vivo markers for the differentiation of stable and unstable plaques. Visualization of early molecular changes has the potential to improve patient-individualized risk-assessment.

Computational screening of biomolecular adsorption and self-assembly on nanoscale surfaces.

PubMed

Heinz, Hendrik

2010-05-01

The quantification of binding properties of ions, surfactants, biopolymers, and other macromolecules to nanometer-scale surfaces is often difficult experimentally and a recurring challenge in molecular simulation. A simple and computationally efficient method is introduced to compute quantitatively the energy of adsorption of solute molecules on a given surface. Highly accurate summation of Coulomb energies as well as precise control of temperature and pressure is required to extract the small energy differences in complex environments characterized by a large total energy. The method involves the simulation of four systems, the surface-solute-solvent system, the solute-solvent system, the solvent system, and the surface-solvent system under consideration of equal molecular volumes of each component under NVT conditions using standard molecular dynamics or Monte Carlo algorithms. Particularly in chemically detailed systems including thousands of explicit solvent molecules and specific concentrations of ions and organic solutes, the method takes into account the effect of complex nonbond interactions and rotational isomeric states on the adsorption behavior on surfaces. As a numerical example, the adsorption of a dodecapeptide on the Au {111} and mica {001} surfaces is described in aqueous solution. Copyright 2009 Wiley Periodicals, Inc.

Organization of Lipids in the Tear Film: A Molecular-Level View

PubMed Central

Wizert, Alicja; Iskander, D. Robert; Cwiklik, Lukasz

2014-01-01

Biophysical properties of the tear film lipid layer are studied at the molecular level employing coarse grain molecular dynamics (MD) simulations with a realistic model of the human tear film. In this model, polar lipids are chosen to reflect the current knowledge on the lipidome of the tear film whereas typical Meibomian-origin lipids are included in the thick non-polar lipids subphase. Simulation conditions mimic those experienced by the real human tear film during blinks. Namely, thermodynamic equilibrium simulations at different lateral compressions are performed to model varying surface pressure, and the dynamics of the system during a blink is studied by non-equilibrium MD simulations. Polar lipids separate their non-polar counterparts from water by forming a monomolecular layer whereas the non-polar molecules establish a thick outermost lipid layer. Under lateral compression, the polar layer undulates and a sorting of polar lipids occurs. Moreover, formation of three-dimensional aggregates of polar lipids in both non-polar and water subphases is observed. We suggest that these three-dimensional structures are abundant under dynamic conditions caused by the action of eye lids and that they act as reservoirs of polar lipids, thus increasing stability of the tear film. PMID:24651175

Analysis of the Sensitivity of K-Type Molecular Sieve-Deposited MWNTs for the Detection of SF6 Decomposition Gases under Partial Discharge

PubMed Central

Zhang, Xiaoxing; Li, Xin; Luo, Chenchen; Dong, Xingchen; Zhou, Lei

2015-01-01

Sulfur hexafluoride (SF6) is widely utilized in gas-insulated switchgear (GIS). However, part of SF6 decomposes into different components under partial discharge (PD) conditions. Previous research has shown that the gas responses of intrinsic and 4 Å-type molecular sieve-deposited multi-wall carbon nanotubes (MWNTs) to SOF2 and SO2F2, two important decomposition components of SF6, are not obvious. In this study, a K-type molecular sieve-deposited MWNTs sensor was developed. Its gas response characteristics and the influence of the mixture ratios of gases on the gas-sensing properties were studied. The results showed that, for sensors with gas mixture ratios of 5:1, 10:1, and 20:1, the resistance change rate increased by nearly 13.0% after SOF2 adsorption, almost 10 times that of MWNTs sensors, while the sensors’ resistance change rate with a mixture ratio of 10:1 reached 17.3% after SO2F2 adsorption, nearly nine times that of intrinsic MWNT sensors. Besides, a good linear relationship was observed between concentration of decomposition components and the resistance change rate of sensors. PMID:26569245

Analysis of the Sensitivity of K-Type Molecular Sieve-Deposited MWNTs for the Detection of SF₆ Decomposition Gases under Partial Discharge.

PubMed

Zhang, Xiaoxing; Li, Xin; Luo, Chenchen; Dong, Xingchen; Zhou, Lei

2015-11-11

Sulfur hexafluoride (SF6) is widely utilized in gas-insulated switchgear (GIS). However, part of SF6 decomposes into different components under partial discharge (PD) conditions. Previous research has shown that the gas responses of intrinsic and 4 Å-type molecular sieve-deposited multi-wall carbon nanotubes (MWNTs) to SOF2 and SO2F2, two important decomposition components of SF6, are not obvious. In this study, a K-type molecular sieve-deposited MWNTs sensor was developed. Its gas response characteristics and the influence of the mixture ratios of gases on the gas-sensing properties were studied. The results showed that, for sensors with gas mixture ratios of 5:1, 10:1, and 20:1, the resistance change rate increased by nearly 13.0% after SOF2 adsorption, almost 10 times that of MWNTs sensors, while the sensors' resistance change rate with a mixture ratio of 10:1 reached 17.3% after SO2F2 adsorption, nearly nine times that of intrinsic MWNT sensors. Besides, a good linear relationship was observed between concentration of decomposition components and the resistance change rate of sensors.

Molecular and Nonmolecular Diagnostic Methods for Invasive Fungal Infections

PubMed Central

Arvanitis, Marios; Anagnostou, Theodora; Fuchs, Beth Burgwyn; Caliendo, Angela M.

2014-01-01

SUMMARY Invasive fungal infections constitute a serious threat to an ever-growing population of immunocompromised individuals and other individuals at risk. Traditional diagnostic methods, such as histopathology and culture, which are still considered the gold standards, have low sensitivity, which underscores the need for the development of new means of detecting fungal infectious agents. Indeed, novel serologic and molecular techniques have been developed and are currently under clinical evaluation. Tests like the galactomannan antigen test for aspergillosis and the β-glucan test for invasive Candida spp. and molds, as well as other antigen and antibody tests, for Cryptococcus spp., Pneumocystis spp., and dimorphic fungi, have already been established as important diagnostic approaches and are implemented in routine clinical practice. On the other hand, PCR and other molecular approaches, such as matrix-assisted laser desorption ionization (MALDI) and fluorescence in situ hybridization (FISH), have proved promising in clinical trials but still need to undergo standardization before their clinical use can become widespread. The purpose of this review is to highlight the different diagnostic approaches that are currently utilized or under development for invasive fungal infections and to identify their performance characteristics and the challenges associated with their use. PMID:24982319

Conceptualizing neurodevelopmental disorders through a mechanistic understanding of fragile X syndrome and Williams syndrome.

PubMed

Fung, Lawrence K; Quintin, Eve-Marie; Haas, Brian W; Reiss, Allan L

2012-04-01

The overarching goal of this review is to compare and contrast the cognitive-behavioral features of fragile X syndrome (FraX) and Williams syndrome and to review the putative neural and molecular underpinnings of these features. Information is presented in a framework that provides guiding principles for conceptualizing gene-brain-behavior associations in neurodevelopmental disorders. Abnormalities, in particular cognitive-behavioral domains with similarities in underlying neurodevelopmental correlates, occur in both FraX and Williams syndrome including aberrant frontostriatal pathways leading to executive function deficits, and magnocellular/dorsal visual stream, superior parietal lobe, inferior parietal lobe, and postcentral gyrus abnormalities contributing to deficits in visuospatial function. Compelling cognitive-behavioral and neurodevelopmental contrasts also exist in these two disorders, for example, aberrant amygdala and fusiform cortex structure and function occurring in the context of contrasting social behavioral phenotypes, and temporal cortical and cerebellar abnormalities potentially underlying differences in language function. Abnormal dendritic development is a shared neurodevelopmental morphologic feature between FraX and Williams syndrome. Commonalities in molecular machinery and processes across FraX and Williams syndrome occur as well - microRNAs involved in translational regulation of major synaptic proteins; scaffolding proteins in excitatory synapses; and proteins involved in axonal development. Although the genetic variations leading to FraX and Williams syndrome are different, important similarities and contrasts in the phenotype, neurocircuitry, molecular machinery, and cellular processes in these two disorders allow for a unique approach to conceptualizing gene-brain-behavior links occurring in neurodevelopmental disorders.

Protonated o-semiquinone radical as a mimetic of the humic acids native radicals: A DFT approach to the molecular structure and EPR properties

NASA Astrophysics Data System (ADS)

Witwicki, Maciej; Jezierska, Julia

2012-06-01

Organic radicals are known to be an indispensable component of the humic acids (HA) structure. In HA two forms of radicals, stable (native) and short-lived (transient), are identified. Importantly, these radical forms can be easily differentiated by electron paramagnetic resonance (EPR) spectroscopy. This article provides a DFT-based insight into the electronic and molecular structure of the native radicals. The molecular models including an increase of the radical aromaticity and the hydrogen bonding between the radical and other functional groups of HA are taken under investigation. In consequence the interesting pieces of information on the structure of the native radical centers in HA are revealed and discussed, especially in terms of differences between the electronic structure of the native and transient forms.

Molecular and Cellular Mechanisms of Axonal Regeneration After Spinal Cord Injury*

PubMed Central

van Niekerk, Erna A.; Tuszynski, Mark H.; Lu, Paul; Dulin, Jennifer N.

2016-01-01

Following axotomy, a complex temporal and spatial coordination of molecular events enables regeneration of the peripheral nerve. In contrast, multiple intrinsic and extrinsic factors contribute to the general failure of axonal regeneration in the central nervous system. In this review, we examine the current understanding of differences in protein expression and post-translational modifications, activation of signaling networks, and environmental cues that may underlie the divergent regenerative capacity of central and peripheral axons. We also highlight key experimental strategies to enhance axonal regeneration via modulation of intraneuronal signaling networks and the extracellular milieu. Finally, we explore potential applications of proteomics to fill gaps in the current understanding of molecular mechanisms underlying regeneration, and to provide insight into the development of more effective approaches to promote axonal regeneration following injury to the nervous system. PMID:26695766

Molecular mechanisms of mechanotransduction in integrin-mediated cell-matrix adhesion

PubMed Central

Li, Zhenhai; Lee, Hyunjung; Zhu, Cheng

2016-01-01

Cell-matrix adhesion complexes are multi-protein structures linking the extracellular matrix (ECM) to the cytoskeleton. They are essential to both cell motility and function by bidirectionally sensing and transmitting mechanical and biochemical stimulations. Several types of cell-matrix adhesions have been identified and they share many key molecular components, such as integrins and actin-integrin linkers. Mechanochemical coupling between ECM molecules and the actin cytoskeleton has been observed from the single cell to the single molecule level and from immune cells to neuronal cells. However, the mechanisms underlying force regulation of integrin-mediated mechanotransduction still need to be elucidated. In this review article, we focus on integrin-mediated adhesions and discuss force regulation of cell-matrix adhesions and key adaptor molecules, three different force-dependent behaviors, and molecular mechanisms for mechanochemical coupling in force regulation. PMID:27720950

Current-voltage characteristics and transition voltage spectroscopy of individual redox proteins.

PubMed

Artés, Juan M; López-Martínez, Montserrat; Giraudet, Arnaud; Díez-Pérez, Ismael; Sanz, Fausto; Gorostiza, Pau

2012-12-19

Understanding how molecular conductance depends on voltage is essential for characterizing molecular electronics devices. We reproducibly measured current-voltage characteristics of individual redox-active proteins by scanning tunneling microscopy under potentiostatic control in both tunneling and wired configurations. From these results, transition voltage spectroscopy (TVS) data for individual redox molecules can be calculated and analyzed statistically, adding a new dimension to conductance measurements. The transition voltage (TV) is discussed in terms of the two-step electron transfer (ET) mechanism. Azurin displays the lowest TV measured to date (0.4 V), consistent with the previously reported distance decay factor. This low TV may be advantageous for fabricating and operating molecular electronic devices for different applications. Our measurements show that TVS is a helpful tool for single-molecule ET measurements and suggest a mechanism for gating of ET between partner redox proteins.

Minimal barcode distance between two water mite species from Madeira Island: a cautionary tale.

PubMed

García-Jiménez, Ricardo; Horreo, Jose Luis; Valdecasas, Antonio G

2017-06-01

In this work, we compare morphological and molecular data in their ability to distinguish between species of water mites (Acari, Prostigmata, Hydrachnidia). We have focused on the two species of the genus Lebertia inhabiting the island of Madeira. While traditional morphological traits were initially sufficient to distinguish between these two species, the molecular data were more dependable on the kind of analysis carried out. Single arbitrary genetic distance (e.g. a K2P distance below 2%) may lead to the conclusion that the specimens under study belong to the same species. Analysing the same specimens with the coalescent model has proved the evolutionary independence of both Lebertia clades in Madeira. Furthermore, multi-rate Poisson Tree Process analysis confirmed both lineages as independent species. Our results agree with previous studies warning of the dangers of rigid species delimitation based on arbitrary molecular distances. In addition, the importance of different molecular data approaches for correct species delimitation in water mites is highlighted.

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

Sotomayor, Marcos

Hair cell mechanotransduction happens in tens of microseconds, involves forces of a few picoNewtons, and is mediated by nanometer-scale molecular conformational changes. As proteins involved in this process become identified and their high resolution structures become available, multiple tools are being used to explore their “single-molecule responses” to force. Optical tweezers and atomic force microscopy offer exquisite force and extension resolution, but cannot reach the high loading rates expected for high frequency auditory stimuli. Molecular dynamics (MD) simulations can reach these fast time scales, and also provide a unique view of the molecular events underlying protein mechanics, but its predictionsmore » must be experimentally verified. Thus a combination of simulations and experiments might be appropriate to study the molecular mechanics of hearing. Here I review the basics of MD simulations and the different methods used to apply force and study protein mechanics in silico. Simulations of tip link proteins are used to illustrate the advantages and limitations of this method.« less

Self-organizing layers from complex molecular anions

DOE PAGES

Warneke, Jonas; McBriarty, Martin E.; Riechers, Shawn L.; ...

2018-05-14

The formation of traditional ionic materials occurs principally via joint accumulation of both anions and cations. Here in this paper, we describe a previously unreported phenomenon by which macroscopic liquid-like thin layers with tunable self-organization properties form through accumulation of stable complex ions of one polarity on surfaces. Using a series of highly stable molecular anions we demonstrate a strong influence of the internal charge distribution of the molecular ions, which is usually shielded by counterions, on the properties of the layers. Detailed characterization reveals that the intrinsically unstable layers of anions on surfaces are stabilized by simultaneous accumulation ofmore » neutral molecules from the background environment. Different phases, self-organization mechanisms and optical properties are observed depending on the molecular properties of the deposited anions, the underlying surface and the coadsorbed neutral molecules. This demonstrates rational control of the macroscopic properties (morphology and size of the formed structures) of the newly discovered anion-based layers.« less

Self-organizing layers from complex molecular anions

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

Warneke, Jonas; McBriarty, Martin E.; Riechers, Shawn L.

The formation of traditional ionic materials occurs principally via joint accumulation of both anions and cations. Here in this paper, we describe a previously unreported phenomenon by which macroscopic liquid-like thin layers with tunable self-organization properties form through accumulation of stable complex ions of one polarity on surfaces. Using a series of highly stable molecular anions we demonstrate a strong influence of the internal charge distribution of the molecular ions, which is usually shielded by counterions, on the properties of the layers. Detailed characterization reveals that the intrinsically unstable layers of anions on surfaces are stabilized by simultaneous accumulation ofmore » neutral molecules from the background environment. Different phases, self-organization mechanisms and optical properties are observed depending on the molecular properties of the deposited anions, the underlying surface and the coadsorbed neutral molecules. This demonstrates rational control of the macroscopic properties (morphology and size of the formed structures) of the newly discovered anion-based layers.« less

Physical vapor deposition as a route to glasses with liquid crystalline order

NASA Astrophysics Data System (ADS)

Gomez, Jaritza

Physical vapor deposition (PVD) is an effective route to prepare glasses with a unique combination of properties. Substrate temperatures near the glass transition (Tg) and slow deposition rates can access enhanced mobility at the surface of the glass allowing molecules at the surface additional time to sample different molecular configurations. The temperature of the substrate can be used to control molecular mobility during deposition and properties in the resulting glasses such as higher density, kinetic stability and preferential molecular orientation. PVD was used to prepare glasses of itraconazole, a smectic A liquid crystal. We characterized molecular orientation using infrared and ellipsometry. Molecular orientation can be controlled by choice of Tsubstrate in a range of temperatures near Tg. Glasses deposited at Tsubstrate = Tg show nearly vertical molecular orientation relative to the substrate; at lower Tsubstrate, molecules are nearly parallel to the substrate. The molecular orientation depends on the temperature of the substrate during preparation and not on the molecular orientation of the underlying layer. This allows preparing samples of layers with differing orientations. We find these glasses are homogeneous solids without evidence of domain boundaries and are molecularly flat. We interpret the combination of properties obtained for vapor-deposited glasses of itraconazole to result from a process where molecular orientation is determined by the structure and dynamics at the free surface of the glass during deposition. We report the thermal and structural properties of glasses prepared using PVD of a rod-like molecule, posaconazole, which does not show equilibrium liquid crystal phases. These glasses show substantial molecular orientation that can be controlled by choice of Tsubstrate during deposition. Ellipsometry and IR indicate that glasses prepared at Tg - 3 K are highly ordered. At these Tsubstrate, molecules show preferential vertical orientation and orientation is similar to that measured in aligned nematic liquid crystal. Our results are consistent with a recently proposed mechanism where molecular orientation in equilibrium liquids can be trapped in PVD glasses and suggest that the orientation at the free surface of posaconazole is nematic-like. In addition, we show posaconazole glasses show high kinetic stability controlled by Tsubstrate.

Comparative assessment of the breakdown of high-molecular flocculants

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

Baichenko, A.A.; Baichenko, A.A.; Kaminskii, V.S.

1977-01-01

In recent years, a much wider range of water-soluble polymer flocculants has come into use to accelerate the clarification of coal and clay-coal suspensions, in which the solid phase comprises flotation tailings or slurry. The major distinguishing feature in this development has been the switch from gel-type flocculants to granular or powder types. Difficulties arise in the use of flocculants, from the relative ease with which they break down during storage or solution preparation. Different polymers behave differently under the same mechanical or chemical forces. Failure to appreciate this often leads to erroneous conclusions regarding the specific effectiveness of variousmore » flocculants. Breakdown data are described on various high-molecular flocculants, showing that the major factors that influence the breakdown of polyoxyethylene (POE) can be traced in other polymer flocculants as well.« less

Elucidation of differences in N-glycosylation between different molecular weight forms of recombinant CLEC-2 by LC MALDI tandem MS.

PubMed

Zhou, Lei; Qian, Yifan; Zhang, Xingwang; Ruan, Yuanyuan; Ren, Shifang; Gu, Jianxin

2015-01-30

C-type lectin-like receptor 2 (CLEC-2) is a newly identified receptor expressed on the platelet surface. It has been reported that CLEC-2 exists as a higher molecular weight (HMW) and a lower molecular weight (LMW) form, which share the same protein core but differ in glycans. The two forms appear to have different ligand-binding abilities, indicating that the differential glycosylation of CLEC-2 possibly produces functionally distinct glycoforms. This study aimed to explore an easy method to directly elucidate the N-glycosylation difference by employing a glycoproteomics approach. The off-line coupling of nano-LC with a MALDI-QIT-TOF mass spectrometer was demonstrated to be capable of sensitive and direct elucidation of the glycosylation difference between HMW and LMW CLEC-2, simultaneously providing information about their oligosaccharide structures and the glycosylation sites. The results reveal that a specific glycosylation site, Asn 134, is differently glycosylated in the two forms, with complex types of bi-antennary, tri-antennary and tetra-antennary, N-linked, fucosylated glycans identified at this site in the HMW form but not in the LMW form. The observed difference in glycosylation might provide new insights into the underlying mechanisms of biological functions of CLEC-2. Because of its simplicity and sensitivity, the method explored in this work suggests that it holds promise as a method of elucidating differences in direct N-glycosylation of target glycoprotein, even in small amount of samples. Copyright © 2014 Elsevier Ltd. All rights reserved.

Development of raphe serotonin neurons from specification to guidance.

PubMed

Kiyasova, Vera; Gaspar, Patricia

2011-11-01

The main features of the development of the serotonin (5-HT) raphe neurons have been known for many years but more recent molecular studies, using mouse genetics, have since unveiled several intriguing aspects of the specification of the raphe serotonergic system. These studies indicated that, although all 5-HT neurons in the raphe follow the same general program for their specification, there are also clear regional differences in the way that these neurons are specified and are guided towards different brain targets. Here we overview recent progress made in the understanding of the developmental programming of serotonergic neurons in the mouse raphe, emphasizing data showing how heterogeneous subsets of 5-HT neurons may be generated. Serotonergic progenitors are produced in the brainstem in different rhombomeres under the influence of a set of secreted factors, sonic hedgehog and fibroblast growth factors, which determine their position in the neural tube. Two main transcriptional gene networks are involved in the specification of 5-HT identity, with Lmx1b and Pet1 transcription factors as main players. A differential requirement for Pet1 was, however, revealed, which underlies an anatomical and functional diversity. Transcriptional programs controlling 5-HT identity could also impact axon guidance mechanisms directing 5-HT neurons to their targets. Although no direct links have yet been established, a large set of molecular determinants have already been shown to be involved in the growth, axon guidance and targeting of 5-HT raphe neurons, particularly within the forebrain. Alterations in the molecular mechanisms involved in 5-HT development are likely to have significant roles in mood disease predisposition. © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Current Methods in the Molecular Typing of Mycobacterium tuberculosis and Other Mycobacteria

PubMed Central

van Ingen, Jakko; Dziadek, Jarosław; Mazur, Paweł K.; Bielecki, Jacek

2014-01-01

In the epidemiology of tuberculosis (TB) and nontuberculous mycobacterial (NTM) diseases, as in all infectious diseases, the key issue is to define the source of infection and to disclose its routes of transmission and dissemination in the environment. For this to be accomplished, the ability of discerning and tracking individual Mycobacterium strains is of critical importance. Molecular typing methods have greatly improved our understanding of the biology of mycobacteria and provide powerful tools to combat the diseases caused by these pathogens. The utility of various typing methods depends on the Mycobacterium species under investigation as well as on the research question. For tuberculosis, different methods have different roles in phylogenetic analyses and person-to-person transmission studies. In NTM diseases, most investigations involve the search for environmental sources or phylogenetic relationships. Here, too, the type of setting determines which methodology is most suitable. Within this review, we summarize currently available molecular methods for strain typing of M. tuberculosis and some NTM species, most commonly associated with human disease. For the various methods, technical practicalities as well as discriminatory power and accomplishments are reviewed. PMID:24527454

Spectral identification/elimination of molecular species in spacecraft glow

NASA Technical Reports Server (NTRS)

Green, B. D.; Marinelli, W. J.; Rawlins, W. T.

