SCIENCE RESULTS INTEGRATION. BRINGING MOLECULAR BIOLOGY TECHNIQUES TO REGIONAL WATER MONITORING PROGRAMS

EPA Science Inventory

EPA's Office of Research and Development (ORD) develops innovative methods for use in environmental monitoring and assessment by scientists in Regions, states, and Tribes. Molecular-biology-based methods are not yet established in the environmental monitoring "tool box". SRI (Sci...

eScience for molecular-scale simulations and the eMinerals project.

PubMed

Salje, E K H; Artacho, E; Austen, K F; Bruin, R P; Calleja, M; Chappell, H F; Chiang, G-T; Dove, M T; Frame, I; Goodwin, A L; Kleese van Dam, K; Marmier, A; Parker, S C; Pruneda, J M; Todorov, I T; Trachenko, K; Tyer, R P; Walker, A M; White, T O H

2009-03-13

We review the work carried out within the eMinerals project to develop eScience solutions that facilitate a new generation of molecular-scale simulation work. Technological developments include integration of compute and data systems, developing of collaborative frameworks and new researcher-friendly tools for grid job submission, XML data representation, information delivery, metadata harvesting and metadata management. A number of diverse science applications will illustrate how these tools are being used for large parameter-sweep studies, an emerging type of study for which the integration of computing, data and collaboration is essential.

A software platform for continuum modeling of ion channels based on unstructured mesh

NASA Astrophysics Data System (ADS)

Tu, B.; Bai, S. Y.; Chen, M. X.; Xie, Y.; Zhang, L. B.; Lu, B. Z.

2014-01-01

Most traditional continuum molecular modeling adopted finite difference or finite volume methods which were based on a structured mesh (grid). Unstructured meshes were only occasionally used, but an increased number of applications emerge in molecular simulations. To facilitate the continuum modeling of biomolecular systems based on unstructured meshes, we are developing a software platform with tools which are particularly beneficial to those approaches. This work describes the software system specifically for the simulation of a typical, complex molecular procedure: ion transport through a three-dimensional channel system that consists of a protein and a membrane. The platform contains three parts: a meshing tool chain for ion channel systems, a parallel finite element solver for the Poisson-Nernst-Planck equations describing the electrodiffusion process of ion transport, and a visualization program for continuum molecular modeling. The meshing tool chain in the platform, which consists of a set of mesh generation tools, is able to generate high-quality surface and volume meshes for ion channel systems. The parallel finite element solver in our platform is based on the parallel adaptive finite element package PHG which wass developed by one of the authors [1]. As a featured component of the platform, a new visualization program, VCMM, has specifically been developed for continuum molecular modeling with an emphasis on providing useful facilities for unstructured mesh-based methods and for their output analysis and visualization. VCMM provides a graphic user interface and consists of three modules: a molecular module, a meshing module and a numerical module. A demonstration of the platform is provided with a study of two real proteins, the connexin 26 and hemolysin ion channels.

Molecular tools for differentiation of non-typeable Haemophilus influenzae from Haemophilus haemolyticus

PubMed Central

Pickering, Janessa; Richmond, Peter C.; Kirkham, Lea-Ann S.

2014-01-01

Non-typeable Haemophilus influenzae (NTHi) and Haemophilus haemolyticus are closely related bacteria that reside in the upper respiratory tract. NTHi is associated with respiratory tract infections that frequently result in antibiotic prescription whilst H. haemolyticus is rarely associated with disease. NTHi and H. haemolyticus can be indistinguishable by traditional culture methods and molecular differentiation has proven difficult. This current review chronologically summarizes the molecular approaches that have been developed for differentiation of NTHi from H. haemolyticus, highlighting the advantages and disadvantages of each target and/or technique. We also provide suggestions for the development of new tools that would be suitable for clinical and research laboratories. PMID:25520712

Method for delivery of small molecules and proteins across the cell wall of algae using molecular transporters

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

Geihe, Erika; Trantow, Brian; Wender, Paul

The introduction of tools to study, control or expand the inner-workings of algae has been slow to develop. Provided are embodiments of a molecular method based on guanidinium-rich molecular transporters (GR-MoTrs) for bringing molecular cargos into algal cells. The methods of the disclosure have been shown to work in wild-type algae that have an intact cell wall. Developed using Chlamydomonas reinhardtii, this method is also successful with less studied algae, including Neochloris oleoabundans and Scenedesmus dimorphus, thus providing a new and versatile tool for algal research and modification. The method of delivering a cargo compound to an algal cell comprisesmore » contacting an algal cell with a guanidinium-rich delivery vehicle comprising a guanidinium-rich molecular transporter (GR-MoTr) linked to a cargo compound desired to be delivered to the algal cell, whereby the guanidinium-rich molecular transporter can traverse the algal cell wall, thereby delivering the cargo compound to the algal cell.« less

Developments in the CCP4 molecular-graphics project.

PubMed

Potterton, Liz; McNicholas, Stuart; Krissinel, Eugene; Gruber, Jan; Cowtan, Kevin; Emsley, Paul; Murshudov, Garib N; Cohen, Serge; Perrakis, Anastassis; Noble, Martin

2004-12-01

Progress towards structure determination that is both high-throughput and high-value is dependent on the development of integrated and automatic tools for electron-density map interpretation and for the analysis of the resulting atomic models. Advances in map-interpretation algorithms are extending the resolution regime in which fully automatic tools can work reliably, but at present human intervention is required to interpret poor regions of macromolecular electron density, particularly where crystallographic data is only available to modest resolution [for example, I/sigma(I) < 2.0 for minimum resolution 2.5 A]. In such cases, a set of manual and semi-manual model-building molecular-graphics tools is needed. At the same time, converting the knowledge encapsulated in a molecular structure into understanding is dependent upon visualization tools, which must be able to communicate that understanding to others by means of both static and dynamic representations. CCP4 mg is a program designed to meet these needs in a way that is closely integrated with the ongoing development of CCP4 as a program suite suitable for both low- and high-intervention computational structural biology. As well as providing a carefully designed user interface to advanced algorithms of model building and analysis, CCP4 mg is intended to present a graphical toolkit to developers of novel algorithms in these fields.

Novel gene expression tools for rice biotechnology

USDA-ARS?s Scientific Manuscript database

Biotechnology is an effective and important method of improving both quality and agronomic traits in rice. We are developing novel molecular tools for genetic engineering, with a focus on developing novel transgene expression control elements (i.e. promoters) for rice. A suite of monocot grass promo...

National Toxicology Program

MedlinePlus

... develops and applies tools of modern toxicology and molecular biology to identify substances in the environment that may ... application of new technologies for modern toxicology and molecular biology. A world leader in toxicology research, NTP has ...

Building bridges between cellular and molecular structural biology.

PubMed

Patwardhan, Ardan; Brandt, Robert; Butcher, Sarah J; Collinson, Lucy; Gault, David; Grünewald, Kay; Hecksel, Corey; Huiskonen, Juha T; Iudin, Andrii; Jones, Martin L; Korir, Paul K; Koster, Abraham J; Lagerstedt, Ingvar; Lawson, Catherine L; Mastronarde, David; McCormick, Matthew; Parkinson, Helen; Rosenthal, Peter B; Saalfeld, Stephan; Saibil, Helen R; Sarntivijai, Sirarat; Solanes Valero, Irene; Subramaniam, Sriram; Swedlow, Jason R; Tudose, Ilinca; Winn, Martyn; Kleywegt, Gerard J

2017-07-06

The integration of cellular and molecular structural data is key to understanding the function of macromolecular assemblies and complexes in their in vivo context. Here we report on the outcomes of a workshop that discussed how to integrate structural data from a range of public archives. The workshop identified two main priorities: the development of tools and file formats to support segmentation (that is, the decomposition of a three-dimensional volume into regions that can be associated with defined objects), and the development of tools to support the annotation of biological structures.

Molecular Dynamics Visualization (MDV): Stereoscopic 3D Display of Biomolecular Structure and Interactions Using the Unity Game Engine.

PubMed

Wiebrands, Michael; Malajczuk, Chris J; Woods, Andrew J; Rohl, Andrew L; Mancera, Ricardo L

2018-06-21

Molecular graphics systems are visualization tools which, upon integration into a 3D immersive environment, provide a unique virtual reality experience for research and teaching of biomolecular structure, function and interactions. We have developed a molecular structure and dynamics application, the Molecular Dynamics Visualization tool, that uses the Unity game engine combined with large scale, multi-user, stereoscopic visualization systems to deliver an immersive display experience, particularly with a large cylindrical projection display. The application is structured to separate the biomolecular modeling and visualization systems. The biomolecular model loading and analysis system was developed as a stand-alone C# library and provides the foundation for the custom visualization system built in Unity. All visual models displayed within the tool are generated using Unity-based procedural mesh building routines. A 3D user interface was built to allow seamless dynamic interaction with the model while being viewed in 3D space. Biomolecular structure analysis and display capabilities are exemplified with a range of complex systems involving cell membranes, protein folding and lipid droplets.

Cross-transferability of SSR markers in Osmanthus

USDA-ARS?s Scientific Manuscript database

Developing a molecular tool kit for hybrid breeding of Osmanthus species and related genera is an important step in creating a systematic breeding program for this species. To date, molecular resources have been aimed solely at O. fragrans with little work to develop markers for other species and cu...

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

Weiss, Paul

Spectroscopic imaging tools and methods, based on scanning tunneling microscopes (STMs), are being developed and applied to examine buried layers and interfaces with ultrahigh resolution. These new methods measure buried contacts, molecule-substrate bonds, buried dipoles in molecular layers, and key structural aspects of adsorbed molecules, such as tilt angles. We are developing the ability to locate lateral projections of molecular parts as a means of determining the structures of molecular layers. We are developing the ability to measure the orientation of buried functionality.

Perspective: Reaches of chemical physics in biology.

PubMed

Gruebele, Martin; Thirumalai, D

2013-09-28

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

Perspective: Reaches of chemical physics in biology

PubMed Central

Gruebele, Martin; Thirumalai, D.

2013-01-01

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

A Diagnostic Assessment for Introductory Molecular and Cell Biology

ERIC Educational Resources Information Center

Shi, Jia; Wood, William B.; Martin, Jennifer M.; Guild, Nancy A.; Vicens, Quentin; Knight, Jennifer K.

2010-01-01

We have developed and validated a tool for assessing understanding of a selection of fundamental concepts and basic knowledge in undergraduate introductory molecular and cell biology, focusing on areas in which students often have misconceptions. This multiple-choice Introductory Molecular and Cell Biology Assessment (IMCA) instrument is designed…

[Clinical applications of molecular imaging methods for patients with ischemic stroke].

PubMed

Yamauchi, Hiroshi; Fukuyama, Hidenao

2007-02-01

Several molecular imaging methods have been developed to visualize pathophysiology of cerebral ischemia in humans in vivo. PET and SPECT with specific ligands have been mainly used as diagnostic tools for the clinical usage of molecular imaging in patients with ischemic stroke. Recently, cellular MR imaging with specific contrast agents has been developed to visualize targeted cells in human stroke patients. This article reviews the current status in the clinical applications of those molecular imaging methods for patients with ischemic stroke.

3D visualization of molecular structures in the MOGADOC database

NASA Astrophysics Data System (ADS)

Vogt, Natalja; Popov, Evgeny; Rudert, Rainer; Kramer, Rüdiger; Vogt, Jürgen

2010-08-01

The MOGADOC database (Molecular Gas-Phase Documentation) is a powerful tool to retrieve information about compounds which have been studied in the gas-phase by electron diffraction, microwave spectroscopy and molecular radio astronomy. Presently the database contains over 34,500 bibliographic references (from the beginning of each method) for about 10,000 inorganic, organic and organometallic compounds and structural data (bond lengths, bond angles, dihedral angles, etc.) for about 7800 compounds. Most of the implemented molecular structures are given in a three-dimensional (3D) presentation. To create or edit and visualize the 3D images of molecules, new tools (special editor and Java-based 3D applet) were developed. Molecular structures in internal coordinates were converted to those in Cartesian coordinates.

Serpentinomics-an emerging new field of study

Treesearch

Jessica Wright; Eric von Wettberg

2009-01-01

"Serpentinomics" is an emerging field of study which has the potential to greatly advance our understanding of serpentine ecology. Several newly developing –omic fields, often using high-throughput tools developed for molecular biology, will advance the field of serpentine ecology, or, "serpentinomics." Using tools from the...

Emancipating Chlamydia: Advances in the Genetic Manipulation of a Recalcitrant Intracellular Pathogen

PubMed Central

Bastidas, Robert J.

2016-01-01

SUMMARY Chlamydia species infect millions of individuals worldwide and are important etiological agents of sexually transmitted disease, infertility, and blinding trachoma. Historically, the genetic intractability of this intracellular pathogen has hindered the molecular dissection of virulence factors contributing to its pathogenesis. The obligate intracellular life cycle of Chlamydia and restrictions on the use of antibiotics as selectable markers have impeded the development of molecular tools to genetically manipulate these pathogens. However, recent developments in the field have resulted in significant gains in our ability to alter the genome of Chlamydia, which will expedite the elucidation of virulence mechanisms. In this review, we discuss the challenges affecting the development of molecular genetic tools for Chlamydia and the work that laid the foundation for recent advancements in the genetic analysis of this recalcitrant pathogen. PMID:27030552

Challenges and Advances for Genetic Engineering of Non-model Bacteria and Uses in Consolidated Bioprocessing

PubMed Central

Yan, Qiang; Fong, Stephen S.

2017-01-01

Metabolic diversity in microorganisms can provide the basis for creating novel biochemical products. However, most metabolic engineering projects utilize a handful of established model organisms and thus, a challenge for harnessing the potential of novel microbial functions is the ability to either heterologously express novel genes or directly utilize non-model organisms. Genetic manipulation of non-model microorganisms is still challenging due to organism-specific nuances that hinder universal molecular genetic tools and translatable knowledge of intracellular biochemical pathways and regulatory mechanisms. However, in the past several years, unprecedented progress has been made in synthetic biology, molecular genetics tools development, applications of omics data techniques, and computational tools that can aid in developing non-model hosts in a systematic manner. In this review, we focus on concerns and approaches related to working with non-model microorganisms including developing molecular genetics tools such as shuttle vectors, selectable markers, and expression systems. In addition, we will discuss: (1) current techniques in controlling gene expression (transcriptional/translational level), (2) advances in site-specific genome engineering tools [homologous recombination (HR) and clustered regularly interspaced short palindromic repeats (CRISPR)], and (3) advances in genome-scale metabolic models (GSMMs) in guiding design of non-model species. Application of these principles to metabolic engineering strategies for consolidated bioprocessing (CBP) will be discussed along with some brief comments on foreseeable future prospects. PMID:29123506

The cognitive life of mechanical molecular models.

PubMed

Charbonneau, Mathieu

2013-12-01

The use of physical models of molecular structures as research tools has been central to the development of biochemistry and molecular biology. Intriguingly, it has received little attention from scholars of science. In this paper, I argue that these physical models are not mere three-dimensional representations but that they are in fact very special research tools: they are cognitive augmentations. Despite the fact that they are external props, these models serve as cognitive tools that augment and extend the modeler's cognitive capacities and performance in molecular modeling tasks. This cognitive enhancement is obtained because of the way the modeler interacts with these models, the models' materiality contributing to the solving of the molecule's structure. Furthermore, I argue that these material models and their component parts were designed, built and used specifically to serve as cognitive facilitators and cognitive augmentations. Copyright © 2013 Elsevier Ltd. All rights reserved.

Plasmid Vectors and Molecular Building Blocks for the Development of Genetic Manipulation Tools for Trypanosoma cruzi

PubMed Central

Bouvier, León A.; Cámara, María de los Milagros; Canepa, Gaspar E.; Miranda, Mariana R.; Pereira, Claudio A.

2013-01-01

The post genomic era revealed the need for developing better performing, easier to use and more sophisticated genetic manipulation tools for the study of Trypanosoma cruzi, the etiological agent of Chagas disease. In this work a series of plasmids that allow genetic manipulation of this protozoan parasite were developed. First of all we focused on useful tools to establish selection strategies for different strains and which can be employed as expression vectors. On the other hand molecular building blocks in the form of diverse selectable markers, modifiable fluorescent protein and epitope-tag coding sequences were produced. Both types of modules were harboured in backbone molecules conceived to offer multiple construction and sub-cloning strategies. These can be used to confer new properties to already available genetic manipulation tools or as starting points for whole novel designs. The performance of each plasmid and building block was determined independently. For illustration purposes, some simple direct practical applications were conducted. PMID:24205392

Molecular genealogy tools for white-tailed deer with chronic wasting disease

PubMed Central

Ernest, Holly B.; Hoar, Bruce R.; Well, Jay A.; O’Rourke, Katherine I.

2010-01-01

Molecular genetic data provide powerful tools for genealogy reconstruction to reveal mechanisms underlying disease ecology. White-tailed deer (Odocoileus virginianus) congregate in matriarchal groups; kin-related close social spacing may be a factor in the spread of infectious diseases. Spread of chronic wasting disease (CWD), a prion disorder of deer and their cervid relatives, is presumed to be associated with direct contact between individuals and by exposure to shared food and water sources contaminated with prions shed by infected deer. Key aspects of disease ecology are yet unknown. DNA tools for pedigree reconstruction were developed to fill knowledge gaps in disease dynamics in prion-infected wild animals. Kinship indices using data from microsatellite loci and sequence haplotypes of mitochondrial DNA were employed to assemble genealogies. Molecular genealogy tools will be useful for landscape-level population genetic research and monitoring, in addition to epidemiologic studies examining transmission of CWD in captive and free-ranging cervids. PMID:20592847

Molecular tools for carotenogenesis analysis in the zygomycete Mucor circinelloides.

PubMed

Torres-Martínez, Santiago; Ruiz-Vázquez, Rosa M; Garre, Victoriano; López-García, Sergio; Navarro, Eusebio; Vila, Ana

2012-01-01

The carotene producer fungus Mucor circinelloides is the zygomycete more amenable to genetic manipulations by using molecular tools. Since the initial development of an effective procedure of genetic transformation, more than two decades ago, the availability of new molecular approaches such as gene replacement techniques and gene expression inactivation by RNA silencing, in addition to the sequencing of its genome, has made Mucor a valuable organism for the study of a number of processes. Here we describe in detail the main techniques and methods currently used to manipulate M. circinelloides, including transformation, gene replacement, gene silencing, RNAi, and immunoprecipitation.

Sig2BioPAX: Java tool for converting flat files to BioPAX Level 3 format.

PubMed

Webb, Ryan L; Ma'ayan, Avi

2011-03-21

The World Wide Web plays a critical role in enabling molecular, cell, systems and computational biologists to exchange, search, visualize, integrate, and analyze experimental data. Such efforts can be further enhanced through the development of semantic web concepts. The semantic web idea is to enable machines to understand data through the development of protocol free data exchange formats such as Resource Description Framework (RDF) and the Web Ontology Language (OWL). These standards provide formal descriptors of objects, object properties and their relationships within a specific knowledge domain. However, the overhead of converting datasets typically stored in data tables such as Excel, text or PDF into RDF or OWL formats is not trivial for non-specialists and as such produces a barrier to seamless data exchange between researchers, databases and analysis tools. This problem is particularly of importance in the field of network systems biology where biochemical interactions between genes and their protein products are abstracted to networks. For the purpose of converting biochemical interactions into the BioPAX format, which is the leading standard developed by the computational systems biology community, we developed an open-source command line tool that takes as input tabular data describing different types of molecular biochemical interactions. The tool converts such interactions into the BioPAX level 3 OWL format. We used the tool to convert several existing and new mammalian networks of protein interactions, signalling pathways, and transcriptional regulatory networks into BioPAX. Some of these networks were deposited into PathwayCommons, a repository for consolidating and organizing biochemical networks. The software tool Sig2BioPAX is a resource that enables experimental and computational systems biologists to contribute their identified networks and pathways of molecular interactions for integration and reuse with the rest of the research community.

Genomic tools for developing markers for postharvest disease resistance in Rosaceae fruit crops

USDA-ARS?s Scientific Manuscript database

A wealth of new plant genomic information and molecular tools have been developed over the past ten years and now the challenge is to learn how to apply this information to address critical production problems, such as disease resistance and abiotic stress tolerance. Malus sieversii, an apple speci...

Computational Molecular Modeling for Evaluating the Toxicity of Environmental Chemicals: Prioritizing Bioassay Requirements

EPA Science Inventory

This commentary provides an overview of the challenges that arise from applying molecular modeling tools developed and commonly used for pharmaceutical discovery to the problem of predicting the potential toxicities of environmental chemicals.

Molecular and Cellular Quantitative Microscopy: theoretical investigations, technological developments and applications to neurobiology

NASA Astrophysics Data System (ADS)

Esposito, Alessandro

2006-05-01

This PhD project aims at the development and evaluation of microscopy techniques for the quantitative detection of molecular interactions and cellular features. The primarily investigated techniques are Fαrster Resonance Energy Transfer imaging and Fluorescence Lifetime Imaging Microscopy. These techniques have the capability to quantitatively probe the biochemical environment of fluorophores. An automated microscope capable of unsupervised operation has been developed that enables the investigation of molecular and cellular properties at high throughput levels and the analysis of cellular heterogeneity. State-of-the-art Förster Resonance Energy Transfer imaging, Fluorescence Lifetime Imaging Microscopy, Confocal Laser Scanning Microscopy and the newly developed tools have been combined with cellular and molecular biology techniques for the investigation of protein-protein interactions, oligomerization and post-translational modifications of α-Synuclein and Tau, two proteins involved in Parkinson’s and Alzheimer’s disease, respectively. The high inter-disciplinarity of this project required the merging of the expertise of both the Molecular Biophysics Group at the Debye Institute - Utrecht University and the Cell Biophysics Group at the European Neuroscience Institute - Gαttingen University. This project was conducted also with the support and the collaboration of the Center for the Molecular Physiology of the Brain (Göttingen), particularly with the groups associated with the Molecular Quantitative Microscopy and Parkinson’s Disease and Aggregopathies areas. This work demonstrates that molecular and cellular quantitative microscopy can be used in combination with high-throughput screening as a powerful tool for the investigation of the molecular mechanisms of complex biological phenomena like those occurring in neurodegenerative diseases.

Emancipating Chlamydia: Advances in the Genetic Manipulation of a Recalcitrant Intracellular Pathogen.

PubMed

Bastidas, Robert J; Valdivia, Raphael H

2016-06-01

Chlamydia species infect millions of individuals worldwide and are important etiological agents of sexually transmitted disease, infertility, and blinding trachoma. Historically, the genetic intractability of this intracellular pathogen has hindered the molecular dissection of virulence factors contributing to its pathogenesis. The obligate intracellular life cycle of Chlamydia and restrictions on the use of antibiotics as selectable markers have impeded the development of molecular tools to genetically manipulate these pathogens. However, recent developments in the field have resulted in significant gains in our ability to alter the genome of Chlamydia, which will expedite the elucidation of virulence mechanisms. In this review, we discuss the challenges affecting the development of molecular genetic tools for Chlamydia and the work that laid the foundation for recent advancements in the genetic analysis of this recalcitrant pathogen. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

In Silico PCR Tools for a Fast Primer, Probe, and Advanced Searching.

PubMed

Kalendar, Ruslan; Muterko, Alexandr; Shamekova, Malika; Zhambakin, Kabyl

2017-01-01

The polymerase chain reaction (PCR) is fundamental to molecular biology and is the most important practical molecular technique for the research laboratory. The principle of this technique has been further used and applied in plenty of other simple or complex nucleic acid amplification technologies (NAAT). In parallel to laboratory "wet bench" experiments for nucleic acid amplification technologies, in silico or virtual (bioinformatics) approaches have been developed, among which in silico PCR analysis. In silico NAAT analysis is a useful and efficient complementary method to ensure the specificity of primers or probes for an extensive range of PCR applications from homology gene discovery, molecular diagnosis, DNA fingerprinting, and repeat searching. Predicting sensitivity and specificity of primers and probes requires a search to determine whether they match a database with an optimal number of mismatches, similarity, and stability. In the development of in silico bioinformatics tools for nucleic acid amplification technologies, the prospects for the development of new NAAT or similar approaches should be taken into account, including forward-looking and comprehensive analysis that is not limited to only one PCR technique variant. The software FastPCR and the online Java web tool are integrated tools for in silico PCR of linear and circular DNA, multiple primer or probe searches in large or small databases and for advanced search. These tools are suitable for processing of batch files that are essential for automation when working with large amounts of data. The FastPCR software is available for download at http://primerdigital.com/fastpcr.html and the online Java version at http://primerdigital.com/tools/pcr.html .

New tools for the analysis of glial cell biology in Drosophila.

PubMed

Awasaki, Takeshi; Lee, Tzumin

2011-09-01

Because of its genetic, molecular, and behavioral tractability, Drosophila has emerged as a powerful model system for studying molecular and cellular mechanisms underlying the development and function of nervous systems. The Drosophila nervous system has fewer neurons and exhibits a lower glia:neuron ratio than is seen in vertebrate nervous systems. Despite the simplicity of the Drosophila nervous system, glial organization in flies is as sophisticated as it is in vertebrates. Furthermore, fly glial cells play vital roles in neural development and behavior. In addition, powerful genetic tools are continuously being created to explore cell function in vivo. In taking advantage of these features, the fly nervous system serves as an excellent model system to study general aspects of glial cell development and function in vivo. In this article, we review and discuss advanced genetic tools that are potentially useful for understanding glial cell biology in Drosophila. Copyright © 2011 Wiley-Liss, Inc.

Molecular detection technologies for arboviruses

USDA-ARS?s Scientific Manuscript database

Arthropod-borne animal viruses (arboviruses) cause significant livestock and economic losses to world agriculture. This paper discusses the current and potential impact of these viruses, as well as the current and developing molecular diagnostic tools for these emerging and re-emerging insect transm...

A sequencing-based linkage map of cucumber

USDA-ARS?s Scientific Manuscript database

Genetic maps are important tools for molecular breeding, gene cloning, and study of meiotic recombination. In cucumber (Cucumis sativus L.), the marker density, resolution and genome coverage of previously developed genetic maps using PCR-based molecular markers are relatively low. In this study we ...

Development of microsatellite markers in Parthenium ssp.

USDA-ARS?s Scientific Manuscript database

Molecular markers provide the most efficient means to study genetic diversity within and among species of a particular genus. In addition, molecular markers can facilitate breeding efforts by providing tools necessary to reduce the time required to obtain recombinant genotypes with improved agricu...

pyPcazip: A PCA-based toolkit for compression and analysis of molecular simulation data

NASA Astrophysics Data System (ADS)

Shkurti, Ardita; Goni, Ramon; Andrio, Pau; Breitmoser, Elena; Bethune, Iain; Orozco, Modesto; Laughton, Charles A.

The biomolecular simulation community is currently in need of novel and optimised software tools that can analyse and process, in reasonable timescales, the large generated amounts of molecular simulation data. In light of this, we have developed and present here pyPcazip: a suite of software tools for compression and analysis of molecular dynamics (MD) simulation data. The software is compatible with trajectory file formats generated by most contemporary MD engines such as AMBER, CHARMM, GROMACS and NAMD, and is MPI parallelised to permit the efficient processing of very large datasets. pyPcazip is a Unix based open-source software (BSD licenced) written in Python.

Molecular plant breeding: methodology and achievements.

PubMed

Varshney, Rajeev K; Hoisington, Dave A; Nayak, Spurthi N; Graner, Andreas

2009-01-01

The progress made in DNA marker technology has been remarkable and exciting in recent years. DNA markers have proved valuable tools in various analyses in plant breeding, for example, early generation selection, enrichment of complex F(1)s, choice of donor parent in backcrossing, recovery of recurrent parent genotype in backcrossing, linkage block analysis and selection. Other main areas of applications of molecular markers in plant breeding include germplasm characterization/fingerprinting, determining seed purity, systematic sampling of germplasm, and phylogenetic analysis. Molecular markers, thus, have proved powerful tools in replacing the bioassays and there are now many examples available to show the efficacy of such markers. We have illustrated some basic concepts and methodology of applying molecular markers for enhancing the selection efficiency in plant breeding. Some successful examples of product developments of molecular breeding have also been presented.

Molecular genetics at the Fort Collins Science Center

USGS Publications Warehouse

Oyler-McCance, S.J.; Stevens, P.D.

2011-01-01

The Fort Collins Science Center operates a molecular genetic and systematics research facility (FORT Molecular Ecology Laboratory) that uses molecular genetic tools to provide genetic information needed to inform natural resource management decisions. For many wildlife species, the data generated have become increasingly important in the development of their long-term management strategies, leading to a better understanding of species diversity, population dynamics and ecology, and future conservation and management needs. The Molecular Ecology Lab serves Federal research and resource management agencies by developing scientifically rigorous research programs using nuclear, mitochondrial and chloroplast DNA to help address many of today's conservation biology and natural resource management issues.

Molecular markers in bladder cancer: Novel research frontiers.

PubMed

Sanguedolce, Francesca; Cormio, Antonella; Bufo, Pantaleo; Carrieri, Giuseppe; Cormio, Luigi

2015-01-01

Bladder cancer (BC) is a heterogeneous disease encompassing distinct biologic features that lead to extremely different clinical behaviors. In the last 20 years, great efforts have been made to predict disease outcome and response to treatment by developing risk assessment calculators based on multiple standard clinical-pathological factors, as well as by testing several molecular markers. Unfortunately, risk assessment calculators alone fail to accurately assess a single patient's prognosis and response to different treatment options. Several molecular markers easily assessable by routine immunohistochemical techniques hold promise for becoming widely available and cost-effective tools for a more reliable risk assessment, but none have yet entered routine clinical practice. Current research is therefore moving towards (i) identifying novel molecular markers; (ii) testing old and new markers in homogeneous patients' populations receiving homogeneous treatments; (iii) generating a multimarker panel that could be easily, and thus routinely, used in clinical practice; (iv) developing novel risk assessment tools, possibly combining standard clinical-pathological factors with molecular markers. This review analyses the emerging body of literature concerning novel biomarkers, ranging from genetic changes to altered expression of a huge variety of molecules, potentially involved in BC outcome and response to treatment. Findings suggest that some of these indicators, such as serum circulating tumor cells and tissue mitochondrial DNA, seem to be easily assessable and provide reliable information. Other markers, such as the phosphoinositide-3-kinase (PI3K)/AKT (serine-threonine kinase)/mTOR (mammalian target of rapamycin) pathway and epigenetic changes in DNA methylation seem to not only have prognostic/predictive value but also, most importantly, represent valuable therapeutic targets. Finally, there is increasing evidence that the development of novel risk assessment tools combining standard clinical-pathological factors with molecular markers represents a major quest in managing this poorly predictable disease.

Molecular dynamics modeling of bonding two materials by atomic scale friction stir welding

NASA Astrophysics Data System (ADS)

Konovalenko S., Iv.; Konovalenko, Ig. S.; Psakhie, S. G.

2017-12-01

Molecular dynamics model of atomic scale friction stir welding has been developed. Formation of a butt joint between two crystallites was modeled by means of rotating rigid conical tool traveling along the butt joint line. The formed joint had an intermixed atomic structure composed of atoms initially belonged to the opposite mated piece of metal. Heat removal was modeled by adding the extra viscous force to peripheral atomic layers. This technique provides the temperature control in the tool-affected zone during welding. Auxiliary vibration action was added to the rotating tool. The model provides the variation of the tool's angular velocity, amplitude, frequency and direction of the auxiliary vibration action to provide modeling different welding modes.

Development of microsatellites from Cornus mas L. (Cornaceae) and characterization of genetic diversity of cornelian cherries from China, central Europe, and the United States

USDA-ARS?s Scientific Manuscript database

Cornelian cherry (Cornus mas L.) is indigenous to central and southeastern Europe and is an ecologically and economically important shrub or small tree. The aim of this study was to develop molecular tools for assessing genetic diversity and provide unique molecular identification of C. mas cultivar...

Radiative transfer in molecular lines

NASA Astrophysics Data System (ADS)

Asensio Ramos, A.; Trujillo Bueno, J.; Cernicharo, J.

2001-07-01

The highly convergent iterative methods developed by Trujillo Bueno and Fabiani Bendicho (1995) for radiative transfer (RT) applications are generalized to spherical symmetry with velocity fields. These RT methods are based on Jacobi, Gauss-Seidel (GS), and SOR iteration and they form the basis of a new NLTE multilevel transfer code for atomic and molecular lines. The benchmark tests carried out so far are presented and discussed. The main aim is to develop a number of powerful RT tools for the theoretical interpretation of molecular spectra.

Solvation Structure and Thermodynamic Mapping (SSTMap): An Open-Source, Flexible Package for the Analysis of Water in Molecular Dynamics Trajectories.

PubMed

Haider, Kamran; Cruz, Anthony; Ramsey, Steven; Gilson, Michael K; Kurtzman, Tom

2018-01-09

We have developed SSTMap, a software package for mapping structural and thermodynamic water properties in molecular dynamics trajectories. The package introduces automated analysis and mapping of local measures of frustration and enhancement of water structure. The thermodynamic calculations are based on Inhomogeneous Fluid Solvation Theory (IST), which is implemented using both site-based and grid-based approaches. The package also extends the applicability of solvation analysis calculations to multiple molecular dynamics (MD) simulation programs by using existing cross-platform tools for parsing MD parameter and trajectory files. SSTMap is implemented in Python and contains both command-line tools and a Python module to facilitate flexibility in setting up calculations and for automated generation of large data sets involving analysis of multiple solutes. Output is generated in formats compatible with popular Python data science packages. This tool will be used by the molecular modeling community for computational analysis of water in problems of biophysical interest such as ligand binding and protein function.

Developing Computational Tools for Application of Toxicogenomics to Environmental Regulations and Risk Assessment

EPA Science Inventory

Toxicogenomics is the study of changes in gene expression, protein, and metabolite profiles within cells and tissues, complementary to more traditional toxicological methods. Genomics tools provide detailed molecular data about the underlying biochemical mechanisms of toxicity, a...

Microbe-ID: An open source toolbox for microbial genotyping and species identification

USDA-ARS?s Scientific Manuscript database

Development of tools to identify species, genotypes, or novel strains of invasive organisms is critical for monitoring emergence and implementing rapid response measures. Molecular markers, although critical to identifying species or genotypes, require bioinformatic tools for analysis. However, user...

Myotonic Dystrophies: State of the Art of New Therapeutic Developments for the CNS

PubMed Central

Gourdon, Genevieve; Meola, Giovanni

2017-01-01

Myotonic dystrophies are multisystemic diseases characterized not only by muscle and heart dysfunction but also by CNS alteration. They are now recognized as brain diseases affecting newborns and children for myotonic dystrophy type 1 and adults for both myotonic dystrophy type 1 and type 2. In the past two decades, much progress has been made in understanding the mechanisms underlying the DM symptoms allowing development of new molecular therapeutic tools with the ultimate aim of curing the disease. This review describes the state of the art for the characterization of CNS related symptoms, the development of molecular strategies to target the CNS as well as the available tools for screening and testing new possible treatments. PMID:28473756

Molecular Imaging of Vulnerable Atherosclerotic Plaques in Animal Models

PubMed Central

Gargiulo, Sara; Gramanzini, Matteo; Mancini, Marcello

2016-01-01

Atherosclerosis is characterized by intimal plaques of the arterial vessels that develop slowly and, in some cases, may undergo spontaneous rupture with subsequent heart attack or stroke. Currently, noninvasive diagnostic tools are inadequate to screen atherosclerotic lesions at high risk of acute complications. Therefore, the attention of the scientific community has been focused on the use of molecular imaging for identifying vulnerable plaques. Genetically engineered murine models such as ApoE−/− and ApoE−/−Fbn1C1039G+/− mice have been shown to be useful for testing new probes targeting biomarkers of relevant molecular processes for the characterization of vulnerable plaques, such as vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, intercellular adhesion molecule (ICAM)-1, P-selectin, and integrins, and for the potential development of translational tools to identify high-risk patients who could benefit from early therapeutic interventions. This review summarizes the main animal models of vulnerable plaques, with an emphasis on genetically altered mice, and the state-of-the-art preclinical molecular imaging strategies. PMID:27618031

Biology Needs Evolutionary Software Tools: Let’s Build Them Right

PubMed Central

Team, Galaxy; Goecks, Jeremy; Taylor, James

2018-01-01

Abstract Research in population genetics and evolutionary biology has always provided a computational backbone for life sciences as a whole. Today evolutionary and population biology reasoning are essential for interpretation of large complex datasets that are characteristic of all domains of today’s life sciences ranging from cancer biology to microbial ecology. This situation makes algorithms and software tools developed by our community more important than ever before. This means that we, developers of software tool for molecular evolutionary analyses, now have a shared responsibility to make these tools accessible using modern technological developments as well as provide adequate documentation and training. PMID:29688462

Genetic, genomic, and molecular tools for studying the protoploid yeast, L. waltii.

PubMed

Di Rienzi, Sara C; Lindstrom, Kimberly C; Lancaster, Ragina; Rolczynski, Lisa; Raghuraman, M K; Brewer, Bonita J

2011-02-01

Sequencing of the yeast Kluyveromyces waltii (recently renamed Lachancea waltii) provided evidence of a whole genome duplication event in the lineage leading to the well-studied Saccharomyces cerevisiae. While comparative genomic analyses of these yeasts have proven to be extremely instructive in modeling the loss or maintenance of gene duplicates, experimental tests of the ramifications following such genome alterations remain difficult. To transform L. waltii from an organism of the computational comparative genomic literature into an organism of the functional comparative genomic literature, we have developed genetic, molecular and genomic tools for working with L. waltii. In particular, we have characterized basic properties of L. waltii (growth, ploidy, molecular karyotype, mating type and the sexual cycle), developed transformation, cell cycle arrest and synchronization protocols, and have created centromeric and non-centromeric vectors as well as a genome browser for L. waltii. We hope that these tools will be used by the community to follow up on the ideas generated by sequence data and lead to a greater understanding of eukaryotic biology and genome evolution. 2010 John Wiley & Sons, Ltd.

Genetic, genomic, and molecular tools for studying the protoploid yeast, L. waltii

PubMed Central

Di Rienzi, Sara C.; Lindstrom, Kimberly C.; Lancaster, Ragina; Rolczynski, Lisa; Raghuraman, M. K.; Brewer, Bonita J.

2011-01-01

Sequencing of the yeast Kluyveromyces waltii (recently renamed Lachancea waltii) provided evidence of a whole genome duplication event in the lineage leading to the well-studied Saccharomyces cerevisiae. While comparative genomic analyses of these yeasts have proven to be extremely instructive in modeling the loss or maintenance of gene duplicates, experimental tests of the ramifications following such genome alterations remain difficult. To transform L. waltii from an organism of the computational comparative genomic literature into an organism of the functional comparative genomic literature, we have developed genetic, molecular and genomic tools for working with L. waltii. In particular, we have characterized basic properties of L. waltii (growth, ploidy, molecular karyotype, mating type and the sexual cycle), developed transformation, cell cycle arrest and synchronization protocols, and have created centromeric and non-centromeric vectors as well as a genome browser for L. waltii. We hope that these tools will be used by the community to follow up on the ideas generated by sequence data and lead to a greater understanding of eukaryotic biology and genome evolution. PMID:21246627

Refining prognosis in lung cancer: A report on the quality and relevance of clinical prognostic tools

PubMed Central

Mahar, Alyson L.; Compton, Carolyn; McShane, Lisa M.; Halabi, Susan; Asamura, Hisao; Rami-Porta, Ramon; Groome, Patti A.

2015-01-01

Introduction Accurate, individualized prognostication for lung cancer patients requires the integration of standard patient and pathologic factors, biologic, genetic, and other molecular characteristics of the tumor. Clinical prognostic tools aim to aggregate information on an individual patient to predict disease outcomes such as overall survival, but little is known about their clinical utility and accuracy in lung cancer. Methods A systematic search of the scientific literature for clinical prognostic tools in lung cancer published Jan 1, 1996-Jan 27, 2015 was performed. In addition, web-based resources were searched. A priori criteria determined by the Molecular Modellers Working Group of the American Joint Committee on Cancer were used to investigate the quality and usefulness of tools. Criteria included clinical presentation, model development approaches, validation strategies, and performance metrics. Results Thirty-two prognostic tools were identified. Patients with metastases were the most frequently considered population in non-small cell lung cancer. All tools for small cell lung cancer covered that entire patient population. Included prognostic factors varied considerably across tools. Internal validity was not formally evaluated for most tools and only eleven were evaluated for external validity. Two key considerations were highlighted for tool development: identification of an explicit purpose related to a relevant clinical population and clear decision-points, and prioritized inclusion of established prognostic factors over emerging factors. Conclusions Prognostic tools will contribute more meaningfully to the practice of personalized medicine if better study design and analysis approaches are used in their development and validation. PMID:26313682

A new molecular diagnostic tool for quantitatively detecting and genotyping “Candidatus Liberibacter species”

USDA-ARS?s Scientific Manuscript database

A new molecular diagnostic method was developed for quantitative detection of “Candidatus Liberibacter” species associated with citrus Huanglongbing (“Ca. Liberibacter asiaticus”, “Ca. Liberibacter africanus” and “Ca. Liberibacter americanus”) and potato zebra chip disorder (“Ca. Liberibacter solana...

[Relevance of big data for molecular diagnostics].

PubMed

Bonin-Andresen, M; Smiljanovic, B; Stuhlmüller, B; Sörensen, T; Grützkau, A; Häupl, T

2018-04-01

Big data analysis raises the expectation that computerized algorithms may extract new knowledge from otherwise unmanageable vast data sets. What are the algorithms behind the big data discussion? In principle, high throughput technologies in molecular research already introduced big data and the development and application of analysis tools into the field of rheumatology some 15 years ago. This includes especially omics technologies, such as genomics, transcriptomics and cytomics. Some basic methods of data analysis are provided along with the technology, however, functional analysis and interpretation requires adaptation of existing or development of new software tools. For these steps, structuring and evaluating according to the biological context is extremely important and not only a mathematical problem. This aspect has to be considered much more for molecular big data than for those analyzed in health economy or epidemiology. Molecular data are structured in a first order determined by the applied technology and present quantitative characteristics that follow the principles of their biological nature. These biological dependencies have to be integrated into software solutions, which may require networks of molecular big data of the same or even different technologies in order to achieve cross-technology confirmation. More and more extensive recording of molecular processes also in individual patients are generating personal big data and require new strategies for management in order to develop data-driven individualized interpretation concepts. With this perspective in mind, translation of information derived from molecular big data will also require new specifications for education and professional competence.

Implementing a modeling software for animated protein-complex interactions using a physics simulation library.

PubMed

Ueno, Yutaka; Ito, Shuntaro; Konagaya, Akihiko

2014-12-01

To better understand the behaviors and structural dynamics of proteins within a cell, novel software tools are being developed that can create molecular animations based on the findings of structural biology. This study proposes our method developed based on our prototypes to detect collisions and examine the soft-body dynamics of molecular models. The code was implemented with a software development toolkit for rigid-body dynamics simulation and a three-dimensional graphics library. The essential functions of the target software system included the basic molecular modeling environment, collision detection in the molecular models, and physical simulations of the movement of the model. Taking advantage of recent software technologies such as physics simulation modules and interpreted scripting language, the functions required for accurate and meaningful molecular animation were implemented efficiently.

TranscriptomeBrowser 3.0: introducing a new compendium of molecular interactions and a new visualization tool for the study of gene regulatory networks.

PubMed

Lepoivre, Cyrille; Bergon, Aurélie; Lopez, Fabrice; Perumal, Narayanan B; Nguyen, Catherine; Imbert, Jean; Puthier, Denis

2012-01-31

Deciphering gene regulatory networks by in silico approaches is a crucial step in the study of the molecular perturbations that occur in diseases. The development of regulatory maps is a tedious process requiring the comprehensive integration of various evidences scattered over biological databases. Thus, the research community would greatly benefit from having a unified database storing known and predicted molecular interactions. Furthermore, given the intrinsic complexity of the data, the development of new tools offering integrated and meaningful visualizations of molecular interactions is necessary to help users drawing new hypotheses without being overwhelmed by the density of the subsequent graph. We extend the previously developed TranscriptomeBrowser database with a set of tables containing 1,594,978 human and mouse molecular interactions. The database includes: (i) predicted regulatory interactions (computed by scanning vertebrate alignments with a set of 1,213 position weight matrices), (ii) potential regulatory interactions inferred from systematic analysis of ChIP-seq experiments, (iii) regulatory interactions curated from the literature, (iv) predicted post-transcriptional regulation by micro-RNA, (v) protein kinase-substrate interactions and (vi) physical protein-protein interactions. In order to easily retrieve and efficiently analyze these interactions, we developed In-teractomeBrowser, a graph-based knowledge browser that comes as a plug-in for Transcriptome-Browser. The first objective of InteractomeBrowser is to provide a user-friendly tool to get new insight into any gene list by providing a context-specific display of putative regulatory and physical interactions. To achieve this, InteractomeBrowser relies on a "cell compartments-based layout" that makes use of a subset of the Gene Ontology to map gene products onto relevant cell compartments. This layout is particularly powerful for visual integration of heterogeneous biological information and is a productive avenue in generating new hypotheses. The second objective of InteractomeBrowser is to fill the gap between interaction databases and dynamic modeling. It is thus compatible with the network analysis software Cytoscape and with the Gene Interaction Network simulation software (GINsim). We provide examples underlying the benefits of this visualization tool for large gene set analysis related to thymocyte differentiation. The InteractomeBrowser plugin is a powerful tool to get quick access to a knowledge database that includes both predicted and validated molecular interactions. InteractomeBrowser is available through the TranscriptomeBrowser framework and can be found at: http://tagc.univ-mrs.fr/tbrowser/. Our database is updated on a regular basis.

Genetics of behavior in the silver fox.

PubMed

Kukekova, Anna V; Temnykh, Svetlana V; Johnson, Jennifer L; Trut, Lyudmila N; Acland, Gregory M

2012-02-01

The silver fox provides a rich resource for investigating the genetics of behavior, with strains developed by intensely selective breeding that display markedly different behavioral phenotypes. Until recently, however, the tools for conducting molecular genetic investigations in this species were very limited. In this review, the history of development of this resource and the tools to exploit it are described. Although the focus is on the genetics of domestication in the silver fox, there is a broader context. In particular, one expectation of the silver fox research is that it will be synergistic with studies in other species, including humans, to yield a more comprehensive understanding of the molecular mechanisms and evolution of a wider range of social cognitive behaviors.

Competency-Based Education for the Molecular Genetic Pathology Fellow

PubMed Central

Talbert, Michael L.; Dunn, S. Terence; Hunt, Jennifer; Hillyard, David R.; Mirza, Imran; Nowak, Jan A.; Van Deerlin, Vivianna; Vnencak-Jones, Cindy L.