1985-01-01

Computer models of molecular electronic and vibrational emission intensities were developed. Known radiative emission rates (Einstein coefficients) permit the determination of relative excited state densities from spectral intensities. These codes were applied to the published spectra of glow above shuttle surface and to the Spacelab 1 results of Torr and Torr. The theoretical high-resolution spectra were convolved with the appropriate instrumental slit functions to allow accurate comparison with data. The published spacelab spectrum is complex but N2+ Meinel emission can be clearly identified in the ram spectrum. M2 First Positive emission does not correlate well with observed features, nor does the CN Red System. Spectral overlay comparisons are presented. The spectrum of glow above shuttle surfaces, in contrast to the ISO data, is not highly structured. Diatomic molecular emission was matched to the observed spectral shape. Source excitation mechanisms such as (oxygen atom)-(surface species) reaction product chemiluminescence, surface recombination, or resonance fluorescent re-emission will be discussed for each tentative assignment. These assignments are the necessary first analytical step toward mechanism identification. Different glow mechanisms will occur above surfaces under different orbital conditions.

Is variation in susceptibility to Phytophthora ramorum correlated with population genetic structure in coast live oak (Quercus agrifolia)?

PubMed

Dodd, Richard S; Hüberli, Daniel; Douhovnikoff, Vlad; Harnik, Tamar Y; Afzal-Rafii, Zara; Garbelotto, Matteo

2005-01-01

California coastal woodlands are suffering severe disease and mortality as a result of infection from Phytophthora ramorum. Quercus agrifolia is one of the major woodland species at risk. This study investigated within- and among-population variation in host susceptibility to inoculation with P. ramorum and compared this with population genetic structure using molecular markers. Susceptibility was assessed using a branch-cutting inoculation test. Trees were selected from seven natural populations in California. Amplified fragment length polymorphism molecular markers were analysed for all trees used in the trials. Lesion sizes varied quantitatively among individuals within populations, with up to an eightfold difference. There was little support for population differences in susceptibility. Molecular structure also showed a strong within-population, and weaker among-population, pattern of variation. Our data suggest that susceptibility of Q. agrifolia to P. ramorum is variable and is under the control of several gene loci. This variation exists within populations, so that less susceptible local genotypes may provide the gene pool for regeneration of woodlands where mortality is high.

Using terahertz time-domain spectroscopical technique to monitor cocrystal formation between piracetam and 2,5-dihydroxybenzoic acid

NASA Astrophysics Data System (ADS)

Du, Yong; Xia, Yi; Zhang, Huili; Hong, Zhi

2013-07-01

Far-infrared vibrational absorption of cocrystal formation between 2,5-dihydroxybenzoic acid (2,5-DHBA) and piracetam compounds under solvent evaporation and grinding methods have been investigated using terahertz time-domain spectroscopy (THz-TDS) at room temperature. The experimental results show large difference among absorption spectra of the formed cocrystals and the involved individual parent molecules in 0.20-1.50 THz region, which probably originated from the intra-molecular and inter-molecular hydrogen bonds due to the presence of two hydroxyl groups in 2,5-DHBA and amide moieties in piracetam compound. The THz absorption spectra of two formed cocrystals with different methods are almost identical. With grinding method, the reaction process can be monitored directly from both time-domain and frequency-domain spectra using THz-TDS technique. The results indicate that THz-TDS technology can absolutely offer us a high potential method to identify and characterize the formed cocrystals, and also provide the rich information about their reaction dynamic process involving two or more molecular crystals in situ to better know the corresponding reaction mechanism in pharmaceutical fields.

Nanomechanics of Carbon and CxByNz Nanotubes: Via a Quantum Molecular Dynamics Method

NASA Technical Reports Server (NTRS)

Srivastava, Deepak; Menon, M.; Cho, Kyeong Jae; Saini, Subhash (Technical Monitor)

1999-01-01

Nanomechanics of single-wall C, BN and BC$_3$ and B doped C nanotubes under axial compression and tension are investigated through a generalized tight-binding molecular dynamics (GTBMD) and {\\it ab-initio} electronic structure methods. The dynamic strength of BN, BC$_3$ and B doped C nanotubes for small axial strain are comparable to each other. The main difference is in the critical strain at which structural collapse occurs. For example, even a shallow doping with B lowers the value of critical strain for C nanotubes. The critical strain for BN nanotube is found to be more than that for the similar C nanotube. Once the structural collapse starts to occur we find that carbon nanotubes irreversibly go into plastic deformation regime via the formation of tetrahedral (four-fold coordinated) bonds at the location of sharp pinches or kinks. This finding is considerably different from the classical MD (molecular dynamics) simulation results known so far. The energetics and electronic densities of states of the collapsed structures, investigated with {\\it ab-initio) methods, will also be discussed.

The mammalian retina as a clock

NASA Technical Reports Server (NTRS)

Tosini, Gianluca; Fukuhara, Chiaki

2002-01-01

Many physiological, cellular, and biochemical parameters in the retina of vertebrates show daily rhythms that, in many cases, also persist under constant conditions. This demonstrates that they are driven by a circadian pacemaker. The presence of an autonomous circadian clock in the retina of vertebrates was first demonstrated in Xenopus laevis and then, several years later, in mammals. In X. laevis and in chicken, the retinal circadian pacemaker has been localized in the photoreceptor layer, whereas in mammals, such information is not yet available. Recent advances in molecular techniques have led to the identification of a group of genes that are believed to constitute the molecular core of the circadian clock. These genes are expressed in the retina, although with a slightly different 24-h profile from that observed in the central circadian pacemaker. This result suggests that some difference (at the molecular level) may exist between the retinal clock and the clock located in the suprachiasmatic nuclei of hypothalamus. The present review will focus on the current knowledge of the retinal rhythmicity and the mechanisms responsible for its control.

Changes of the Components of Fresh Seaweed, Undaria pinnatifida, by Different Strage Conditions

NASA Astrophysics Data System (ADS)

Onodera, Munenaka; Yoshie-Stark, Yumiko; Suzuki, Takesh

This study was performed to keep the quality and to prolong the shelf life of fresh Undaria pinnatifida, by different storage conditions. Changes of the contents of chlorophyll a (Chl a) and its derivatives, β-carotene, pH, molecular weight of alginate and molecular weight distribution were determined during the storage of U. pinnatifida. The conditions of cold storage at -3 to 7°C with air or O2, storage in seawater, and storage in slurry ice made of seawater were tested. Chl a and β-carotene contents, and the pH of U. pinnatifida were decreased following the increment of storage days. Significant decrease of Chl a content and molecular weight of U. pinnatifida was detected under cold storage especially at 7°C. The storage by icing in slurry ice and by super chilling at -3°C inhibited the degradation of Chl a and β-carotene of U. pinnatifida. The content of pheophorbide a or pH were recognized as useful factors to evaluate the quality and freshness of U. pinnatifida.

Modeling of metal thin film growth: Linking angstrom-scale molecular dynamics results to micron-scale film topographies

NASA Astrophysics Data System (ADS)

Hansen, U.; Rodgers, S.; Jensen, K. F.

2000-07-01

A general method for modeling ionized physical vapor deposition is presented. As an example, the method is applied to growth of an aluminum film in the presence of an ionized argon flux. Molecular dynamics techniques are used to examine the surface adsorption, reflection, and sputter reactions taking place during ionized physical vapor deposition. We predict their relative probabilities and discuss their dependence on energy and incident angle. Subsequently, we combine the information obtained from molecular dynamics with a line of sight transport model in a two-dimensional feature, incorporating all effects of reemission and resputtering. This provides a complete growth rate model that allows inclusion of energy- and angular-dependent reaction rates. Finally, a level-set approach is used to describe the morphology of the growing film. We thus arrive at a computationally highly efficient and accurate scheme to model the growth of thin films. We demonstrate the capabilities of the model predicting the major differences on Al film topographies between conventional and ionized sputter deposition techniques studying thin film growth under ionized physical vapor deposition conditions with different Ar fluxes.

Cellular and genetic regulation of the development of the cerebellar system.

PubMed

Sotelo, Constantino

2004-04-01

Recent advances in molecular biology have drastically changed our vision on the development of the nervous system, the cerebellum in particular. After a classical descriptive period, we are now in a modern mechanistic epoch as we begin to answer crucial questions in our quest to understand the mechanisms underlying the emergence of brain complexity. This review begins with an analysis of the role of the "isthmic organizer" in the induction and specification of the cerebellar territory and progresses through cerebellar development to the formation of cerebellar maps. It gathers information about the control of the proliferation of granule cell precursors by Purkinje cells and the role of Shh/Gli-patched signaling. The migratory routes for cerebellar and precerebellar neurons, together with the long-range and short-range cues guiding gliophilic and, particularly, neurophilic migrations, are also discussed. Because these cues are similar to those involved in axon guidance, both processes are under the same molecular constraints. Finally, using primarily the olivocerebellar projection as a model, the cellular and molecular mechanisms involved in the formation of cerebellar maps are discussed. During embryonic development, Purkinje cells in the cerebellum and neurons in the inferior olive follow a simultaneous, but independent, process of intrinsic parcellation, giving rise to subsets of biochemically different cortical compartments. The occurrence of positional information shared between olivary axons and their postsynaptic targets, the Purkinje cells, provides a molecular code for the formation of coarse-grained maps. Activity-dependent mechanisms are required for the transition from crude to fine-grained maps. This important refinement, which confers ultimate specificity to the maps, is under the regulation of parallel fiber-Purkinje cell synaptic activity.

Stereoselective Degradation and Molecular Ecological Mechanism of Chiral Pesticides Beta-Cypermethrin in Soils with Different pH Values.

PubMed

Yang, Zhong-Hua; Ji, Guo-Dong

2015-12-15

For decades, pesticides have been widely used for agricultural activities around the world, and the environmental problems caused by these compounds have raised widespread concern. However, the different enantioselective behaviors of chiral pesticide enantiomers are often ignored. Here, the selective degradation patterns and mechanisms of chiral pesticide enantiomers were successfully investigated for the first time in the soils of three cultivation areas with different pH values. Beta-cypermethrin was chosen as the target analyte. We found that the degradation rates of the four isomers of beta-cypermethrin were different. We used stepwise regression equations between degradation rates and functional genes to quantitatively study their relationships. Quantitative response analysis revealed that different isomers have different equations even under identical conditions. The results of path analysis showed that a single functional gene can make different direct and indirect contributions to the degradation of different isomers. Finally, the high-throughput technology was used to analysis the genome of the three tested soils and then compared the main microbial communities in them. We have successfully devised a method to investigate the molecular biological mechanisms of the selective degradation behavior of chiral compounds, thus enabling us to better understand these mechanisms.

Distinct dissociation kinetics between ion pairs: Solvent-coordinate free-energy landscape analysis.

PubMed

Yonetani, Yoshiteru

2015-07-28

Different ion pairs exhibit different dissociation kinetics; however, while the nature of this process is vital for understanding various molecular systems, the underlying mechanism remains unclear. In this study, to examine the origin of different kinetic rate constants for this process, molecular dynamics simulations were conducted for LiCl, NaCl, KCl, and CsCl in water. The results showed substantial differences in dissociation rate constant, following the trend kLiCl < kNaCl < kKCl < kCsCl. Analysis of the free-energy landscape with a solvent reaction coordinate and subsequent rate component analysis showed that the differences in these rate constants arose predominantly from the variation in solvent-state distribution between the ion pairs. The formation of a water-bridging configuration, in which the water molecule binds to an anion and a cation simultaneously, was identified as a key step in this process: water-bridge formation lowers the related dissociation free-energy barrier, thereby increasing the probability of ion-pair dissociation. Consequently, a higher probability of water-bridge formation leads to a higher ion-pair dissociation rate.

Proteomic approach toward molecular backgrounds of drug resistance of osteosarcoma cells in spheroid culture system.

PubMed

Arai, Kazuya; Sakamoto, Ruriko; Kubota, Daisuke; Kondo, Tadashi

2013-08-01

Chemoresistance is one of the most critical prognostic factors in osteosarcoma, and elucidation of the molecular backgrounds of chemoresistance may lead to better clinical outcomes. Spheroid cells resemble in vivo cells and are considered an in vitro model for the drug discovery. We found that spheroid cells displayed more chemoresistance than conventional monolayer cells across 11 osteosarcoma cell lines. To investigate the molecular mechanisms underlying the resistance to chemotherapy, we examined the proteomic differences between the monolayer and spheroid cells by 2D-DIGE. Of the 4762 protein species observed, we further investigated 435 species with annotated mass spectra in the public proteome database, Genome Medicine Database of Japan Proteomics. Among the 435 protein species, we found that 17 species exhibited expression level differences when the cells formed spheroids in more than five cell lines and four species out of these 17 were associated with spheroid-formation associated resistance to doxorubicin. We confirmed the upregulation of cathepsin D in spheroid cells by western blotting. Cathepsin D has been implicated in chemoresistance of various malignancies but has not previously been implemented in osteosarcoma. Our study suggested that the spheroid system may be a useful tool to reveal the molecular backgrounds of chemoresistance in osteosarcoma. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Multi-Targeted Molecular Effects of Hibiscus sabdariffa Polyphenols: An Opportunity for a Global Approach to Obesity

PubMed Central

Herranz-López, María; Olivares-Vicente, Mariló; Barrajón-Catalán, Enrique; Segura-Carretero, Antonio; Joven, Jorge; Micol, Vicente

2017-01-01

Improper diet can alter gene expression by breaking the energy balance equation and changing metabolic and oxidative stress biomarkers, which can result in the development of obesity-related metabolic disorders. The pleiotropic effects of dietary plant polyphenols are capable of counteracting by modulating different key molecular targets at the cell, as well as through epigenetic modifications. Hibiscus sabdariffa (HS)-derived polyphenols are known to ameliorate various obesity-related conditions. Recent evidence leads to propose the complex nature of the underlying mechanism of action. This multi-targeted mechanism includes the regulation of energy metabolism, oxidative stress and inflammatory pathways, transcription factors, hormones and peptides, digestive enzymes, as well as epigenetic modifications. This article reviews the accumulated evidence on the multiple anti-obesity effects of HS polyphenols in cell and animal models, as well as in humans, and its putative molecular targets. In silico studies reveal the capacity of several HS polyphenols to act as putative ligands for different digestive and metabolic enzymes, which may also deserve further attention. Therefore, a global approach including integrated and networked omics techniques, virtual screening and epigenetic analysis is necessary to fully understand the molecular mechanisms of HS polyphenols and metabolites involved, as well as their possible implications in the design of safe and effective polyphenolic formulations for obesity. PMID:28825642

Biomimetic Silica Nanoparticles Prepared by a Combination of Solid-Phase Imprinting and Ostwald Ripening.

PubMed

Piletska, Elena; Yawer, Heersh; Canfarotta, Francesco; Moczko, Ewa; Smolinska-Kempisty, Katarzyna; Piletsky, Stanislav S; Guerreiro, Antonio; Whitcombe, Michael J; Piletsky, Sergey A

2017-09-14

Herein we describe the preparation of molecularly imprinted silica nanoparticles by Ostwald ripening in the presence of molecular templates immobilised on glass beads (the solid-phase). To achieve this, a seed material (12 nm diameter silica nanoparticles) was incubated in phosphate buffer in the presence of the solid-phase. Phosphate ions act as a catalyst in the ripening process which is driven by differences in surface energy between particles of different size, leading to the preferential growth of larger particles. Material deposited in the vicinity of template molecules results in the formation of sol-gel molecular imprints after around 2 hours. Selective washing and elution allows the higher affinity nanoparticles to be isolated. Unlike other strategies commonly used to prepare imprinted silica nanoparticles this approach is extremely simple in nature and can be performed under physiological conditions, making it suitable for imprinting whole proteins and other biomacromolecules in their native conformations. We have demonstrated the generic nature of this method by preparing imprinted silica nanoparticles against targets of varying molecular mass (melamine, vancomycin and trypsin). Binding to the imprinted particles was demonstrated in an immunoassay (ELISA) format in buffer and complex media (milk or blood plasma) with sub-nM detection ability.

Using Solid-state NMR to Monitor the Molecular Consequences of Cryptococcus neoformans Melanization with Different Catecholamine Precursors

PubMed Central

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

2012-01-01

Melanins are a class of natural pigments associated with a wide range of biological functions, including microbial virulence, energy transduction, and protection against solar radiation. Because of their insolubility and structural heterogeneity, solid-state nuclear magnetic resonance (NMR) spectroscopy provides an unprecedented means to define the molecular architecture of these enigmatic pigments. The requirement of obligatory catecholamines for melanization of the pathogenic fungus Cryptococcus neoformans also offers unique opportunities for investigating melanin development. In the current study, pigments produced with L-dopa, methyl-L-dopa, epinephrine, and norepinephrine precursors are compared structurally using 13C and 1H magic-angle spinning (MAS) NMR. Striking structural differences were observed for both aromatic and aliphatic molecular constituents of the mature fungal pigment assemblies, thus making it possible to redefine the molecular prerequisites for formation of the aromatic domains of insoluble indole-based biopolymers, to rationalize their distinctive physical characteristics, and to delineate the role of cellular constituents in assembly of the melanized macromolecules with polysaccharides and fatty acyl chain-containing moieties. By achieving an augmented understanding of the mechanisms of C. neoformans melanin biosynthesis and cellular assembly, such studies can guide future drug discovery efforts related to melanin-associated virulence, resistance to tumor therapy, and production of melanin mimetics under cell-free conditions. PMID:22765382

Multi-Targeted Molecular Effects of Hibiscus sabdariffa Polyphenols: An Opportunity for a Global Approach to Obesity.

PubMed

Herranz-López, María; Olivares-Vicente, Mariló; Encinar, José Antonio; Barrajón-Catalán, Enrique; Segura-Carretero, Antonio; Joven, Jorge; Micol, Vicente

2017-08-20

Improper diet can alter gene expression by breaking the energy balance equation and changing metabolic and oxidative stress biomarkers, which can result in the development of obesity-related metabolic disorders. The pleiotropic effects of dietary plant polyphenols are capable of counteracting by modulating different key molecular targets at the cell, as well as through epigenetic modifications. Hibiscus sabdariffa (HS)-derived polyphenols are known to ameliorate various obesity-related conditions. Recent evidence leads to propose the complex nature of the underlying mechanism of action. This multi-targeted mechanism includes the regulation of energy metabolism, oxidative stress and inflammatory pathways, transcription factors, hormones and peptides, digestive enzymes, as well as epigenetic modifications. This article reviews the accumulated evidence on the multiple anti-obesity effects of HS polyphenols in cell and animal models, as well as in humans, and its putative molecular targets. In silico studies reveal the capacity of several HS polyphenols to act as putative ligands for different digestive and metabolic enzymes, which may also deserve further attention. Therefore, a global approach including integrated and networked omics techniques, virtual screening and epigenetic analysis is necessary to fully understand the molecular mechanisms of HS polyphenols and metabolites involved, as well as their possible implications in the design of safe and effective polyphenolic formulations for obesity.

How PEGylation enhances the stability and potency of insulin: a molecular dynamics simulation.

PubMed

Yang, Cheng; Lu, Diannan; Liu, Zheng

2011-04-05

While the effectiveness of PEGylation in enhancing the stability and potency of protein pharmaceuticals has been validated for years, the underlying mechanism remains poorly understood, particularly at the molecular level. A molecular dynamics simulation was developed using an annealing procedure that allowed an all-atom level examination of the interaction between PEG polymers of different chain lengths and a conjugated protein represented by insulin. It was shown that PEG became entangled around the protein surface through hydrophobic interaction and concurrently formed hydrogen bonds with the surrounding water molecules. In addition to enhancing its structural stability, as indicated by the root-mean-square difference (rmsd) and secondary structure analyses, conjugation increased the size of the protein drug while decreasing the solvent accessible surface area of the protein. All these thus led to prolonged circulation life despite kidney filtration, proteolysis, and immunogenic side effects, as experimentally demonstrated elsewhere. Moreover, the simulation results indicated that an optimal chain length exists that would maximize drug potency underpinned by the parameters mentioned above. The simulation provided molecular insight into the interaction between PEG and the conjugated protein at the all-atom level and offered a tool that would allow for the design of PEGylated protein pharmaceuticals for given applications.

Taverna: a tool for building and running workflows of services

PubMed Central

Hull, Duncan; Wolstencroft, Katy; Stevens, Robert; Goble, Carole; Pocock, Mathew R.; Li, Peter; Oinn, Tom

2006-01-01

Taverna is an application that eases the use and integration of the growing number of molecular biology tools and databases available on the web, especially web services. It allows bioinformaticians to construct workflows or pipelines of services to perform a range of different analyses, such as sequence analysis and genome annotation. These high-level workflows can integrate many different resources into a single analysis. Taverna is available freely under the terms of the GNU Lesser General Public License (LGPL) from . PMID:16845108

Electronic structure and properties of unsubstituted rhodamine in different electron states

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

Artyukhov, V.Ya.

1988-04-01

An analysis is given of the electron density distribution, dipole moment variation, and proton acceptor properties of unsubstituted rhodamine molecules in different electron states. It is shown that the electron density redistribution between the pyronine and benzoin parts of rhodamine may be large and strongly affect the molecular properties. In one of the electron transitions (S/sub 4/) producing the third absorption band the proton acceptor power markedly increases, giving rise to a protonated form under suitable conditions.

Electronic structure and properties of unsubstituted rhodamine in different electron states

NASA Astrophysics Data System (ADS)

Artyukhov, V. Ya.

1987-10-01

An analysis is given of the electron density distribution, dipole moment variation, and proton acceptor properties of unsubstituted rhodamine molecules in different electron states. It is shown that the electron density redistribution between the pyronine and benzoin parts of rhodamine may be large and strongly affect the molecular properties. In one of the electron transitions (S4) producing the third absorption band the proton acceptor power markedly increases, giving rise to a protonated form under suitable conditions.

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

PubMed

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.

Unifying hydrotropy under Gibbs phase rule.

PubMed

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.

Phenotyping bananas for drought resistance

PubMed Central

Ravi, Iyyakkutty; Uma, Subbaraya; Vaganan, Muthu Mayil; Mustaffa, Mohamed M.