2009-01-01

The following report represents guidelines for competency-based fellowship training in Molecular Genetic Pathology (MGP) developed by the Association for Molecular Pathology Training and Education Committee and Directors of MGP Programs in the United States. The goals of the effort were to describe each of the Accreditation Council for Graduate Medical Education competencies as they apply to MGP fellowship training, provide a summary of goals and objectives, and recommend assessment tools. These guidelines are particularly pertinent to MGP training, which is a relatively new specialty that operates within a rapidly changing scientific and technological arena. It is hoped that this document will provide additional material for directors of existing MGP programs to consider for improvement of program objectives and enhancement of evaluation tools already in place. In addition, the guidelines should provide a valuable framework for the development of new MGP programs. PMID:19797613

Open source bioimage informatics for cell biology.

PubMed

Swedlow, Jason R; Eliceiri, Kevin W

2009-11-01

Significant technical advances in imaging, molecular biology and genomics have fueled a revolution in cell biology, in that the molecular and structural processes of the cell are now visualized and measured routinely. Driving much of this recent development has been the advent of computational tools for the acquisition, visualization, analysis and dissemination of these datasets. These tools collectively make up a new subfield of computational biology called bioimage informatics, which is facilitated by open source approaches. We discuss why open source tools for image informatics in cell biology are needed, some of the key general attributes of what make an open source imaging application successful, and point to opportunities for further operability that should greatly accelerate future cell biology discovery.

Molecular diagnostics for Chagas disease: up to date and novel methodologies.

PubMed

Alonso-Padilla, Julio; Gallego, Montserrat; Schijman, Alejandro G; Gascon, Joaquim

2017-07-01

Chagas disease is caused by the parasite Trypanosoma cruzi. It affects 7 million people, mainly in Latin America. Diagnosis is usually made serologically, but at some clinical scenarios serology cannot be used. Then, molecular detection is required for early detection of congenital transmission, treatment response follow up, and diagnosis of immune-suppression reactivation. However, present tests are technically demanding and require well-equipped laboratories which make them unfeasible in low-resources endemic regions. Areas covered: Available molecular tools for detection of T. cruzi DNA, paying particular attention to quantitative PCR protocols, and to the latest developments of user-friendly molecular diagnostic methodologies. Expert commentary: In the absence of appropriate biomarkers, molecular diagnosis is the only option for the assessment of treatment response. Besides, it is very useful for the early detection of acute infections, like congenital cases. Since current Chagas disease molecular tests are restricted to referential labs, research efforts must focus in the implementation of easy-to-use diagnostic tools in order to overcome the access to diagnosis gap.

Systems biology for molecular life sciences and its impact in biomedicine.

PubMed

Medina, Miguel Ángel

2013-03-01

Modern systems biology is already contributing to a radical transformation of molecular life sciences and biomedicine, and it is expected to have a real impact in the clinical setting in the next years. In this review, the emergence of systems biology is contextualized with a historic overview, and its present state is depicted. The present and expected future contribution of systems biology to the development of molecular medicine is underscored. Concerning the present situation, this review includes a reflection on the "inflation" of biological data and the urgent need for tools and procedures to make hidden information emerge. Descriptions of the impact of networks and models and the available resources and tools for applying them in systems biology approaches to molecular medicine are provided as well. The actual current impact of systems biology in molecular medicine is illustrated, reviewing two cases, namely, those of systems pharmacology and cancer systems biology. Finally, some of the expected contributions of systems biology to the immediate future of molecular medicine are commented.

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.

Genome-Enabled Molecular Tools for Reductive Dehalogenation

DTIC Science & Technology

2011-11-01

Genome-Enabled Molecular Tools for Reductive Dehalogenation - A Shift in Paradigm for Bioremediation - Alfred M. Spormann Departments of Chemical...Genome-Enabled Molecular Tools for Reductive Dehalogenation 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d...Applications Technical Session No. 3D C-77 GENOME-ENABLED MOLECULAR TOOLS FOR REDUCTIVE DEHALOGENATION PROFESSOR ALFRED SPORMANN Stanford

Biotechnological Advancements and Begomovirus Management in Okra (Abelmoschus esculentus L.): Status and Perspectives

PubMed Central

Mishra, Gyan P.; Singh, Bijendra; Seth, Tania; Singh, Achuit K.; Halder, Jaydeep; Krishnan, Nagendran; Tiwari, Shailesh K.; Singh, Prabhakar M.

2017-01-01

Despite the importance of okra, as one of the important vegetable crop, very little attention has been paid to its genetic improvement using advanced biotechnological tools. The exploitation of marker assisted breeding in okra is often limited due to the availability of a few molecular markers, the absence of molecular genetic-map(s), and other molecular tools. Chromosome linkage-groups were not yet constructed for this crop and reports on marker development are very scanty and mostly hovering around cultivar characterization. Besides, very little progress has been observed for transgenic development. However, high throughput biotechnological tools like chromosome engineering, RNA interference (RNAi), marker-assisted recurrent selection (MARS), genome-wide selection (GWS), targeted gene replacement, next generation sequencing (NGS), and nanobiotechnology can provide a rapid way for okra improvement. Further, the etiology of many deadly viral diseases like the yellow vein mosaic virus (YVMV) and okra enation leaf curl virus (OELCV) in okra is broadly indistinct and has been shown to be caused by various begomovirus species. These diseases cause systemic infections and have a very effective mode of transmission; thus, preventing their spread has been very complicated. Biotechnological interventions have the potential to enhance okra production even under different viral-stress conditions. In this background, this review deals with the biotechnological advancements in okra per se along with the begomoviruses infecting okra, and special emphasis has been laid on the exploitation of advanced genomic tools for the development of resistant varieties. PMID:28367155

Characteristics and evolution of the ecosystem of software tools supporting research in molecular biology.

PubMed

Pazos, Florencio; Chagoyen, Monica

2018-01-16

Daily work in molecular biology presently depends on a large number of computational tools. An in-depth, large-scale study of that 'ecosystem' of Web tools, its characteristics, interconnectivity, patterns of usage/citation, temporal evolution and rate of decay is crucial for understanding the forces that shape it and for informing initiatives aimed at its funding, long-term maintenance and improvement. In particular, the long-term maintenance of these tools is compromised because of their specific development model. Hundreds of published studies become irreproducible de facto, as the software tools used to conduct them become unavailable. In this study, we present a large-scale survey of >5400 publications describing Web servers within the two main bibliographic resources for disseminating new software developments in molecular biology. For all these servers, we studied their citation patterns, the subjects they address, their citation networks and the temporal evolution of these factors. We also analysed how these factors affect the availability of these servers (whether they are alive). Our results show that this ecosystem of tools is highly interconnected and adapts to the 'trendy' subjects in every moment. The servers present characteristic temporal patterns of citation/usage, and there is a worrying rate of server 'death', which is influenced by factors such as the server popularity and the institutions that hosts it. These results can inform initiatives aimed at the long-term maintenance of these resources. © The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

TRAINING AND TECHNOLOGY TRANSFER OF ORD-DEVELOPED MOLECULAR BIOLOGY-BASED TOOLS: 1. ENDOCRINE DISRUPTING CHEMICAL FATHEAD MINNOW BIOASSAY; 2. MICROBIAL SOURCE TRACKING METHODS; 3. FIELD IDENTIFICATION OF GENETICALLY MODIFIED CROP PLANTS

EPA Science Inventory

Region 9 RSL and ORD/NERL scientists developed a course for the RSC (Regional Science Council)-sponsored training class on Molecular Biology Concepts. The training will take place as part of the technology transfer of a fish EDC (endocrine disrupting chemical) bioassay to the Reg...

Molecular brain imaging in the multimodality era

PubMed Central

Price, Julie C

2012-01-01

Multimodality molecular brain imaging encompasses in vivo visualization, evaluation, and measurement of cellular/molecular processes. Instrumentation and software developments over the past 30 years have fueled advancements in multimodality imaging platforms that enable acquisition of multiple complementary imaging outcomes by either combined sequential or simultaneous acquisition. This article provides a general overview of multimodality neuroimaging in the context of positron emission tomography as a molecular imaging tool and magnetic resonance imaging as a structural and functional imaging tool. Several image examples are provided and general challenges are discussed to exemplify complementary features of the modalities, as well as important strengths and weaknesses of combined assessments. Alzheimer's disease is highlighted, as this clinical area has been strongly impacted by multimodality neuroimaging findings that have improved understanding of the natural history of disease progression, early disease detection, and informed therapy evaluation. PMID:22434068

Online and Certifiable Spectroscopy Courses Using Information and Communication Tools. a Model for Classrooms and Beyond

NASA Astrophysics Data System (ADS)

Krishnan, Mangala Sunder

2015-06-01

Online education tools and flipped (reverse) class models for teaching and learning and pedagogic and andragogic approaches to self-learning have become quite mature in the last few years because of the revolution in video, interactive software and social learning tools. Open Educational resources of dependable quality and variety are also becoming available throughout the world making the current era truly a renaissance period for higher education using Internet. In my presentation, I shall highlight structured course content preparation online in several areas of spectroscopy and also the design and development of virtual lab tools and kits for studying optical spectroscopy. Both elementary and advanced courses on molecular spectroscopy are currently under development jointly with researchers in other institutions in India. I would like to explore participation from teachers throughout the world in the teaching-learning process using flipped class methods for topics such as experimental and theoretical microwave spectroscopy of semi-rigid and non-rigid molecules, molecular complexes and aggregates. In addition, courses in Raman, Infrared spectroscopy experimentation and advanced electronic spectroscopy courses are also envisaged for free, online access. The National Programme on Technology Enhanced Learning (NPTEL) and the National Mission on Education through Information and Communication Technology (NMEICT) are two large Government of India funded initiatives for producing certified and self-learning courses with financial support for moderated discussion forums. The learning tools and interactive presentations so developed can be used in classrooms throughout the world using flipped mode of teaching. They are very much sought after by learners and researchers who are in other areas of learning but want to contribute to research and development through inter-disciplinary learning. NPTEL is currently is experimenting with Massive Open Online Course (MOOC) strategy, but with proctored and certified examination processes for large numbers in some of the above courses. I would like to present a summary of developments in these areas to help focus classroom (online and offline) learning of Molecular spectroscopy.

Current applications of molecular imaging and luminescence-based techniques in traditional Chinese medicine.

PubMed

Li, Jinhui; Wan, Haitong; Zhang, Hong; Tian, Mei

2011-09-01

Traditional Chinese medicine (TCM), which is fundamentally different from Western medicine, has been widely investigated using various approaches. Cellular- or molecular-based imaging has been used to investigate and illuminate the various challenges identified and progress made using therapeutic methods in TCM. Insight into the processes of TCM at the cellular and molecular changes and the ability to image these processes will enhance our understanding of various diseases of TCM and will provide new tools to diagnose and treat patients. Various TCM therapies including herbs and formulations, acupuncture and moxibustion, massage, Gua Sha, and diet therapy have been analyzed using positron emission tomography, single photon emission computed tomography, functional magnetic resonance imaging and ultrasound and optical imaging. These imaging tools have kept pace with developments in molecular biology, nuclear medicine, and computer technology. We provide an overview of recent developments in demystifying ancient knowledge - like the power of energy flow and blood flow meridians, and serial naturopathies - which are essential to visually and vividly recognize the body using modern technology. In TCM, treatment can be individualized in a holistic or systematic view that is consistent with molecular imaging technologies. Future studies might include using molecular imaging in conjunction with TCM to easily diagnose or monitor patients naturally and noninvasively. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Role of Molecular Profiling in Soft Tissue Sarcoma.

PubMed

Lindsay, Timothy; Movva, Sujana

2018-05-01

Diagnosis and treatment of soft tissue sarcoma (STS) is a particularly daunting task, largely due to the profound heterogeneity that characterizes these malignancies. Molecular profiling has emerged as a useful tool to confirm histologic diagnoses and more accurately classify these malignancies. Recent large-scale, multiplatform analyses have begun the work of establishing a more complete understanding of molecular profiling in STS subtypes and to identify new molecular alterations that may guide the development of novel targeted therapies. This review provides a brief and general overview of the role that molecular profiling has in STS, highlighting select sarcoma subtypes that are notable for recent developments. The role of molecular profiling as it relates to diagnostic strategies is discussed, along with ways that molecular profiling may provide guidance for potential therapeutic interventions. Copyright © 2018 by the National Comprehensive Cancer Network.

The Development and Comparison of Molecular Dynamics Simulation and Monte Carlo Simulation

NASA Astrophysics Data System (ADS)

Chen, Jundong

2018-03-01

Molecular dynamics is an integrated technology that combines physics, mathematics and chemistry. Molecular dynamics method is a computer simulation experimental method, which is a powerful tool for studying condensed matter system. This technique not only can get the trajectory of the atom, but can also observe the microscopic details of the atomic motion. By studying the numerical integration algorithm in molecular dynamics simulation, we can not only analyze the microstructure, the motion of particles and the image of macroscopic relationship between them and the material, but can also study the relationship between the interaction and the macroscopic properties more conveniently. The Monte Carlo Simulation, similar to the molecular dynamics, is a tool for studying the micro-molecular and particle nature. In this paper, the theoretical background of computer numerical simulation is introduced, and the specific methods of numerical integration are summarized, including Verlet method, Leap-frog method and Velocity Verlet method. At the same time, the method and principle of Monte Carlo Simulation are introduced. Finally, similarities and differences of Monte Carlo Simulation and the molecular dynamics simulation are discussed.

Opportunities for CRISPR/Cas9 Gene Editing in Retinal Regeneration Research

PubMed Central

Campbell, Leah J.; Hyde, David R.

2017-01-01

While retinal degeneration and disease results in permanent damage and vision loss in humans, the severely damaged zebrafish retina has a high capacity to regenerate lost neurons and restore visual behaviors. Advancements in understanding the molecular and cellular basis of this regeneration response give hope that strategies and therapeutics may be developed to restore sight to blind and visually-impaired individuals. Our current understanding has been facilitated by the amenability of zebrafish to molecular tools, imaging techniques, and forward and reverse genetic approaches. Accordingly, the zebrafish research community has developed a diverse array of research tools for use in developing and adult animals, including toolkits for facilitating the generation of transgenic animals, systems for inducible, cell-specific transgene expression, and the creation of knockout alleles for nearly every protein coding gene. As CRISPR/Cas9 genome editing has begun to revolutionize molecular biology research, the zebrafish community has responded in stride by developing CRISPR/Cas9 techniques for the zebrafish as well as incorporating CRISPR/Cas9 into available toolsets. The application of CRISPR/Cas9 to retinal regeneration research will undoubtedly bring us closer to understanding the mechanisms underlying retinal repair and vision restoration in the zebrafish, as well as developing therapeutic approaches that will restore vision to blind and visually-impaired individuals. This review focuses on how CRISPR/Cas9 has been integrated into zebrafish research toolsets and how this new tool will revolutionize the field of retinal regeneration research. PMID:29218308

Role of Open Source Tools and Resources in Virtual Screening for Drug Discovery.

PubMed

Karthikeyan, Muthukumarasamy; Vyas, Renu

2015-01-01

Advancement in chemoinformatics research in parallel with availability of high performance computing platform has made handling of large scale multi-dimensional scientific data for high throughput drug discovery easier. In this study we have explored publicly available molecular databases with the help of open-source based integrated in-house molecular informatics tools for virtual screening. The virtual screening literature for past decade has been extensively investigated and thoroughly analyzed to reveal interesting patterns with respect to the drug, target, scaffold and disease space. The review also focuses on the integrated chemoinformatics tools that are capable of harvesting chemical data from textual literature information and transform them into truly computable chemical structures, identification of unique fragments and scaffolds from a class of compounds, automatic generation of focused virtual libraries, computation of molecular descriptors for structure-activity relationship studies, application of conventional filters used in lead discovery along with in-house developed exhaustive PTC (Pharmacophore, Toxicophores and Chemophores) filters and machine learning tools for the design of potential disease specific inhibitors. A case study on kinase inhibitors is provided as an example.

Molecular epidemiology of African sleeping sickness.

PubMed

Hide, G; Tait, A

2009-10-01

Human sleeping sickness in Africa, caused by Trypanosoma brucei spp. raises a number of questions. Despite the widespread distribution of the tsetse vectors and animal trypanosomiasis, human disease is only found in discrete foci which periodically give rise to epidemics followed by periods of endemicity A key to unravelling this puzzle is a detailed knowledge of the aetiological agents responsible for different patterns of disease--knowledge that is difficult to achieve using traditional microscopy. The science of molecular epidemiology has developed a range of tools which have enabled us to accurately identify taxonomic groups at all levels (species, subspecies, populations, strains and isolates). Using these tools, we can now investigate the genetic interactions within and between populations of Trypanosoma brucei and gain an understanding of the distinction between human- and nonhuman-infective subspecies. In this review, we discuss the development of these tools, their advantages and disadvantages and describe how they have been used to understand parasite genetic diversity, the origin of epidemics, the role of reservoir hosts and the population structure. Using the specific case of T.b. rhodesiense in Uganda, we illustrate how molecular epidemiology has enabled us to construct a more detailed understanding of the origins, generation and dynamics of sleeping sickness epidemics.

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

PubMed

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

2013-01-01

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

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.

Open source bioimage informatics for cell biology

PubMed Central

Swedlow, Jason R.; Eliceiri, Kevin W.

2009-01-01

Significant technical advances in imaging, molecular biology and genomics have fueled a revolution in cell biology, in that the molecular and structural processes of the cell are now visualized and measured routinely. Driving much of this recent development has been the advent of computational tools for the acquisition, visualization, analysis and dissemination of these datasets. These tools collectively make up a new subfield of computational biology called bioimage informatics, which is facilitated by open source approaches. We discuss why open source tools for image informatics in cell biology are needed, some of the key general attributes of what make an open source imaging application successful, and point to opportunities for further operability that should greatly accelerate future cell biology discovery. PMID:19833518

Recent progress and challenges in population genetics of polyploid organisms: an overview of current state-of-the-art molecular and statistical tools.

PubMed

Dufresne, France; Stift, Marc; Vergilino, Roland; Mable, Barbara K

2014-01-01

Despite the importance of polyploidy and the increasing availability of new genomic data, there remain important gaps in our knowledge of polyploid population genetics. These gaps arise from the complex nature of polyploid data (e.g. multiple alleles and loci, mixed inheritance patterns, association between ploidy and mating system variation). Furthermore, many of the standard tools for population genetics that have been developed for diploids are often not feasible for polyploids. This review aims to provide an overview of the state-of-the-art in polyploid population genetics and to identify the main areas where further development of molecular techniques and statistical theory is required. We review commonly used molecular tools (amplified fragment length polymorphism, microsatellites, Sanger sequencing, next-generation sequencing and derived technologies) and their challenges associated with their use in polyploid populations: that is, allele dosage determination, null alleles, difficulty of distinguishing orthologues from paralogues and copy number variation. In addition, we review the approaches that have been used for population genetic analysis in polyploids and their specific problems. These problems are in most cases directly associated with dosage uncertainty and the problem of inferring allele frequencies and assumptions regarding inheritance. This leads us to conclude that for advancing the field of polyploid population genetics, most priority should be given to development of new molecular approaches that allow efficient dosage determination, and to further development of analytical approaches to circumvent dosage uncertainty and to accommodate 'flexible' modes of inheritance. In addition, there is a need for more simulation-based studies that test what kinds of biases could result from both existing and novel approaches. © 2013 John Wiley & Sons Ltd.

Software Tools | Office of Cancer Clinical Proteomics Research

Cancer.gov

The CPTAC program develops new approaches to elucidate aspects of the molecular complexity of cancer made from large-scale proteogenomic datasets, and advance them toward precision medicine.  Part of the CPTAC mission is to make data and tools available and accessible to the greater research community to accelerate the discovery process.

Do online prognostication tools represent a valid alternative to genomic profiling in the context of adjuvant treatment of early breast cancer? A systematic review of the literature.

PubMed

El Hage Chehade, Hiba; Wazir, Umar; Mokbel, Kinan; Kasem, Abdul; Mokbel, Kefah

2018-01-01

Decision-making regarding adjuvant chemotherapy has been based on clinical and pathological features. However, such decisions are seldom consistent. Web-based predictive models have been developed using data from cancer registries to help determine the need for adjuvant therapy. More recently, with the recognition of the heterogenous nature of breast cancer, genomic assays have been developed to aid in the therapeutic decision-making. We have carried out a comprehensive literature review regarding online prognostication tools and genomic assays to assess whether online tools could be used as valid alternatives to genomic profiling in decision-making regarding adjuvant therapy in early breast cancer. Breast cancer has been recently recognized as a heterogenous disease based on variations in molecular characteristics. Online tools are valuable in guiding adjuvant treatment, especially in resource constrained countries. However, in the era of personalized therapy, molecular profiling appears to be superior in predicting clinical outcome and guiding therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

Value and Methods for Molecular Subtyping of Bacteria

NASA Astrophysics Data System (ADS)

Moorman, Mark; Pruett, Payton; Weidman, Martin

Tracking sources of microbial contaminants has been a concern since the early days of commercial food processing; however, recent advances in the development of molecular subtyping methods have provided tools that allow more rapid and highly accurate determinations of these sources. Only individuals with an understanding of the molecular subtyping methods, and the epidemiological techniques used, can evaluate the reliability of a link between a food-manufacturing plant, a food, and a foodborne disease outbreak.

Computational assignment of redox states to Coulomb blockade diamonds.

PubMed

Olsen, Stine T; Arcisauskaite, Vaida; Hansen, Thorsten; Kongsted, Jacob; Mikkelsen, Kurt V

2014-09-07

With the advent of molecular transistors, electrochemistry can now be studied at the single-molecule level. Experimentally, the redox chemistry of the molecule manifests itself as features in the observed Coulomb blockade diamonds. We present a simple theoretical method for explicit construction of the Coulomb blockade diamonds of a molecule. A combined quantum mechanical/molecular mechanical method is invoked to calculate redox energies and polarizabilities of the molecules, including the screening effect of the metal leads. This direct approach circumvents the need for explicit modelling of the gate electrode. From the calculated parameters the Coulomb blockade diamonds are constructed using simple theory. We offer a theoretical tool for assignment of Coulomb blockade diamonds to specific redox states in particular, and a study of chemical details in the diamonds in general. With the ongoing experimental developments in molecular transistor experiments, our tool could find use in molecular electronics, electrochemistry, and electrocatalysis.

MOLECULAR GENETIC TOOLS FOR ASSESSING THE STATUS AND VULNERABILITY OF AQUATIC RESOURCES

EPA Science Inventory

Development of ecological indicators that efficiently capture the present condition and project future vulnerabilities of biological resources is critical to sound environmental management. For this reason, the ORD's Ecological Research Program is developing genetic methodologies...

NEW FRONTIER IN UNDERSTANDING THE MECHANISMS OF DEVELOPMENTAL ABNORMALITIES

EPA Science Inventory

Recent advancements in molecular developmental biology afford an opportunity to apply newly developed tools for understanding the mechanisms of both normal and abnormal development. lthough a number of agents have been identified as causing developmental abnormalities, knowledge ...

Recent Developments in Molecular Brain Imaging of Neuropsychiatric Disorders.

PubMed

Slifstein, Mark; Abi-Dargham, Anissa

2017-01-01

Molecular imaging with PET or SPECT has been an important research tool in psychiatry for as long as these modalities have been available. Here, we discuss two areas of neuroimaging relevant to current psychiatry research. The first is the use of imaging to study neurotransmission. We discuss the use of pharmacologic probes to induce changes in levels of neurotransmitters that can be inferred through their effects on outcome measures of imaging experiments, from their historical origins focusing on dopamine transmission through recent developments involving serotonin, GABA, and glutamate. Next, we examine imaging of neuroinflammation in the context of psychiatry. Imaging markers of neuroinflammation have been studied extensively in other areas of brain research, but they have more recently attracted interest in psychiatry research, based on accumulating evidence that there may be an inflammatory component to some psychiatric conditions. Furthermore, new probes are under development that would allow unprecedented insights into cellular processes. In summary, molecular imaging would continue to offer great potential as a unique tool to further our understanding of brain function in health and disease. Copyright © 2017 Elsevier Inc. All rights reserved.

The Use of the Free, Open-Source Program Jmol To Generate an Interactive Web Site To Teach Molecular Symmetry

NASA Astrophysics Data System (ADS)

Cass, Marion E.; Rzepa, Henry S.

2005-11-01

Illustrating and manipulating molecules in three dimensions are some of the truly wonderful advantages that computer technologies offer to chemistry teachers. In the following article we discuss our use of the program Jmol for the presentation of interactive materials to teach molecular symmetry. Jmol is an open-source code program that is free to all users and thus ideally suited for the development of teaching materials. Three primary pedagogic goals have been at the forefront in the development of our site. Our first goal was to animate symmetry operations and include interactive tools. Our second goal was to provide a library of molecules for student exercises to supplement their study of symmetry, using generic HTML templates populated using automatic tools based on Javascript. Our third goal in the development of our site was to include International Chemical Identifiers (InChIs) for each molecule to introduce students and educators to a new mechanism for identifying molecular resources and enabling their discovery using the Web search engines.

Improved Infrastucture for Cdms and JPL Molecular Spectroscopy Catalogues

NASA Astrophysics Data System (ADS)

Endres, Christian; Schlemmer, Stephan; Drouin, Brian; Pearson, John; Müller, Holger S. P.; Schilke, P.; Stutzki, Jürgen

2014-06-01

Over the past years a new infrastructure for atomic and molecular databases has been developed within the framework of the Virtual Atomic and Molecular Data Centre (VAMDC). Standards for the representation of atomic and molecular data as well as a set of protocols have been established which allow now to retrieve data from various databases through one portal and to combine the data easily. Apart from spectroscopic databases such as the Cologne Database for Molecular Spectroscopy (CDMS), the Jet Propulsion Laboratory microwave, millimeter and submillimeter spectral line catalogue (JPL) and the HITRAN database, various databases on molecular collisions (BASECOL, KIDA) and reactions (UMIST) are connected. Together with other groups within the VAMDC consortium we are working on common user tools to simplify the access for new customers and to tailor data requests for users with specified needs. This comprises in particular tools to support the analysis of complex observational data obtained with the ALMA telescope. In this presentation requests to CDMS and JPL will be used to explain the basic concepts and the tools which are provided by VAMDC. In addition a new portal to CDMS will be presented which has a number of new features, in particular meaningful quantum numbers, references linked to data points, access to state energies and improved documentation. Fit files are accessible for download and queries to other databases are possible.

Molecular phylogenetic analysis of Enterobius vermicularis and development of an 18S ribosomal DNA-targeted diagnostic PCR.

PubMed

Zelck, Ulrike E; Bialek, Ralf; Weiss, Michael

2011-04-01

We genetically characterized pinworms obtained from 37 children from different regions of Germany and established new species-specific molecular diagnostic tools. No ribosomal DNA diversity was found; the phylogenetic position of Enterobius vermicularis within the Oxyurida order and its close relationship to the Ascaridida and Spirurida orders was confirmed.

Molecular Biology at the Cutting Edge: A Review on CRISPR/CAS9 Gene Editing for Undergraduates

ERIC Educational Resources Information Center

Thurtle-Schmidt, Deborah M.; Lo, Te-Wen

2018-01-01

Disrupting a gene to determine its effect on an organism's phenotype is an indispensable tool in molecular biology. Such techniques are critical for understanding how a gene product contributes to the development and cellular identity of organisms. The explosion of genomic sequencing technologies combined with recent advances in genome-editing…

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

ERIC Educational Resources Information Center

Terrell, Cassidy R.; Listenberger, Laura L.

2017-01-01

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

Development of Public Immortal Mapping Populations, Molecular Markers and Linkage Maps for Rapid Cycling Brassica rapa and B. oleracea

USDA-ARS?s Scientific Manuscript database

In this study we describe public immortal mapping populations of self-compatible lines, molecular markers, and linkage maps for Brassica rapa and B. oleracea. We propose that these resources are valuable reference tools for the Brassica community. The B. rapa population consists of 150 recombinant...

Novel molecular diagnostic tools for malaria elimination: a review of options from the point of view of high-throughput and applicability in resource limited settings.

PubMed

Britton, Sumudu; Cheng, Qin; McCarthy, James S

2016-02-16

As malaria transmission continues to decrease, an increasing number of countries will enter pre-elimination and elimination. To interrupt transmission, changes in control strategies are likely to require more accurate identification of all carriers of Plasmodium parasites, both symptomatic and asymptomatic, using diagnostic tools that are highly sensitive, high throughput and with fast turnaround times preferably performed in local health service settings. Currently available immunochromatographic lateral flow rapid diagnostic tests and field microscopy are unlikely to consistently detect infections at parasite densities less than 100 parasites/µL making them insufficiently sensitive for detecting all carriers. Molecular diagnostic platforms, such as PCR and LAMP, are currently available in reference laboratories, but at a cost both financially and in turnaround time. This review describes the recent progress in developing molecular diagnostic tools in terms of their capacity for high throughput and potential for performance in non-reference laboratories for malaria elimination.

SketchBio: a scientist's 3D interface for molecular modeling and animation.

PubMed

Waldon, Shawn M; Thompson, Peter M; Hahn, Patrick J; Taylor, Russell M

2014-10-30

Because of the difficulties involved in learning and using 3D modeling and rendering software, many scientists hire programmers or animators to create models and animations. This both slows the discovery process and provides opportunities for miscommunication. Working with multiple collaborators, a tool was developed (based on a set of design goals) to enable them to directly construct models and animations. SketchBio is presented, a tool that incorporates state-of-the-art bimanual interaction and drop shadows to enable rapid construction of molecular structures and animations. It includes three novel features: crystal-by-example, pose-mode physics, and spring-based layout that accelerate operations common in the formation of molecular models. Design decisions and their consequences are presented, including cases where iterative design was required to produce effective approaches. The design decisions, novel features, and inclusion of state-of-the-art techniques enabled SketchBio to meet all of its design goals. These features and decisions can be incorporated into existing and new tools to improve their effectiveness.

Live Imaging of Centriole Dynamics by Fluorescently Tagged Proteins in Starfish Oocyte Meiosis.

PubMed

Borrego-Pinto, Joana; Somogyi, Kálmán; Lénárt, Péter

2016-01-01

High throughput DNA sequencing, the decreasing costs of DNA synthesis, and universal techniques for genetic manipulation have made it much easier and quicker to establish molecular tools for any organism than it has been 5 years ago. This opens a great opportunity for reviving "nonconventional" model organisms, which are particularly suited to study a specific biological process and many of which have already been established before the era of molecular biology. By taking advantage of transcriptomics, in particular, these systems can now be easily turned into full fetched models for molecular cell biology.As an example, here we describe how we established molecular tools in the starfish Patiria miniata, which has been a popular model for cell and developmental biology due to the synchronous and rapid development, transparency, and easy handling of oocytes, eggs, and embryos. Here, we detail how we used a de novo assembled transcriptome to produce molecular markers and established conditions for live imaging to investigate the molecular mechanisms underlying centriole elimination-a poorly understood process essential for sexual reproduction of animal species.

Gene Ontology-Based Analysis of Zebrafish Omics Data Using the Web Tool Comparative Gene Ontology.

PubMed

Ebrahimie, Esmaeil; Fruzangohar, Mario; Moussavi Nik, Seyyed Hani; Newman, Morgan

2017-10-01

Gene Ontology (GO) analysis is a powerful tool in systems biology, which uses a defined nomenclature to annotate genes/proteins within three categories: "Molecular Function," "Biological Process," and "Cellular Component." GO analysis can assist in revealing functional mechanisms underlying observed patterns in transcriptomic, genomic, and proteomic data. The already extensive and increasing use of zebrafish for modeling genetic and other diseases highlights the need to develop a GO analytical tool for this organism. The web tool Comparative GO was originally developed for GO analysis of bacterial data in 2013 ( www.comparativego.com ). We have now upgraded and elaborated this web tool for analysis of zebrafish genetic data using GOs and annotations from the Gene Ontology Consortium.

Chemical Sensor Array Response Modeling Using Quantitative Structure-Activity Relationships Technique

NASA Astrophysics Data System (ADS)

Shevade, Abhijit V.; Ryan, Margaret A.; Homer, Margie L.; Zhou, Hanying; Manfreda, Allison M.; Lara, Liana M.; Yen, Shiao-Pin S.; Jewell, April D.; Manatt, Kenneth S.; Kisor, Adam K.

We have developed a Quantitative Structure-Activity Relationships (QSAR) based approach to correlate the response of chemical sensors in an array with molecular descriptors. A novel molecular descriptor set has been developed; this set combines descriptors of sensing film-analyte interactions, representing sensor response, with a basic analyte descriptor set commonly used in QSAR studies. The descriptors are obtained using a combination of molecular modeling tools and empirical and semi-empirical Quantitative Structure-Property Relationships (QSPR) methods. The sensors under investigation are polymer-carbon sensing films which have been exposed to analyte vapors at parts-per-million (ppm) concentrations; response is measured as change in film resistance. Statistically validated QSAR models have been developed using Genetic Function Approximations (GFA) for a sensor array for a given training data set. The applicability of the sensor response models has been tested by using it to predict the sensor activities for test analytes not considered in the training set for the model development. The validated QSAR sensor response models show good predictive ability. The QSAR approach is a promising computational tool for sensing materials evaluation and selection. It can also be used to predict response of an existing sensing film to new target analytes.

Development of the Next Generation of Biogeochemistry Simulations Using EMSL's NWChem Molecular Modeling Software

NASA Astrophysics Data System (ADS)

Bylaska, E. J.; Kowalski, K.; Apra, E.; Govind, N.; Valiev, M.

2017-12-01

Methods of directly simulating the behavior of complex strongly interacting atomic systems (molecular dynamics, Monte Carlo) have provided important insight into the behavior of nanoparticles, biogeochemical systems, mineral/fluid systems, nanoparticles, actinide systems and geofluids. The limitation of these methods to even wider applications is the difficulty of developing accurate potential interactions in these systems at the molecular level that capture their complex chemistry. The well-developed tools of quantum chemistry and physics have been shown to approach the accuracy required. However, despite the continuous effort being put into improving their accuracy and efficiency, these tools will be of little value to condensed matter problems without continued improvements in techniques to traverse and sample the high-dimensional phase space needed to span the ˜10^12 time scale differences between molecular simulation and chemical events. In recent years, we have made considerable progress in developing electronic structure and AIMD methods tailored to treat biochemical and geochemical problems, including very efficient implementations of many-body methods, fast exact exchange methods, electron-transfer methods, excited state methods, QM/MM, and new parallel algorithms that scale to +100,000 cores. The poster will focus on the fundamentals of these methods and the realities in terms of system size, computational requirements and simulation times that are required for their application to complex biogeochemical systems.

"Plasmo2D": an ancillary proteomic tool to aid identification of proteins from Plasmodium falciparum.

PubMed

Khachane, Amit; Kumar, Ranjit; Jain, Sanyam; Jain, Samta; Banumathy, Gowrishankar; Singh, Varsha; Nagpal, Saurabh; Tatu, Utpal

2005-01-01

Bioinformatics tools to aid gene and protein sequence analysis have become an integral part of biology in the post-genomic era. Release of the Plasmodium falciparum genome sequence has allowed biologists to define the gene and the predicted protein content as well as their sequences in the parasite. Using pI and molecular weight as characteristics unique to each protein, we have developed a bioinformatics tool to aid identification of proteins from Plasmodium falciparum. The tool makes use of a Virtual 2-DE generated by plotting all of the proteins from the Plasmodium database on a pI versus molecular weight scale. Proteins are identified by comparing the position of migration of desired protein spots from an experimental 2-DE and that on a virtual 2-DE. The procedure has been automated in the form of user-friendly software called "Plasmo2D". The tool can be downloaded from http://144.16.89.25/Plasmo2D.zip.

Diagnosing schistosomiasis: where are we?

PubMed

Gomes, Luciana Inácia; Enk, Martin Johannes; Rabello, Ana

2014-01-01

In light of the World Health Organization's initiative to extend schistosomiasis morbidity and mortality control programs by including a disease elimination strategy in low endemic settings, this paper reviews diagnostic tools described during the last decades and provide an overview of ongoing efforts in making an efficient diagnostic tool available worldwide. A literature search on PubMed using the search criteria schistosomiasis and diagnosis within the period from 1978 to 2013 was carried out. Articles with abstract in English and that used laboratory techniques specifically developed for the detection of schistosomiasis in humans were included. Publications were categorized according to the methodology applied (parasitological, immunological, or molecular) and stage of development (in house development, limited field, or large scale field testing). The initial research generated 4,535 publications, of which only 643 met the inclusion criteria. The vast majority (537) of the publications focused on immunological techniques; 81 focused on parasitological diagnosis, and 25 focused on molecular diagnostic methods. Regarding the stage of development, 307 papers referred to in-house development, 202 referred to limited field tests, and 134 referred to large scale field testing. The data obtained show that promising new diagnostic tools, especially for Schistosoma antigen and deoxyribonucleic acid (DNA) detection, which are characterized by high sensitivity and specificity, are being developed. In combination with international funding initiatives these tools may result in a significant step forward in successful disease elimination and surveillance, which is to make efficient tests accessible and its large use self-sustainable for control programs in endemic countries.

Rational Design of Molecular Gelator - Solvent Systems Guided by Solubility Parameters

NASA Astrophysics Data System (ADS)

Lan, Yaqi

Self-assembled architectures, such as molecular gels, have attracted wide interest among chemists, physicists and engineers during the past decade. However, the mechanism behind self-assembly remains largely unknown and no capability exists to predict a priori whether a small molecule will gelate a specific solvent or not. The process of self-assembly, in molecular gels, is intricate and must balance parameters influencing solubility and those contrasting forces that govern epitaxial growth into axially symmetric elongated aggregates. Although the gelator-gelator interactions are of paramount importance in understanding gelation, the solvent-gelator specific (i.e., H-bonding) and nonspecific (dipole-dipole, dipole-induced and instantaneous dipole induced forces) intermolecular interactions are equally important. Solvent properties mediate the self-assembly of molecular gelators into their self-assembled fibrillar networks. Herein, solubility parameters of solvents, ranging from partition coefficients (logP), to Henry's law constants (HLC), to solvatochromic ET(30) parameters, to Kamlet-Taft parameters (beta, alpha and pi), to Hansen solubility parameters (deltap, deltad, deltah), etc., are correlated with the gelation ability of numerous classes of molecular gelators. Advanced solvent clustering techniques have led to the development of a priori tools that can identify the solvents that will be gelled and not gelled by molecular gelators. These tools will greatly aid in the development of novel gelators without solely relying on serendipitous discoveries.

An interactive web-tool for molecular analyses links naturally occurring mutation data with three-dimensional structures of the rhodopsin-like glycoprotein hormone receptors.

PubMed

Kleinau, Gunnar; Kreuchwig, Annika; Worth, Catherine L; Krause, Gerd

2010-06-01

The collection, description and molecular analysis of naturally occurring (pathogenic) mutations are important for understanding the functional mechanisms and malfunctions of biological units such as proteins. Numerous databases collate a huge amount of functional data or descriptions of mutations, but tools to analyse the molecular effects of genetic variations are as yet poorly provided. The goal of this work was therefore to develop a translational web-application that facilitates the interactive linkage of functional and structural data and which helps improve our understanding of the molecular basis of naturally occurring gain- or loss- of function mutations. Here we focus on the human glycoprotein hormone receptors (GPHRs), for which a huge number of mutations are known to cause diseases. We describe new options for interactive data analyses within three-dimensional structures, which enable the assignment of molecular relationships between structure and function. Strikingly, as the functional data are converted into relational percentage values, the system allows the comparison and classification of data from different GPHR subtypes and different experimental approaches. Our new application has been incorporated into a freely available database and website for the GPHRs (http://www.ssfa-gphr.de), but the principle development would also be applicable to other macromolecules.

Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS): A web-based tool for addressing the challenges of cross-species extrapolation of chemical toxicity

EPA Science Inventory

Conservation of a molecular target across species can be used as a line-of-evidence to predict the likelihood of chemical susceptibility. The web-based Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS) tool was developed to simplify, streamline, and quantitat...

"Caenorhabditis Elegans" as an Undergraduate Educational Tool for Teaching RNAi

ERIC Educational Resources Information Center

Andersen, Janet; Krichevsky, Alexander; Leheste, Joerg R.; Moloney, Daniel J.

2008-01-01

Discovery of RNA-mediated interference (RNAi) is widely recognized as one of the most significant molecular biology breakthroughs in the past 10 years. There is a need for science educators to develop teaching tools and laboratory activities that demonstrate the power of this new technology and help students to better understand the RNAi process.…

Recent advances in omic technologies for meat quality management.

PubMed

Picard, B; Lebret, B; Cassar-Malek, I; Liaubet, L; Berri, C; Le Bihan-Duval, E; Hocquette, J F; Renand, G

2015-11-01

The knowledge of the molecular organization of living organisms evolved considerably during the last years. The methodologies associated also progressed with the development of the high-throughput sequencing (SNP array, RNAseq, etc.) and of genomic tools allowing the simultaneous analysis of hundreds or thousands of genes, proteins or metabolites. In farm animals, some proteins, mRNAs or metabolites whose abundance has been associated with meat quality traits have been detected in pig, cattle, chicken. They constitute biomarkers for the assessment and prediction of qualities of interest in each species, with potential biomarkers across species. The ongoing development of rapid methods will allow their use for decision-making and management tools in slaughterhouses, to better allocate carcasses or cuts to the appropriate markets. Besides, their application on living animals will help to improve genetic selection and to adapt a breeding system to fulfill expected quality level. The ultimate goal is to propose effective molecular tools for the management of product quality in meat production chains. Copyright © 2015 Elsevier Ltd. All rights reserved.

Nucleic acid tool enzymes-aided signal amplification strategy for biochemical analysis: status and challenges.

PubMed

Qing, Taiping; He, Dinggeng; He, Xiaoxiao; Wang, Kemin; Xu, Fengzhou; Wen, Li; Shangguan, Jingfang; Mao, Zhengui; Lei, Yanli

2016-04-01

Owing to their highly efficient catalytic effects and substrate specificity, the nucleic acid tool enzymes are applied as 'nano-tools' for manipulating different nucleic acid substrates both in the test-tube and in living organisms. In addition to the function as molecular scissors and molecular glue in genetic engineering, the application of nucleic acid tool enzymes in biochemical analysis has also been extensively developed in the past few decades. Used as amplifying labels for biorecognition events, the nucleic acid tool enzymes are mainly applied in nucleic acids amplification sensing, as well as the amplification sensing of biorelated variations of nucleic acids. With the introduction of aptamers, which can bind different target molecules, the nucleic acid tool enzymes-aided signal amplification strategies can also be used to sense non-nucleic targets (e.g., ions, small molecules, proteins, and cells). This review describes and discusses the amplification strategies of nucleic acid tool enzymes-aided biosensors for biochemical analysis applications. Various analytes, including nucleic acids, ions, small molecules, proteins, and cells, are reviewed briefly. This work also addresses the future trends and outlooks for signal amplification in nucleic acid tool enzymes-aided biosensors.

FESetup: Automating Setup for Alchemical Free Energy Simulations.

PubMed

Loeffler, Hannes H; Michel, Julien; Woods, Christopher

2015-12-28

FESetup is a new pipeline tool which can be used flexibly within larger workflows. The tool aims to support fast and easy setup of alchemical free energy simulations for molecular simulation packages such as AMBER, GROMACS, Sire, or NAMD. Post-processing methods like MM-PBSA and LIE can be set up as well. Ligands are automatically parametrized with AM1-BCC, and atom mappings for a single topology description are computed with a maximum common substructure search (MCSS) algorithm. An abstract molecular dynamics (MD) engine can be used for equilibration prior to free energy setup or standalone. Currently, all modern AMBER force fields are supported. Ease of use, robustness of the code, and automation where it is feasible are the main development goals. The project follows an open development model, and we welcome contributions.

Molecular nanomagnets and magnetic nanoparticles: the EMR contribution to a common approach.

PubMed

Fittipaldi, M; Sorace, L; Barra, A-L; Sangregorio, C; Sessoli, R; Gatteschi, D

2009-08-21

The current status and future developments of the use of electron magnetic resonance (EMR) for the investigation of magnetic nano-systems is here reviewed. The aim is to stimulate efforts to provide a unified view of the properties of magnetic nanoparticles (MNP) comprising a few hundred magnetic centres, and molecular nanomagnets which contain up to ca. one hundred magnetic centres (MNM). The size of the systems is becoming the same but the approaches to the interpretation of their properties are still different, being bottom up for the latter and top down for the former. We make the point here of the need for a common viewpoint, highlighting the status of the two fields and giving some hints for the future developments. EMR has been a powerful tool for the investigation of magnetic nano-objects and it can provide a tool of fundamental importance for the development of a unified view.

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.

SHAPEMOL: the companion to SHAPE in the molecular era of ALMA and HERSCHEL

NASA Astrophysics Data System (ADS)

Santander-García, M.; Bujarrabal, V.; Alcolea, J.

2013-05-01

Modern instrumentation in radioastronomy constitutes a valuable tool for studying the Universe: ALMA will reach unprecedented sensitivities and spatial resolution, while Herschel/HIFI has opened a new window (most of the sub-mm and far infrared ranges are only accessible from space) for probing molecular warm gas (˜50-1000 K), complementing ground-based telescopes, which are better suited to study molecular molecular gas with temperatures under ˜100 K. On the other hand, the SHAPE software has emerged in the last few years as the standard tool for determinging the morphology and velocity field of different kinds of gaseous nebulae (mainly planetary nebulae, protoplanetary nebulae and nebulae around massive stars, although it can also be applied to H II regions and molecular clouds) via spatio-kinematical modelling. Standard SHAPE implements radiative transfer solving, but it is only available for atomic species and not for molecules. Being aware of the growing importance of the development of tools for easying the analyses of molecular data from new era observatories, we introduce the computer code shapemol, a plug-in for SHAPE with which we intend to fill the so far empty molecular niche. shapemol enables spatio-kinematic modeling with accurate non-LTE calculations of line excitation and radiative transfer in molecular species. This code has been succesfully tested in the study of the excitation conditions of the molecular envelope of the planetary nebula NGC 7027 using data from Herschel/HIFI and IRAM 30m. Currently, it allows radiative transfer solving in the ^{12}CO and ^{13}CO J=1-0 to J=17-16 lines. shapemol, used along SHAPE, allows to easily generate synthetic maps to test against interferometric observations, as well as synthetic line profiles to match single-dish observations.

Molecular Phylogenetic Analysis of Enterobius vermicularis and Development of an 18S Ribosomal DNA-Targeted Diagnostic PCR▿

PubMed Central

Zelck, Ulrike E.; Bialek, Ralf; Weiß, Michael

2011-01-01

We genetically characterized pinworms obtained from 37 children from different regions of Germany and established new species-specific molecular diagnostic tools. No ribosomal DNA diversity was found; the phylogenetic position of Enterobius vermicularis within the Oxyurida order and its close relationship to the Ascaridida and Spirurida orders was confirmed. PMID:21248085

The Impact of Designing and Evaluating Molecular Animations on How Well Middle School Students Understand the Particulate Nature of Matter

ERIC Educational Resources Information Center

Chang, Hsin-Yi; Quintana, Chris; Krajcik, Joseph S.