2012-01-01

Drought has emerged as one of the major constraints in banana production. Its effects are pronounced substantially in the tropics and sub-tropics of the world due to climate change. Bananas are quite sensitive to drought; however, genotypes with “B” genome are more tolerant to abiotic stresses than those solely based on “A” genome. In particular, bananas with “ABB” genomes are more tolerant to drought and other abiotic stresses than other genotypes. A good phenotyping plan is a prerequisite for any improvement program for targeted traits. In the present article, known drought tolerant traits of other crop plants are validated in bananas with different genomic backgrounds and presented. Since, banana is recalcitrant to breeding, strategies for making hybrids between different genomic backgrounds are also discussed. Stomatal conductance, cell membrane stability (CMS), leaf emergence rate, rate of leaf senescence, RWC, and bunch yield under soil moisture deficit stress are some of the traits associated with drought tolerance. Among these stress bunch yield under drought should be given top priority for phenotyping. In the light of recently released Musa genome draft sequence, the molecular breeders may have interest in developing molecular markers for drought resistance. PMID:23443573

Evolution of Local Mutation Rate and Its Determinants.

PubMed

Terekhanova, Nadezhda V; Seplyarskiy, Vladimir B; Soldatov, Ruslan A; Bazykin, Georgii A

2017-05-01

Mutation rate varies along the human genome, and part of this variation is explainable by measurable local properties of the DNA molecule. Moreover, mutation rates differ between orthologous genomic regions of different species, but the drivers of this change are unclear. Here, we use data on human divergence from chimpanzee, human rare polymorphism, and human de novo mutations to predict the substitution rate at orthologous regions of non-human mammals. We show that the local mutation rates are very similar between human and apes, implying that their variation has a strong underlying cryptic component not explainable by the known genomic features. Mutation rates become progressively less similar in more distant species, and these changes are partially explainable by changes in the local genomic features of orthologous regions, most importantly, in the recombination rate. However, they are much more rapid, implying that the cryptic component underlying the mutation rate is more ephemeral than the known genomic features. These findings shed light on the determinants of mutation rate evolution. local mutation rate, molecular evolution, recombination rate. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Removal of natural organic matter by titanium tetrachloride: The effect of total hardness and ionic strength.

PubMed

Zhao, Y X; Shon, H K; Phuntsho, S; Gao, B Y

2014-02-15

This study is the first attempt to investigate the effect of total hardness and ionic strength on coagulation performance and the floc characteristics of titanium tetrachloride (TiCl4). Membrane fouling under different total hardness and ionic strength conditions was also evaluated during a coagulation-ultrafiltration (C-UF) hybrid process. Coagulation experiments were performed with two simulated waters, using humic acid (HA, high molecular weight) and fulvic acid (FA, relatively low molecular weight), respectively, as model natural organic matter (NOM). Results show that both particle and organic matter removal can be enhanced by increasing total hardness and ionic strength. Floc characteristics were significantly influenced by total hardness and ionic strength and were improved in terms of floc size, growth rate, strength, recoverability and compactness. The results of the UF tests show that the pre-coagulation with TiCl4 significantly improves the membrane permeate fluxes. Under different total hardness and ionic strength conditions, the membrane permeate flux varied according to both NOM and floc characteristics. The increase in total hardness and ionic strength improved the membrane permeate flux in the case of HA simulated water treatment. Copyright © 2014 Elsevier Ltd. All rights reserved.

BK Channels Mediate Synaptic Plasticity Underlying Habituation in Rats.

PubMed

Zaman, Tariq; De Oliveira, Cleusa; Smoka, Mahabba; Narla, Chakravarthi; Poulter, Michael O; Schmid, Susanne

2017-04-26

Habituation is a basic form of implicit learning and represents a sensory filter that is disrupted in autism, schizophrenia, and several other mental disorders. Despite extensive research in the past decades on habituation of startle and other escape responses, the underlying neural mechanisms are still not fully understood. There is evidence from previous studies indicating that BK channels might play a critical role in habituation. We here used a wide array of approaches to test this hypothesis. We show that BK channel activation and subsequent phosphorylation of these channels are essential for synaptic depression presumably underlying startle habituation in rats, using patch-clamp recordings and voltage-sensitive dye imaging in slices. Furthermore, positive modulation of BK channels in vivo can enhance short-term habituation. Although results using different approaches do not always perfectly align, together they provide convincing evidence for a crucial role of BK channel phosphorylation in synaptic depression underlying short-term habituation of startle. We also show that this mechanism can be targeted to enhance short-term habituation and therefore to potentially ameliorate sensory filtering deficits associated with psychiatric disorders. SIGNIFICANCE STATEMENT Short-term habituation is the most fundamental form of implicit learning. Habituation also represents a filter for inundating sensory information, which is disrupted in autism, schizophrenia, and other psychiatric disorders. Habituation has been studied in different organisms and behavioral models and is thought to be caused by synaptic depression in respective pathways. The underlying molecular mechanisms, however, are poorly understood. We here identify, for the first time, a BK channel-dependent molecular synaptic mechanism leading to synaptic depression that is crucial for habituation, and we discuss the significance of our findings for potential treatments enhancing habituation. Copyright © 2017 the authors 0270-6474/17/374540-12$15.00/0.

Anisotropic responses and initial decomposition of condensed-phase β-HMX under shock loadings via molecular dynamics simulations in conjunction with multiscale shock technique.

PubMed

Ge, Ni-Na; Wei, Yong-Kai; Song, Zhen-Fei; Chen, Xiang-Rong; Ji, Guang-Fu; Zhao, Feng; Wei, Dong-Qing

2014-07-24

Molecular dynamics simulations in conjunction with multiscale shock technique (MSST) are performed to study the initial chemical processes and the anisotropy of shock sensitivity of the condensed-phase HMX under shock loadings applied along the a, b, and c lattice vectors. A self-consistent charge density-functional tight-binding (SCC-DFTB) method was employed. Our results show that there is a difference between lattice vector a (or c) and lattice vector b in the response to a shock wave velocity of 11 km/s, which is investigated through reaction temperature and relative sliding rate between adjacent slipping planes. The response along lattice vectors a and c are similar to each other, whose reaction temperature is up to 7000 K, but quite different along lattice vector b, whose reaction temperature is only up to 4000 K. When compared with shock wave propagation along the lattice vectors a (18 Å/ps) and c (21 Å/ps), the relative sliding rate between adjacent slipping planes along lattice vector b is only 0.2 Å/ps. Thus, the small relative sliding rate between adjacent slipping planes results in the temperature and energy under shock loading increasing at a slower rate, which is the main reason leading to less sensitivity under shock wave compression along lattice vector b. In addition, the C-H bond dissociation is the primary pathway for HMX decomposition in early stages under high shock loading from various directions. Compared with the observation for shock velocities V(imp) = 10 and 11 km/s, the homolytic cleavage of N-NO2 bond was obviously suppressed with increasing pressure.

Incorporation of Eu(III) into Calcite under Recrystallization conditions.

PubMed

Hellebrandt, S E; Hofmann, S; Jordan, N; Barkleit, A; Schmidt, M

2016-09-13

The interaction of calcite with trivalent europium under recrystallization conditions was studied on the molecular level using site-selective time-resolved laser fluorescence spectroscopy (TRLFS). We conducted batch studies with a reaction time from seven days up to three years with three calcite powders, which differed in their specific surface area, recrystallization rates and impurities content. With increase of the recrystallization rate incorporation of Eu(3+) occurs faster and its speciation comes to be dominated by one species with its excitation maximum at 578.8 nm, so far not identified during previous investigations of this process under growth and phase transformation conditions. A long lifetime of 3750 μs demonstrates complete loss of hydration, consequently Eu must have been incorporated into the bulk crystal. The results show a strong dependence of the incorporation kinetics on the recrystallization rate of the different calcites. Furthermore the investigation of the effect of different background electrolytes (NaCl and KCl) demonstrate that the incorporation process under recrystallization conditions strongly depends on the availability of Na(+). These findings emphasize the different retention potential of calcite as a primary and secondary mineral e.g. in a nuclear waste disposal site.

Incorporation of Eu(III) into Calcite under Recrystallization conditions

PubMed Central

Hellebrandt, S. E.; Hofmann, S.; Jordan, N.; Barkleit, A.; Schmidt, M.

2016-01-01

The interaction of calcite with trivalent europium under recrystallization conditions was studied on the molecular level using site-selective time-resolved laser fluorescence spectroscopy (TRLFS). We conducted batch studies with a reaction time from seven days up to three years with three calcite powders, which differed in their specific surface area, recrystallization rates and impurities content. With increase of the recrystallization rate incorporation of Eu3+ occurs faster and its speciation comes to be dominated by one species with its excitation maximum at 578.8 nm, so far not identified during previous investigations of this process under growth and phase transformation conditions. A long lifetime of 3750 μs demonstrates complete loss of hydration, consequently Eu must have been incorporated into the bulk crystal. The results show a strong dependence of the incorporation kinetics on the recrystallization rate of the different calcites. Furthermore the investigation of the effect of different background electrolytes (NaCl and KCl) demonstrate that the incorporation process under recrystallization conditions strongly depends on the availability of Na+. These findings emphasize the different retention potential of calcite as a primary and secondary mineral e.g. in a nuclear waste disposal site. PMID:27618958

Carbon Isotopes of Alkanes in Hydrothermal Abiotic Organic Synthesis Processes at High Temperatures and Pressures: An Experimental Study

NASA Technical Reports Server (NTRS)

Fu, Qi; Socki, Richard A.; Niles, Paul B.

2010-01-01

Observation of methane in the Martian atmosphere has been reported by different detection techniques [1-4]. With more evidence showing extensive water-rock interaction in Martian history [5-7], abiotic formation by Fischer-Tropsch Type (FTT) synthesis during serpentization reactions may be one possible process responsible for methane generation on Mars [8, 9]. While the experimental studies performed to date leave little doubt that chemical reactions exist for the abiotic synthesis of organic compounds by mineral surface-catalyzed reactions [10-12], little is known about the reaction pathways by which CO2 and/or CO are reduced under hydrothermal conditions. Carbon and hydrogen isotope measurements of alkanes have been used as an effective tool to constrain the origin and reaction pathways of hydrocarbon formation. Alkanes generated by thermal breakdown of high molecular weight organic compounds have carbon and hydrogen isotopic signatures completely distinct from those formed abiotically [13-15]. Recent experimental studies, however, showed that different abiogenic hydrocarbon formation processes (e.g., polymerization vs. depolymerization) may have different carbon and hydrogen isotopic patterns [16]. Results from previous experiments studying decomposition of higher molecular weight organic compounds (lignite) also suggested that pressure could be a crucial factor affecting fractionation of carbon isotopes [17]. Under high pressure conditions, no experimental data are available describing fractionation of carbon isotope during mineral catalyzed FTT synthesis. Thus, hydrothermal experiments present an excellent opportunity to provide the requisite carbon isotope data. Such data can also be used to identify reaction pathways of abiotic organic synthesis under experimental conditions.

Characterizing Bonding Patterns in Diradicals and Triradicals by Density-Based Wave Function Analysis: A Uniform Approach.

PubMed

Orms, Natalie; Rehn, Dirk R; Dreuw, Andreas; Krylov, Anna I

2018-02-13

Density-based wave function analysis enables unambiguous comparisons of the electronic structure computed by different methods and removes ambiguity of orbital choices. We use this tool to investigate the performance of different spin-flip methods for several prototypical diradicals and triradicals. In contrast to previous calibration studies that focused on energy gaps between high- and low spin-states, we focus on the properties of the underlying wave functions, such as the number of effectively unpaired electrons. Comparison of different density functional and wave function theory results provides insight into the performance of the different methods when applied to strongly correlated systems such as polyradicals. We show that canonical molecular orbitals for species like large copper-containing diradicals fail to correctly represent the underlying electronic structure due to highly non-Koopmans character, while density-based analysis of the same wave function delivers a clear picture of the bonding pattern.

Loading direction-dependent shear behavior at different temperatures of single-layer chiral graphene sheets

NASA Astrophysics Data System (ADS)

Zhao, Yang; Dong, Shuhong; Yu, Peishi; Zhao, Junhua

2018-06-01

The loading direction-dependent shear behavior of single-layer chiral graphene sheets at different temperatures is studied by molecular dynamics (MD) simulations. Our results show that the shear properties (such as shear stress-strain curves, buckling strains, and failure strains) of chiral graphene sheets strongly depend on the loading direction due to the structural asymmetry. The maximum values of both the critical buckling shear strain and the failure strain under positive shear deformation can be around 1.4 times higher than those under negative shear deformation. For a given chiral graphene sheet, both its failure strain and failure stress decrease with increasing temperature. In particular, the amplitude to wavelength ratio of wrinkles for different chiral graphene sheets under shear deformation using present MD simulations agrees well with that from the existing theory. These findings provide physical insights into the origins of the loading direction-dependent shear behavior of chiral graphene sheets and their potential applications in nanodevices.

Recent technological advancements in tuberculosis diagnostics - A review.

PubMed

Gupta, Shagun; Kakkar, Vipan

2018-09-15

Early diagnosis and on-time effective treatment are indispensable for Tuberculosis (TB) control - a life threatening infectious communicable disease. The conventional techniques for diagnosing TB normally take two to three weeks. This delay in diagnosis and further increase in detection complexity due to the emerging risks of XDR-TB (Extensively drug Resistant-TB) and MDR-TB (Multidrug Resistant-TB) are evoking interest of researchers in the field of developing rapid TB detection techniques such as biosensing and other point-of-care (POC) techniques. Biosensing technologies along with the collaboration with nanotechnology have enormous potential to boost the MTB detection and for overall management in clinical diagnosis. A diverse range of portable, sensitive and rapid biosensors based on different signal transducer principles and with different biomarkers detection capabilities have been developed for TB detection in the early stages. Further, a lot of progress has been achieved over the years in developing various point-of-care diagnostic tools including non-molecular methods and molecular techniques. The objective of this study is to present a succinct review of the available TB detection techniques that are either in use or under development. The focus of this review is on the current developments occurred in nano-biosensing technologies. A synopsis of ameliorations in different non-molecular diagnostic tools and progress in the field of molecular techniques along with the role of emerging Lab-on-Chip technology for diagnosing and mitigating the TB consequences have also been presented. Copyright © 2018 Elsevier B.V. All rights reserved.

The genomic heritage of lymph node metastases: implications for clinical management of patients with breast cancer.

PubMed

Becker, Tyson E; Ellsworth, Rachel E; Deyarmin, Brenda; Patney, Heather L; Jordan, Rick M; Hooke, Jeffrey A; Shriver, Craig D; Ellsworth, Darrell L

2008-04-01

Metastatic breast cancer is an aggressive disease associated with recurrence and decreased survival. To improve outcomes and develop more effective treatment strategies for patients with breast cancer, it is important to understand the molecular mechanisms underlying metastasis. We used allelic imbalance (AI) to determine the molecular heritage of primary breast tumors and corresponding metastases to the axillary lymph nodes. Paraffin-embedded samples from primary breast tumors and matched metastases (n = 146) were collected from 26 patients with node-positive breast cancer involving multiple axillary nodes. Hierarchical clustering was used to assess overall differences in the patterns of AI, and phylogenetic analysis inferred the molecular heritage of axillary lymph node metastases. Overall frequencies of AI were significantly higher (P < 0.01) in primary breast tumors (23%) than in lymph node metastases (15%), and there was a high degree of discordance in patterns of AI between primary breast carcinomas and the metastases. Metastatic tumors in the axillary nodes showed different patterns of chromosomal changes, suggesting that multiple molecular mechanisms may govern the process of metastasis in individual patients. Some metastases progressed with few genomic alterations, while others harbored many chromosomal alterations present in the primary tumor. The extent of genomic heterogeneity in axillary lymph node metastases differs markedly among individual patients. Genomic diversity may be associated with response to adjuvant therapy, recurrence, and survival, and thus may be important in improving clinical management of breast cancer patients.

Analyzing the Coordinated Gene Network Underlying Temperature-Dependent Sex Determination in Reptiles

PubMed Central

Shoemaker, Christina M.; Crews, David

2009-01-01

Although gonadogenesis has been extensively studied in vertebrates with genetic sex determination, investigations at the molecular level in nontraditional model organisms with temperature-dependent sex determination are a relatively new area of research. Results show that while the key players of the molecular network underlying gonad development appear to be retained, their functions range from conserved to novel roles. In this review, we summarize experiments investigating candidate molecular players underlying temperature-dependent sex determination. We discuss some of the problems encountered unraveling this network, pose potential solutions, and suggest rewarding future directions of research. PMID:19022389

MOLECULAR DESORPTION OF BAKED STAINLESS STEEL FROM IRRADIATION WITH 9 GeV/NUCLEON Au79+, 10 GeV/NUCLEON Cu29+, AND 23GeV p+ UNDER PERPENDICULAR IMPACT.

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

FISCHER,W.; IRISO, U.; MUSTAFIN, E.

We report on molecular desorption of baked stainless steel from irradiation with high energy ions under perpendicular impact. Ion induced molecular desorption has affected the performance of a number of ion accelerators, in which the beam loss typically occurs under small angles. However, experimental parameters can be easier controlled in measurements with perpendicular impact. Desorption coefficients for small angle impact can be estimated from these measurements. The measurements were carried out at Brookhaven's Relativistic Heavy Ion Collider.

Using sex differences in the developing brain to identify nodes of influence for seizure susceptibility and epileptogenesis.

PubMed

Kight, Katherine E; McCarthy, Margaret M

2014-12-01

Sexual differentiation of the developing brain organizes the neural architecture differently between males and females, and the main influence on this process is exposure to gonadal steroids during sensitive periods of prenatal and early postnatal development. Many molecular and cellular processes are influenced by steroid hormones in the developing brain, including gene expression, cell birth and death, neurite outgrowth and synaptogenesis, and synaptic activity. Perturbations in these processes can alter neuronal excitability and circuit activity, leading to increased seizure susceptibility and the promotion of pathological processes that constitute epileptogenesis. In this review, we will provide a general overview of sex differences in the early developing brain that may be relevant for altered seizure susceptibility in early life, focusing on limbic areas of the brain. Sex differences that have the potential to alter the progress of epileptogenesis are evident at molecular and cellular levels in the developing brain, and include differences in neuronal excitability, response to environmental insult, and epigenetic control of gene expression. Knowing how these processes differ between the sexes can help us understand fundamental mechanisms underlying gender differences in seizure susceptibility and epileptogenesis. Copyright © 2014 Elsevier Inc. All rights reserved.

Identification of a New Mullet Species Complex Based on an Integrative Molecular and Cytogenetic Investigation of Mugil hospes (Mugilidae: Mugiliformes).

PubMed

Nirchio, Mauro; Paim, Fabilene G; Milana, Valentina; Rossi, Anna R; Oliveira, Claudio

2018-01-01

Mullets are very common fishes included in the family Mugilidae, (Mugiliformes), which are characterized by both a remarkably uniform external morphology and internal anatomy. Recently, within this family, different species complexes were molecularly identified within Mugil , a genus which is characterized by lineages that sometimes show very different karyotypes. Here we report the results of cytogenetic and molecular analyses conducted on Mugil hospes , commonly known as the hospe mullet, from Ecuador. The study aims to verify whether the original described species from the Pacific Ocean corresponds to that identified in the Atlantic Ocean, and to identify species-specific chromosome markers that can add new comparative data about Mugilidae karyotype evolution. The karyotype of M. hospes from Ecuador is composed of 48 acrocentric chromosomes and shows two active nucleolar organizer regions (NORs). In situ hybridization, using different types of repetitive sequences (rDNAs, U1 snDNA, telomeric repeats) as probes, identified species-specific chromosome markers that have been compared with those of other species of the genus Mugil . Cytochrome c oxidase subunit I (COI) sequence analysis shows only 92-93% similarity with sequences previously deposited under this species name in GenBank, all of which were from the Atlantic Ocean. Phylogenetic reconstructions indicate the presence of three well-supported hospe mullet lineages whose molecular divergence is compatible with the presence of distinct species. Indeed, the first lineage includes samples from Ecuador, whereas the other two lineages include the Atlantic samples and correspond to M. brevirostris from Brazil and Mugil sp. R from Belize/Venezuela. Results here provided reiterate the pivotal importance of an integrative molecular and cytogenetic approach in the reconstruction of the relationships within Mugilidae.

Identification of a New Mullet Species Complex Based on an Integrative Molecular and Cytogenetic Investigation of Mugil hospes (Mugilidae: Mugiliformes)

PubMed Central

Nirchio, Mauro; Paim, Fabilene G.; Milana, Valentina; Rossi, Anna R.; Oliveira, Claudio

2018-01-01

Mullets are very common fishes included in the family Mugilidae, (Mugiliformes), which are characterized by both a remarkably uniform external morphology and internal anatomy. Recently, within this family, different species complexes were molecularly identified within Mugil, a genus which is characterized by lineages that sometimes show very different karyotypes. Here we report the results of cytogenetic and molecular analyses conducted on Mugil hospes, commonly known as the hospe mullet, from Ecuador. The study aims to verify whether the original described species from the Pacific Ocean corresponds to that identified in the Atlantic Ocean, and to identify species-specific chromosome markers that can add new comparative data about Mugilidae karyotype evolution. The karyotype of M. hospes from Ecuador is composed of 48 acrocentric chromosomes and shows two active nucleolar organizer regions (NORs). In situ hybridization, using different types of repetitive sequences (rDNAs, U1 snDNA, telomeric repeats) as probes, identified species-specific chromosome markers that have been compared with those of other species of the genus Mugil. Cytochrome c oxidase subunit I (COI) sequence analysis shows only 92–93% similarity with sequences previously deposited under this species name in GenBank, all of which were from the Atlantic Ocean. Phylogenetic reconstructions indicate the presence of three well-supported hospe mullet lineages whose molecular divergence is compatible with the presence of distinct species. Indeed, the first lineage includes samples from Ecuador, whereas the other two lineages include the Atlantic samples and correspond to M. brevirostris from Brazil and Mugil sp. R from Belize/Venezuela. Results here provided reiterate the pivotal importance of an integrative molecular and cytogenetic approach in the reconstruction of the relationships within Mugilidae. PMID:29459882

Molecular Force Spectroscopy on Cells

NASA Astrophysics Data System (ADS)

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.

Simulations of X-ray diffraction of shock-compressed single-crystal tantalum with synchrotron undulator sources.