2010-01-01

In this study, we investigated whether the understanding of the particulate nature of matter by students was improved by allowing them to design and evaluate molecular animations of chemical phenomena. We developed Chemation, a learner-centered animation tool, to allow seventh-grade students to construct flipbook-like simple animations to show…

A molecular engineering toolbox for the structural biologist

PubMed Central

Debelouchina, Galia T.; Muir, Tom W.

2018-01-01

Exciting new technological developments have pushed the boundaries of structural biology, and have enabled studies of biological macromolecules and assemblies that would have been unthinkable not long ago. Yet, the enhanced capabilities of structural biologists to pry into the complex molecular world have also placed new demands on the abilities of protein engineers to reproduce this complexity into the test tube. With this challenge in mind, we review the contents of the modern molecular engineering toolbox that allow the manipulation of proteins in a site-specific and chemically well-defined fashion. Thus, we cover concepts related to the modification of cysteines and other natural amino acids, native chemical ligation, intein and sortase-based approaches, amber suppression, as well as chemical and enzymatic bio-conjugation strategies. We also describe how these tools can be used to aid methodology development in X-ray crystallography, nuclear magnetic resonance, cryo-electron microscopy and in the studies of dynamic interactions. It is our hope that this monograph will inspire structural biologists and protein engineers alike to apply these tools to novel systems, and to enhance and broaden their scope to meet the outstanding challenges in understanding the molecular basis of cellular processes and disease. PMID:29233219

A molecular engineering toolbox for the structural biologist.

PubMed

Debelouchina, Galia T; Muir, Tom W

2017-01-01

Exciting new technological developments have pushed the boundaries of structural biology, and have enabled studies of biological macromolecules and assemblies that would have been unthinkable not long ago. Yet, the enhanced capabilities of structural biologists to pry into the complex molecular world have also placed new demands on the abilities of protein engineers to reproduce this complexity into the test tube. With this challenge in mind, we review the contents of the modern molecular engineering toolbox that allow the manipulation of proteins in a site-specific and chemically well-defined fashion. Thus, we cover concepts related to the modification of cysteines and other natural amino acids, native chemical ligation, intein and sortase-based approaches, amber suppression, as well as chemical and enzymatic bio-conjugation strategies. We also describe how these tools can be used to aid methodology development in X-ray crystallography, nuclear magnetic resonance, cryo-electron microscopy and in the studies of dynamic interactions. It is our hope that this monograph will inspire structural biologists and protein engineers alike to apply these tools to novel systems, and to enhance and broaden their scope to meet the outstanding challenges in understanding the molecular basis of cellular processes and disease.

Accelerating the use of molecular modeling in the high school classroom with VMD Lite.

PubMed

Lundquist, Karl; Herndon, Conner; Harty, Tyson H; Gumbart, James C

2016-01-01

It is often difficult for students to develop an intuition about molecular processes, which occur in a realm far different from day-to-day life. For example, thermal fluctuations take on hurricane-like proportions at the molecular scale. Students need a way to visualize realistic depictions of molecular processes to appreciate them. To this end, we have developed a simplified graphical interface to the widely used molecular visualization and analysis tool Visual Molecular Dynamics (VMD) called VMD lite. We demonstrate the use of VMD lite through a module on diffusion and the hydrophobic effect as they relate to membrane formation. Trajectories from molecular dynamics simulations, which students can interact with freely, illustrate the dynamical behavior of lipid molecules and water. VMD lite was tested by ∼70 students with overall positive reception. Remaining deficiencies in conceptual understanding were noted, however, and the module has been revised in response. © 2016 The International Union of Biochemistry and Molecular Biology.

Issues in contemporary and potential future molecular diagnostics for dengue.

PubMed

Sekaran, Shamala Devi; Soe, Hui Jen

2017-03-01

Dengue has been the most common arbovirus infection worldwide with 2.5 billion people living in over 100 endemic tropical and subtropical regions. Due to the high number of asymptomatic cases and the signs and symptoms being rather unspecific, dengue cases are often under-reported and might influence dengue surveillance programs. Therefore, a rapid, easy to use, inexpensive, and highly sensitive and specific diagnostic tool is essential for early and accurate diagnosis to ease the clinical management of patients as well as for the development of new interventions. Areas covered: This report discusses the contemporary dengue diagnostic tool, mainly from the aspect of molecular diagnosis where an overview of several nuclei acid amplification tests has been included. Potential molecular diagnostic tools such as biosensor and microarray are also discussed in this report. Expert commentary: Rapidness and accuracy in terms of sensitivity and specificity is imperative in dengue diagnosis for both clinical management and surveillance of dengue to ensure early treatment and corrective control measures can be carried out. In the next five years it is expected that there will be newer tests developed using not only the lateral flow techniques but more specifically biosensors and nanotechnology. These new technologies will have to be validated with the appropriate number and category of samples and to address the issue of cross-reactivity.

Defining a Computational Framework for the Assessment of ...

EPA Pesticide Factsheets

The Adverse Outcome Pathway (AOP) framework describes the effects of environmental stressors across multiple scales of biological organization and function. This includes an evaluation of the potential for each key event to occur across a broad range of species in order to determine the taxonomic applicability of each AOP. Computational tools are needed to facilitate this process. Recently, we developed a tool that uses sequence homology to evaluate the applicability of molecular initiating events across species (Lalone et al., Toxicol. Sci., 2016). To extend our ability to make computational predictions at higher levels of biological organization, we have created the AOPdb. This database links molecular targets identified associated with key events in the AOPwiki to publically available data (e.g. gene-protein, pathway, species orthology, ontology, chemical, disease) including ToxCast assay information. The AOPdb combines different data types in order to characterize the impacts of chemicals to human health and the environment and serves as a decision support tool for case study development in the area of taxonomic applicability. As a proof of concept, the AOPdb allows identification of relevant molecular targets, biological pathways, and chemical and disease associations across species for four AOPs from the AOP-Wiki (https://aopwiki.org): Estrogen receptor antagonism leading to reproductive dysfunction (Aop:30); Aromatase inhibition leading to reproductive d

Application of molecular genetic tools for forest pathology

Treesearch

Mee-Sook Kim; John Hanna; Amy Ross-Davis; Ned Klopfenstein

2012-01-01

In recent years, advances in molecular genetics have provided powerful tools to address critical issues in forest pathology to help promote resilient forests. Although molecular genetic tools are initially applied to understand individual components of forest pathosystems, forest pathosystems involve dynamic interactions among biotic and abiotic components of the...

Sex chromosomal abnormalities associated with equine infertility: validation of a simple molecular screening tool in the Purebred Spanish Horse.

PubMed

Anaya, G; Molina, A; Valera, M; Moreno-Millán, M; Azor, P; Peral-García, P; Demyda-Peyrás, S

2017-08-01

Chromosomal abnormalities in the sex chromosome pair (ECAX and ECAY) are widely associated with reproductive problems in horses. However, a large proportion of these abnormalities remains undiagnosed due to the lack of an affordable diagnostic tool that allows for avoiding karyotyping tests. Hereby, we developed an STR (single-tandem-repeat)-based molecular method to determine the presence of the main sex chromosomal abnormalities in horses in a fast, cheap and reliable way. The frequency of five ECAX-linked (LEX026, LEX003, TKY38, TKY270 and UCDEQ502) and two ECAY-linked (EcaYH12 and SRY) markers was characterized in 261 Purebred Spanish Horses to determine the efficiency of the methodology developed to be used as a chromosomal diagnostic tool. All the microsatellites analyzed were highly polymorphic, with a sizeable number of alleles (polymorphic information content > 0.5). Based on this variability, the methodology showed 100% sensitivity and 99.82% specificity to detect the most important sex chromosomal abnormalities reported in horses (chimerism, Turner's syndrome and sex reversal syndromes). The method was also validated with 100% efficiency in 10 individuals previously diagnosed as chromosomally aberrant. This STR screening panel is an efficient and reliable molecular-cytogenetic tool for the early detection of sex chromosomal abnormalities in equines that could be included in breeding programs to save money, effort and time of veterinary practitioners and breeders. © 2017 Stichting International Foundation for Animal Genetics.

Molecular and chemical engineering of bacteriophages for potential medical applications.

PubMed

Hodyra, Katarzyna; Dąbrowska, Krystyna

2015-04-01

Recent progress in molecular engineering has contributed to the great progress of medicine. However, there are still difficult problems constituting a challenge for molecular biology and biotechnology, e.g. new generation of anticancer agents, alternative biosensors or vaccines. As a biotechnological tool, bacteriophages (phages) offer a promising alternative to traditional approaches. They can be applied as anticancer agents, novel platforms in vaccine design, or as target carriers in drug discovery. Phages also offer solutions for modern cell imaging, biosensor construction or food pathogen detection. Here we present a review of bacteriophage research as a dynamically developing field with promising prospects for further development of medicine and biotechnology.

Current molecular and emerging nanobiotechnology approaches for the detection of microbial pathogens.

PubMed

Theron, Jacques; Eugene Cloete, Thomas; de Kwaadsteniet, Michele

2010-11-01

Waterborne microbial diseases are escalating worldwide increasing the need for powerful and sensitive diagnostics tools. Molecular methodologies, including immunological and nucleic acid-based methods, have only recently been applied in the water sector. Advances in nanotechnology and nanomaterials have opened the door for the development of new diagnostic tools with increased sensitivity and speed, and reduced cost and labor. Quantum dots, flo dots, gold nanoparticles, magnetic nanoparticles, carbon nanotubes, nanowires, and nanocantilevers, with their unique optical and physical properties, have already been applied in nanodiagnostics. Nanobiotechnology, once remaining technical and practical problems has been addressed, will play an important role in the detection of microbial pathogens.

Immersive virtual reality in computational chemistry: Applications to the analysis of QM and MM data.

PubMed

Salvadori, Andrea; Del Frate, Gianluca; Pagliai, Marco; Mancini, Giordano; Barone, Vincenzo

2016-11-15

The role of Virtual Reality (VR) tools in molecular sciences is analyzed in this contribution through the presentation of the Caffeine software to the quantum chemistry community. Caffeine, developed at Scuola Normale Superiore, is specifically tailored for molecular representation and data visualization with VR systems, such as VR theaters and helmets. Usefulness and advantages that can be gained by exploiting VR are here reported, considering few examples specifically selected to illustrate different level of theory and molecular representation.

POLYANA-A tool for the calculation of molecular radial distribution functions based on Molecular Dynamics trajectories

NASA Astrophysics Data System (ADS)

Dimitroulis, Christos; Raptis, Theophanes; Raptis, Vasilios

2015-12-01

We present an application for the calculation of radial distribution functions for molecular centres of mass, based on trajectories generated by molecular simulation methods (Molecular Dynamics, Monte Carlo). When designing this application, the emphasis was placed on ease of use as well as ease of further development. In its current version, the program can read trajectories generated by the well-known DL_POLY package, but it can be easily extended to handle other formats. It is also very easy to 'hack' the program so it can compute intermolecular radial distribution functions for groups of interaction sites rather than whole molecules.

MIiSR: Molecular Interactions in Super-Resolution Imaging Enables the Analysis of Protein Interactions, Dynamics and Formation of Multi-protein Structures.

PubMed

Caetano, Fabiana A; Dirk, Brennan S; Tam, Joshua H K; Cavanagh, P Craig; Goiko, Maria; Ferguson, Stephen S G; Pasternak, Stephen H; Dikeakos, Jimmy D; de Bruyn, John R; Heit, Bryan

2015-12-01

Our current understanding of the molecular mechanisms which regulate cellular processes such as vesicular trafficking has been enabled by conventional biochemical and microscopy techniques. However, these methods often obscure the heterogeneity of the cellular environment, thus precluding a quantitative assessment of the molecular interactions regulating these processes. Herein, we present Molecular Interactions in Super Resolution (MIiSR) software which provides quantitative analysis tools for use with super-resolution images. MIiSR combines multiple tools for analyzing intermolecular interactions, molecular clustering and image segmentation. These tools enable quantification, in the native environment of the cell, of molecular interactions and the formation of higher-order molecular complexes. The capabilities and limitations of these analytical tools are demonstrated using both modeled data and examples derived from the vesicular trafficking system, thereby providing an established and validated experimental workflow capable of quantitatively assessing molecular interactions and molecular complex formation within the heterogeneous environment of the cell.

[Development of laboratory sequence analysis software based on WWW and UNIX].

PubMed

Huang, Y; Gu, J R

2001-01-01

Sequence analysis tools based on WWW and UNIX were developed in our laboratory to meet the needs of molecular genetics research in our laboratory. General principles of computer analysis of DNA and protein sequences were also briefly discussed in this paper.

Development and Testing of Environmental DNA (eDNA) Protocols for the Endangered James Spinymussel (Pleurobema collina)

DOT National Transportation Integrated Search

2017-12-01

Molecular genetic techniques provide tools that may be used to locate, monitor, and survey cryptic aquatic species. This study developed genetic markers useful in determining if the James Spinymussel (Pleurobema collina), an endangered species, can b...

SHAPEMOL: Modelling molecular line emission in protoplanetary and planetary nebulae with SHAPE

NASA Astrophysics Data System (ADS)

Santander-García, M.; Bujarrabal, V.; Steffen, W.; Koning, N.

2014-04-01

Modern instrumentation in radioastronomy constitutes a valuable tool for studying the Universe: ALMA will reach unprecedented sensitivities and spatial resolution, while Herschel/HIFI has opened a new window for probing molecular warm gas (˜50-1000 K). On the other hand, the SHAPE software has emerged in the last few years as the standard tool for determining the morphology and velocity field of different kinds of gaseous emission nebulae via spatio-kinematical modelling. Standard SHAPE implements radiative transfer solving, but it is only available for atomic species and not for molecules. Being aware of the growing importance of the development of tools for easying the analyses of molecular data from new era observatories, we introduce the computer code shapemol, a plug-in for SHAPE v5.0 with which we intend to fill the so far empty molecular niche. Shapemol enables spatio-kinematic modeling with accurate non-LTE calculations of line excitation and radiative transfer in molecular species. This code has been succesfully tested in the study of the excitation conditions of the molecular envelope of the young planetary nebula NGC 7027 using data from Herschel/HIFI and IRAM 30m. Currently, it allows radiative transfer solving in the 12CO and 13CO J=1-0 to J=17-16 lines. Shapemol, used along SHAPE, allows to easily generate synthetic maps to test against interferometric observations, as well as synthetic line profiles to match single-dish observations.

Molecular Profiles for Lung Cancer Pathogenesis and Detection in US Veterans

DTIC Science & Technology

2011-10-01

expression data was analyzed using the BRB-ArrayTools v .4.1.0 developed by Dr. Richard Simon and the BRB-ArrayTools Development Team and then normalized...14. Spira A, Beane J, Shah V , et al. Effects of cigarette smoke on the human airway epithelial cell transcriptome. Proc Natl Acad Sci U S A 2004;101...10143-10148 15. Spira A, Beane JE, Shah V , et al. Airway epithelial gene expression in the diagnostic evaluation of smokers with suspect lung cancer

Molecular Profiles for Lung Cancer Pathogenesis and Detection in US Veterans

DTIC Science & Technology

2011-10-01

using the BRB-ArrayTools v .4.1.0 developed by Dr. Richard Simon and the BRB-ArrayTools Development Team and then normalized and log-transformed by...C. V Figure 23. Expression of genes located at chromosome 3q26-3q29. RPKM values were obtained for...airway epithelium of cigarette smokers. Am J Respir Cell Mol Biol 2003;29:331-343 14. Spira A, Beane J, Shah V , et al. Effects of cigarette smoke on

Molecular Profiles for Lung Cancer Pathogenesis and Detection in US Veterans

DTIC Science & Technology

2011-10-01

data was analyzed using the BRB-ArrayTools v .4.1.0 developed by Dr. Richard Simon and the BRB-ArrayTools Development Team and then normalized and log...Spira A, Beane J, Shah V , et al. Effects of cigarette smoke on the human airway epithelial cell transcriptome. Proc Natl Acad Sci U S A 2004;101:10143...10148 15. Spira A, Beane JE, Shah V , et al. Airway epithelial gene expression in the diagnostic evaluation of smokers with suspect lung cancer. Nat

Design and implementation of a library-based information service in molecular biology and genetics at the University of Pittsburgh

PubMed Central

Chattopadhyay, Ansuman; Tannery, Nancy Hrinya; Silverman, Deborah A. L.; Bergen, Phillip; Epstein, Barbara A.

2006-01-01

Setting: In summer 2002, the Health Sciences Library System (HSLS) at the University of Pittsburgh initiated an information service in molecular biology and genetics to assist researchers with identifying and utilizing bioinformatics tools. Program Components: This novel information service comprises hands-on training workshops and consultation on the use of bioinformatics tools. The HSLS also provides an electronic portal and networked access to public and commercial molecular biology databases and software packages. Evaluation Mechanisms: Researcher feedback gathered during the first three years of workshops and individual consultation indicate that the information service is meeting user needs. Next Steps/Future Directions: The service's workshop offerings will expand to include emerging bioinformatics topics. A frequently asked questions database is also being developed to reuse advice on complex bioinformatics questions. PMID:16888665

The yeast p53 functional assay: a new tool for molecular epidemiology. Hopes and facts.

PubMed

Fronza, G; Inga, A; Monti, P; Scott, G; Campomenosi, P; Menichini, P; Ottaggio, L; Viaggi, S; Burns, P A; Gold, B; Abbondandolo, A

2000-04-01

The assumption of molecular epidemiology that carcinogens leave fingerprints has suggested that analysis of the frequency, type, and site of mutations in genes frequently altered in carcinogenesis may provide clues to the identification of the factors contributing to carcinogenesis. In this mini-review, we revise the development, and validation of the yeast-based p53 functional assay as a new tool for molecular epidemiology. We show that this assay has some very interesting virtues but also has some drawbacks. The yeast functional assay can be used to determine highly specific mutation fingerprints in the human p53 cDNA sequence. Discrimination is possible when comparing mutation spectra induced by sufficiently different mutagens. However, we also reported that the same carcinogen may induce distinguishable mutation spectra due to known influencing factors.

Zoonotic Potential and Molecular Epidemiology of Giardia Species and Giardiasis†

PubMed Central

Feng, Yaoyu; Xiao, Lihua

2011-01-01

Summary: Molecular diagnostic tools have been used recently in assessing the taxonomy, zoonotic potential, and transmission of Giardia species and giardiasis in humans and animals. The results of these studies have firmly established giardiasis as a zoonotic disease, although host adaptation at the genotype and subtype levels has reduced the likelihood of zoonotic transmission. These studies have also identified variations in the distribution of Giardia duodenalis genotypes among geographic areas and between domestic and wild ruminants and differences in clinical manifestations and outbreak potentials of assemblages A and B. Nevertheless, our efforts in characterizing the molecular epidemiology of giardiasis and the roles of various animals in the transmission of human giardiasis are compromised by the lack of case-control and longitudinal cohort studies and the sampling and testing of humans and animals living in the same community, the frequent occurrence of infections with mixed genotypes and subtypes, and the apparent heterozygosity at some genetic loci for some G. duodenalis genotypes. With the increased usage of multilocus genotyping tools, the development of next-generation subtyping tools, the integration of molecular analysis in epidemiological studies, and an improved understanding of the population genetics of G. duodenalis in humans and animals, we should soon have a better appreciation of the molecular epidemiology of giardiasis, the disease burden of zoonotic transmission, the taxonomy status and virulences of various G. duodenalis genotypes, and the ecology of environmental contamination. PMID:21233509

phylo-node: A molecular phylogenetic toolkit using Node.js.

PubMed

O'Halloran, Damien M

2017-01-01

Node.js is an open-source and cross-platform environment that provides a JavaScript codebase for back-end server-side applications. JavaScript has been used to develop very fast and user-friendly front-end tools for bioinformatic and phylogenetic analyses. However, no such toolkits are available using Node.js to conduct comprehensive molecular phylogenetic analysis. To address this problem, I have developed, phylo-node, which was developed using Node.js and provides a stable and scalable toolkit that allows the user to perform diverse molecular and phylogenetic tasks. phylo-node can execute the analysis and process the resulting outputs from a suite of software options that provides tools for read processing and genome alignment, sequence retrieval, multiple sequence alignment, primer design, evolutionary modeling, and phylogeny reconstruction. Furthermore, phylo-node enables the user to deploy server dependent applications, and also provides simple integration and interoperation with other Node modules and languages using Node inheritance patterns, and a customized piping module to support the production of diverse pipelines. phylo-node is open-source and freely available to all users without sign-up or login requirements. All source code and user guidelines are openly available at the GitHub repository: https://github.com/dohalloran/phylo-node.

Biomarkers as drug development tools: discovery, validation, qualification and use.

PubMed

Kraus, Virginia B

2018-06-01

The 21st Century Cures Act, approved in the USA in December 2016, has encouraged the establishment of the national Precision Medicine Initiative and the augmentation of efforts to address disease prevention, diagnosis and treatment on the basis of a molecular understanding of disease. The Act adopts into law the formal process, developed by the FDA, of qualification of drug development tools, including biomarkers and clinical outcome assessments, to increase the efficiency of clinical trials and encourage an era of molecular medicine. The FDA and European Medicines Agency (EMA) have developed similar processes for the qualification of biomarkers intended for use as companion diagnostics or for development and regulatory approval of a drug or therapeutic. Biomarkers that are used exclusively for the diagnosis, monitoring or stratification of patients in clinical trials are not subject to regulatory approval, although their qualification can facilitate the conduct of a trial. In this Review, the salient features of biomarker discovery, analytical validation, clinical qualification and utilization are described in order to provide an understanding of the process of biomarker development and, through this understanding, convey an appreciation of their potential advantages and limitations.

National Center for Biotechnology Information Celebrates 25th Anniversary | NIH MedlinePlus the Magazine

MedlinePlus

... is a national and international resource for molecular biology information. It creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and ...

Translational research of optical molecular imaging for personalized medicine.

PubMed

Qin, C; Ma, X; Tian, J

2013-12-01

In the medical imaging field, molecular imaging is a rapidly developing discipline and forms many imaging modalities, providing us effective tools to visualize, characterize, and measure molecular and cellular mechanisms in complex biological processes of living organisms, which can deepen our understanding of biology and accelerate preclinical research including cancer study and medicine discovery. Among many molecular imaging modalities, although the penetration depth of optical imaging and the approved optical probes used for clinics are limited, it has evolved considerably and has seen spectacular advances in basic biomedical research and new drug development. With the completion of human genome sequencing and the emergence of personalized medicine, the specific drug should be matched to not only the right disease but also to the right person, and optical molecular imaging should serve as a strong adjunct to develop personalized medicine by finding the optimal drug based on an individual's proteome and genome. In this process, the computational methodology and imaging system as well as the biomedical application regarding optical molecular imaging will play a crucial role. This review will focus on recent typical translational studies of optical molecular imaging for personalized medicine followed by a concise introduction. Finally, the current challenges and the future development of optical molecular imaging are given according to the understanding of the authors, and the review is then concluded.

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

PubMed

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

2011-07-01

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

Toward theragnostics.