PubMed

Tang, M X; Zhang, Y Y; E, J C; Luo, S N

2018-05-01

Polychromatic synchrotron undulator X-ray sources are useful for ultrafast single-crystal diffraction under shock compression. Here, simulations of X-ray diffraction of shock-compressed single-crystal tantalum with realistic undulator sources are reported, based on large-scale molecular dynamics simulations. Purely elastic deformation, elastic-plastic two-wave structure, and severe plastic deformation under different impact velocities are explored, as well as an edge release case. Transmission-mode diffraction simulations consider crystallographic orientation, loading direction, incident beam direction, X-ray spectrum bandwidth and realistic detector size. Diffraction patterns and reciprocal space nodes are obtained from atomic configurations for different loading (elastic and plastic) and detection conditions, and interpretation of the diffraction patterns is discussed.

Simulations of X-ray diffraction of shock-compressed single-crystal tantalum with synchrotron undulator sources

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

Tang, M. X.; Zhang, Y. Y.; E, J. C.

Polychromatic synchrotron undulator X-ray sources are useful for ultrafast single-crystal diffraction under shock compression. Here, simulations of X-ray diffraction of shock-compressed single-crystal tantalum with realistic undulator sources are reported, based on large-scale molecular dynamics simulations. Purely elastic deformation, elastic–plastic two-wave structure, and severe plastic deformation under different impact velocities are explored, as well as an edge release case. Transmission-mode diffraction simulations consider crystallographic orientation, loading direction, incident beam direction, X-ray spectrum bandwidth and realistic detector size. Diffraction patterns and reciprocal space nodes are obtained from atomic configurations for different loading (elastic and plastic) and detection conditions, and interpretation of themore » diffraction patterns is discussed.« less

Layer-by-Layer Enabled Nanomaterials for Chemical Sensing and Energy Conversion

NASA Astrophysics Data System (ADS)

Paterno, Leonardo G.; Soler, Maria A. G.

2013-06-01

The layer-by-layer (LbL) technique is a wet chemical method for the assembly of ultrathin films, with thicknesses up to 100 nm. This method is based on the successive transfer of molecular layers to a solid substrate that is dipped into cationic and anionic solutions in an alternating fashion. The adsorption is mainly driven by electrostatic interactions so that many molecular and nanomaterial systems can be engineered under this method. Moreover, it is inexpensive, can be easily performed, and does not demand sophisticated equipment or clean rooms. The most explored use of the LbL technique is to build up molecular devices for chemical sensing and energy conversion. Both applications require ultrathin films where specific elements must be organized with high control of thickness and spatial distribution, preferably in the nanolength and mesolength scales. In chemical sensors, the LbL technique is employed to assemble specific sensoactive materials such as conjugated polymers, enzymes, and immunological elements onto appropriated electrodes. Molecular recognition events are thus transduced by the assembled sensoactive layer. In energy-conversion devices, the LbL technique can be employed to fabricate different device's parts including electrodes, active layers, and auxiliary layers. In both applications, the devices' performance can be fully modulated and improved by simply varying film thickness and molecular architecture. The present review article highlights the main features of the LbL technique and provides a brief description of different (bio)chemical sensors, solar cells, and organic light-emitting diodes enabled by the LbL approach.

Abiotic and Biotic Stressors Causing Equivalent Mortality Induce Highly Variable Transcriptional Responses in the Soybean Aphid

PubMed Central

Enders, Laramy S.; Bickel, Ryan D.; Brisson, Jennifer A.; Heng-Moss, Tiffany M.; Siegfried, Blair D.; Zera, Anthony J.; Miller, Nicholas J.

2014-01-01

Environmental stress affects basic organismal functioning and can cause physiological, developmental, and reproductive impairment. However, in many nonmodel organisms, the core molecular stress response remains poorly characterized and the extent to which stress-induced transcriptional changes differ across qualitatively different stress types is largely unexplored. The current study examines the molecular stress response of the soybean aphid (Aphis glycines) using RNA sequencing and compares transcriptional responses to multiple stressors (heat, starvation, and plant defenses) at a standardized stress level (27% adult mortality). Stress-induced transcriptional changes showed remarkable variation, with starvation, heat, and plant defensive stress altering the expression of 3985, 510, and 12 genes, respectively. Molecular responses showed little overlap across all three stressors. However, a common transcriptional stress response was identified under heat and starvation, involved with up-regulation of glycogen biosynthesis and molecular chaperones and down-regulation of bacterial endosymbiont cellular and insect cuticular components. Stressor-specific responses indicated heat affected expression of heat shock proteins and cuticular components, whereas starvation altered a diverse set of genes involved in primary metabolism, oxidative reductive processes, nucleosome and histone assembly, and the regulation of DNA repair and replication. Exposure to host plant defenses elicited the weakest response, of which half of the genes were of unknown function. This study highlights the need for standardizing stress levels when comparing across stress types and provides a basis for understanding the role of general vs. stressor specific molecular responses in aphids. PMID:25538100

Inhibition of O-linked N-acetylglucosamine transferase activity in PC12 cells - A molecular mechanism of organophosphate flame retardants developmental neurotoxicity.

PubMed

Gu, Yuxin; Yang, Yu; Wan, Bin; Li, Minjie; Guo, Liang-Hong

2018-06-01

Organophosphate flame retardants (OPFRs), as alternatives of brominated flame retardants, can cause neurodevelopmental effects similar to organophosphate pesticides. However, the molecular mechanisms underlying the toxicity remain elusive. O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) regulates numerous neural processes through the O-GlcNAcylation modification of nuclear and cytoplasmic proteins. In this study, we aimed to investigate the molecular mechanisms accounting for the developmental neurotoxicity of OPFRs by identifying potential targets of OPFRs and the attendant effects. Twelve OPFRs were evaluated for inhibition of OGT activity using an electrochemical biosensor. Their potency differed with substituent groups. The alkyl group substituted OPFRs had no inhibitory effect. Instead, the six OPFRs substituted with aromatic or chlorinated alkyl groups inhibited OGT activity significantly, with tri-m-cresyl phosphate (TCrP) being the strongest. The six OPFRs (0-100 μM exposure) also inhibited OGT activity in PC12 cells and decreased protein O-GlcNAcylation level. Inhibition of OGT by OPFRs might be involved in the subsequent toxic effects, including intracellular reactive oxygen species (ROS), calcium level, as well as cell proliferation and autophagy. Molecular docking of the OGT/OPFR complexes provided rationales for the difference in their structure-dependent inhibition potency. Our findings may provide a new biological target of OPFRs in their neurotoxicological actions, which might be a major molecular mechanism of OPFRs developmental neurotoxicity. Copyright © 2018 Elsevier Inc. All rights reserved.

Stability and free energy calculation of LNA modified quadruplex: a molecular dynamics study

NASA Astrophysics Data System (ADS)

Chaubey, Amit Kumar; Dubey, Kshatresh Dutta; Ojha, Rajendra Prasad

2012-03-01

Telomeric ends of chromosomes, which comprise noncoding repeat sequences of guanine-rich DNA, which are the fundamental in protecting the cell from recombination and degradation. Telomeric DNA sequences can form four stranded quadruplex structures, which are involved in the structure of telomere ends. The formation and stabilization of telomeric quadruplexes has been shown to inhibit the activity of telomerase, thus establishing telomeric DNA quadrulex as an attractive target for cancer therapeutic intervention. Molecular dynamic simulation offers the prospects of detailed description of the dynamical structure with ion and water at molecular level. In this work we have taken a oligomeric part of human telomeric DNA, d(TAGGGT) to form different monomeric quadruplex structures d(TAGGGT)4. Here we report the relative stabilities of these structures under K+ ion conditions and binding interaction between the strands, as determined by molecular dynamic simulations followed by energy calculation. We have taken locked nucleic acid (LNA) in this study. The free energy molecular mechanics Poission Boltzman surface area calculations are performed for the determination of most stable complex structure between all modified structures. We calculated binding free energy for the combination of different strands as the ligand and receptor for all structures. The energetic study shows that, a mixed hybrid type quadruplex conformation in which two parallel strands are bind with other two antiparallel strands, are more stable than other conformations. The possible mechanism for the inhibition of the cancerous growth has been discussed. Such studies may be helpful for the rational drug designing.

Extended Solution Gate OFET-based Biosensor for Label-free Glial Fibrillary Acidic Protein Detection with Polyethylene Glycol-Containing Bioreceptor Layer.

PubMed

Song, Jian; Dailey, Jennifer; Li, Hui; Jang, Hyun-June; Zhang, Pengfei; Wang, Jeff Tza-Huei; Everett, Allen D; Katz, Howard E

2017-05-25

A novel organic field effect transistor (OFET) -based biosensor is described for label-free glial fibrillary acidic protein (GFAP) detection. We report the first use of an extended solution gate structure where the sensing area and the organic semiconductor are separated, and a reference electrode is not needed. Different molecular weight polyethylene glycols (PEGs) are mixed into the bio-receptor layer to help extend the Debye screening length. The drain current change was significantly increased with the help of higher molecular weight PEGs, as they are known to reduce the dielectric constant. We also investigated the sensing performance under different gate voltage (V g ). The sensitivity increased after we decreased V g from -5 V to -2 V, because the lower V g is much closer to the OFET threshold voltage and the influence of attached negatively charged proteins become more apparent. Finally, the selectivity experiments toward different interferents were performed. The stability and selectivity are promising for clinical applications.

Electronic Structure of C60/Zinc Phthalocyanine/V₂O₅ Interfaces Studied Using Photoemission Spectroscopy for Organic Photovoltaic Applications.

PubMed

Lim, Chang Jin; Park, Min Gyu; Kim, Min Su; Han, Jeong Hwa; Cho, Soohaeng; Cho, Mann-Ho; Yi, Yeonjin; Lee, Hyunbok; Cho, Sang Wan

2018-02-18

The interfacial electronic structures of a bilayer of fullerene (C 60 ) and zinc phthalocyanine (ZnPc) grown on vanadium pentoxide (V₂O₅) thin films deposited using radio frequency sputtering under various conditions were studied using X-ray and ultraviolet photoelectron spectroscopy. The energy difference between the highest occupied molecular orbital (HOMO) level of the ZnPc layer and the lowest unoccupied molecular orbital (LUMO) level of the C 60 layer was determined and compared with that grown on an indium tin oxide (ITO) substrate. The energy difference of a heterojunction on all V₂O₅ was found to be 1.3~1.4 eV, while that on ITO was 1.1 eV. This difference could be due to the higher binding energy of the HOMO of ZnPc on V₂O₅ than that on ITO regardless of work functions of the substrates. We also determined the complete energy level diagrams of C 60 /ZnPc on V₂O₅ and ITO.

Bacterial computing: a form of natural computing and its applications.

PubMed

Lahoz-Beltra, Rafael; Navarro, Jorge; Marijuán, Pedro C

2014-01-01

The capability to establish adaptive relationships with the environment is an essential characteristic of living cells. Both bacterial computing and bacterial intelligence are two general traits manifested along adaptive behaviors that respond to surrounding environmental conditions. These two traits have generated a variety of theoretical and applied approaches. Since the different systems of bacterial signaling and the different ways of genetic change are better known and more carefully explored, the whole adaptive possibilities of bacteria may be studied under new angles. For instance, there appear instances of molecular "learning" along the mechanisms of evolution. More in concrete, and looking specifically at the time dimension, the bacterial mechanisms of learning and evolution appear as two different and related mechanisms for adaptation to the environment; in somatic time the former and in evolutionary time the latter. In the present chapter it will be reviewed the possible application of both kinds of mechanisms to prokaryotic molecular computing schemes as well as to the solution of real world problems.

Gene expression profile of Musculus longissimus dorsi in bulls of a Charolais × Holstein F2-cross with divergent intramuscular fat content.

PubMed

Komolka, Katrin; Ponsuksili, Siriluck; Albrecht, Elke; Kühn, Christa; Wimmers, Klaus; Maak, Steffen

2016-03-01

Transcriptomes of Musculus longissimus dorsi (MLD) were compared between bulls from a F2-cross derived from Charolais and Holstein Friesian. Two groups of 10 bulls were selected which differed significantly in intramuscular fat (IMF) deposition despite standardized husbandry and feeding conditions and identical sires in both groups. Consequently, genetic factors underlying the different capability of IMF deposition should be identified. A total of 32 differentially expressed genes (DEGs) were found of which 11 were up-regulated and 21 were down-regulated in the high IMF group. Ingenuity Pathway Analysis (IPA) identified a gene network comprising DEGs with functions in carbohydrate metabolism, lipid metabolism and molecular transport. The data from this study were deposited in NCBI's Gene Expression Omnibus and are accessible through GEO Series accession number GSE75347. We provide here a dataset which is of potential value to dissect molecular pathways influencing differences in IMF deposition in crossbred cattle with standardized genetic background.

Bacterial computing: a form of natural computing and its applications

PubMed Central

Lahoz-Beltra, Rafael; Navarro, Jorge; Marijuán, Pedro C.

2014-01-01

The capability to establish adaptive relationships with the environment is an essential characteristic of living cells. Both bacterial computing and bacterial intelligence are two general traits manifested along adaptive behaviors that respond to surrounding environmental conditions. These two traits have generated a variety of theoretical and applied approaches. Since the different systems of bacterial signaling and the different ways of genetic change are better known and more carefully explored, the whole adaptive possibilities of bacteria may be studied under new angles. For instance, there appear instances of molecular “learning” along the mechanisms of evolution. More in concrete, and looking specifically at the time dimension, the bacterial mechanisms of learning and evolution appear as two different and related mechanisms for adaptation to the environment; in somatic time the former and in evolutionary time the latter. In the present chapter it will be reviewed the possible application of both kinds of mechanisms to prokaryotic molecular computing schemes as well as to the solution of real world problems. PMID:24723912

Molecular architecture of botulinum neurotoxin E revealed by single particle electron microscopy.

PubMed

Fischer, Audrey; Garcia-Rodriguez, Consuelo; Geren, Isin; Lou, Jianlong; Marks, James D; Nakagawa, Terunaga; Montal, Mauricio

2008-02-15

Clostridial botulinum neurotoxin (BoNT) causes a neuroparalytic condition recognized as botulism by arresting synaptic vesicle exocytosis. Although the crystal structures of full-length BoNT/A and BoNT/B holotoxins are known, the molecular architecture of the five other serotypes remains elusive. Here, we present the structures of BoNT/A and BoNT/E using single particle electron microscopy. Labeling of the particles with three different monoclonal antibodies raised against BoNT/E revealed the positions of their epitopes in the electron microscopy structure, thereby identifying the three hallmark domains of BoNT (protease, translocation, and receptor binding). Correspondingly, these antibodies selectively inhibit BoNT translocation activity as detected using a single molecule assay. The global structure of BoNT/E is strikingly different from that of BoNT/A despite strong sequence similarity. We postulate that the unique architecture of functionally conserved modules underlies the distinguishing attributes of BoNT/E and contributes to differences with BoNT/A.

Structural evolution of Colloidal Gels under Flow

NASA Astrophysics Data System (ADS)

Boromand, Arman; Maia, Joao; Jamali, Safa

Colloidal suspensions are ubiquitous in different industrial applications ranging from cosmetic and food industries to soft robotics and aerospace. Owing to the fact that mechanical properties of colloidal gels are controlled by its microstructure and network topology, we trace the particles in the networks formed under different attraction potentials and try to find a universal behavior in yielding of colloidal gels. Many authors have implemented different simulation techniques such as molecular dynamics (MD) and Brownian dynamics (BD) to capture better picture during phase separation and yielding mechanism in colloidal system with short-ranged attractive force. However, BD neglects multi-body hydrodynamic interactions (HI) which are believed to be responsible for the second yielding of colloidal gels. We envision using dissipative particle dynamics (DPD) with modified depletion potential and hydrodynamic interactions, as a coarse-grain model, can provide a robust simulation package to address the gel formation process and yielding in short ranged-attractive colloidal systems. The behavior of colloidal gels with different attraction potentials under flow is examined and structural fingerprints of yielding in these systems will be discussed.

Alleles versus mutations: Understanding the evolution of genetic architecture requires a molecular perspective on allelic origins.

PubMed

Remington, David L

2015-12-01

Perspectives on the role of large-effect quantitative trait loci (QTL) in the evolution of complex traits have shifted back and forth over the past few decades. Different sets of studies have produced contradictory insights on the evolution of genetic architecture. I argue that much of the confusion results from a failure to distinguish mutational and allelic effects, a limitation of using the Fisherian model of adaptive evolution as the lens through which the evolution of adaptive variation is examined. A molecular-based perspective reveals that allelic differences can involve the cumulative effects of many mutations plus intragenic recombination, a model that is supported by extensive empirical evidence. I discuss how different selection regimes could produce very different architectures of allelic effects under a molecular-based model, which may explain conflicting insights on genetic architecture from studies of variation within populations versus between divergently selected populations. I address shortcomings of genome-wide association study (GWAS) practices in light of more suitable models of allelic evolution, and suggest alternate GWAS strategies to generate more valid inferences about genetic architecture. Finally, I discuss how adopting more suitable models of allelic evolution could help redirect research on complex trait evolution toward addressing more meaningful questions in evolutionary biology. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

Stretch or contraction induced inversion of rectification in diblock molecular junctions

NASA Astrophysics Data System (ADS)

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

2013-09-01

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

Genetic and phenotypic variations of inherited retinal diseases in dogs: the power of within- and across-breed studies

PubMed Central

Acland, Gregory M.

2014-01-01

Considerable clinical and molecular variations have been known in retinal blinding diseases in man and also in dogs. Different forms of retinal diseases occur in specific breed(s) caused by mutations segregating within each isolated breeding population. While molecular studies to find genes and mutations underlying retinal diseases in dogs have benefited largely from the phenotypic and genetic uniformity within a breed, within- and across-breed variations have often played a key role in elucidating the molecular basis. The increasing knowledge of phenotypic, allelic, and genetic heterogeneities in canine retinal degeneration has shown that the overall picture is rather more complicated than initially thought. Over the past 20 years, various approaches have been developed and tested to search for genes and mutations underlying genetic traits in dogs, depending on the availability of genetic tools and sample resources. Candidate gene, linkage analysis, and genome-wide association studies have so far identified 24 mutations in 18 genes underlying retinal diseases in at least 58 dog breeds. Many of these genes have been associated with retinal diseases in humans, thus providing opportunities to study the role in pathogenesis and in normal vision. Application in therapeutic interventions such as gene therapy has proven successful initially in a naturally occurring dog model followed by trials in human patients. Other genes whose human homologs have not been associated with retinal diseases are potential candidates to explain equivalent human diseases and contribute to the understanding of their function in vision. PMID:22065099

Genetic and phenotypic variations of inherited retinal diseases in dogs: the power of within- and across-breed studies.

PubMed

Miyadera, Keiko; Acland, Gregory M; Aguirre, Gustavo D

2012-02-01

Considerable clinical and molecular variations have been known in retinal blinding diseases in man and also in dogs. Different forms of retinal diseases occur in specific breed(s) caused by mutations segregating within each isolated breeding population. While molecular studies to find genes and mutations underlying retinal diseases in dogs have benefited largely from the phenotypic and genetic uniformity within a breed, within- and across-breed variations have often played a key role in elucidating the molecular basis. The increasing knowledge of phenotypic, allelic, and genetic heterogeneities in canine retinal degeneration has shown that the overall picture is rather more complicated than initially thought. Over the past 20 years, various approaches have been developed and tested to search for genes and mutations underlying genetic traits in dogs, depending on the availability of genetic tools and sample resources. Candidate gene, linkage analysis, and genome-wide association studies have so far identified 24 mutations in 18 genes underlying retinal diseases in at least 58 dog breeds. Many of these genes have been associated with retinal diseases in humans, thus providing opportunities to study the role in pathogenesis and in normal vision. Application in therapeutic interventions such as gene therapy has proven successful initially in a naturally occurring dog model followed by trials in human patients. Other genes whose human homologs have not been associated with retinal diseases are potential candidates to explain equivalent human diseases and contribute to the understanding of their function in vision.

A molecular scale perspective: Monte Carlo simulation for rupturing of ultra thin polymer film melts

NASA Astrophysics Data System (ADS)

Singh, Satya Pal

2017-04-01

Monte Carlo simulation has been performed to study the rupturing process of thin polymer film under strong confinement. The change in mean square displacement; pair correlation function; density distribution; average bond length and microscopic viscosity are sampled by varying the molecular interaction parameters such as the strength and the equilibrium positions of the bonding, non-bonding potentials and the sizes of the beads. The variation in mean square angular displacement χθ = [ < Δθ2 > - < Δθ>2 ] fits very well to a function of type y (t) = A + B *e-t/τ. This may help to study the viscous properties of the films and its dependence on different parameters. The ultra thin film annealed at high temperature gets ruptured and holes are created in the film mimicking spinodal dewetting. The pair correlation function and density profile reveal rich information about the equilibrium structure of the film. The strength and equilibrium bond length of finite extensible non-linear elastic potential (FENE) and non-bonding Morse potential have clear impact on microscopic rupturing of the film. The beads show Rouse or repetition motion forming rim like structures near the holes created inside the film. The higher order interaction as dipole-quadrupole may get prominence under strong confinement. The enhanced excluded volume interaction under strong confinement may overlap with the molecular dispersion forces. It can work to reorganize the molecules at the bottom of the scale and can imprint its signature in complex patterns evolved.

Radiative interactions in molecular gases under local and nonlocal thermodynamic equilibrium conditions

NASA Technical Reports Server (NTRS)

Tiwari, S. N.; Jha, M. K.

1993-01-01

Basic formulations, analyses, and numerical procedures are presented to investigate radiative heat interactions in diatomic and polyatomic gases under local and nonlocal thermodynamic equilibrium conditions. Essential governing equations are presented for both gray and nongray gases. Information is provided on absorption models, relaxation times, and transfer equations. Radiative flux equations are developed which are applicable under local and nonlocal thermodynamic equilibrium conditions. The problem is solved for fully developed laminar incompressible flows between two parallel plates under the boundary condition of a uniform surface heat flux. For specific applications, three diatomic and three polyatomic gases are considered. The results are obtained numerically by employing the method of variation of parameters. The results are compared under local and nonlocal thermodynamic equilibrium conditions at different temperature and pressure conditions. Both gray and nongray studies are conducted extensively for all molecular gases considered. The particular gases selected for this investigation are CO, NO, OH, CO2, H2O, and CH4. The temperature and pressure range considered are 300-2000 K and 0.1-10 atmosphere, respectively. In general, results demonstrate that the gray gas approximation overestimates the effect of radiative interaction for all conditions. The conditions of NLTE, however, result in underestimation of radiative interactions. The method developed for this study can be extended to solve complex problems of radiative heat transfer involving nonequilibrium phenomena.