PubMed

Pene, Frédéric; Courtine, Emilie; Cariou, Alain; Mira, Jean-Paul

2009-01-01

Theragnostics is a treatment strategy that combines therapeutics with diagnostics. It associates both a diagnostic test that identifies patients most likely to be helped or harmed by a new medication, and targeted drug therapy based on the test results. Bioinformatics, genomics, proteomics, and functional genomics are molecular biology tools essential for the progress of molecular theragnostics. These tools generate the genetic and protein information required for the development of diagnostic assays. Theragnostics includes a wide range of subjects, including personalized medicine, pharmacogenomics, and molecular imaging to develop efficient new targeted therapies with adequate benefit/risk to patients and a better molecular understanding of how to optimize drug selection. Furthermore, theragnostics aims to monitor the response to the treatment, to increase drug efficacy and safety. In addition, theragnostics could eliminate the unnecessary treatment of patients for whom therapy is not appropriate, resulting in significant drug cost savings for the healthcare system. However, the introduction of theragnostic tests into routine health care requires both a demonstration of cost-effectiveness and the availability of appropriate accessible testing systems. This review reports validation studies in oncology and infectious diseases that have demonstrated the benefits of such approach in well-defined subpopulations of patients, moving the field from the drug development process toward clinical practice and routine application. Theragnostics may change the usual business model of pharmaceutical companies from the classic blockbuster model toward targeted therapies.

Development of molecular tools for use in beech bark disease management

Treesearch

Jennifer L. Koch; David W. Carey; Mary E. Mason; C. Dana Nelson; Abdelali Barakat; John E. Carlson; David Neale

2011-01-01

Beech bark disease (BBD) has been killing American beech trees in eastern North America since the late 1890s. The disease is initiated by feeding of the beech scale insect, Cryptococcus fagisuga, which leads to the development of small fissures in the bark.

Conservation Biological Control of Pests in the Molecular Era: New Opportunities to Address Old Constraints

PubMed Central

Gurr, Geoff M.; You, Minsheng

2016-01-01

Biological control has long been considered a potential alternative to pesticidal strategies for pest management but its impact and level of use globally remain modest and inconsistent. A rapidly expanding range of molecular – particularly DNA-related – techniques is currently revolutionizing many life sciences. This review identifies a series of constraints on the development and uptake of conservation biological control and considers the contemporary and likely future influence of molecular methods on these constraints. Molecular approaches are now often used to complement morphological taxonomic methods for the identification and study of biological control agents including microbes. A succession of molecular techniques has been applied to ‘who eats whom’ questions in food-web ecology. Polymerase chain reaction (PCR) approaches have largely superseded immunological approaches such as enzyme-linked immunosorbent assay (ELISA) and now – in turn – are being overtaken by next generation sequencing (NGS)-based approaches that offer unparalleled power at a rapidly diminishing cost. There is scope also to use molecular techniques to manipulate biological control agents, which will be accelerated with the advent of gene editing tools, the CRISPR/Cas9 system in particular. Gene editing tools also offer unparalleled power to both elucidate and manipulate plant defense mechanisms including those that involve natural enemy attraction to attacked plants. Rapid advances in technology will allow the development of still more novel pest management options for which uptake is likely to be limited chiefly by regulatory hurdles. PMID:26793225

Impact of gastrointestinal parasitic nematodes of sheep, and the role of advanced molecular tools for exploring epidemiology and drug resistance - an Australian perspective

PubMed Central

2013-01-01

Parasitic nematodes (roundworms) of small ruminants and other livestock have major economic impacts worldwide. Despite the impact of the diseases caused by these nematodes and the discovery of new therapeutic agents (anthelmintics), there has been relatively limited progress in the development of practical molecular tools to study the epidemiology of these nematodes. Specific diagnosis underpins parasite control, and the detection and monitoring of anthelmintic resistance in livestock parasites, presently a major concern around the world. The purpose of the present article is to provide a concise account of the biology and knowledge of the epidemiology of the gastrointestinal nematodes (order Strongylida), from an Australian perspective, and to emphasize the importance of utilizing advanced molecular tools for the specific diagnosis of nematode infections for refined investigations of parasite epidemiology and drug resistance detection in combination with conventional methods. It also gives a perspective on the possibility of harnessing genetic, genomic and bioinformatic technologies to better understand parasites and control parasitic diseases. PMID:23711194

Molecular Neuroanatomy: A Generation of Progress

PubMed Central

Pollock, Jonathan D.; Wu, Da-Yu; Satterlee, John

2014-01-01

The neuroscience research landscape has changed dramatically over the past decade. An impressive array of neuroscience tools and technologies have been generated, including brain gene expression atlases, genetically encoded proteins to monitor and manipulate neuronal activity and function, cost effective genome sequencing, new technologies enabling genome manipulation, new imaging methods and new tools for mapping neuronal circuits. However, despite these technological advances, several significant scientific challenges must be overcome in the coming decade to enable a better understanding of brain function and to develop next generation cell type-targeted therapeutics to treat brain disorders. For example, we do not have an inventory of the different types of cells that exist in the brain, nor do we know how to molecularly phenotype them. We also lack robust technologies to map connections between cells. This review will provide an overview of some of the tools and technologies neuroscientists are currently using to move the field of molecular neuroanatomy forward and also discuss emerging technologies that may enable neuroscientists to address these critical scientific challenges over the coming decade. PMID:24388609

The R.E.D. tools: advances in RESP and ESP charge derivation and force field library building.

PubMed

Dupradeau, François-Yves; Pigache, Adrien; Zaffran, Thomas; Savineau, Corentin; Lelong, Rodolphe; Grivel, Nicolas; Lelong, Dimitri; Rosanski, Wilfried; Cieplak, Piotr

2010-07-28

Deriving atomic charges and building a force field library for a new molecule are key steps when developing a force field required for conducting structural and energy-based analysis using molecular mechanics. Derivation of popular RESP charges for a set of residues is a complex and error prone procedure because it depends on numerous input parameters. To overcome these problems, the R.E.D. Tools (RESP and ESP charge Derive, ) have been developed to perform charge derivation in an automatic and straightforward way. The R.E.D. program handles chemical elements up to bromine in the periodic table. It interfaces different quantum mechanical programs employed for geometry optimization and computing molecular electrostatic potential(s), and performs charge fitting using the RESP program. By defining tight optimization criteria and by controlling the molecular orientation of each optimized geometry, charge values are reproduced at any computer platform with an accuracy of 0.0001 e. The charges can be fitted using multiple conformations, making them suitable for molecular dynamics simulations. R.E.D. allows also for defining charge constraints during multiple molecule charge fitting, which are used to derive charges for molecular fragments. Finally, R.E.D. incorporates charges into a force field library, readily usable in molecular dynamics computer packages. For complex cases, such as a set of homologous molecules belonging to a common family, an entire force field topology database is generated. Currently, the atomic charges and force field libraries have been developed for more than fifty model systems and stored in the RESP ESP charge DDataBase. Selected results related to non-polarizable charge models are presented and discussed.

Modeling Natural Anti-Inflammatory Compounds by Molecular Topology

PubMed Central

Galvez-Llompart, María; Zanni, Riccardo; García-Domenech, Ramón

2011-01-01

One of the main pharmacological problems today in the treatment of chronic inflammation diseases consists of the fact that anti-inflammatory drugs usually exhibit side effects. The natural products offer a great hope in the identification of bioactive lead compounds and their development into drugs for treating inflammatory diseases. Computer-aided drug design has proved to be a very useful tool for discovering new drugs and, specifically, Molecular Topology has become a good technique for such a goal. A topological-mathematical model, obtained by linear discriminant analysis, has been developed for the search of new anti-inflammatory natural compounds. An external validation obtained with the remaining compounds (those not used in building up the model), has been carried out. Finally, a virtual screening on natural products was performed and 74 compounds showed actual anti-inflammatory activity. From them, 54 had been previously described as anti-inflammatory in the literature. This can be seen as a plus in the model validation and as a reinforcement of the role of Molecular Topology as an efficient tool for the discovery of new anti-inflammatory natural compounds. PMID:22272145

Molecular Biology of Anaerobic Aromatic Biodegradation.

DTIC Science & Technology

1992-08-14

degradation from the bacterium, Rhodopseudomonas palustris . These tools have enabled us to identify genes specifying two enzymes that initiate the...hydroxybenzoate - by one bacterial species - Rhodopseudomonas palustris . Our emphasis has been on developing tools to explore the genetic basis of aromatic acid...1991. Regulation of benzoate-CoA ligase in Rhodopseudomonas palustris . FEMS Microbiol. Letts. 83:199-204. Dispensa, M., C. T. Thomas, M.-K. Kim, J. A

Predicting the excess solubility of acetanilide, acetaminophen, phenacetin, benzocaine, and caffeine in binary water/ethanol mixtures via molecular simulation.

PubMed

Paluch, Andrew S; Parameswaran, Sreeja; Liu, Shuai; Kolavennu, Anasuya; Mobley, David L

2015-01-28

We present a general framework to predict the excess solubility of small molecular solids (such as pharmaceutical solids) in binary solvents via molecular simulation free energy calculations at infinite dilution with conventional molecular models. The present study used molecular dynamics with the General AMBER Force Field to predict the excess solubility of acetanilide, acetaminophen, phenacetin, benzocaine, and caffeine in binary water/ethanol solvents. The simulations are able to predict the existence of solubility enhancement and the results are in good agreement with available experimental data. The accuracy of the predictions in addition to the generality of the method suggests that molecular simulations may be a valuable design tool for solvent selection in drug development processes.

Predicting the excess solubility of acetanilide, acetaminophen, phenacetin, benzocaine, and caffeine in binary water/ethanol mixtures via molecular simulation

NASA Astrophysics Data System (ADS)

Paluch, Andrew S.; Parameswaran, Sreeja; Liu, Shuai; Kolavennu, Anasuya; Mobley, David L.

2015-01-01

We present a general framework to predict the excess solubility of small molecular solids (such as pharmaceutical solids) in binary solvents via molecular simulation free energy calculations at infinite dilution with conventional molecular models. The present study used molecular dynamics with the General AMBER Force Field to predict the excess solubility of acetanilide, acetaminophen, phenacetin, benzocaine, and caffeine in binary water/ethanol solvents. The simulations are able to predict the existence of solubility enhancement and the results are in good agreement with available experimental data. The accuracy of the predictions in addition to the generality of the method suggests that molecular simulations may be a valuable design tool for solvent selection in drug development processes.

Molecular Rift: Virtual Reality for Drug Designers.

PubMed

Norrby, Magnus; Grebner, Christoph; Eriksson, Joakim; Boström, Jonas

2015-11-23

Recent advances in interaction design have created new ways to use computers. One example is the ability to create enhanced 3D environments that simulate physical presence in the real world--a virtual reality. This is relevant to drug discovery since molecular models are frequently used to obtain deeper understandings of, say, ligand-protein complexes. We have developed a tool (Molecular Rift), which creates a virtual reality environment steered with hand movements. Oculus Rift, a head-mounted display, is used to create the virtual settings. The program is controlled by gesture-recognition, using the gaming sensor MS Kinect v2, eliminating the need for standard input devices. The Open Babel toolkit was integrated to provide access to powerful cheminformatics functions. Molecular Rift was developed with a focus on usability, including iterative test-group evaluations. We conclude with reflections on virtual reality's future capabilities in chemistry and education. Molecular Rift is open source and can be downloaded from GitHub.

GLOBAL EXPRESSION PROFILING AS A TOOL TO DEVELOP MOLECULAR MARKERS LINKED TO HERBICIDE STRESS IN ARABIDOPSIS

EPA Science Inventory

Herbicide drift (unintentional physical movement from target to off-target plants) is a cause of crop loss in US. Low-dose, high-potency herbicides that have short environmental persistence times constrain efforts to develop or identify metabolite or biochemical markers of exposu...

Development of the Central Dogma Concept Inventory (CDCI) Assessment Tool

ERIC Educational Resources Information Center

Newman, Dina L.; Snyder, Christopher W.; Fisk, J. Nick; Wright, L. Kate

2016-01-01

Scientific teaching requires scientifically constructed, field-tested instruments to accurately evaluate student thinking and gauge teacher effectiveness. We have developed a 23-question, multiple select--format assessment of student understanding of the essential concepts of the central dogma of molecular biology that is appropriate for all…

Micro and nanotechnology for biological and biomedical applications.

PubMed

Lim, Chwee Teck; Han, Jongyoon; Guck, Jochen; Espinosa, Horacio

2010-10-01

This special issue contains some of the current state-of-the-art development and use of micro and nanotechnological tools, devices and techniques for both biological and biomedical research and applications. These include nanoparticles for bioimaging and biosensing, optical and biophotonic techniques for probing diseases at the nanoscale, micro and nano-fabricated tools for elucidating molecular mechanisms of mechanotransduction in cell and molecular biology and cell separation microdevices and techniques for isolating and enriching targeted cells for disease detection and diagnosis. Although some of these works are still at the research stage, there is no doubt that some of the important outcomes will eventually see actual biomedical applications in the not too distant future.

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

Atomdroid: a computational chemistry tool for mobile platforms.

PubMed

Feldt, Jonas; Mata, Ricardo A; Dieterich, Johannes M

2012-04-23

We present the implementation of a new molecular mechanics program designed for use in mobile platforms, the first specifically built for these devices. The software is designed to run on Android operating systems and is compatible with several modern tablet-PCs and smartphones available in the market. It includes molecular viewer/builder capabilities with integrated routines for geometry optimizations and Monte Carlo simulations. These functionalities allow it to work as a stand-alone tool. We discuss some particular development aspects, as well as the overall feasibility of using computational chemistry software packages in mobile platforms. Benchmark calculations show that through efficient implementation techniques even hand-held devices can be used to simulate midsized systems using force fields.

BioAssay Research Database (BARD): chemical biology and probe-development enabled by structured metadata and result types

PubMed Central

Howe, E.A.; de Souza, A.; Lahr, D.L.; Chatwin, S.; Montgomery, P.; Alexander, B.R.; Nguyen, D.-T.; Cruz, Y.; Stonich, D.A.; Walzer, G.; Rose, J.T.; Picard, S.C.; Liu, Z.; Rose, J.N.; Xiang, X.; Asiedu, J.; Durkin, D.; Levine, J.; Yang, J.J.; Schürer, S.C.; Braisted, J.C.; Southall, N.; Southern, M.R.; Chung, T.D.Y.; Brudz, S.; Tanega, C.; Schreiber, S.L.; Bittker, J.A.; Guha, R.; Clemons, P.A.

2015-01-01

BARD, the BioAssay Research Database (https://bard.nih.gov/) is a public database and suite of tools developed to provide access to bioassay data produced by the NIH Molecular Libraries Program (MLP). Data from 631 MLP projects were migrated to a new structured vocabulary designed to capture bioassay data in a formalized manner, with particular emphasis placed on the description of assay protocols. New data can be submitted to BARD with a user-friendly set of tools that assist in the creation of appropriately formatted datasets and assay definitions. Data published through the BARD application program interface (API) can be accessed by researchers using web-based query tools or a desktop client. Third-party developers wishing to create new tools can use the API to produce stand-alone tools or new plug-ins that can be integrated into BARD. The entire BARD suite of tools therefore supports three classes of researcher: those who wish to publish data, those who wish to mine data for testable hypotheses, and those in the developer community who wish to build tools that leverage this carefully curated chemical biology resource. PMID:25477388

The contribution of molecular epidemiology to the understanding and control of viral diseases of salmonid aquaculture

PubMed Central

2011-01-01

Molecular epidemiology is a science which utilizes molecular biology to define the distribution of disease in a population (descriptive epidemiology) and relies heavily on integration of traditional (or analytical) epidemiological approaches to identify the etiological determinants of this distribution. The study of viral pathogens of aquaculture has provided many exciting opportunities to apply such tools. This review considers the extent to which molecular epidemiological studies have contributed to better understanding and control of disease in aquaculture, drawing on examples of viral diseases of salmonid fish of commercial significance including viral haemorrhagic septicaemia virus (VHSV), salmonid alphavirus (SAV) and infectious salmon anaemia virus (ISAV). Significant outcomes of molecular epidemiological studies include: Improved taxonomic classification of viruses A better understanding of the natural distribution of viruses An improved understanding of the origins of viral pathogens in aquaculture An improved understanding of the risks of translocation of pathogens outwith their natural host range An increased ability to trace the source of new disease outbreaks Development of a basis for ensuring development of appropriate diagnostic tools An ability to classify isolates and thus target future research aimed at better understanding biological function While molecular epidemiological studies have no doubt already made a significant contribution in these areas, the advent of new technologies such as pyrosequencing heralds a quantum leap in the ability to generate descriptive molecular sequence data. The ability of molecular epidemiology to fulfil its potential to translate complex disease pathways into relevant fish health policy is thus unlikely to be limited by the generation of descriptive molecular markers. More likely, full realisation of the potential to better explain viral transmission pathways will be dependent on the ability to assimilate and analyse knowledge from a range of more traditional information sources. The development of methods to systematically record and share such epidemiologically important information thus represents a major challenge for fish health professionals in making the best future use of molecular data in supporting fish health policy and disease control. PMID:21466673

iDrug: a web-accessible and interactive drug discovery and design platform

PubMed Central

2014-01-01

Background The progress in computer-aided drug design (CADD) approaches over the past decades accelerated the early-stage pharmaceutical research. Many powerful standalone tools for CADD have been developed in academia. As programs are developed by various research groups, a consistent user-friendly online graphical working environment, combining computational techniques such as pharmacophore mapping, similarity calculation, scoring, and target identification is needed. Results We presented a versatile, user-friendly, and efficient online tool for computer-aided drug design based on pharmacophore and 3D molecular similarity searching. The web interface enables binding sites detection, virtual screening hits identification, and drug targets prediction in an interactive manner through a seamless interface to all adapted packages (e.g., Cavity, PocketV.2, PharmMapper, SHAFTS). Several commercially available compound databases for hit identification and a well-annotated pharmacophore database for drug targets prediction were integrated in iDrug as well. The web interface provides tools for real-time molecular building/editing, converting, displaying, and analyzing. All the customized configurations of the functional modules can be accessed through featured session files provided, which can be saved to the local disk and uploaded to resume or update the history work. Conclusions iDrug is easy to use, and provides a novel, fast and reliable tool for conducting drug design experiments. By using iDrug, various molecular design processing tasks can be submitted and visualized simply in one browser without installing locally any standalone modeling softwares. iDrug is accessible free of charge at http://lilab.ecust.edu.cn/idrug. PMID:24955134

Molecular imaging to track Parkinson's disease and atypical parkinsonisms: New imaging frontiers.

PubMed

Strafella, Antonio P; Bohnen, Nicolaas I; Perlmutter, Joel S; Eidelberg, David; Pavese, Nicola; Van Eimeren, Thilo; Piccini, Paola; Politis, Marios; Thobois, Stephane; Ceravolo, Roberto; Higuchi, Makoto; Kaasinen, Valtteri; Masellis, Mario; Peralta, M Cecilia; Obeso, Ignacio; Pineda-Pardo, Jose Ángel; Cilia, Roberto; Ballanger, Benedicte; Niethammer, Martin; Stoessl, Jon A

2017-02-01

Molecular imaging has proven to be a powerful tool for investigation of parkinsonian disorders. One current challenge is to identify biomarkers of early changes that may predict the clinical trajectory of parkinsonian disorders. Exciting new tracer developments hold the potential for in vivo markers of underlying pathology. Herein, we provide an overview of molecular imaging advances and how these approaches help us to understand PD and atypical parkinsonisms. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

Molecular Chemistry as Diagnostic tool for Starbursts and AGNs The Molecular ISM of NGC 4418

NASA Astrophysics Data System (ADS)

Monje, R. R.; Aalto, S.

We present a brief discussion of the statistical surveys of HCN, HNC, HCO+ and HC3N that are used to model the extreme environments in the nuclei of starbursts and AGNs. Molecular studies are particularly useful for probing the deeply enshrouded dusty nuclei of luminous infrared galaxies. Here we present NGC 4418 as an example, one of the closest LIRG with high obscuration of the inner region. The interpretation of the observed line ratios require parallel development of theoretical chemical and radiative transport models.

BATMAN-TCM: a Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine.

PubMed

Liu, Zhongyang; Guo, Feifei; Wang, Yong; Li, Chun; Zhang, Xinlei; Li, Honglei; Diao, Lihong; Gu, Jiangyong; Wang, Wei; Li, Dong; He, Fuchu

2016-02-16

Traditional Chinese Medicine (TCM), with a history of thousands of years of clinical practice, is gaining more and more attention and application worldwide. And TCM-based new drug development, especially for the treatment of complex diseases is promising. However, owing to the TCM's diverse ingredients and their complex interaction with human body, it is still quite difficult to uncover its molecular mechanism, which greatly hinders the TCM modernization and internationalization. Here we developed the first online Bioinformatics Analysis Tool for Molecular mechANism of TCM (BATMAN-TCM). Its main functions include 1) TCM ingredients' target prediction; 2) functional analyses of targets including biological pathway, Gene Ontology functional term and disease enrichment analyses; 3) the visualization of ingredient-target-pathway/disease association network and KEGG biological pathway with highlighted targets; 4) comparison analysis of multiple TCMs. Finally, we applied BATMAN-TCM to Qishen Yiqi dripping Pill (QSYQ) and combined with subsequent experimental validation to reveal the functions of renin-angiotensin system responsible for QSYQ's cardioprotective effects for the first time. BATMAN-TCM will contribute to the understanding of the "multi-component, multi-target and multi-pathway" combinational therapeutic mechanism of TCM, and provide valuable clues for subsequent experimental validation, accelerating the elucidation of TCM's molecular mechanism. BATMAN-TCM is available at http://bionet.ncpsb.org/batman-tcm.

Game On, Science - How Video Game Technology May Help Biologists Tackle Visualization Challenges

PubMed Central

Da Silva, Franck; Empereur-mot, Charly; Chavent, Matthieu; Baaden, Marc

2013-01-01

The video games industry develops ever more advanced technologies to improve rendering, image quality, ergonomics and user experience of their creations providing very simple to use tools to design new games. In the molecular sciences, only a small number of experts with specialized know-how are able to design interactive visualization applications, typically static computer programs that cannot easily be modified. Are there lessons to be learned from video games? Could their technology help us explore new molecular graphics ideas and render graphics developments accessible to non-specialists? This approach points to an extension of open computer programs, not only providing access to the source code, but also delivering an easily modifiable and extensible scientific research tool. In this work, we will explore these questions using the Unity3D game engine to develop and prototype a biological network and molecular visualization application for subsequent use in research or education. We have compared several routines to represent spheres and links between them, using either built-in Unity3D features or our own implementation. These developments resulted in a stand-alone viewer capable of displaying molecular structures, surfaces, animated electrostatic field lines and biological networks with powerful, artistic and illustrative rendering methods. We consider this work as a proof of principle demonstrating that the functionalities of classical viewers and more advanced novel features could be implemented in substantially less time and with less development effort. Our prototype is easily modifiable and extensible and may serve others as starting point and platform for their developments. A webserver example, standalone versions for MacOS X, Linux and Windows, source code, screen shots, videos and documentation are available at the address: http://unitymol.sourceforge.net/. PMID:23483961

Game on, science - how video game technology may help biologists tackle visualization challenges.

PubMed

Lv, Zhihan; Tek, Alex; Da Silva, Franck; Empereur-mot, Charly; Chavent, Matthieu; Baaden, Marc

2013-01-01

The video games industry develops ever more advanced technologies to improve rendering, image quality, ergonomics and user experience of their creations providing very simple to use tools to design new games. In the molecular sciences, only a small number of experts with specialized know-how are able to design interactive visualization applications, typically static computer programs that cannot easily be modified. Are there lessons to be learned from video games? Could their technology help us explore new molecular graphics ideas and render graphics developments accessible to non-specialists? This approach points to an extension of open computer programs, not only providing access to the source code, but also delivering an easily modifiable and extensible scientific research tool. In this work, we will explore these questions using the Unity3D game engine to develop and prototype a biological network and molecular visualization application for subsequent use in research or education. We have compared several routines to represent spheres and links between them, using either built-in Unity3D features or our own implementation. These developments resulted in a stand-alone viewer capable of displaying molecular structures, surfaces, animated electrostatic field lines and biological networks with powerful, artistic and illustrative rendering methods. We consider this work as a proof of principle demonstrating that the functionalities of classical viewers and more advanced novel features could be implemented in substantially less time and with less development effort. Our prototype is easily modifiable and extensible and may serve others as starting point and platform for their developments. A webserver example, standalone versions for MacOS X, Linux and Windows, source code, screen shots, videos and documentation are available at the address: http://unitymol.sourceforge.net/.

Molecular beacon sequence design algorithm.

PubMed

Monroe, W Todd; Haselton, Frederick R

2003-01-01

A method based on Web-based tools is presented to design optimally functioning molecular beacons. Molecular beacons, fluorogenic hybridization probes, are a powerful tool for the rapid and specific detection of a particular nucleic acid sequence. However, their synthesis costs can be considerable. Since molecular beacon performance is based on its sequence, it is imperative to rationally design an optimal sequence before synthesis. The algorithm presented here uses simple Microsoft Excel formulas and macros to rank candidate sequences. This analysis is carried out using mfold structural predictions along with other free Web-based tools. For smaller laboratories where molecular beacons are not the focus of research, the public domain algorithm described here may be usefully employed to aid in molecular beacon design.

Strategic placement of stereogenic centers in molecular materials for second harmonic generation.

PubMed

Gangopadhyay, P; Rao, D Narayana; Agranat, Israel; Radhakrishnan, T P

2002-01-01

Basic aspects of the nonlinear optical phenomenon of second harmonic generation (SHG) and the assembly of molecular materials for SHG are reviewed. Extensive use of chirality as a convenient tool to generate noncentrosymmetricity in molecular lattices, an essential requirement for the development of quadratic nonlinear optical materials, is noted. An overview of our investigations of chiral diaminodicyanoquinodimethanes is presented, which provides insight into a systematic approach to the effective deployment of chirality to achieve optimal molecular orientations for enhanced solid state SHG. Extension of these ideas to the realization of strong SHG in materials based on helical superstructures is outlined.

Foundational concepts and underlying theories for majors in "biochemistry and molecular biology".

PubMed

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

2013-01-01

Over the past two years, through an NSF RCN UBE grant, the ASBMB has held regional workshops for faculty members and science educators from around the country that focused on identifying: 1) core principles of biochemistry and molecular biology, 2) essential concepts and underlying theories from physics, chemistry, and mathematics, and 3) foundational skills that undergraduate majors in biochemistry and molecular biology must understand to complete their major coursework. Using information gained from these workshops, as well as from the ASBMB accreditation working group and the NSF Vision and Change report, the Core Concepts working group has developed a consensus list of learning outcomes and objectives based on five foundational concepts (evolution, matter and energy transformation, homeostasis, information flow, and macromolecular structure and function) that represent the expected conceptual knowledge base for undergraduate degrees in biochemistry and molecular biology. This consensus will aid biochemistry and molecular biology educators in the development of assessment tools for the new ASBMB recommended curriculum. © 2013 by The International Union of Biochemistry and Molecular Biology.

Bioinformatics and molecular modeling in glycobiology

PubMed Central

Schloissnig, Siegfried

2010-01-01

The field of glycobiology is concerned with the study of the structure, properties, and biological functions of the family of biomolecules called carbohydrates. Bioinformatics for glycobiology is a particularly challenging field, because carbohydrates exhibit a high structural diversity and their chains are often branched. Significant improvements in experimental analytical methods over recent years have led to a tremendous increase in the amount of carbohydrate structure data generated. Consequently, the availability of databases and tools to store, retrieve and analyze these data in an efficient way is of fundamental importance to progress in glycobiology. In this review, the various graphical representations and sequence formats of carbohydrates are introduced, and an overview of newly developed databases, the latest developments in sequence alignment and data mining, and tools to support experimental glycan analysis are presented. Finally, the field of structural glycoinformatics and molecular modeling of carbohydrates, glycoproteins, and protein–carbohydrate interaction are reviewed. PMID:20364395

Delta opioid receptor analgesia: recent contributions from pharmacology and molecular approaches

PubMed Central

Gavériaux-Ruff, Claire; Kieffer, Brigitte Lina

2012-01-01

Delta opioid receptors represent a promising target for the development of novel analgesics. A number of tools have been developed recently that have significantly improved our knowledge of delta receptor function in pain control. These include several novel delta agonists with potent analgesic properties, as well as genetic mouse models with targeted mutations in the delta opioid receptor gene. Also, recent findings have further documented the regulation of delta receptor function at cellular level, which impacts on the pain-reducing activity of the receptor. These regulatory mechanisms occur at transcriptional and post-translational levels, along agonist-induced receptor activation, signaling and trafficking, or in interaction with other receptors and neuromodulatory systems. All these tools for in vivo research, as well as proposed mechanisms at molecular level, have tremendously increased our understanding of delta receptor physiology, and contribute to designing innovative strategies for the treatment of chronic pain and other diseases such as mood disorders. PMID:21836459

Current and future molecular diagnostics in colorectal cancer and colorectal adenoma.

PubMed

Tsang, Andy Hin-Fung; Cheng, Ka-Ho; Wong, Apple Siu-Ping; Ng, Simon Siu-Man; Ma, Brigette Buig-Yue; Chan, Charles Ming-Lok; Tsui, Nancy Bo-Yin; Chan, Lawrence Wing-Chi; Yung, Benjamin Yat-Ming; Wong, Sze-Chuen Cesar

2014-04-14

Colorectal cancer (CRC) is one of the most prevalent cancers in developed countries. On the other hand, CRC is also one of the most curable cancers if it is detected in early stages through regular colonoscopy or sigmoidoscopy. Since CRC develops slowly from precancerous lesions, early detection can reduce both the incidence and mortality of the disease. Fecal occult blood test is a widely used non-invasive screening tool for CRC. Although fecal occult blood test is simple and cost-effective in screening CRC, there is room for improvement in terms of the accuracy of the test. Genetic dysregulations have been found to play an important role in CRC development. With better understanding of the molecular basis of CRC, there is a growing expectation on the development of diagnostic tests based on more sensitive and specific molecular markers and those tests may provide a breakthrough to the limitations of current screening tests for CRC. In this review, the molecular basis of CRC development, the characteristics and applications of different non-invasive molecular biomarkers, as well as the technologies available for the detection were discussed. This review intended to provide a summary on the current and future molecular diagnostics in CRC and its pre-malignant state, colorectal adenoma.

Current and future molecular diagnostics in colorectal cancer and colorectal adenoma

PubMed Central

Tsang, Andy Hin-Fung; Cheng, Ka-Ho; Wong, Apple Siu-Ping; Ng, Simon Siu-Man; Ma, Brigette Buig-Yue; Chan, Charles Ming-Lok; Tsui, Nancy Bo-Yin; Chan, Lawrence Wing-Chi; Yung, Benjamin Yat-Ming; Wong, Sze-Chuen Cesar

2014-01-01

Colorectal cancer (CRC) is one of the most prevalent cancers in developed countries. On the other hand, CRC is also one of the most curable cancers if it is detected in early stages through regular colonoscopy or sigmoidoscopy. Since CRC develops slowly from precancerous lesions, early detection can reduce both the incidence and mortality of the disease. Fecal occult blood test is a widely used non-invasive screening tool for CRC. Although fecal occult blood test is simple and cost-effective in screening CRC, there is room for improvement in terms of the accuracy of the test. Genetic dysregulations have been found to play an important role in CRC development. With better understanding of the molecular basis of CRC, there is a growing expectation on the development of diagnostic tests based on more sensitive and specific molecular markers and those tests may provide a breakthrough to the limitations of current screening tests for CRC. In this review, the molecular basis of CRC development, the characteristics and applications of different non-invasive molecular biomarkers, as well as the technologies available for the detection were discussed. This review intended to provide a summary on the current and future molecular diagnostics in CRC and its pre-malignant state, colorectal adenoma. PMID:24744577

Picture this: The value of multiple visual representations for student learning of quantum concepts in general chemistry

NASA Astrophysics Data System (ADS)

Allen, Emily Christine

Mental models for scientific learning are often defined as, "cognitive tools situated between experiments and theories" (Duschl & Grandy, 2012). In learning, these cognitive tools are used to not only take in new information, but to help problem solve in new contexts. Nancy Nersessian (2008) describes a mental model as being "[loosely] characterized as a representation of a system with interactive parts with representations of those interactions. Models can be qualitative, quantitative, and/or simulative (mental, physical, computational)" (p. 63). If conceptual parts used by the students in science education are inaccurate, then the resulting model will not be useful. Students in college general chemistry courses are presented with multiple abstract topics and often struggle to fit these parts into complete models. This is especially true for topics that are founded on quantum concepts, such as atomic structure and molecular bonding taught in college general chemistry. The objectives of this study were focused on how students use visual tools introduced during instruction to reason with atomic and molecular structure, what misconceptions may be associated with these visual tools, and how visual modeling skills may be taught to support students' use of visual tools for reasoning. The research questions for this study follow from Gilbert's (2008) theory that experts use multiple representations when reasoning and modeling a system, and Kozma and Russell's (2005) theory of representational competence levels. This study finds that as students developed greater command of their understanding of abstract quantum concepts, they spontaneously provided additional representations to describe their more sophisticated models of atomic and molecular structure during interviews. This suggests that when visual modeling with multiple representations is taught, along with the limitations of the representations, it can assist students in the development of models for reasoning about abstract topics such as atomic and molecular structure. There is further gain if students' difficulties with these representations are targeted through the use additional instruction such as a workbook that requires the students to exercise their visual modeling skills.

FPV: fast protein visualization using Java 3D.

PubMed

Can, Tolga; Wang, Yujun; Wang, Yuan-Fang; Su, Jianwen

2003-05-22

Many tools have been developed to visualize protein structures. Tools that have been based on Java 3D((TM)) are compatible among different systems and they can be run remotely through web browsers. However, using Java 3D for visualization has some performance issues with it. The primary concerns about molecular visualization tools based on Java 3D are in their being slow in terms of interaction speed and in their inability to load large molecules. This behavior is especially apparent when the number of atoms to be displayed is huge, or when several proteins are to be displayed simultaneously for comparison. In this paper we present techniques for organizing a Java 3D scene graph to tackle these problems. We have developed a protein visualization system based on Java 3D and these techniques. We demonstrate the effectiveness of the proposed method by comparing the visualization component of our system with two other Java 3D based molecular visualization tools. In particular, for van der Waals display mode, with the efficient organization of the scene graph, we could achieve up to eight times improvement in rendering speed and could load molecules three times as large as the previous systems could. EPV is freely available with source code at the following URL: http://www.cs.ucsb.edu/~tcan/fpv/

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

PubMed

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

2017-06-06

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

Microcutting characteristics on the single crystal diamond tool with edge radius using molecular dynamics

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

Kim, Jeong-Du; Moon, Chan-Hong

1995-12-31

Ultraprecision metal cutting (UPMC) technology which makes possible submicrometer form accuracy and manometer roughness is developed to reach the 1nm nominal (undeformed) thickness of cut. At this thickness level, a few of atom`s layers should be considered. In this paper using the Molecuar Dynamics simulation, the phenomena of microcutting with a subnanometer chip thickness, the cutting mechanism for tool edge configuration to consider the sharp edge and round edge tool, the cut material and cutting speed are evaluated. Cutting mechanism of subnanometer depth of cut is evaluated.

Educational websites--Bioinformatics Tools II.

PubMed

Lomberk, Gwen

2009-01-01

In this issue, the highlighted websites are a continuation of a series of educational websites; this one in particular from a couple of years ago, Bioinformatics Tools [Pancreatology 2005;5:314-315]. These include sites that are valuable resources for many research needs in genomics and proteomics. Bioinformatics has become a laboratory tool to map sequences to databases, develop models of molecular interactions, evaluate structural compatibilities, describe differences between normal and disease-associated DNA, identify conserved motifs within proteins, and chart extensive signaling networks, all in silico. Copyright 2008 S. Karger AG, Basel and IAP.

Characterizing the heterogeneity of tumor tissues from spatially resolved molecular measures

PubMed Central

Zavodszky, Maria I.

2017-01-01

Background Tumor heterogeneity can manifest itself by sub-populations of cells having distinct phenotypic profiles expressed as diverse molecular, morphological and spatial distributions. This inherent heterogeneity poses challenges in terms of diagnosis, prognosis and efficient treatment. Consequently, tools and techniques are being developed to properly characterize and quantify tumor heterogeneity. Multiplexed immunofluorescence (MxIF) is one such technology that offers molecular insight into both inter-individual and intratumor heterogeneity. It enables the quantification of both the concentration and spatial distribution of 60+ proteins across a tissue section. Upon bioimage processing, protein expression data can be generated for each cell from a tissue field of view. Results The Multi-Omics Heterogeneity Analysis (MOHA) tool was developed to compute tissue heterogeneity metrics from MxIF spatially resolved tissue imaging data. This technique computes the molecular state of each cell in a sample based on a pathway or gene set. Spatial states are then computed based on the spatial arrangements of the cells as distinguished by their respective molecular states. MOHA computes tissue heterogeneity metrics from the distributions of these molecular and spatially defined states. A colorectal cancer cohort of approximately 700 subjects with MxIF data is presented to demonstrate the MOHA methodology. Within this dataset, statistically significant correlations were found between the intratumor AKT pathway state diversity and cancer stage and histological tumor grade. Furthermore, intratumor spatial diversity metrics were found to correlate with cancer recurrence. Conclusions MOHA provides a simple and robust approach to characterize molecular and spatial heterogeneity of tissues. Research projects that generate spatially resolved tissue imaging data can take full advantage of this useful technique. The MOHA algorithm is implemented as a freely available R script (see supplementary information). PMID:29190747

State of the Art Assessment of Simulation in Advanced Materials Development

NASA Technical Reports Server (NTRS)

Wise, Kristopher E.

2008-01-01

Advances in both the underlying theory and in the practical implementation of molecular modeling techniques have increased their value in the advanced materials development process. The objective is to accelerate the maturation of emerging materials by tightly integrating modeling with the other critical processes: synthesis, processing, and characterization. The aims of this report are to summarize the state of the art of existing modeling tools and to highlight a number of areas in which additional development is required. In an effort to maintain focus and limit length, this survey is restricted to classical simulation techniques including molecular dynamics and Monte Carlo simulations.

Developing Pedagogical Tools to Improve Teaching Multiple Models of the Gene in High School

ERIC Educational Resources Information Center

Auckaraaree, Nantaya

2013-01-01

Multiple models of the gene are used to explore genetic phenomena in scientific practices and in the classroom. In genetics curricula, the classical and molecular models are presented in disconnected domains. Research demonstrates that, without explicit connections, students have difficulty developing an understanding of the gene that spans…

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.

Predicting the excess solubility of acetanilide, acetaminophen, phenacetin, benzocaine, and caffeine in binary water/ethanol mixtures via molecular simulation

PubMed Central

Paluch, Andrew S.; Parameswaran, Sreeja; Liu, Shuai; Kolavennu, Anasuya; Mobley, David L.

2015-01-01

We present a general framework to predict the excess solubility of small molecular solids (such as pharmaceutical solids) in binary solvents via molecular simulation free energy calculations at infinite dilution with conventional molecular models. The present study used molecular dynamics with the General AMBER Force Field to predict the excess solubility of acetanilide, acetaminophen, phenacetin, benzocaine, and caffeine in binary water/ethanol solvents. The simulations are able to predict the existence of solubility enhancement and the results are in good agreement with available experimental data. The accuracy of the predictions in addition to the generality of the method suggests that molecular simulations may be a valuable design tool for solvent selection in drug development processes. PMID:25637996

Characterization and application of newly developed polymorphic microsatellite markers in the Ezo red fox (Vulpes vulpes schrencki).

PubMed

Tada, T; Seki, Y; Kameyama, Y; Kikkawa, Y; Wada, K

2016-12-19

The Ezo red fox (Vulpes vulpes schrencki), a subspecies endemic to Hokkaido island, Japan, is a known host species for the tapeworm Echinococcus multilocularis. To develop tools for molecular ecological studies, we isolated 28 microsatellite regions from the genome of Ezo red fox, and developed 18 polymorphic microsatellite markers. These markers were characterized using 7 individuals and 22 fecal samples of the Ezo red fox. The number of alleles for these markers ranged from 1 to 7, and the observed heterozygosity, estimated on the basis of the genotypes of 7 individuals, ranged from 0.29 to 1.00. All markers, except DvNok5, were in Hardy-Weinberg equilibrium (P > 0.05), and no linkage disequilibrium was detected among these loci, except between DvNok14 and DvNok28 (P = 0.01). Moreover, six microsatellite loci were successfully genotyped using feces-derived DNA from the Ezo red fox. The markers developed in our study might serve as a useful tool for molecular ecological studies of the Ezo red fox.

Lymph Node Metastases Optical Molecular Diagnostic and Radiation Therapy

DTIC Science & Technology

2017-03-01

structures and not molecular functions. The one tool commonly used for metastases imaging is nuclear medicine. Positron emission tomography, PET, is...be visualized at a relevant stage., largely because most imaging is based upon structures and not molecular functions. But there are no tools to...system suitable for imaging signals from in small animals on the standard radiation therapy tools. (3) To evaluate the limits on structural , metabolic

Expanding the scale of molecular biophysics.

PubMed

Levine, Herbert

2016-10-07

Here, I argue that some of the secrets of complex biological function rely on assemblies of many heterogeneous proteins that together enable sophisticated sensing and actuating processes. Evolution seems to delight in making these structures and in continually elaborating upon their capabilities. Developing tools that can go beyond the few protein limit, both on the experimental frontier and from a theoretical, conceptual framework, should be an extremely high priority for the next generation of molecular biophysicists.

Leaving the structural ivory tower, assisted by interactive 3D PDF.

PubMed

Kumar, Pravin; Ziegler, Alexander; Grahn, Alexander; Hee, Chee Seng; Ziegler, Andreas

2010-08-01

The ability to embed interactive three-dimensional (3D) models into electronic publications in portable document format (PDF) greatly enhances the accessibility of molecular structures. Here, we report advances in this procedure and discuss what is needed to develop this format into a truly useful tool for the structural biology community as well as for readers who are less well trained in molecular visualization. Copyright 2010 Elsevier Ltd. All rights reserved.

Phytophthora database 2.0: update and future direction.

PubMed

Park, Bongsoo; Martin, Frank; Geiser, David M; Kim, Hye-Seon; Mansfield, Michele A; Nikolaeva, Ekaterina; Park, Sook-Young; Coffey, Michael D; Russo, Joseph; Kim, Seong H; Balci, Yilmaz; Abad, Gloria; Burgess, Treena; Grünwald, Niklaus J; Cheong, Kyeongchae; Choi, Jaeyoung; Lee, Yong-Hwan; Kang, Seogchan

2013-12-01

The online community resource Phytophthora database (PD) was developed to support accurate and rapid identification of Phytophthora and to help characterize and catalog the diversity and evolutionary relationships within the genus. Since its release in 2008, the sequence database has grown to cover 1 to 12 loci for ≈2,600 isolates (representing 138 described and provisional species). Sequences of multiple mitochondrial loci were added to complement nuclear loci-based phylogenetic analyses and diagnostic tool development. Key characteristics of most newly described and provisional species have been summarized. Other additions to improve the PD functionality include: (i) geographic information system tools that enable users to visualize the geographic origins of chosen isolates on a global-scale map, (ii) a tool for comparing genetic similarity between isolates via microsatellite markers to support population genetic studies, (iii) a comprehensive review of molecular diagnostics tools and relevant references, (iv) sequence alignments used to develop polymerase chain reaction-based diagnostics tools to support their utilization and new diagnostic tool development, and (v) an online community forum for sharing and preserving experience and knowledge accumulated in the global Phytophthora community. Here we present how these improvements can support users and discuss the PD's future direction.

A molecular signaling approach to linking intraspecific variation and macro-evolutionary patterns.

PubMed

Swanson, Eli M; Snell-Rood, Emilie C

2014-11-01

Macro-evolutionary comparisons are a valued tool in evolutionary biology. Nevertheless, our understanding of how systems involved in molecular signaling change in concert with phenotypic diversification has lagged. We argue that integrating our understanding of the evolution of molecular signaling systems with phylogenetic comparative methods is an important step toward understanding the processes linking variation among individuals with variation among species. Focusing mostly on the endocrine system, we discuss how the complexity and mechanistic nature of molecular signaling systems may influence the application and interpretation of macro-evolutionary comparisons. We also detail five hypotheses concerning the role that physiological mechanisms can play in shaping macro-evolutionary patterns, and discuss ways in which these hypotheses could influence phenotypic diversification. Finally, we review a series of tools able to analyze the complexity of physiological systems and the way they change in concert with the phenotypes for which they coordinate development. © The Author 2014. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

Bio-AIMS Collection of Chemoinformatics Web Tools based on Molecular Graph Information and Artificial Intelligence Models.

PubMed

Munteanu, Cristian R; Gonzalez-Diaz, Humberto; Garcia, Rafael; Loza, Mabel; Pazos, Alejandro

2015-01-01

The molecular information encoding into molecular descriptors is the first step into in silico Chemoinformatics methods in Drug Design. The Machine Learning methods are a complex solution to find prediction models for specific biological properties of molecules. These models connect the molecular structure information such as atom connectivity (molecular graphs) or physical-chemical properties of an atom/group of atoms to the molecular activity (Quantitative Structure - Activity Relationship, QSAR). Due to the complexity of the proteins, the prediction of their activity is a complicated task and the interpretation of the models is more difficult. The current review presents a series of 11 prediction models for proteins, implemented as free Web tools on an Artificial Intelligence Model Server in Biosciences, Bio-AIMS (http://bio-aims.udc.es/TargetPred.php). Six tools predict protein activity, two models evaluate drug - protein target interactions and the other three calculate protein - protein interactions. The input information is based on the protein 3D structure for nine models, 1D peptide amino acid sequence for three tools and drug SMILES formulas for two servers. The molecular graph descriptor-based Machine Learning models could be useful tools for in silico screening of new peptides/proteins as future drug targets for specific treatments.

The supersonic molecular beam injector as a reliable tool for plasma fueling and physics experiment on HL-2A.

PubMed

Chen, C Y; Yu, D L; Feng, B B; Yao, L H; Song, X M; Zang, L G; Gao, X Y; Yang, Q W; Duan, X R

2016-09-01

On HL-2A tokamak, supersonic molecular beam injection (SMBI) has been developed as a routine refueling method. The key components of the system are an electromagnetic valve and a conic nozzle. The valve and conic nozzle are assembled to compose the simplified Laval nozzle for generating the pulsed beam. The appurtenance of the system includes the cooling system serving the cooled SMBI generation and the in situ calibration component for quantitative injection. Compared with the conventional gas puffing, the SMBI features prompt response and larger fueling flux. These merits devote the SMBI a good fueling method, an excellent plasma density feedback control tool, and an edge localized mode mitigation resource.

Molecular neuroanatomy: a generation of progress.

PubMed

Pollock, Jonathan D; Wu, Da-Yu; Satterlee, John S

2014-02-01

The neuroscience research landscape has changed dramatically over the past decade. Specifically, an impressive array of new tools and technologies have been generated, including but not limited to: brain gene expression atlases, genetically encoded proteins to monitor and manipulate neuronal activity, and new methods for imaging and mapping circuits. However, despite these technological advances, several significant challenges must be overcome to enable a better understanding of brain function and to develop cell type-targeted therapeutics to treat brain disorders. This review provides an overview of some of the tools and technologies currently being used to advance the field of molecular neuroanatomy, and also discusses emerging technologies that may enable neuroscientists to address these crucial scientific challenges over the coming decade. Published by Elsevier Ltd.