An implicit divalent counterion force field for RNA molecular dynamics

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

Henke, Paul S.; Mak, Chi H., E-mail: cmak@usc.edu; Center of Applied Mathematical Sciences, University of Southern California, Los Angeles, California 90089

How to properly account for polyvalent counterions in a molecular dynamics simulation of polyelectrolytes such as nucleic acids remains an open question. Not only do counterions such as Mg{sup 2+} screen electrostatic interactions, they also produce attractive intrachain interactions that stabilize secondary and tertiary structures. Here, we show how a simple force field derived from a recently reported implicit counterion model can be integrated into a molecular dynamics simulation for RNAs to realistically reproduce key structural details of both single-stranded and base-paired RNA constructs. This divalent counterion model is computationally efficient. It works with existing atomistic force fields, or coarse-grainedmore » models may be tuned to work with it. We provide optimized parameters for a coarse-grained RNA model that takes advantage of this new counterion force field. Using the new model, we illustrate how the structural flexibility of RNA two-way junctions is modified under different salt conditions.« less

Scanning Tunneling Microscopy Analysis of a Pentacene/Graphene/SiC(0001) system

NASA Astrophysics Data System (ADS)

Yost, Andrew; Suzer, Ozgun; Smerdon, Joseph; Chien, Teyu; Guest, Jeffrey

2014-03-01

A complete understanding of the structure of molecular assemblies, as well as an understanding of donor-acceptor interactions is crucial in the development of emergent molecular electronics technologies such as organic photovoltaics. The pentacene (C22H14) is a good electron donor in Pentacene-C60 system, which is a model system of an organic photovoltaic cell.. Here we present scanning tunneling microscopy studies of the pentacene(Pn) molecule on Graphene(G) that is epitaxially grown on SiC(0001). In addition to the morphologies reported in literature, several new structures of Pn on on G/SiC(0001) were observed with different periodicity and registry both in monolayer and bilayer coverages of molecules on the surface. Preliminary scanning tunneling spectroscopy of the molecular system is also discussed; well-isolated states and a large HOMO-LUMO gap indicate the Pn is weakly coupled to the grapheme and underlying substrate.

[Allergy and autoimmunity: Molecular diagnostics, therapy, and presumable pathogenesis].

PubMed

Arefieva, A S; Smoldovskaya, O V; Tikhonov, A A; Rubina, A Yu

2017-01-01

Allergic and autoimmune diseases represent immunopathological reactions of an organism to antigens. Despite that the allergy is a result of exaggerated immune response to foreign antigens (allergens) and autoimmune diseases are characterized by the pathological response to internal antigens (autoantigens), the underlying mechanisms of these diseases are probably common. Thus, both types of diseases represent variations in the hypersensitivity reaction. A large percentage of both the adult and pediatric population is in need of early diagnostics of these pathologies of the immune system. Considering the diversity of antibodies produced in allergic and autoimmune disease and the difficulties accompanying clinical diagnosing, molecular diagnostics of these pathological processes should be carried out in several stages, including screening and confirmatory studies. In this review, we summarize the available data on the molecular diagnostics and therapy of allergic and autoimmune diseases and discuss the basic similarities and differences in the mechanisms of their development.

Crystallization and preliminary X-ray analysis of Leishmania major glyoxalase I

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

Ariza, Antonio; Vickers, Tim J.; Greig, Neil

2005-08-01

The detoxification enzyme glyoxalase I from L. major has been crystallized. Preliminary molecular-replacement calculations indicate the presence of three glyoxalase I dimers in the asymmetric unit. Glyoxalase I (GLO1) is a putative drug target for trypanosomatids, which are pathogenic protozoa that include the causative agents of leishmaniasis. Significant sequence and functional differences between Leishmania major and human GLO1 suggest that it may make a suitable template for rational inhibitor design. L. major GLO1 was crystallized in two forms: the first is extremely disordered and does not diffract, while the second, an orthorhombic form, produces diffraction to 2.0 Å. Molecular-replacement calculationsmore » indicate that there are three GLO1 dimers in the asymmetric unit, which take up a helical arrangement with their molecular dyads arranged approximately perpendicular to the c axis. Further analysis of these data are under way.« less

Mechanoregulation of molecular motors in flagella

NASA Astrophysics Data System (ADS)

Gadelha, Hermes

2014-11-01

Molecular motors are nano-biological machines responsible for exerting forces that drive movement in living organisms, from cargo transport to cell division and motility. Interestingly, despite the inherent complexity of many interacting motors, order and structure may arise naturally, as exemplified by the harmonic, self-organized undulatory motion of the flagellum. The real mechanisms behind this collective spontaneous oscillation are still unknown, and it is challenging task to measure experimentally the molecular motor dynamics within the flagellar structure in real time. In this talk we will explore different competing hypotheses that are capable of generating flagellar bending waves that ``resemble'' in-vitro observations, emphasizing the need for further mathematical analysis and model validation. It also highlight that this is a fertile and challenging area of inter-disciplinary research for applied mathematicians and demonstrates the importance of future observational and theoretical studies in understanding the underlying mechanics of these motile cell appendages.

Light microscopy applications in systems biology: opportunities and challenges

PubMed Central

2013-01-01

Biological systems present multiple scales of complexity, ranging from molecules to entire populations. Light microscopy is one of the least invasive techniques used to access information from various biological scales in living cells. The combination of molecular biology and imaging provides a bottom-up tool for direct insight into how molecular processes work on a cellular scale. However, imaging can also be used as a top-down approach to study the behavior of a system without detailed prior knowledge about its underlying molecular mechanisms. In this review, we highlight the recent developments on microscopy-based systems analyses and discuss the complementary opportunities and different challenges with high-content screening and high-throughput imaging. Furthermore, we provide a comprehensive overview of the available platforms that can be used for image analysis, which enable community-driven efforts in the development of image-based systems biology. PMID:23578051

Multiplexed Five-Color Molecular Imaging of Cancer Cells and Tumor Tissues with Carbon Nanotube Raman Tags in the Near-Infrared

PubMed Central

Liu, Zhuang; Tabakman, Scott; Sherlock, Sarah; Li, Xiaolin; Chen, Zhuo; Jiang, Kaili; Fan, Shoushan; Dai, Hongjie

2011-01-01

Single-walled carbon nanotubes (SWNTs) with five different C13/C12 isotope compositions and well-separated Raman peaks have been synthesized and conjugated to five targeting ligands in order to impart molecular specificity. Multiplexed Raman imaging of live cells has been carried out by highly specific staining of cells with a five-color mixture of SWNTs. Ex vivo multiplexed Raman imaging of tumor samples uncovers a surprising up-regulation of epidermal growth factor receptor (EGFR) on LS174T colon cancer cells from cell culture to in vivo tumor growth. This is the first time five-color multiplexed molecular imaging has been performed in the near-infrared (NIR) region under a single laser excitation. Near zero interfering background of imaging is achieved due to the sharp Raman peaks unique to nanotubes over the low, smooth autofluorescence background of biological species. PMID:21442006

Fine refinement of solid state structure of racemic form of phospho-tyrosine employing NMR Crystallography approach.

PubMed

Paluch, Piotr; Pawlak, Tomasz; Oszajca, Marcin; Lasocha, Wieslaw; Potrzebowski, Marek J

2015-02-01

We present step by step facets important in NMR Crystallography strategy employing O-phospho-dl-tyrosine as model sample. The significance of three major techniques being components of this approach: solid state NMR (SS NMR), X-ray diffraction of powdered sample (PXRD) and theoretical calculations (Gauge Invariant Projector Augmented Wave; GIPAW) is discussed. Each experimental technique provides different set of structural constraints. From the PXRD measurement the size of the unit cell, space group and roughly refined molecular structure are established. SS NMR provides information about content of crystallographic asymmetric unit, local geometry, molecular motion in the crystal lattice and hydrogen bonding pattern. GIPAW calculations are employed for validation of quality of elucidation and fine refinement of structure. Crystal and molecular structure of O-phospho-dl-tyrosine solved by NMR Crystallography is deposited at Cambridge Crystallographic Data Center under number CCDC 1005924. Copyright © 2014 Elsevier Inc. All rights reserved.

Hemimetabolous genomes reveal molecular basis of termite eusociality.

PubMed

Harrison, Mark C; Jongepier, Evelien; Robertson, Hugh M; Arning, Nicolas; Bitard-Feildel, Tristan; Chao, Hsu; Childers, Christopher P; Dinh, Huyen; Doddapaneni, Harshavardhan; Dugan, Shannon; Gowin, Johannes; Greiner, Carolin; Han, Yi; Hu, Haofu; Hughes, Daniel S T; Huylmans, Ann-Kathrin; Kemena, Carsten; Kremer, Lukas P M; Lee, Sandra L; Lopez-Ezquerra, Alberto; Mallet, Ludovic; Monroy-Kuhn, Jose M; Moser, Annabell; Murali, Shwetha C; Muzny, Donna M; Otani, Saria; Piulachs, Maria-Dolors; Poelchau, Monica; Qu, Jiaxin; Schaub, Florentine; Wada-Katsumata, Ayako; Worley, Kim C; Xie, Qiaolin; Ylla, Guillem; Poulsen, Michael; Gibbs, Richard A; Schal, Coby; Richards, Stephen; Belles, Xavier; Korb, Judith; Bornberg-Bauer, Erich

2018-03-01

Around 150 million years ago, eusocial termites evolved from within the cockroaches, 50 million years before eusocial Hymenoptera, such as bees and ants, appeared. Here, we report the 2-Gb genome of the German cockroach, Blattella germanica, and the 1.3-Gb genome of the drywood termite Cryptotermes secundus. We show evolutionary signatures of termite eusociality by comparing the genomes and transcriptomes of three termites and the cockroach against the background of 16 other eusocial and non-eusocial insects. Dramatic adaptive changes in genes underlying the production and perception of pheromones confirm the importance of chemical communication in the termites. These are accompanied by major changes in gene regulation and the molecular evolution of caste determination. Many of these results parallel molecular mechanisms of eusocial evolution in Hymenoptera. However, the specific solutions are remarkably different, thus revealing a striking case of convergence in one of the major evolutionary transitions in biological complexity.

Are Phenacoccus solani Ferris and P. defectus Ferris (Hemiptera: Pseudococcidae) distinct species?

PubMed

Chatzidimitriou, Evangelia; Simonato, Mauro; Watson, Gillian W; Martinez-Sañudo, Isabel; Tanaka, Hirotaka; Zhao, Jing; Pellizzari, Giuseppina

2016-03-24

Among the Nearctic species of Phenacoccus (Hemiptera: Pseudococcidae), Phenacoccus solani Ferris and P. defectus Ferris are morphologically similar and it can be difficult to separate them on the basis of microscopic morphological characters of the adult female alone. In order to resolve their identity, a canonical variates morphological analysis of 199 specimens from different geographical origins and host plants and a molecular analysis of the COI and 28S genes were performed. The morphological analysis supported synonymy of the two species, as although the type specimens of the "species" are widely separated from each other in the canonical variates plot, they are all part of a continuous range of variation. The molecular analysis showed that P. solani and P. defectus are grouped in the same clade. On the basis of the morphological and molecular analyses, P. defectus is synonymized under the senior name P. solani, syn. n.

GPCRs: What Can We Learn from Molecular Dynamics Simulations?

PubMed

Velgy, Naushad; Hedger, George; Biggin, Philip C

2018-01-01

Advances in the structural biology of G-protein Coupled Receptors have resulted in a significant step forward in our understanding of how this important class of drug targets function at the molecular level. However, it has also become apparent that they are very dynamic molecules, and moreover, that the underlying dynamics is crucial in shaping the response to different ligands. Molecular dynamics simulations can provide unique insight into the dynamic properties of GPCRs in a way that is complementary to many experimental approaches. In this chapter, we describe progress in three distinct areas that are particularly difficult to study with other techniques: atomic level investigation of the conformational changes that occur when moving between the various states that GPCRs can exist in, the pathways that ligands adopt during binding/unbinding events and finally, the influence of lipids on the conformational dynamics of GPCRs.

What Controls Thermo-osmosis? Molecular Simulations Show the Critical Role of Interfacial Hydrodynamics

NASA Astrophysics Data System (ADS)

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.

Theoretical and Experimental Triple Differential Cross Sections for Electron Impact Ionization of SF6

NASA Astrophysics Data System (ADS)

Chaluvadi, Hari; Nixon, Kate; Murray, Andrew; Ning, Chuangang; Colgan, James; Madison, Don

2014-10-01

Experimental and theoretical Triply Differential Cross Sections (TDCS) will be presented for electron-impact ionization of sulfur hexafluoride (SF6) for the molecular orbital 1t1g. M3DW (molecular 3-body distorted wave) results will be compared with experiment for coplanar geometry and for perpendicular plane geometry (a plane which is perpendicular to the incident beam direction). In both cases, the final state electron energies and observation angles are symmetric and the final state electron energies range from 5 eV to 40 eV. It will be shown that there is a large difference between using the OAMO (orientation averaged molecular orbital) approximation and the proper average over all orientations and also that the proper averaged results are in much better agreement with experiment. Work supported by NSF under Grant Number PHY-1068237. Computational work was performed with Institutional resources made available through Los Alamos National Laboratory.

What Controls Thermo-osmosis? Molecular Simulations Show the Critical Role of Interfacial Hydrodynamics.

PubMed

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.

Spectroscopic and molecular modeling studies of the interaction between cytidine and human serum albumin and its analytical application.

PubMed

Cui, Fengling; Wang, Junli; Yao, Xiaojun; Wang, Li; Zhang, Qiangzhai; Qu, Guirong

In this study, the interaction between cytidine and human serum albumin (HSA) was investigated for the first time by fluorescence spectroscopy in combination with UV absorption spectrum and molecular modeling under simulative physiological conditions. Experimental results indicated that cytidine had a strong ability to quench the intrinsic fluorescence of human serum albumin. The binding constants (K) at different temperatures, thermodynamic parameter enthalpy changes (DeltaH) and entropy changes (DeltaS) of HSA-cytidine had been calculated according to the relevant fluorescence data, which indicated that the hydrophobic and electrostatic interactions played a major role, which was in agreement with the results of molecular modeling study. In addition, the effects of other ions on the binding constants were also studied. Furthermore, synchronous fluorescence technology was successfully applied to the determination of human serum albumin added into the cytidine solution.

Systems Biology-Driven Hypotheses Tested In Vivo: The Need to Advancing Molecular Imaging Tools.

PubMed

Verma, Garima; Palombo, Alessandro; Grigioni, Mauro; La Monaca, Morena; D'Avenio, Giuseppe

2018-01-01

Processing and interpretation of biological images may provide invaluable insights on complex, living systems because images capture the overall dynamics as a "whole." Therefore, "extraction" of key, quantitative morphological parameters could be, at least in principle, helpful in building a reliable systems biology approach in understanding living objects. Molecular imaging tools for system biology models have attained widespread usage in modern experimental laboratories. Here, we provide an overview on advances in the computational technology and different instrumentations focused on molecular image processing and analysis. Quantitative data analysis through various open source software and algorithmic protocols will provide a novel approach for modeling the experimental research program. Besides this, we also highlight the predictable future trends regarding methods for automatically analyzing biological data. Such tools will be very useful to understand the detailed biological and mathematical expressions under in-silico system biology processes with modeling properties.

The Drosophila Circadian Pacemaker Circuit: Pas de Deux or Tarantella?

PubMed Central

Sheeba, Vasu; Kaneko, Maki; Sharma, Vijay Kumar; Holmes, Todd C.

2008-01-01

Molecular genetic analysis of the fruit fly Drosophila melanogaster has revolutionized our understanding of the transcription/translation loop mechanisms underlying the circadian molecular oscillator. More recently, Drosophila has been used to understand how different neuronal groups within the circadian pacemaker circuit interact to regulate the overall behavior of the fly in response to daily cyclic environmental cues as well as seasonal changes. Our present understanding of circadian timekeeping at the molecular and circuit level is discussed with a critical evaluation of the strengths and weaknesses of present models. Two models for circadian neural circuits are compared: one that posits that two anatomically distinct oscillators control the synchronization to the two major daily morning and evening transitions, versus a distributed network model that posits that many cell-autonomous oscillators are coordinated in a complex fashion and respond via plastic mechanisms to changes in environmental cues. PMID:18307108

Secondary ion emission from arachidic acid LB-layers under Ar +, Xe +, Ga + and SF 5+ primary ion bombardment

NASA Astrophysics Data System (ADS)

Stapel, D.; Brox, O.; Benninghoven, A.

1999-02-01

The influence of primary ion energy, mass and composition on sputtering and secondary ion emission of arachidic acid Langmuir-Blodgett mono- and multilayers, deposited on gold substrates, has been investigated. Ga +, Ar +, 129Xe+ and SF 5+ in the energy range 5-25 keV were used as primary ions. Yields Y, damage cross-sections σ, and ion formation efficiencies E have been determined for selected secondary ions, characterizing the molecular overlayer, the overlayer substrate interface and the substrate. We found a strong influence of layer thickness and of primary ion energy, mass and composition on Y, σ and E. Information depth increases with increasing ion energy and decreasing mass of primary ions, being higher for SF 5+ than for Xe +. Y, σ and E increase with increasing primary ion mass. They are considerably higher for a molecular (SF 5+) than for atomic ions of comparable mass ( 129Xe+). The experimental results supply information on the extension of impact cascades, generated in different substrate materials by different primary ion species and different energies. They demonstrate that in analytical SIMS application information depths can be minimized and yields and ion formation efficiencies can be maximized by the use of molecular primary ions.

A hybrid molecular dynamics study on the non-Newtonian rheological behaviors of shear thickening fluid.

PubMed

Chen, Kaihui; Wang, Yu; Xuan, Shouhu; Gong, Xinglong

2017-07-01

To investigate the microstructural evolution dependency on the apparent viscosity in shear-thickening fluids (STFs), a hybrid mesoscale model combined with stochastic rotation dynamics (SRD) and molecular dynamics (MD) is used. Muller-Plathe reverse perturbation method is adopted to analyze the viscosities of STFs in a two-dimensional model. The characteristic of microstructural evolution of the colloidal suspensions under different shear rate is studied. The effect of diameter of colloidal particles and the phase volume fraction on the shear thickening behavior is investigated. Under low shear rate, the two-atom structure is formed, because of the strong particle attractions in adjacent layers. At higher shear rate, the synergetic pair structure extends to layered structure along flow direction because of the increasing hydrodynamics action. As the shear rate rises continuously, the layered structure rotates and collides with other particles, then turned to be individual particles under extension or curve string structure under compression. Finally, at the highest shear rate, the strings curve more severely and get into two-dimensional cluster. The apparent viscosity of the system changes from shear-thinning behavior to the shear-thickening behavior. This work presents valuable information for further understanding the shear thickening mechanism. Copyright © 2017 Elsevier Inc. All rights reserved.

Changes in mycelia growth, sporulation, and virulence of Phytophthora capsici when challenged by heavy metals (Cu2+, Cr2+ and Hg2+) under acid pH stress.

PubMed

Liu, Peiqing; Wei, Mengyao; Zhang, Jinzhu; Wang, Rongbo; Li, Benjin; Chen, Qinghe; Weng, Qiyong

2018-04-01

Phytophthora capsici, an economically devastating oomycete pathogen, causes devastating disease epidemics on a wide range of vegetable plants and pose a grave threat to global vegetables production. Heavy metals and acid pH are newly co-occurring stresses to soil micro-organisms, but what can be expected for mycelia growth and virulence and how they injure the oomycetes (especially P. capsici) remains unknown. Here, the effects of different heavy metals (Cu 2+ , Cr 2+ , and Hg 2+ ) on mycelia growth and virulence were investigated at different pHs (4.0 vs. 7.0) and the plausible molecular and physiological mechanisms were analyzed. In the present study, we compared the effective inhibition of different heavy metals (Cu 2+ , Cr 2+ , and Hg 2+ ) and acid pH on a previously genome sequenced P. capsici virulent strain LT1534. Both stress factors independently affected its mycelia growth and sporulation. Next, we investigated whether ROS participated in the pH-inhibited mycelial growth, finding that the ROS scavenger, catalase (CAT), significantly inhibited the acid pH-induced ROS in mycelia. Additionally, because MAPK specially transmits different stress responsive signals in environment into cells, we employed CAT and a p38-MAPK pathway inhibitor to investigate ROS and p38-MAPK roles in heavy metal-inhibited mycelia growth at different pHs (4.0 vs. 7.0), finding that they significantly inhibited growth. Furthermore, ROS and p38-MAPK influenced the heavy metal-induced TBARS content, total antioxidant capacity (TAC), and CAT activity at different pHs, and also reduced the expression of infection-related laccases (PcLAC2) and an effector-related protein (PcNLP14). We propose that acid pH stress accelerates how heavy metals inhibit mycelium growth, sporulation, and virulence change in P. capsici, and posit that ROS and p38-MAPK function to regulate the molecular and physiological mechanisms underlying this toxicity. Although these stresses induce molecular and physiological challenges to oomycetes, much remains to be known the mechanisms dedicated to resolve these environmental stresses. Copyright © 2018 Elsevier Ltd. All rights reserved.

A Computational Framework for 3D Mechanical Modeling of Plant Morphogenesis with Cellular Resolution

PubMed Central

Gilles, Benjamin; Hamant, Olivier; Boudaoud, Arezki; Traas, Jan; Godin, Christophe

2015-01-01

The link between genetic regulation and the definition of form and size during morphogenesis remains largely an open question in both plant and animal biology. This is partially due to the complexity of the process, involving extensive molecular networks, multiple feedbacks between different scales of organization and physical forces operating at multiple levels. Here we present a conceptual and modeling framework aimed at generating an integrated understanding of morphogenesis in plants. This framework is based on the biophysical properties of plant cells, which are under high internal turgor pressure, and are prevented from bursting because of the presence of a rigid cell wall. To control cell growth, the underlying molecular networks must interfere locally with the elastic and/or plastic extensibility of this cell wall. We present a model in the form of a three dimensional (3D) virtual tissue, where growth depends on the local modulation of wall mechanical properties and turgor pressure. The model shows how forces generated by turgor-pressure can act both cell autonomously and non-cell autonomously to drive growth in different directions. We use simulations to explore lateral organ formation at the shoot apical meristem. Although different scenarios lead to similar shape changes, they are not equivalent and lead to different, testable predictions regarding the mechanical and geometrical properties of the growing lateral organs. Using flower development as an example, we further show how a limited number of gene activities can explain the complex shape changes that accompany organ outgrowth. PMID:25569615

Effect of molecular topology on the transport properties of dendrimers in dilute solution at Θ temperature: A Brownian dynamics study

NASA Astrophysics Data System (ADS)

Bosko, Jaroslaw T.; Ravi Prakash, J.

2008-01-01

Structure and transport properties of dendrimers in dilute solution are studied with the aid of Brownian dynamics simulations. To investigate the effect of molecular topology on the properties, linear chain, star, and dendrimer molecules of comparable molecular weights are studied. A bead-spring chain model with finitely extensible springs and fluctuating hydrodynamic interactions is used to represent polymer molecules under Θ conditions. Structural properties as well as the diffusivity and zero-shear-rate intrinsic viscosity of polymers with varied degrees of branching are analyzed. Results for the free-draining case are compared to and found in very good agreement with the Rouse model predictions. Translational diffusivity is evaluated and the difference between the short-time and long-time behavior due to dynamic correlations is observed. Incorporation of hydrodynamic interactions is found to be sufficient to reproduce the maximum in the intrinsic viscosity versus molecular weight observed experimentally for dendrimers. Results of the nonequilibrium Brownian dynamics simulations of dendrimers and linear chain polymers subjected to a planar shear flow in a wide range of strain rates are also reported. The flow-induced molecular deformation of molecules is found to decrease hydrodynamic interactions and lead to the appearance of shear thickening. Further, branching is found to suppress flow-induced molecular alignment and deformation.

Molecular classification of gastric cancer.

PubMed

Chia, N-Y; Tan, P

2016-05-01

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

Time Domains of the Hypoxic Ventilatory Response and Their Molecular Basis

PubMed Central

Pamenter, Matthew E.; Powell, Frank L.

2016-01-01

Ventilatory responses to hypoxia vary widely depending on the pattern and length of hypoxic exposure. Acute, prolonged, or intermittent hypoxic episodes can increase or decrease breathing for seconds to years, both during the hypoxic stimulus, and also after its removal. These myriad effects are the result of a complicated web of molecular interactions that underlie plasticity in the respiratory control reflex circuits and ultimately control the physiology of breathing in hypoxia. Since the time domains of the physiological hypoxic ventilatory response (HVR) were identified, considerable research effort has gone toward elucidating the underlying molecular mechanisms that mediate these varied responses. This research has begun to describe complicated and plastic interactions in the relay circuits between the peripheral chemoreceptors and the ventilatory control circuits within the central nervous system. Intriguingly, many of these molecular pathways seem to share key components between the different time domains, suggesting that varied physiological HVRs are the result of specific modifications to overlapping pathways. This review highlights what has been discovered regarding the cell and molecular level control of the time domains of the HVR, and highlights key areas where further research is required. Understanding the molecular control of ventilation in hypoxia has important implications for basic physiology and is emerging as an important component of several clinical fields. PMID:27347896

Molecular and genetic bases of pancreatic cancer.

PubMed

Vaccaro, Vanja; Gelibter, Alain; Bria, Emilio; Iapicca, Pierluigi; Cappello, Paola; Di Modugno, Francesca; Pino, Maria Simona; Nuzzo, Carmen; Cognetti, Francesco; Novelli, Francesco; Nistico, Paola; Milella, Michele

2012-06-01

Pancreatic cancer remains a formidable challenge for oncologists and patients alike. Despite intensive efforts, attempts at improving survival in the past 15 years, particularly in advanced disease, have failed. This is true even with the introduction of molecularly targeted agents, chosen on the basis of their action on pathways that were supposedly important in pancreatic cancer development and progression: indeed, with the notable exception of the epidermal growth factor receptor (EGFR) inhibitor erlotinib, that has provided a minimal survival improvement when added to gemcitabine, other agents targeting EGFR, matrix metallo-proteases, farnesyl transferase, or vascular endothelial growth factor have not succeeded in improving outcomes over standard gemcitabine monotherapy for a variety of different reasons. However, recent developments in the molecular epidemiology of pancreatic cancer and an ever evolving understanding of the molecular mechanisms underlying pancreatic cancer initiation and progression raise renewed hope to find novel, relevant therapeutic targets that could be pursued in the clinical setting. In this review we focus on molecular epidemiology of pancreatic cancer, epithelial-to-mesenchymal transition and its influence on sensitivity to EGFR-targeted approaches, apoptotic pathways, hypoxia-related pathways, developmental pathways (such as the hedgehog and Notch pathways), and proteomic analysis as keys to a better understanding of pancreatic cancer biology and, most importantly, as a source of novel molecular targets to be exploited therapeutically.

Glucose-6-phosphate dehydrogenase laboratory assay: How, when, and why?

PubMed

Minucci, Angelo; Giardina, Bruno; Zuppi, Cecilia; Capoluongo, Ettore

2009-01-01

Glucose 6-phosphate dehydrogenase (G6PD) deficiency is the most common defect of red blood cells. Although some different laboratory techniques or methods are employed for the biochemical screening, a strict relationship between biochemists, clinicians, and molecular biologists is necessary for a definitive diagnosis. This article represents an overview on the current laboratory tests finalized to the screening or to the definitive diagnosis of G6PD-deficiency, underlying the problems regarding the biochemical and molecular identification of heterozygote females other than those regarding the standardization of the clinical and laboratory diagnostic procedures. Finally, this review is aimed to give a flow-chart for the complete diagnostic approach of G6PD-deficiency.

Vasculogenesis and Angiogenesis: Molecular and Cellular Controls

PubMed Central

Kubis, N.; Levy, B.I.

2003-01-01

Summary Angiogenesis characterizes embryonic development, but also occurs in adulthood in physiological situations such as adaptation to muscle exercise, and in pathological conditions like cancer. Major advances have been made in understanding the molecular mechanisms responsible for vasculogenesis and angiogenesis, largely due to the use of “knock-out mice”, i.e. mice in which the gene coding for the protein under investigation has been inactivated. Interestingly, the same growth factors and their receptors are equally involved in the different aspects of vasculogenesis and angiogenesis during development and in adulthood. This review aims to describe in detail their respective roles and how interactions between them lead to a newly formed vessel. PMID:20591248

Molecule signatures in photoluminescence spectra of transition metal dichalcogenides

NASA Astrophysics Data System (ADS)

Feierabend, Maja; Berghäuser, Gunnar; Selig, Malte; Brem, Samuel; Shegai, Timur; Eigler, Siegfried; Malic, Ermin

2018-01-01

Monolayer transition metal dichalcogenides (TMDs) show an optimal surface-to-volume ratio and are thus promising candidates for novel molecule sensor devices. It was recently predicted that a certain class of molecules exhibiting a large dipole moment can be detected through the activation of optically inaccessible (dark) excitonic states in absorption spectra of tungsten-based TMDs. In this paper, we investigate the molecule signatures in photoluminescence spectra in dependence of a number of different experimentally accessible quantities, such as excitation density, temperature, as well as molecular characteristics including the dipole moment and its orientation, molecule-TMD distance, molecular coverage, and distribution. We show that under certain optimal conditions even room-temperature detection of molecules can be achieved.

Biopython: freely available Python tools for computational molecular biology and bioinformatics

PubMed Central

Cock, Peter J. A.; Antao, Tiago; Chang, Jeffrey T.; Chapman, Brad A.; Cox, Cymon J.; Dalke, Andrew; Friedberg, Iddo; Hamelryck, Thomas; Kauff, Frank; Wilczynski, Bartek; de Hoon, Michiel J. L.

2009-01-01

Summary: The Biopython project is a mature open source international collaboration of volunteer developers, providing Python libraries for a wide range of bioinformatics problems. Biopython includes modules for reading and writing different sequence file formats and multiple sequence alignments, dealing with 3D macro molecular structures, interacting with common tools such as BLAST, ClustalW and EMBOSS, accessing key online databases, as well as providing numerical methods for statistical learning. Availability: Biopython is freely available, with documentation and source code at www.biopython.org under the Biopython license. Contact: All queries should be directed to the Biopython mailing lists, see www.biopython.org/wiki/_Mailing_listspeter.cock@scri.ac.uk. PMID:19304878

Report on the Symposium “Molecular Mechanisms Involved in Neurodegeneration”

PubMed Central

Pentón-Rol, Giselle; Cervantes-Llanos, Majel

2018-01-01

The prevalence of neurodegenerative diseases is currently a major concern in public health because of the lack of neuroprotective and neuroregenerative drugs. The symposium on Molecular Mechanisms Involved in Neurodegeneration held in Varadero, Cuba, updated the participants on the basic mechanisms of neurodegeneration, on the different approaches for drug discovery, and on early research results on therapeutic approaches for the treatment of neurodegenerative diseases. Alzheimer’s disease and in silico research were covered by many of the presentations in the symposium, under the umbrella of the “State of the Art of Non-clinical Models for Neurodegenerative Diseases” International Congress, held from 20 to 24 June 2017. This paper summarizes the highlights of the symposium. PMID:29346273

[Vitamin K3-induced activation of molecular oxygen in glioma cells].

PubMed

Krylova, N G; Kulagova, T A; Semenkova, G N; Cherenkevich, S N

2009-01-01

It has been shown by the method of fluorescent analysis that the rate of hydrogen peroxide generation in human U251 glioma cells under the effect of lipophilic (menadione) or hydrophilic (vikasol) analogues of vitamin K3 was different. Analyzing experimental data we can conclude that menadione underwent one- and two-electron reduction by intracellular reductases in glioma cells. Reduced forms of menadione interact with molecular oxygen leading to reactive oxygen species (ROS) generation. The theoretical model of ROS generation including two competitive processes of one- and two-electron reduction of menadione has been proposed. Rate constants of ROS generation mediated by one-electron reduction process have been estimated.

Spin Seebeck effect in a metal-single-molecule-magnet-metal junction

NASA Astrophysics Data System (ADS)

Niu, Pengbin; Liu, Lixiang; Su, Xiaoqiang; Dong, Lijuan; Luo, Hong-Gang

2018-01-01

We investigate the nonlinear regime of temperature-driven spin-related currents through a single molecular magnet (SMM), which is connected with two metal electrodes. Under a large spin approximation, the SMM is simplified to a natural two-channel model possessing spin-opposite configuration and Coulomb interaction. We find that in temperature-driven case the system can generate spin-polarized currents. More interestingly, at electron-hole symmetry point, the competition of the two channels induces a temperature-driven pure spin current. This device demonstrates that temperature-driven SMM junction shows some results different from the usual quantum dot model, which may be useful in the future design of thermal-based molecular spintronic devices.

Capillary wave propagation during the delamination of graphene by the precursor films in electro-elasto-capillarity

PubMed Central

Zhu, Xueyan; Yuan, Quanzi; Zhao, Ya-Pu

2012-01-01

Molecular dynamics simulations were carried out to explore the capillary wave propagation induced by the competition between one upper precursor film (PF) on the graphene and one lower PF on the substrate in electro-elasto-capillarity (EEC). During the wave propagation, the graphene was gradually delaminated from the substrate by the lower PF. The physics of the capillary wave was explored by the molecular kinetic theory. Besides, the dispersion relation of the wave was obtained theoretically. The theory showed that the wave was controlled by the driving work difference of the two PFs. Simulating the EEC process under different electric field intensities (E), the wave velocity was found insensitive to E. We hope this research could expand our knowledge on the wetting, electrowetting and EEC. As a potential application, the electrowetting of the PF between the graphene and the substrate is a promising candidate for delaminating graphene from substrate. PMID:23226593

Clues for biomimetics from natural composite materials

PubMed Central

Lapidot, Shaul; Meirovitch, Sigal; Sharon, Sigal; Heyman, Arnon; Kaplan, David L; Shoseyov, Oded

2013-01-01

Bio-inspired material systems are derived from different living organisms such as plants, arthropods, mammals and marine organisms. These biomaterial systems from nature are always present in the form of composites, with molecular-scale interactions optimized to direct functional features. With interest in replacing synthetic materials with natural materials due to biocompatibility, sustainability and green chemistry issues, it is important to understand the molecular structure and chemistry of the raw component materials to also learn from their natural engineering, interfaces and interactions leading to durable and highly functional material architectures. This review will focus on applications of biomaterials in single material forms, as well as biomimetic composites inspired by natural organizational features. Examples of different natural composite systems will be described, followed by implementation of the principles underlying their composite organization into artificial bio-inspired systems for materials with new functional features for future medicine. PMID:22994958

Clues for biomimetics from natural composite materials.

PubMed

Lapidot, Shaul; Meirovitch, Sigal; Sharon, Sigal; Heyman, Arnon; Kaplan, David L; Shoseyov, Oded

2012-09-01

Bio-inspired material systems are derived from different living organisms such as plants, arthropods, mammals and marine organisms. These biomaterial systems from nature are always present in the form of composites, with molecular-scale interactions optimized to direct functional features. With interest in replacing synthetic materials with natural materials due to biocompatibility, sustainability and green chemistry issues, it is important to understand the molecular structure and chemistry of the raw component materials to also learn from their natural engineering, interfaces and interactions leading to durable and highly functional material architectures. This review will focus on applications of biomaterials in single material forms, as well as biomimetic composites inspired by natural organizational features. Examples of different natural composite systems will be described, followed by implementation of the principles underlying their composite organization into artificial bio-inspired systems for materials with new functional features for future medicine.

Crystal nucleation and metastable bcc phase in charged colloids: A molecular dynamics study

NASA Astrophysics Data System (ADS)

Ji, Xinqiang; Sun, Zhiwei; Ouyang, Wenze; Xu, Shenghua

2018-05-01

The dynamic process of homogenous nucleation in charged colloids is investigated by brute-force molecular dynamics simulation. To check if the liquid-solid transition will pass through metastable bcc, simulations are performed at the state points that definitely lie in the phase region of thermodynamically stable fcc. The simulation results confirm that, in all of these cases, the preordered precursors, acting as the seeds of nucleation, always have predominant bcc symmetry consistent with Ostwald's step rule and the Alexander-McTague mechanism. However, the polymorph selection is not straightforward because the crystal structures formed are not often determined by the symmetry of intermediate precursors but have different characters under different state points. The region of the state point where bcc crystal structures of large enough size are formed during crystallization is narrow, which gives a reasonable explanation as to why the metastable bcc phase in charged colloidal suspensions is rarely detected in macroscopic experiments.

Interactions between pyrazole derived enantiomers and Chiralcel OJ: Prediction of enantiomer absolute configurations and elution order by molecular dynamics simulations.

PubMed

Hu, Guixiang; Huang, Meilan; Luo, Chengcai; Wang, Qi; Zou, Jian-Wei

2016-05-01

The separation of enantiomers and confirmation of their absolute configurations is significant in the development of chiral drugs. The interactions between the enantiomers of chiral pyrazole derivative and polysaccharide-based chiral stationary phase cellulose tris(4-methylbenzoate) (Chiralcel OJ) in seven solvents and under different temperature were studied using molecular dynamics simulations. The results show that solvent effect has remarkable influence on the interactions. Structure analysis discloses that the different interactions between two isomers and chiral stationary phase are dependent on the nature of solvents, which may invert the elution order. The computational method in the present study can be used to predict the elution order and the absolute configurations of enantiomers in HPLC separations and therefore would be valuable in development of chiral drugs. Copyright © 2016 Elsevier Inc. All rights reserved.

In situ sum-frequency generation spectroscopy of ethylene-glycol and poly-N-isopropylacrylamide films

NASA Astrophysics Data System (ADS)

Kurz, Volker; Koelsch, Patrick

2009-03-01

Ethylene-glycol(EG)-based self-assembled monolayers (SAMs) are often used as a model systems for thin liquid films. Temperature series in heavy water were measured using a unique sample cell developed for in situ sum-frequency generation (SFG) spectroscopy experiments. Results obtained from model EG-SAMs with different lengths and terminating groups in various ionic solutions showed temperature-dependent changes in the molecular order. Films of poly-N-isopropylacrylamide(pNIPAM) were also characterized by in situ SFG spectroscopy in the CH, OH, OD and amide spectral regions under different polarization combinations. These systems have many applications as thermo-responsive polymers due to their ability to change solubility in water at the biologically relevant temperature of 32 C. This so-called lower critical solution temperature (LCST) phase transition was characterized in depth, allowing for the identification of the molecular groups involved in this process.

Evolution of the Human Nervous System Function, Structure, and Development.

PubMed

Sousa, André M M; Meyer, Kyle A; Santpere, Gabriel; Gulden, Forrest O; Sestan, Nenad

2017-07-13

The nervous system-in particular, the brain and its cognitive abilities-is among humans' most distinctive and impressive attributes. How the nervous system has changed in the human lineage and how it differs from that of closely related primates is not well understood. Here, we consider recent comparative analyses of extant species that are uncovering new evidence for evolutionary changes in the size and the number of neurons in the human nervous system, as well as the cellular and molecular reorganization of its neural circuits. We also discuss the developmental mechanisms and underlying genetic and molecular changes that generate these structural and functional differences. As relevant new information and tools materialize at an unprecedented pace, the field is now ripe for systematic and functionally relevant studies of the development and evolution of human nervous system specializations. Copyright © 2017 Elsevier Inc. All rights reserved.

Protein sterilization method of firefly luciferase using reduced pressure and molecular sieves

NASA Technical Reports Server (NTRS)

Chappelle, E. W.; Rich, E., Jr. (Inventor)

1973-01-01

The sterilization of the protein fruitfly luciferase under conditions that prevent denaturation is examined. Denaturation is prevented by heating the protein in contact with molecular seives and under a reduced pressure of the order of 0.00005 millimeters of mercury.

Characterization of two coleopteran α-amylases and molecular insights into their differential inhibition by synthetic α-amylase inhibitor, acarbose.

PubMed

Channale, Sonal M; Bhide, Amey J; Yadav, Yashpal; Kashyap, Garima; Pawar, Pankaj K; Maheshwari, V L; Ramasamy, Sureshkumar; Giri, Ashok P

2016-07-01

Post-harvest insect infestation of stored grains makes them unfit for human consumption and leads to severe economic loss. Here, we report functional and structural characterization of two coleopteran α-amylases viz. Callosobruchus chinensis α-amylase (CcAmy) and Tribolium castaneum α-amylase (TcAmy) along with their interactions with proteinaceous and non-proteinaceous α-amylase inhibitors. Secondary structural alignment of CcAmy and TcAmy with other coleopteran α-amylases revealed conserved motifs, active sites, di-sulfide bonds and two point mutations at spatially conserved substrate or inhibitor-binding sites. Homology modeling and molecular docking showed structural differences between these two enzymes. Both the enzymes had similar optimum pH values but differed in their optimum temperature. Overall, pattern of enzyme stabilities were similar under various temperature and pH conditions. Further, CcAmy and TcAmy differed in their substrate affinity and catalytic efficiency towards starch and amylopectin. HPLC analysis detected common amylolytic products like maltose and malto-triose while glucose and malto-tetrose were unique in CcAmy and TcAmy catalyzed reactions respectively. At very low concentrations, wheat α-amylase inhibitor was found to be superior over the acarbose as far as complete inhibition of amylolytic activities of CcAmy and TcAmy was concerned. Mechanism underlying differential amylolytic reaction inhibition by acarbose was discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

Fluorescence spectroscopy as a specific tool for the interaction study of two surfactants with natural and synthetic organic compounds

NASA Astrophysics Data System (ADS)

Jung, Aude-Valérie; Frochot, Céline; Bersillon, Jean-Luc

2016-04-01

Four different techniques were used to study the binding of cationic cetyltrimethylammonium bromide (CTAB) and non-ionic nonylphenylethoxyl (NPE) surfactants to three synthetic organic components that mimic humic-like aggregates and to two natural aggregated humic substances (HS) extracted from aquatic suspended matter. The composition of synthetic organic components were chosen to be similar to high molecular weight highly processed terrigenous HS and low and high molecular weight less processed terrigenous (or aquatic terrigenous) HS. The natural HS were extracted under two different meteorological conditions (rainy and dry periods). No significant interaction between the non-ionic surfactant and any of the studied compounds was found. Concerning CTAB; pH, conductivity and turbidity measurements, along with fluorescence spectroscopy were combined to provide a better understanding of interactions between organic aggregates and the surfactant. The spectroscopic data show that a "highly processed terrigenous HS" fluorophore interacts in a different way with the cationic surfactant than an "aquatic terrigenous (or less processed terrigenous) HS" fluorophore does. Under similar conditions, some spectral changes in the fluorescence signal are correlated to changes in non-specific physical-chemical parameters (pH, turbidity, conductivity) for the organic compounds tested. The complexation mechanism is essentially governed by charge neutralization, which can be monitored specifically by the fluorescence of the organic moieties.

The adsorption of oleate on powellite and fluorapatite: A joint experimental and theoretical simulation study

NASA Astrophysics Data System (ADS)

Zhen, Wang

2017-07-01

Flotation and adsorption performance of sodium oleate(NaOl)on powellite and fluorapatite were investigated in this work through micro-flotation tests, work of adhesion calculations, molecular dynamics simulation, micro-topography studies and FTIR measurements. The micro-flotation results show a similar flotation behaviors of powellite and fluorapatite under alkaline conditions, but a considerable difference in mineral recoveries in the pH range 2-7, which demonstrates the possibilities for separating powillite from fluorapatite under acidic conditions. The great difference in mineral recovery displays a good accordance with the obvious difference in the work of adhesion of powellite and fluorapatite at NaOl dosage range of 40-80 mg/L, obtained from flotation and contact angle measurements, respectively. The more negative interaction energy (ΔE) between NaOl and powellite/water interface from molecular dynamics simulation reveals a more easily adsorption of NaOl onto powellite than onto fluorapatite, which excellently matches with the results of flotation and work of adhesion. The results of micro-topography study shows that the adsorption of NaOl on powellite is mainly ascribed to the chemisorption of oleate ions with Ca2+ on powellite lattice or the precipitation of calcium dioleate agglomerates on powellite surface when it was in the solution without or with Ca2+, respectively. The FTIR measurements further confirm the chemisorption of oleate ions with Ca2+ active sites on powellite surface.

Comparison of Perturbed Pathways in Two Different Cell Models for Parkinson's Disease with Structural Equation Model.

PubMed

Pepe, Daniele; Do, Jin Hwan

2015-12-16

Increasing evidence indicates that different morphological types of cell death coexist in the brain of patients with Parkinson's disease (PD), but the molecular explanation for this is still under investigation. In this study, we identified perturbed pathways in two different cell models for PD through the following procedures: (1) enrichment pathway analysis with differentially expressed genes and the Reactome pathway database, and (2) construction of the shortest path model for the enriched pathway and detection of significant shortest path model with fitting time-course microarray data of each PD cell model to structural equation model. Two PD cell models constructed by the same neurotoxin showed different perturbed pathways. That is, one showed perturbation of three Reactome pathways, including cellular senescence, chromatin modifying enzymes, and chromatin organization, while six modules within metabolism pathway represented perturbation in the other. This suggests that the activation of common upstream cell death pathways in PD may result in various down-stream processes, which might be associated with different morphological types of cell death. In addition, our results might provide molecular clues for coexistence of different morphological types of cell death in PD patients.

Assessment of PDF Micromixing Models Using DNS Data for a Two-Step Reaction

NASA Astrophysics Data System (ADS)

Tsai, Kuochen; Chakrabarti, Mitali; Fox, Rodney O.; Hill, James C.

1996-11-01

Although the probability density function (PDF) method is known to treat the chemical reaction terms exactly, its application to turbulent reacting flows have been overshadowed by the ability to model the molecular mixing terms satisfactorily. In this study, two PDF molecular mixing models, the linear-mean-square-estimation (LMSE or IEM) model and the generalized interaction-by-exchange-with-the-mean (GIEM) model, are compared with the DNS data in decaying turbulence with a two-step parallel-consecutive reaction and two segregated initial conditions: ``slabs" and ``blobs". Since the molecular mixing model is expected to have a strong effect on the mean values of chemical species under such initial conditions, the model evaluation is intended to answer the following questions: Can the PDF models predict the mean values of chemical species correctly with completely segregated initial conditions? (2) Is a single molecular mixing timescale sufficient for the PDF models to predict the mean values with different initial conditions? (3) Will the chemical reactions change the molecular mixing timescales of the reacting species enough to affect the accuracy of the model's prediction for the mean values of chemical species?

Molecular pathogenesis of viral hemorrhagic fever.

PubMed

Basler, Christopher F

2017-07-01

The clinical syndrome referred to as viral hemorrhagic fever (VHF) can be caused by several different families of RNA viruses, including select members of the arenaviruses, bunyaviruses, filoviruses, and flaviviruses. VHF is characterized by malaise, fever, vascular permeability, decreased plasma volume, coagulation abnormalities, and varying degrees of hemorrhage. Study of the filovirus Ebola virus has demonstrated a critical role for suppression of innate antiviral defenses in viral pathogenesis. Additionally, antigen-presenting cells are targets of productive infection and immune dysregulation. Among these cell populations, monocytes and macrophages are proposed to produce damaging inflammatory cytokines, while infected dendritic cells fail to undergo proper maturation, potentially impairing adaptive immunity. Uncontrolled virus replication and accompanying inflammatory responses are thought to promote vascular leakage and coagulopathy. However, the specific molecular pathways that underlie these features of VHF remain poorly understood. The arenavirus Lassa virus and the flavivirus yellow fever virus exhibit similar molecular pathogenesis suggesting common underlying mechanisms. Because non-human primate models that closely mimic VHF are available for Ebola, Lassa, and yellow fever viruses, we propose that comparative molecular studies using these models will yield new insights into the molecular underpinnings of VHF and suggest new therapeutic approaches.

Molecular thermodynamics for prevention of asphaltene precipitation

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

Wu, Jianzhong; Prausnitz, J.M.

Crude petroleum is a complex mixture of compounds with different chemical structures and molecular weights. Asphaltenes, the heaviest and most polar fraction of crude oil, are insoluble in normal alkanes such as n-heptane, but they are soluble in aromatic solvents such as toluene. The molecular nature of asphaltenes and their role in production and processing of crude oils have been the topic of numerous studies. Under some conditions, asphaltenes precipitate from a petroleum fluid, causing severe problems in production and transportation Our research objective is to develop a theoretically based, but engineering-oriented, molecular-thermodynamic model which can describe the phase behaviormore » of asphaltene precipitation in petroleum fluids, to provide guidance for petroleum-engineering design and production. In this progress report, particular attention is given to the potential of mean force between asphaltene molecules in a medium of asphaltene-free solvent. This potential of mean force is derived using the principles of colloid science. It depends on the properties of asphaltene and those of the solvent as well as on temperature and pressure. The effect of a solvent on interactions between asphaltenes is taken into account through its density and through its molecular dispersion properties.« less

Hydrogen exchange mass spectrometry of bacteriorhodopsin reveals light-induced changes in the structural dynamics of a biomolecular machine.

PubMed

Pan, Yan; Brown, Leonid; Konermann, Lars

2011-12-21

Many proteins act as molecular machines that are fuelled by a nonthermal energy source. Examples include transmembrane pumps and stator-rotor complexes. These systems undergo cyclic motions (CMs) that are being driven along a well-defined conformational trajectory. Superimposed on these CMs are thermal fluctuations (TFs) that are coupled to stochastic motions of the solvent. Here we explore whether the TFs of a molecular machine are affected by the occurrence of CMs. Bacteriorhodopsin (BR) is a light-driven proton pump that serves as a model system in this study. The function of BR is based on a photocycle that involves trans/cis isomerization of a retinal chromophore, as well as motions of transmembrane helices. Hydrogen/deuterium exchange (HDX) mass spectrometry was used to monitor the TFs of BR, focusing on the monomeric form of the protein. Comparative HDX studies were conducted under illumination and in the dark. The HDX kinetics of BR are dramatically accelerated in the presence of light. The isotope exchange rates and the number of backbone amides involved in EX2 opening transitions increase roughly 2-fold upon illumination. In contrast, light/dark control experiments on retinal-free protein produced no discernible differences. It can be concluded that the extent of TFs in BR strongly depends on photon-driven CMs. The light-induced differences in HDX behavior are ascribed to protein destabilization. Specifically, the thermodynamic stability of the dark-adapted protein is estimated to be 5.5 kJ mol(-1) under the conditions of our work. This value represents the free energy difference between the folded state F and a significantly unfolded conformer U. Illumination reduces the stability of F by 2.2 kJ mol(-1). Mechanical agitation caused by isomerization of the chromophore is transferred to the surrounding protein scaffold, and subsequently, the energy dissipates into the solvent. Light-induced retinal motions therefore act analogously to an internal heat source that promotes the occurrence of TFs. Overall, our data highlight the potential of HDX methods for probing the structural dynamics of molecular machines under "engine on" and "engine off" conditions. © 2011 American Chemical Society

Testing thermal gradient driving force for grain boundary migration using molecular dynamics simulations

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

Bai, Xian-Ming; Zhang, Yongfeng; Tonks, Michael R.

2015-02-01

Strong thermal gradients in low-thermal-conductivity ceramics may drive extended defects, such as grain boundaries and voids, to migrate in preferential directions. In this work, molecular dynamics simulations are conducted to study thermal gradient driven grain boundary migration and to verify a previously proposed thermal gradient driving force equation, using uranium dioxide as a model system. It is found that a thermal gradient drives grain boundaries to migrate up the gradient and the migration velocity increases under a constant gradient owing to the increase in mobility with temperature. Different grain boundaries migrate at very different rates due to their different intrinsicmore » mobilities. The extracted mobilities from the thermal gradient driven simulations are compared with those calculated from two other well-established methods and good agreement between the three different methods is found, demonstrating that the theoretical equation of the thermal gradient driving force is valid, although a correction of one input parameter should be made. The discrepancy in the grain boundary mobilities between modeling and experiments is also discussed.« less

Distinguishing polymorphs of the semiconducting pigment copper phthalocyanine by solid-state NMR and Raman spectroscopy.

PubMed

Shaibat, Medhat A; Casabianca, Leah B; Siberio-Pérez, Diana Y; Matzger, Adam J; Ishii, Yoshitaka

2010-04-08

Cu(II)(phthalocyanine) (CuPc) is broadly utilized as an archetypal molecular semiconductor and is the most widely used blue printing pigment. CuPc crystallizes in six different forms; the chemical and physical properties are substantially modulated by its molecular packing among these polymorphs. Despite the growing importance of this system, spectroscopic identification of different polymorphs for CuPc has posed difficulties. This study presents the first example of spectroscopic distinction of alpha- and beta-forms of CuPc, the most widely used polymorphs, by solid-state NMR (SSNMR) and Raman spectroscopy. (13)C high-resolution SSNMR spectra of alpha- and beta-CuPc using very-fast magic angle spinning (VFMAS) at 20 kHz show that hyperfine shifts sensitively reflect polymorphs of CuPc. The experimental results were confirmed by ab initio chemical shift calculations. (13)C and (1)H SSNMR relaxation times of alpha- and beta-CuPc under VFMAS also showed marked differences, presumably because of the difference in electronic spin correlation times in the two forms. Raman spectroscopy also provided another reliable method of differentiation between the two polymorphs.

Modeling Molecular Interactions in Water: From Pairwise to Many-Body Potential Energy Functions

PubMed Central

2016-01-01

Almost 50 years have passed from the first computer simulations of water, and a large number of molecular models have been proposed since then to elucidate the unique behavior of water across different phases. In this article, we review the recent progress in the development of analytical potential energy functions that aim at correctly representing many-body effects. Starting from the many-body expansion of the interaction energy, specific focus is on different classes of potential energy functions built upon a hierarchy of approximations and on their ability to accurately reproduce reference data obtained from state-of-the-art electronic structure calculations and experimental measurements. We show that most recent potential energy functions, which include explicit short-range representations of two-body and three-body effects along with a physically correct description of many-body effects at all distances, predict the properties of water from the gas to the condensed phase with unprecedented accuracy, thus opening the door to the long-sought “universal model” capable of describing the behavior of water under different conditions and in different environments. PMID:27186804

Differential response of cell-cycle and cell-expansion regulators to heat stress in apple (Malus domestica) fruitlets.

PubMed

Flaishman, Moshe A; Peles, Yuval; Dahan, Yardena; Milo-Cochavi, Shira; Frieman, Aviad; Naor, Amos

2015-04-01

Temperature is one of the most significant factors affecting physiological and biochemical aspects of fruit development. Current and progressing global warming is expected to change climate in the traditional deciduous fruit tree cultivation regions. In this study, 'Golden Delicious' trees, grown in a controlled environment or commercial orchard, were exposed to different periods of heat treatment. Early fruitlet development was documented by evaluating cell number, cell size and fruit diameter for 5-70 days after full bloom. Normal activities of molecular developmental and growth processes in apple fruitlets were disrupted under daytime air temperatures of 29°C and higher as a result of significant temporary declines in cell-production and cell-expansion rates, respectively. Expression screening of selected cell cycle and cell expansion genes revealed the influence of high temperature on genetic regulation of apple fruitlet development. Several core cell-cycle and cell-expansion genes were differentially expressed under high temperatures. While expression levels of B-type cyclin-dependent kinases and A- and B-type cyclins declined moderately in response to elevated temperatures, expression of several cell-cycle inhibitors, such as Mdwee1, Mdrbr and Mdkrps was sharply enhanced as the temperature rose, blocking the cell-cycle cascade at the G1/S and G2/M transition points. Moreover, expression of several expansin genes was associated with high temperatures, making them potentially useful as molecular platforms to enhance cell-expansion processes under high-temperature regimes. Understanding the molecular mechanisms of heat tolerance associated with genes controlling cell cycle and cell expansion may lead to the development of novel strategies for improving apple fruit productivity under global warming. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Transcriptome analysis of hexaploid hulless oat in response to salinity stress

PubMed Central

Wu, Bin; Hu, Yani; Huo, Pengjie; Zhang, Qian; Chen, Xin; Zhang, Zongwen

2017-01-01

Background Oat is a cereal crop of global importance used for food, feed, and forage. Understanding salinity stress tolerance mechanisms in plants is an important step towards generating crop varieties that can cope with environmental stresses. To date, little is known about the salt tolerance of oat at the molecular level. To better understand the molecular mechanisms underlying salt tolerance in oat, we investigated the transcriptomes of control and salt-treated oat using RNA-Seq. Results Using Illumina HiSeq 4000 platform, we generated 72,291,032 and 356,891,432 reads from non-stressed control and salt-stressed oat, respectively. Assembly of 64 Gb raw sequence data yielded 128,414 putative unique transcripts with an average length of 1,189 bp. Analysis of the assembled unigenes from the salt stressed and control libraries indicated that about 65,000 unigenes were differentially expressed at different stages. Functional annotation showed that ABC transporters, plant hormone signal transduction, plant-pathogen interactions, starch and sucrose metabolism, arginine and proline metabolism, and other secondary metabolite pathways were enriched under salt stress. Based on the RPKM values of assembled unigenes, 24 differentially expressed genes under salt stress were selected for quantitative RT-PCR validation, which successfully confirmed the results of RNA-Seq. Furthermore, we identified 18,039 simple sequence repeats, which may help further elucidate salt tolerance mechanisms in oat. Conclusions Our global survey of transcriptome profiles of oat plants in response to salt stress provides useful insights into the molecular mechanisms underlying salt tolerance in this crop. These findings also represent a rich resource for further analysis of salt tolerance and for breeding oat with improved salt tolerance through the use of salt-related genes. PMID:28192458

The plastic response of Tantalum in Quasi-Isentropic Compression Ramp and Release

NASA Astrophysics Data System (ADS)

Moore, Alexander; Brown, Justin; Lim, Hojun; Lane, J. Matthew D.

2017-06-01

The mechanical response of various forms of tantalum under extreme pressures and strain rates is studied using dynamic quasi-isentropic compression loading conditions in atomistic simulations. Ramp compression in bcc metals under these conditions tend to show a significant strengthening effect with increasing pressure; however, due to limitations of experimental methods in such regimes, the underlying physics for this phenomenon is not well understood. Molecular dynamics simulations provide important information about the plasticity mechanisms and can be used to investigate this strengthening. MD simulations are performed on nanocrystalline Ta and single crystal defective Ta with dislocations and point defects to uncover how the material responds and the underlying plasticity mechanisms. The different systems of solid Ta are seen to plastically deform through different mechanisms. Fundamental understanding of tantalum plasticity in these high pressure and strain rate regimes is needed to model and fully understand experimental results. Sandia National Labs is a multi program laboratory managed and operated by Sandia Corp., a wholly owned subsidiary of Lockheed Martin Corp., for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000.

Parent stress across molecular subtypes of children with Angelman syndrome.

PubMed

Miodrag, N; Peters, S

2015-09-01

Parenting stress has been consistently reported among parents of children with developmental disabilities. However, to date, no studies have investigated the impact of a molecular subtype of Angelman syndrome (AS) on parent stress, despite distinct phenotypic differences among subtypes. Data for 124 families of children with three subtypes of AS: class I and II deletions (n = 99), imprinting centre defects (IC defects; n = 11) and paternal uniparental disomy (UPD; n = 14) were drawn from the AS Rare Diseases Clinical Research Network (RDCRN) database and collected from five research sites across the Unites States. The AS study at the RDCRN gathered health information to understand how the syndrome develops and how to treat it. Parents completed questionnaires on their perceived psychological stress, the severity of children's aberrant behaviour and children's sleep patterns. Children's adaptive functioning and developmental levels were clinically evaluated. Child-related stress reached clinical levels for 40% of parents of children with deletions, 100% for IC defects and 64.3% for UPD. Sleep difficulties were similar and elevated across subtypes. There were no differences between molecular subtypes for overall child and parent-related stress. However, results showed greater isolation and lack of perceived parenting skills for parents of children with UPD compared with deletions. Better overall cognition for children with deletions was significantly related to more child-related stress while their poorer adaptive functioning was associated with more child-related stress. For all three groups, the severity of children's inappropriate behaviour was positively related to different aspects of stress. How parents react to stress depends, in part, on children's AS molecular subtype. Despite falling under the larger umbrella term of AS, it is important to acknowledge the unique aspects associated with children's molecular subtype. Identifying these factors can lead to tailored interventions that fit the particular needs of families of children with different AS subtypes. © 2015 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

Raman spectroscopic analysis of the responds of desert cyanobacterium Nostoc sp under UV-B radiation

NASA Astrophysics Data System (ADS)

Wang, Gaohong; Hao, Zongjie; Hu, Chunxiang; Liu, Yongding

Cyanobacteria are renowned for tolerating extremes of desiccation, UV radiation, freezethaw cycles, hypersalinity and oligotrophy, which make them as candidate par excellence for terraforming in extraterrestrial planet. Recently Raman spectrum was applied to study the biochemical information changes in different field of life science. In this study, we investigated the respond of desert cyanobactreium Nostoc sp under UV-B radiation via FT-Raman spectra. It was found that the spectral biomarkers of protectant molecular of UV radiation such as β-carotene and scytonemin were induced by UV-B radiation, but Chlorophyll a content was decreased, and also the photosynthesis activity was inhibited significantly. After light adaptation without UV-B radiation, the Chlorophyll a content and photosynthesis activity returned to high level, butβ-carotene and scytonemin content remained in the cells. Those results indicated that desert Cyanobacteria have good adaptation ability for UV-B radiation and synthesis of protectant molecular may be an effective strategy for its adaptation in evolution.

Spatial structure of disordered proteins dictates conductance and selectivity in nuclear pore complex mimics

PubMed Central

Frey, Steffen; Dwarkasing, Arvind; Versloot, Roderick; van der Giessen, Erik

2018-01-01

Nuclear pore complexes (NPCs) lined with intrinsically disordered FG-domains act as selective gatekeepers for molecular transport between the nucleus and the cytoplasm in eukaryotic cells. The underlying physical mechanism of the intriguing selectivity is still under debate. Here, we probe the transport of ions and transport receptors through biomimetic NPCs consisting of Nsp1 domains attached to the inner surface of solid-state nanopores. We examine both wildtype FG-domains and hydrophilic SG-mutants. FG-nanopores showed a clear selectivity as transport receptors can translocate across the pore whereas other proteins cannot. SG mutant pores lack such selectivity. To unravel this striking difference, we present coarse-grained molecular dynamics simulations that reveal that FG-pores exhibit a high-density, nonuniform protein distribution, in contrast to a uniform and significantly less-dense protein distribution in the SG-mutant. We conclude that the sequence-dependent density distribution of disordered proteins inside the NPC plays a key role for its conductivity and selective permeability. PMID:29442997

Molecular equilibria and condensation sequences in carbon rich gases

NASA Technical Reports Server (NTRS)

Sharp, C. M.; Wasserburg, G. J.

1993-01-01

Chemical equilibria in stellar atmospheres have been investigated by many authors. Lattimer, Schramm, and Grossman presented calculations in both O rich and C rich environments and predicted possible presolar condensates. A recent paper by Cherchneff and Barker considered a C rich composition with PAH's included in the calculations. However, the condensation sequences of C bearing species have not been investigated in detail. In a carbon rich gas surrounding an AGB star, it is often assumed that graphite (or diamond) condenses out before TiC and SiC. However, Lattimer et al. found some conditions under which TiC condenses before graphite. We have performed molecular equilibrium calculations to establish the stability fields of C(s), TiC(s), and SiC(s) and other high temperature phases under conditions of different pressures and C/O. The preserved presolar interstellar dust grains so far discovered in meteorites are graphite, diamond, SiC, TiC, and possibly Al2O3.

Surface antigens from Escherichia coli O2 and O78 strains of avian origin.

PubMed Central

Dho-Moulin, M; van den Bosch, J F; Girardeau, J P; Brée, A; Barat, T; Lafont, J P

1990-01-01

Fimbriae from O2 and O78 virulent strains of avian Escherichia coli were compared with type 1A fimbriae with regard to the apparent molecular weights of their subunits and their antigenic relationships. Under static broth culture conditions, most O78 strains expressed fimbriae closely related to those of type 1A. Under the same culture conditions, another type of fimbriae, sharing some common properties with type 1A fimbriae, was observed only on O2 strains; however, these fimbriae differed from type 1A fimbriae in the apparent molecular weights of their subunits and in the expression of specific epitopes. They were called type 1-like fimbriae. Homologies in lipopolysaccharide and outer membrane protein profiles were also demonstrated among the strains expressing type 1-like fimbriae, which suggests the existence of a clonal relationship among O2:K1 avian E. coli strains. The O78 strains studied did not appear to be clonally related. Images PMID:1968434

Near-Resonant Raman Amplification in the Rotational Quantum Wave Packets of Nitrogen Molecular Ions Generated by Strong Field Ionization

NASA Astrophysics Data System (ADS)

Liu, Zhaoxiang; Yao, Jinping; Chen, Jinming; Xu, Bo; Chu, Wei; Cheng, Ya

2018-02-01

The generation of laserlike narrow bandwidth emissions from nitrogen molecular ions (N2+ ) generated in intense near- and mid infrared femtosecond laser fields has aroused much interest because of the mysterious physics underlying such a phenomenon. Here, we perform a pump-probe measurement on the nonlinear interaction of rotational quantum wave packets of N2+ generated in midinfrared (e.g., at a wavelength centered at 1580 nm) femtosecond laser fields with an ultrashort probe pulse whose broad spectrum overlaps both P - and R -branch rotational transition lines between the electronic states N2+(B2Σu+,v'=0 ) and N2+(X2Σg+,v =0 ) . The results indicate the occurrence of highly efficient near-resonant stimulated Raman scattering in the quantum wave packets of N2+ ions generated in strong laser fields in the midinfrared region, of which the underlying mechanism is different from that of the air lasers generated in atmospheric environment when pumping with 800 nm intense pulses.

Biomedical Applications of Mid-Infrared Spectroscopic Imaging and Multivariate Data Analysis: Contribution to the Understanding of Diabetes Pathogenesis

NASA Astrophysics Data System (ADS)

Aboualizadeh, Ebrahim

Diabetic retinopathy (DR) is a microvascular complication of diabetes and a leading cause of adult vision loss. Although a great deal of progress has been made in ophthalmological examinations and clinical approaches to detect the signs of retinopathy in patients with diabetes, there still remain outstanding questions regarding the molecular and biochemical changes involved. To discover the biochemical mechanisms underlying the development and progression of changes in the retina as a result of diabetes, a more comprehensive understanding of the bio-molecular processes, in individual retinal cells subjected to hyperglycemia, is required. Animal models provide a suitable resource for temporal detection of the underlying pathophysiological and biochemical changes associated with DR, which is not fully attainable in human studies. In the present study, I aimed to determine the nature of diabetes-induced, highly localized biochemical changes in the retinal tissue from Ins2Akita/+ (Akita/+; a model of Type I diabetes) male mice with different duration of diabetes. Employing label-free, spatially resolved Fourier transform infrared (FT-IR) imaging engaged with chemometric tools enabled me to identify temporal-dependent reproducible biomarkers of the diabetic retinal tissue from mice with 6 or 12 weeks, and 6 or 10 months of diabetes. I report, for the first time, the origin of molecular changes in the biochemistry of individual retinal layers with different duration of diabetes. A robust classification between distinctive retinal layers - namely photoreceptor layer (PRL), outer plexiform layer (OPL), inner nuclear layer (INL), and inner plexiform layer (IPL) - and associated temporal-dependent spectral biomarkers, were delineated. Spatially-resolved super resolution chemical images revealed oxidative stress-induced structural and morphological alterations within the nucleus of the photoreceptors. Comparison among the PRL, OPL, INL, and IPL suggested that the photoreceptor layer is the most susceptible layer to the oxidative stress with short-duration of diabetes. Moreover, for the first time, we present the temporal-dependent molecular alterations for the PRL, OPL, INL, and IPL from Akita/+ mice, with progression of diabetes. These findings are potentially important and may be of particular benefit in understanding the molecular and biological activity of retinal cells during oxidative stress in diabetes. Our integrating paradigm provides a new conceptual framework and a significant rationale for a better understanding of the molecular and cellular mechanisms underlying the development and progression of DR. This approach may yield alternative and potentially complimentary methods for the assessment of diabetes changes. It is expected that the conclusions drawn from this work will bridge the gap in our knowledge regarding the biochemical mechanisms of the DR and address some critical needs in the biomedical community.

Heat and pH stability of alkali-extractable corn arabinoxylan and its xylanase-hydrolyzate and their viscosity behavior.

PubMed

Rumpagaporn, Pinthip; Kaur, Amandeep; Campanella, Osvaldo H; Patterson, John A; Hamaker, Bruce R

2012-01-01

In in vitro batch fermentations, both alkali-extractable corn arabinoxylan (CAX) and its xylanase-hydrolyzate (CH) were utilized by human fecal microbiota and produced similar short chain fatty acid (SCFA) contents and desirable long fermentation profiles with low initial gas production. Fortification of these arabinoxylans into processed foods would contribute desirable dietary fiber benefits to humans. Heat and pH stability, as well as viscosity behavior of CAX and CH were investigated. Size exclusion chromatography was used to analyze the molecular size distribution after treatment at different pH's and heating temperatures for different time periods. Treated under boiling and pressure cooking conditions at pH 3, CAX was degraded to a smaller molecular size, whereas the molecular size of the CH showed only a minor decrease. CAX and CH were mostly stable at neutral pH, except when CAX was treated under pressure for 60 min that slightly lowered molecular size. At 37 °C, neither CAX nor CH was adversely affected by treatment at low or neutral pH. The viscosities of solutions containing 5% and 10% of CAX were 48.7 and 637.0 mPa.s, respectively that were higher than those of solutions containing 5% and 10% of its hydrolyzate at shear rate 1 s⁻¹. The CAX solutions showed Newtonian flow behavior, whereas shear-thinning behavior was observed in CH solutions. In conclusion, the hydrolyzate of CAX has potential to be used in high fiber drinks due to its favorable fermentation properties, higher pH and heat stability, lower and shear-thinning viscosity, and lighter color than the native CAX. Arabinoxylan extracted by an alkali from corn bran is a soluble fiber with a desirable low initial and extended fermentation property. Corn arabinoxylan hydrolyzate using an endoxylanase was much more stable at different levels of acidity and heat than the native arabinoxylan, and showed lower solution viscosity and shear-thinning property that indicates its potential as an alternative functional dietary fiber for the beverage industry. © 2011 Institute of Food Technologists®

Conceptualizing neurodevelopmental disorders through a mechanistic understanding of fragile X syndrome and Williams syndrome

PubMed Central

Fung, Lawrence K.; Quintin, Eve-Marie; Haas, Brian W.

2013-01-01

Purpose of review The overarching goal of this review is to compare and contrast the cognitive-behavioral features of fragile X syndrome (FraX) and Williams syndrome and to review the putative neural and molecular underpinnings of these features. Information is presented in a framework that provides guiding principles for conceptualizing gene-brain-behavior associations in neurodevelopmental disorders. Recent findings Abnormalities, in particular cognitive-behavioral domains with similarities in underlying neurodevelopmental correlates, occur in both FraX and Williams syndrome including aberrant frontostriatal pathways leading to executive function deficits, and magnocellular/dorsal visual stream, superior parietal lobe, inferior parietal lobe, and postcentral gyrus abnormalities contributing to deficits in visuospatial function. Compelling cognitive–behavioral and neurodevelopmental contrasts also exist in these two disorders, for example, aberrant amygdala and fusiform cortex structure and function occurring in the context of contrasting social behavioral phenotypes, and temporal cortical and cerebellar abnormalities potentially underlying differences in language function. Abnormal dendritic development is a shared neurodevelopmental morphologic feature between FraX and Williams syndrome. Commonalities in molecular machinery and processes across FraX and Williams syndrome occur as well – microRNAs involved in translational regulation of major synaptic proteins; scaffolding proteins in excitatory synapses; and proteins involved in axonal development. Summary Although the genetic variations leading to FraX and Williams syndrome are different, important similarities and contrasts in the phenotype, neurocircuitry, molecular machinery, and cellular processes in these two disorders allow for a unique approach to conceptualizing gene–brain–behavior links occurring in neurodevelopmental disorders. PMID:22395002

The DNA Triangle and Its Application to Learning Meiosis.

PubMed

Wright, L Kate; Catavero, Christina M; Newman, Dina L

2017-01-01

Although instruction on meiosis is repeated many times during the undergraduate curriculum, many students show poor comprehension even as upper-level biology majors. We propose that the difficulty lies in the complexity of understanding DNA, which we explain through a new model, the DNA triangle The DNA triangle integrates three distinct scales at which one can think about DNA: chromosomal , molecular , and informational Through analysis of interview and survey data from biology faculty and students through the lens of the DNA triangle, we illustrate important differences in how novices and experts are able to explain the concepts of ploidy , homology , and mechanism of homologous pairing Similarly, analysis of passages from 16 different biology textbooks shows a large divide between introductory and advanced material, with introductory books omitting explanations of meiosis-linked concepts at the molecular level of DNA. Finally, backed by textbook findings and feedback from biology experts, we show that the DNA triangle can be applied to teaching and learning meiosis. By applying the DNA triangle to topics on meiosis we present a new framework for educators and researchers that ties concepts of ploidy, homology, and mechanism of homologous pairing to knowledge about DNA on the chromosomal, molecular, and informational levels. © 2017 L. K. Wright et al. CBE—Life Sciences Education © 2017 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

[THE SOMATIC MUTATIONS AND ABERRANT METHYLATION AS POTENTIAL GENETIC MARKERS OF URINARY BLADDER CANCER].

PubMed

Mikhailenko, D S; Kushlinskii, N E

2016-02-01

All around the world, more than 330 thousands cases of bladder cancer are registered annually hence representing actual problem of modern oncology. Still in demand are search and characteristic of new molecular markers of bladder cancer detecting in tumor cells from urinary sediment and having high diagnostic accuracy. The studies of last decade, especially using methods of genome-wide sequencing, permitted to receive a large amount of experimental data concerning development and progression of bladder cancer The review presents systematic analysis of publications available in PubMed data base mainly of last five years. The original studies of molecular genetic disorders under bladder cancer and meta-analyzes were considered This approach permitted to detected the most common local alterations of DNA under bladder cancer which can be detected using routine genetic methods indifferent clinical material and present prospective interest for development of test-systems. The molecular genetic markers of disease can be activating missense mutations in 7 and 10 exons of gene of receptor of growth factor of fibroblasts 3 (FGFR3), 9 and 20 exons of gene of Phosphatidylinositol-4,5-bi-phosphate-3-kinase (PIK3CA) and mutation in -124 and -146 nucleotides in promoter of gene of catalytic subunit telomerase (TERT). The development of test-systems on the basis of aberrant methylation of CpG-islets of genes-suppressors still is seemed as a difficult task because of differences in pattern of methylation of different primary tumors at various stages of clonal evolution of bladder cancer though they can be considered as potential markers.

The molecular mechanics of eukaryotic translation.

PubMed

Kapp, Lee D; Lorsch, Jon R

2004-01-01

Great advances have been made in the past three decades in understanding the molecular mechanics underlying protein synthesis in bacteria, but our understanding of the corresponding events in eukaryotic organisms is only beginning to catch up. In this review we describe the current state of our knowledge and ignorance of the molecular mechanics underlying eukaryotic translation. We discuss the mechanisms conserved across the three kingdoms of life as well as the important divergences that have taken place in the pathway.

Space Science

NASA Image and Video Library

2003-10-28

These gels were obtained by two-dimensional (2D) electrophoresis, in which proteins move different substances through a polyacrylamide gel matrix based on their molecular weight and total charge in an electric field. The gels illustrate principal investigator David Niesel’s findings that exposure to modeled microgravity results in some Streptoccoccus Pneumonia’s proteins being upregulated and others being downregulated. In 2D protein profiles of whole cell lysates of Streptoccoccus Pneumonia, 6,304 cultured under normal gravity (left), appear to be expressed at higher levels indicated with black circles. Red circles (right) indicate proteins that were grown under modeled microgravity in a high aspect ratio vessel HARV).

The Impact of the Tree Prior on Molecular Dating of Data Sets Containing a Mixture of Inter- and Intraspecies Sampling.

PubMed

Ritchie, Andrew M; Lo, Nathan; Ho, Simon Y W

2017-05-01

In Bayesian phylogenetic analyses of genetic data, prior probability distributions need to be specified for the model parameters, including the tree. When Bayesian methods are used for molecular dating, available tree priors include those designed for species-level data, such as the pure-birth and birth-death priors, and coalescent-based priors designed for population-level data. However, molecular dating methods are frequently applied to data sets that include multiple individuals across multiple species. Such data sets violate the assumptions of both the speciation and coalescent-based tree priors, making it unclear which should be chosen and whether this choice can affect the estimation of node times. To investigate this problem, we used a simulation approach to produce data sets with different proportions of within- and between-species sampling under the multispecies coalescent model. These data sets were then analyzed under pure-birth, birth-death, constant-size coalescent, and skyline coalescent tree priors. We also explored the ability of Bayesian model testing to select the best-performing priors. We confirmed the applicability of our results to empirical data sets from cetaceans, phocids, and coregonid whitefish. Estimates of node times were generally robust to the choice of tree prior, but some combinations of tree priors and sampling schemes led to large differences in the age estimates. In particular, the pure-birth tree prior frequently led to inaccurate estimates for data sets containing a mixture of inter- and intraspecific sampling, whereas the birth-death and skyline coalescent priors produced stable results across all scenarios. Model testing provided an adequate means of rejecting inappropriate tree priors. Our results suggest that tree priors do not strongly affect Bayesian molecular dating results in most cases, even when severely misspecified. However, the choice of tree prior can be significant for the accuracy of dating results in the case of data sets with mixed inter- and intraspecies sampling. [Bayesian phylogenetic methods; model testing; molecular dating; node time; tree prior.]. © The authors 2016. Published by Oxford University Press, on behalf of the Society of Systematic Biologists. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.

Molecular profiling of the Phytophthora plurivora secretome: a step towards understanding the cross-talk between plant pathogenic oomycetes and their hosts.

PubMed

Severino, Valeria; Farina, Annarita; Fleischmann, Frank; Dalio, Ronaldo J D; Di Maro, Antimo; Scognamiglio, Monica; Fiorentino, Antonio; Parente, Augusto; Osswald, Wolfgang; Chambery, Angela

2014-01-01

The understanding of molecular mechanisms underlying host-pathogen interactions in plant diseases is of crucial importance to gain insights on different virulence strategies of pathogens and unravel their role in plant immunity. Among plant pathogens, Phytophthora species are eliciting a growing interest for their considerable economical and environmental impact. Plant infection by Phytophthora phytopathogens is a complex process coordinated by a plethora of extracellular signals secreted by both host plants and pathogens. The characterization of the repertoire of effectors secreted by oomycetes has become an active area of research for deciphering molecular mechanisms responsible for host plants colonization and infection. Putative secreted proteins by Phytophthora species have been catalogued by applying high-throughput genome-based strategies and bioinformatic approaches. However, a comprehensive analysis of the effective secretome profile of Phytophthora is still lacking. Here, we report the first large-scale profiling of P. plurivora secretome using a shotgun LC-MS/MS strategy. To gain insight on the molecular signals underlying the cross-talk between plant pathogenic oomycetes and their host plants, we also investigate the quantitative changes of secreted protein following interaction of P. plurivora with the root exudate of Fagus sylvatica which is highly susceptible to the root pathogen. We show that besides known effectors, the expression and/or secretion levels of cell-wall-degrading enzymes were altered following the interaction with the host plant root exudate. In addition, a characterization of the F. sylvatica root exudate was performed by NMR and amino acid analysis, allowing the identification of the main released low-molecular weight components, including organic acids and free amino acids. This study provides important insights for deciphering the extracellular network involved in the highly susceptible P. plurivora-F. sylvatica interaction.

An autonomous chemically fuelled small-molecule motor

NASA Astrophysics Data System (ADS)

Wilson, Miriam R.; Solà, Jordi; Carlone, Armando; Goldup, Stephen M.; Lebrasseur, Nathalie; Leigh, David A.

2016-06-01

Molecular machines are among the most complex of all functional molecules and lie at the heart of nearly every biological process. A number of synthetic small-molecule machines have been developed, including molecular muscles, synthesizers, pumps, walkers, transporters and light-driven and electrically driven rotary motors. However, although biological molecular motors are powered by chemical gradients or the hydrolysis of adenosine triphosphate (ATP), so far there are no synthetic small-molecule motors that can operate autonomously using chemical energy (that is, the components move with net directionality as long as a chemical fuel is present). Here we describe a system in which a small molecular ring (macrocycle) is continuously transported directionally around a cyclic molecular track when powered by irreversible reactions of a chemical fuel, 9-fluorenylmethoxycarbonyl chloride. Key to the design is that the rate of reaction of this fuel with reactive sites on the cyclic track is faster when the macrocycle is far from the reactive site than when it is near to it. We find that a bulky pyridine-based catalyst promotes carbonate-forming reactions that ratchet the displacement of the macrocycle away from the reactive sites on the track. Under reaction conditions where both attachment and cleavage of the 9-fluorenylmethoxycarbonyl groups occur through different processes, and the cleavage reaction occurs at a rate independent of macrocycle location, net directional rotation of the molecular motor continues for as long as unreacted fuel remains. We anticipate that autonomous chemically fuelled molecular motors will find application as engines in molecular nanotechnology.

The Molecular Basis of Development.

ERIC Educational Resources Information Center

Gehring, Walter J.

1985-01-01

Basic architecture of embryo development appears to be under homeobox control (a short stretch of DNA). Outlines research on this genetic segment in fruit flies which led to identification of this control on the embryo's spatial organization. Indicates that molecular mechanisms underlying development may be much more universal than previously…

Elucidation of the molecular mechanisms underlying adverse reactions associated with a kinase inhibitor using systems toxicology

PubMed Central

Amemiya, Takahiro; Honma, Masashi; Kariya, Yoshiaki; Ghosh, Samik; Kitano, Hiroaki; Kurachi, Yoshihisa; Fujita, Ken-ichi; Sasaki, Yasutsuna; Homma, Yukio; Abernethy, Darrel R; Kume, Haruki; Suzuki, Hiroshi

2015-01-01

Background/Objectives: Targeted kinase inhibitors are an important class of agents in anticancer therapeutics, but their limited tolerability hampers their clinical performance. Identification of the molecular mechanisms underlying the development of adverse reactions will be helpful in establishing a rational method for the management of clinically adverse reactions. Here, we selected sunitinib as a model and demonstrated that the molecular mechanisms underlying the adverse reactions associated with kinase inhibitors can efficiently be identified using a systems toxicological approach. Methods: First, toxicological target candidates were short-listed by comparing the human kinase occupancy profiles of sunitinib and sorafenib, and the molecular mechanisms underlying adverse reactions were predicted by sequential simulations using publicly available mathematical models. Next, to evaluate the probability of these predictions, a clinical observation study was conducted in six patients treated with sunitinib. Finally, mouse experiments were performed for detailed confirmation of the hypothesized molecular mechanisms and to evaluate the efficacy of a proposed countermeasure against adverse reactions to sunitinib. Results: In silico simulations indicated the possibility that sunitinib-mediated off-target inhibition of phosphorylase kinase leads to the generation of oxidative stress in various tissues. Clinical observations of patients and mouse experiments confirmed the validity of this prediction. The simulation further suggested that concomitant use of an antioxidant may prevent sunitinib-mediated adverse reactions, which was confirmed in mouse experiments. Conclusions: A systems toxicological approach successfully predicted the molecular mechanisms underlying clinically adverse reactions associated with sunitinib and was used to plan a rational method for the management of these adverse reactions. PMID:28725458

Endocytotic uptake of HPMA-based polymers by different cancer cells: impact of extracellular acidosis and hypoxia

PubMed Central

Gündel, Daniel; Allmeroth, Mareli; Reime, Sarah; Zentel, Rudolf; Thews, Oliver

2017-01-01

Background Polymeric nanoparticles allow to selectively transport chemotherapeutic drugs to the tumor tissue. These nanocarriers have to be taken up into the cells to release the drug. In addition, tumors often show pathological metabolic characteristics (hypoxia and acidosis) which might affect the polymer endocytosis. Materials and methods Six different N-(2-hydroxypropyl)methacrylamide (HPMA)-based polymer structures (homopolymer as well as random and block copolymers with lauryl methacrylate containing hydrophobic side chains) varying in molecular weight and size were analyzed in two different tumor models. The cellular uptake of fluorescence-labeled polymers was measured under hypoxic (pO2 ≈1.5 mmHg) and acidic (pH 6.6) conditions. By using specific inhibitors, different endocytotic routes (macropinocytosis and clathrin-mediated, dynamin-dependent, cholesterol-dependent endocytosis) were analyzed separately. Results The current results revealed that the polymer uptake depends on the molecular structure, molecular weight and tumor line used. In AT1 cells, the uptake of random copolymer was five times stronger than the homopolymer, whereas in Walker-256 cells, the uptake of all polymers was much stronger, but this was independent of the molecular structure and size. Acidosis increased the uptake of random copolymer in AT1 cells but reduced the intracellular accumulation of homopolymer and block copolymer. Hypoxia reduced the uptake of all polymers in Walker-256 cells. Hydrophilic polymers (homopolymer and block copolymer) were taken up by all endocytotic routes studied, whereas the more lipophilic random copolymer seemed to be taken up preferentially by cholesterol- and dynamin-dependent endocytosis. Conclusion The study indicates that numerous parameters of the polymer (structure, size) and of the tumor (perfusion, vascular permeability, pH, pO2) modulate drug delivery, which makes it difficult to select the appropriate polymer for the individual patient. PMID:28831253

Endocytotic uptake of HPMA-based polymers by different cancer cells: impact of extracellular acidosis and hypoxia.

PubMed

Gündel, Daniel; Allmeroth, Mareli; Reime, Sarah; Zentel, Rudolf; Thews, Oliver

2017-01-01

Polymeric nanoparticles allow to selectively transport chemotherapeutic drugs to the tumor tissue. These nanocarriers have to be taken up into the cells to release the drug. In addition, tumors often show pathological metabolic characteristics (hypoxia and acidosis) which might affect the polymer endocytosis. Six different N -(2-hydroxypropyl)methacrylamide (HPMA)-based polymer structures (homopolymer as well as random and block copolymers with lauryl methacrylate containing hydrophobic side chains) varying in molecular weight and size were analyzed in two different tumor models. The cellular uptake of fluorescence-labeled polymers was measured under hypoxic (pO 2 ≈1.5 mmHg) and acidic (pH 6.6) conditions. By using specific inhibitors, different endocytotic routes (macropinocytosis and clathrin-mediated, dynamin-dependent, cholesterol-dependent endocytosis) were analyzed separately. The current results revealed that the polymer uptake depends on the molecular structure, molecular weight and tumor line used. In AT1 cells, the uptake of random copolymer was five times stronger than the homopolymer, whereas in Walker-256 cells, the uptake of all polymers was much stronger, but this was independent of the molecular structure and size. Acidosis increased the uptake of random copolymer in AT1 cells but reduced the intracellular accumulation of homopolymer and block copolymer. Hypoxia reduced the uptake of all polymers in Walker-256 cells. Hydrophilic polymers (homopolymer and block copolymer) were taken up by all endocytotic routes studied, whereas the more lipophilic random copolymer seemed to be taken up preferentially by cholesterol- and dynamin-dependent endocytosis. The study indicates that numerous parameters of the polymer (structure, size) and of the tumor (perfusion, vascular permeability, pH, pO 2 ) modulate drug delivery, which makes it difficult to select the appropriate polymer for the individual patient.

Molecular Dynamics in Mixed Solvents Reveals Protein-Ligand Interactions, Improves Docking, and Allows Accurate Binding Free Energy Predictions.

PubMed

Arcon, Juan Pablo; Defelipe, Lucas A; Modenutti, Carlos P; López, Elias D; Alvarez-Garcia, Daniel; Barril, Xavier; Turjanski, Adrián G; Martí, Marcelo A

2017-04-24

One of the most important biological processes at the molecular level is the formation of protein-ligand complexes. Therefore, determining their structure and underlying key interactions is of paramount relevance and has direct applications in drug development. Because of its low cost relative to its experimental sibling, molecular dynamics (MD) simulations in the presence of different solvent probes mimicking specific types of interactions have been increasingly used to analyze protein binding sites and reveal protein-ligand interaction hot spots. However, a systematic comparison of different probes and their real predictive power from a quantitative and thermodynamic point of view is still missing. In the present work, we have performed MD simulations of 18 different proteins in pure water as well as water mixtures of ethanol, acetamide, acetonitrile and methylammonium acetate, leading to a total of 5.4 μs simulation time. For each system, we determined the corresponding solvent sites, defined as space regions adjacent to the protein surface where the probability of finding a probe atom is higher than that in the bulk solvent. Finally, we compared the identified solvent sites with 121 different protein-ligand complexes and used them to perform molecular docking and ligand binding free energy estimates. Our results show that combining solely water and ethanol sites allows sampling over 70% of all possible protein-ligand interactions, especially those that coincide with ligand-based pharmacophoric points. Most important, we also show how the solvent sites can be used to significantly improve ligand docking in terms of both accuracy and precision, and that accurate predictions of ligand binding free energies, along with relative ranking of ligand affinity, can be performed.