TOXCAST, A TOOL FOR CATEGORIZATION AND ...

EPA Pesticide Factsheets

Across several EPA Program Offices (e.g., OPPTS, OW, OAR), there is a clear need to develop strategies and methods to screen large numbers of chemicals for potential toxicity, and to use the resulting information to prioritize the use of testing resources towards those entities and endpoints that present the greatest likelihood of risk to human health and the environment. This need could be addressed using the experience of the pharmaceutical industry in the use of advanced modern molecular biology and computational chemistry tools for the development of new drugs, with appropriate adjustment to the needs and desires of environmental toxicology. A conceptual approach named ToxCast has been developed to address the needs of EPA Program Offices in the area of prioritization and screening. Modern computational chemistry and molecular biology tools bring enabling technologies forward that can provide information about the physical and biological properties of large numbers of chemicals. The essence of the proposal is to conduct a demonstration project based upon a rich toxicological database (e.g., registered pesticides, or the chemicals tested in the NTP bioassay program), select a fairly large number (50-100 or more chemicals) representative of a number of differing structural classes and phenotypic outcomes (e.g., carcinogens, reproductive toxicants, neurotoxicants), and evaluate them across a broad spectrum of information domains that modern technology has pro

Development of the Central Dogma Concept Inventory (CDCI) Assessment Tool

PubMed Central

Newman, Dina L.; Snyder, Christopher W.; Fisk, J. Nick; Wright, L. Kate

2016-01-01

Scientific teaching requires scientifically constructed, field-tested instruments to accurately evaluate student thinking and gauge teacher effectiveness. We have developed a 23-question, multiple select–format assessment of student understanding of the essential concepts of the central dogma of molecular biology that is appropriate for all levels of undergraduate biology. Questions for the Central Dogma Concept Inventory (CDCI) tool were developed and iteratively revised based on student language and review by experts. The ability of the CDCI to discriminate between levels of understanding of the central dogma is supported by field testing (N = 54), and large-scale beta testing (N = 1733). Performance on the assessment increased with experience in biology; scores covered a broad range and showed no ceiling effect, even with senior biology majors, and pre/posttesting of a single class focused on the central dogma showed significant improvement. The multiple-select format reduces the chances of correct answers by random guessing, allows students at different levels to exhibit the extent of their knowledge, and provides deeper insight into the complexity of student thinking on each theme. To date, the CDCI is the first tool dedicated to measuring student thinking about the central dogma of molecular biology, and version 5 is ready to use. PMID:27055775

Diagnosis and therapy with CRISPR advanced CRISPR based tools for point of care diagnostics and early therapies.

PubMed

Uppada, Vanita; Gokara, Mahesh; Rasineni, Girish Kumar

2018-05-20

Molecular diagnostics is of critical importance to public health worldwide. It facilitates not only detection and characterization of diseases, but also monitors drug responses, assists in the identification of genetic modifiers and disease susceptibility. Based upon DNA variation, a wide range of molecular-based tests are available to assess/diagnose diseases. The CRISPR-Cas9 system has recently emerged as a versatile tool for biological and medical research. In this system, a single guide RNA (sgRNA) directs the endonuclease Cas9 to a targeted DNA sequence for site-specific manipulation. As designing CRISPR-guided nucleases can be done easily and relatively fast, the CRISPR/Cas9 system has evolved as widely used DNA editing tool. This technique led to a large number of gene editing studies in variety of organisms. CRISPR/Cas9-mediated diagnosis and therapy has picked up pace due to specificity and accuracy of CRISPR. The aim is not only to identify specific pathogens, especially virus but also to repair disease-causing alleles by changing the DNA sequence at the exact location on the chromosome. At present, PCR-based molecular diagnostic testing predominates; however, alternative technologies aimed at reducing genome complexity without PCR are anticipated to gain momentum in the coming years. Furthermore, development of integrated chip devices should allow point-of-care testing and facilitate genetic readouts from single cells and molecules. Together with molecular based therapy CRISPR based diagnostic testing will be a revolution in modern health care settings. In this review, we emphasize on current developing diagnostic techniques based upon CRISPR Cas approach along with short insights on its therapeutic usage. Copyright © 2018 Elsevier B.V. All rights reserved.

A web platform for the network analysis of high-throughput data in melanoma and its use to investigate mechanisms of resistance to anti-PD1 immunotherapy.

PubMed

Dreyer, Florian S; Cantone, Martina; Eberhardt, Martin; Jaitly, Tanushree; Walter, Lisa; Wittmann, Jürgen; Gupta, Shailendra K; Khan, Faiz M; Wolkenhauer, Olaf; Pützer, Brigitte M; Jäck, Hans-Martin; Heinzerling, Lucie; Vera, Julio

2018-06-01

Cellular phenotypes are established and controlled by complex and precisely orchestrated molecular networks. In cancer, mutations and dysregulations of multiple molecular factors perturb the regulation of these networks and lead to malignant transformation. High-throughput technologies are a valuable source of information to establish the complex molecular relationships behind the emergence of malignancy, but full exploitation of this massive amount of data requires bioinformatics tools that rely on network-based analyses. In this report we present the Virtual Melanoma Cell, an online tool developed to facilitate the mining and interpretation of high-throughput data on melanoma by biomedical researches. The platform is based on a comprehensive, manually generated and expert-validated regulatory map composed of signaling pathways important in malignant melanoma. The Virtual Melanoma Cell is a tool designed to accept, visualize and analyze user-generated datasets. It is available at: https://www.vcells.net/melanoma. To illustrate the utilization of the web platform and the regulatory map, we have analyzed a large publicly available dataset accounting for anti-PD1 immunotherapy treatment of malignant melanoma patients. Copyright © 2018 Elsevier B.V. All rights reserved.

Extension of least squares spectral resolution algorithm to high-resolution lipidomics data.

PubMed

Zeng, Ying-Xu; Mjøs, Svein Are; David, Fabrice P A; Schmid, Adrien W

2016-03-31

Lipidomics, which focuses on the global study of molecular lipids in biological systems, has been driven tremendously by technical advances in mass spectrometry (MS) instrumentation, particularly high-resolution MS. This requires powerful computational tools that handle the high-throughput lipidomics data analysis. To address this issue, a novel computational tool has been developed for the analysis of high-resolution MS data, including the data pretreatment, visualization, automated identification, deconvolution and quantification of lipid species. The algorithm features the customized generation of a lipid compound library and mass spectral library, which covers the major lipid classes such as glycerolipids, glycerophospholipids and sphingolipids. Next, the algorithm performs least squares resolution of spectra and chromatograms based on the theoretical isotope distribution of molecular ions, which enables automated identification and quantification of molecular lipid species. Currently, this methodology supports analysis of both high and low resolution MS as well as liquid chromatography-MS (LC-MS) lipidomics data. The flexibility of the methodology allows it to be expanded to support more lipid classes and more data interpretation functions, making it a promising tool in lipidomic data analysis. Copyright © 2016 Elsevier B.V. All rights reserved.

Rosetta Structure Prediction as a Tool for Solving Difficult Molecular Replacement Problems.

PubMed

DiMaio, Frank

2017-01-01

Molecular replacement (MR), a method for solving the crystallographic phase problem using phases derived from a model of the target structure, has proven extremely valuable, accounting for the vast majority of structures solved by X-ray crystallography. However, when the resolution of data is low, or the starting model is very dissimilar to the target protein, solving structures via molecular replacement may be very challenging. In recent years, protein structure prediction methodology has emerged as a powerful tool in model building and model refinement for difficult molecular replacement problems. This chapter describes some of the tools available in Rosetta for model building and model refinement specifically geared toward difficult molecular replacement cases.

Multiplexed and Microparticle-based Analyses: Quantitative Tools for the Large-Scale Analysis of Biological Systems

PubMed Central

Nolan, John P.; Mandy, Francis

2008-01-01

While the term flow cytometry refers to the measurement of cells, the approach of making sensitive multiparameter optical measurements in a flowing sample stream is a very general analytical approach. The past few years have seen an explosion in the application of flow cytometry technology for molecular analysis and measurements using micro-particles as solid supports. While microsphere-based molecular analyses using flow cytometry date back three decades, the need for highly parallel quantitative molecular measurements that has arisen from various genomic and proteomic advances has driven the development in particle encoding technology to enable highly multiplexed assays. Multiplexed particle-based immunoassays are now common place, and new assays to study genes, protein function, and molecular assembly. Numerous efforts are underway to extend the multiplexing capabilities of microparticle-based assays through new approaches to particle encoding and analyte reporting. The impact of these developments will be seen in the basic research and clinical laboratories, as well as in drug development. PMID:16604537

AN ECOLOGICAL PERSPECTIVE OF GENOMICS: ASSESSING ECOLOGICAL RISK THROUGH PARTNERSHIPS

EPA Science Inventory

The application of new molecular biological tools to environmental toxicology was discussed at an international workshop attended by
approximately 60 government, academic, and industrial scientists. The sequencing of the human genome, development of microarrays and
DNA chip...

Molecular Survey of Microbial Communities Involved in Concrete Corrosion in Wastewater Collection Systems

EPA Science Inventory

This information is relevant to the development of condition assessment tools associated with the aging water infrastructure research program Corrosion of wastewater collection infrastructure, especially concrete sewers, is a significant cause of deterioration and premature failu...

Prediction of Hydrolysis Products of Organic Chemicals under Environmental pH Conditions

EPA Science Inventory

Cheminformatics-based software tools can predict the molecular structure of transformation products using a library of transformation reaction schemes. This paper presents the development of such a library for abiotic hydrolysis of organic chemicals under environmentally relevant...

Accelerating Adverse Outcome Pathway (AOP) development via computationally predicted AOP networks

EPA Science Inventory

The Adverse Outcome Pathway (AOP) framework is increasingly being adopted as a tool for organizing and summarizing the mechanistic information connecting molecular perturbations by environmental stressors with adverse outcomes relevant for ecological and human health outcomes. Ho...

Gall-ID: Tools for genotyping gall-causing phytopathogenic bacteria

USDA-ARS?s Scientific Manuscript database

Understanding the population structure and genetic diversity of plant pathogens, as well as the effect of agricultural practices on pathogen evolution, are important for disease management. Developments in molecular methods have contributed to increasing the resolution for accurate pathogen identifi...

Using ecological models to investigate stressor effects throughout the life cycle of mummichogs

EPA Science Inventory

Ecological models of mummichogs (Fundulus heteroclitus) provide valuable tools to link controlled laboratory experiments to field observations. Mummichogs are useful study organisms due to their amenability to laboratory conditions, the availability of well-developed molecular to...

FIXATION OF FISH TISSUES. IN: THE LABORATORY FISH.

EPA Science Inventory

This chapter deals with the fixation of fish tissues and whole fish. Traditionally, fixation has been applied to animal tissues mainly for histological or pathological studies. Development of new molecular and immunologic tools now allows tissue and cellular localization of nucle...

Live immunization against East Coast fever--current status.

PubMed

Di Giulio, Giuseppe; Lynen, Godelieve; Morzaria, Subhash; Oura, Chris; Bishop, Richard

2009-02-01

The infection-and-treatment method (ITM) for immunization of cattle against East Coast fever has historically been used only on a limited scale because of logistical and policy constraints. Recent large-scale deployment among pastoralists in Tanzania has stimulated demand. Concurrently, a suite of molecular tools, developed from the Theileria parva genome, has enabled improved quality control of the immunizing stabilate and post-immunization monitoring of the efficacy and biological impact of ITM in the field. This article outlines the current status of ITM immunization in the field, with associated developments in the molecular epidemiology of T. parva.

Commercial Molecular Tests for Fungal Diagnosis from a Practical Point of View.

PubMed

Lackner, Michaela; Lass-Flörl, Cornelia

2017-01-01

The increasing interest in molecular diagnostics is a result of tremendously improved knowledge on fungal infections in the past 20 years and the rapid development of new methods, in particular polymerase chain reaction. High expectations have been placed on molecular diagnostics, and the number of laboratories now using the relevant technology is rapidly increasing-resulting in an obvious need for standardization and definition of laboratory organization. In the past 10 years, multiple new molecular tools were marketed for the detection of DNA, antibodies, cell wall components, or other antigens. In contrast to classical culture methods, molecular methods do not detect a viable organisms, but only molecules which indicate its presence; this can be nucleic acids, cell components (antigens), or antibodies (Fig. 1). In this chapter, an overview is provided on commercially available detection tools, their strength and how to use them. A main focus is laid on providing tips and tricks that make daily life easier. We try to focus and mention methodical details which are not highlighted in the manufacturer's instructions of these test kits, but are based on our personal experience in the laboratory. Important to keep in mind is that molecular tools cannot replace culture, microscopy, or a critical view on patients' clinical history, signs, and symptoms, but provide a valuable add on tool. Diagnosis should not be based solely on a molecular test, but molecular tools might deliver an important piece of information that helps matching the diagnostic puzzle to a diagnosis, in particular as few tests are in vitro diagnostic tests (IVD) or only part of the whole test carries the IVD certificate (e.g., DNA extraction is often not included). Please be aware that the authors do not claim to provide a complete overview on all commercially available diagnostic assays being currently marketed for fungal detection, as those are subject to constant change. A main focus is put on commonly used panfungal assays and pathogen-specific assays, including Aspergillus-specific, Candida-specific, Cryptococcus specific, Histoplasma-specific, and Pneumocystis-specific assays. Assays are categorized according to their underlying principle in either antigen-detecting or antibody-detecting or DNA-detecting (Fig. 1). Other non-DNA-detecting nucleic acid methods such as FISH and PNA FISH are not summarized in this chapter and an overview on test performance, common false positives, and the clinical evaluation of commercial tests in studies is provided already in a previous book series by Javier Yugueros Marcos and David H. Pincus (Marcos and Pincus, Methods Mol Biol 968:25-54, 2013).

A cricket Gene Index: a genomic resource for studying neurobiology, speciation, and molecular evolution

PubMed Central

Danley, Patrick D; Mullen, Sean P; Liu, Fenglong; Nene, Vishvanath; Quackenbush, John; Shaw, Kerry L

2007-01-01

Background As the developmental costs of genomic tools decline, genomic approaches to non-model systems are becoming more feasible. Many of these systems may lack advanced genetic tools but are extremely valuable models in other biological fields. Here we report the development of expressed sequence tags (EST's) in an orthopteroid insect, a model for the study of neurobiology, speciation, and evolution. Results We report the sequencing of 14,502 EST's from clones derived from a nerve cord cDNA library, and the subsequent construction of a Gene Index from these sequences, from the Hawaiian trigonidiine cricket Laupala kohalensis. The Gene Index contains 8607 unique sequences comprised of 2575 tentative consensus (TC) sequences and 6032 singletons. For each of the unique sequences, an attempt was made to assign a provisional annotation and to categorize its function using a Gene Ontology-based classification through a sequence-based comparison to known proteins. In addition, a set of unique 70 base pair oligomers that can be used for DNA microarrays was developed. All Gene Index information is posted at the DFCI Gene Indices web page Conclusion Orthopterans are models used to understand the neurophysiological basis of complex motor patterns such as flight and stridulation. The sequences presented in the cricket Gene Index will provide neurophysiologists with many genetic tools that have been largely absent in this field. The cricket Gene Index is one of only two gene indices to be developed in an evolutionary model system. Species within the genus Laupala have speciated recently, rapidly, and extensively. Therefore, the genes identified in the cricket Gene Index can be used to study the genomics of speciation. Furthermore, this gene index represents a significant EST resources for basal insects. As such, this resource is a valuable comparative tool for the understanding of invertebrate molecular evolution. The sequences presented here will provide much needed genomic resources for three distinct but overlapping fields of inquiry: neurobiology, speciation, and molecular evolution. PMID:17459168

Pydna: a simulation and documentation tool for DNA assembly strategies using python.

PubMed

Pereira, Filipa; Azevedo, Flávio; Carvalho, Ângela; Ribeiro, Gabriela F; Budde, Mark W; Johansson, Björn

2015-05-02

Recent advances in synthetic biology have provided tools to efficiently construct complex DNA molecules which are an important part of many molecular biology and biotechnology projects. The planning of such constructs has traditionally been done manually using a DNA sequence editor which becomes error-prone as scale and complexity of the construction increase. A human-readable formal description of cloning and assembly strategies, which also allows for automatic computer simulation and verification, would therefore be a valuable tool. We have developed pydna, an extensible, free and open source Python library for simulating basic molecular biology DNA unit operations such as restriction digestion, ligation, PCR, primer design, Gibson assembly and homologous recombination. A cloning strategy expressed as a pydna script provides a description that is complete, unambiguous and stable. Execution of the script automatically yields the sequence of the final molecule(s) and that of any intermediate constructs. Pydna has been designed to be understandable for biologists with limited programming skills by providing interfaces that are semantically similar to the description of molecular biology unit operations found in literature. Pydna simplifies both the planning and sharing of cloning strategies and is especially useful for complex or combinatorial DNA molecule construction. An important difference compared to existing tools with similar goals is the use of Python instead of a specifically constructed language, providing a simulation environment that is more flexible and extensible by the user.

Development of a New Molecular Subtyping Tool for Salmonella enterica Serovar Enteritidis Based on Single Nucleotide Polymorphism Genotyping Using PCR

PubMed Central

Kelly, Hilary; Dupras, Andrée Ann; Belanger, Sebastien; Devenish, John

2014-01-01

The lack of a sufficiently discriminatory molecular subtyping tool for Salmonella enterica serovar Enteritidis has hindered source attribution efforts and impeded regulatory actions required to disrupt its food-borne transmission. The underlying biological reason for the ineffectiveness of current molecular subtyping tools such as pulsed-field gel electrophoresis (PFGE) and phage typing appears to be related to the high degree of clonality of S. Enteritidis. By interrogating the organism's genome, we previously identified single nucleotide polymorphisms (SNP) distributed throughout the chromosome and have designed a highly discriminatory PCR-based SNP typing test based on 60 polymorphic loci. The application of the SNP-PCR method to DNA samples from S. Enteritidis strains (n = 55) obtained from a variety of sources has led to the differentiation and clustering of the S. Enteritidis isolates into 12 clades made up of 2 to 9 isolates per clade. Significantly, the SNP-PCR assay was able to further differentiate predominant PFGE types (e.g., XAI.0003) and phage types (e.g., phage type 8) into smaller subsets. The SNP-PCR subtyping test proved to be an accurate, precise, and quantitative tool for evaluating the relationships among the S. Enteritidis isolates tested in this study and should prove useful for clustering related S. Enteritidis isolates involved in outbreaks. PMID:25297333

Progress in molecular imaging in endoscopy and endomicroscopy for cancer imaging

PubMed Central

Khondee, Supang; Wang, Thomas D.

2014-01-01

Imaging is an essential tool for effective cancer management. Endoscopes are important medical instruments for performing in vivo imaging in hollow organs. Early detection of cancer can be achieved with surveillance using endoscopy, and has been shown to reduce mortality and to improve outcomes. Recently, great advancements have been made in endoscopic instruments, including new developments in optical designs, light sources, optical fibers, miniature scanners, and multimodal systems, allowing for improved resolution, greater tissue penetration, and multispectral imaging. In addition, progress has been made in the development of highly-specific optical probes, allowing for improved specificity for molecular targets. Integration of these new endoscopic instruments with molecular probes provides a unique opportunity for significantly improving patient outcomes and has potential to further improve early detection, image guided therapy, targeted therapy, and personalized medicine. This work summarizes current and evolving endoscopic technologies, and provides an overview of various promising optical molecular probes. PMID:23502247

ANDSystem: an Associative Network Discovery System for automated literature mining in the field of biology

PubMed Central

2015-01-01

Background Sufficient knowledge of molecular and genetic interactions, which comprise the entire basis of the functioning of living systems, is one of the necessary requirements for successfully answering almost any research question in the field of biology and medicine. To date, more than 24 million scientific papers can be found in PubMed, with many of them containing descriptions of a wide range of biological processes. The analysis of such tremendous amounts of data requires the use of automated text-mining approaches. Although a handful of tools have recently been developed to meet this need, none of them provide error-free extraction of highly detailed information. Results The ANDSystem package was developed for the reconstruction and analysis of molecular genetic networks based on an automated text-mining technique. It provides a detailed description of the various types of interactions between genes, proteins, microRNA's, metabolites, cellular components, pathways and diseases, taking into account the specificity of cell lines and organisms. Although the accuracy of ANDSystem is comparable to other well known text-mining tools, such as Pathway Studio and STRING, it outperforms them in having the ability to identify an increased number of interaction types. Conclusion The use of ANDSystem, in combination with Pathway Studio and STRING, can improve the quality of the automated reconstruction of molecular and genetic networks. ANDSystem should provide a useful tool for researchers working in a number of different fields, including biology, biotechnology, pharmacology and medicine. PMID:25881313

Functional Interfaces Constructed by Controlled/Living Radical Polymerization for Analytical Chemistry.

PubMed

Wang, Huai-Song; Song, Min; Hang, Tai-Jun

2016-02-10

The high-value applications of functional polymers in analytical science generally require well-defined interfaces, including precisely synthesized molecular architectures and compositions. Controlled/living radical polymerization (CRP) has been developed as a versatile and powerful tool for the preparation of polymers with narrow molecular weight distributions and predetermined molecular weights. Among the CRP system, atom transfer radical polymerization (ATRP) and reversible addition-fragmentation chain transfer (RAFT) are well-used to develop new materials for analytical science, such as surface-modified core-shell particles, monoliths, MIP micro- or nanospheres, fluorescent nanoparticles, and multifunctional materials. In this review, we summarize the emerging functional interfaces constructed by RAFT and ATRP for applications in analytical science. Various polymers with precisely controlled architectures including homopolymers, block copolymers, molecular imprinted copolymers, and grafted copolymers were synthesized by CRP methods for molecular separation, retention, or sensing. We expect that the CRP methods will become the most popular technique for preparing functional polymers that can be broadly applied in analytical chemistry.

The GCP molecular marker toolkit, an instrument for use in breeding food security crops.

PubMed

Van Damme, Veerle; Gómez-Paniagua, Humberto; de Vicente, M Carmen

2011-12-01

Crop genetic resources carry variation useful for overcoming the challenges of modern agriculture. Molecular markers can facilitate the selection of agronomically important traits. The pervasiveness of genomics research has led to an overwhelming number of publications and databases, which are, nevertheless, scattered and hence often difficult for plant breeders to access, particularly those in developing countries. This situation separates them from developed countries, which have better endowed programs for developing varieties. To close this growing knowledge gap, we conducted an intensive literature review and consulted with more than 150 crop experts on the use of molecular markers in the breeding program of 19 food security crops. The result was a list of effectively used and highly reproducible sequence tagged site (STS), simple sequence repeat (SSR), single nucleotide polymorphism (SNP), and sequence characterized amplified region (SCAR) markers. However, only 12 food crops had molecular markers suitable for improvement. That is, marker-assisted selection is not yet used for Musa spp., coconut, lentils, millets, pigeonpea, sweet potato, and yam. For the other 12 crops, 214 molecular markers were found to be effectively used in association with 74 different traits. Results were compiled as the GCP Molecular Marker Toolkit, a free online tool that aims to promote the adoption of molecular approaches in breeding activities.

BATMAN-TCM: a Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine

NASA Astrophysics Data System (ADS)

Liu, Zhongyang; Guo, Feifei; Wang, Yong; Li, Chun; Zhang, Xinlei; Li, Honglei; Diao, Lihong; Gu, Jiangyong; Wang, Wei; Li, Dong; He, Fuchu

2016-02-01

Traditional Chinese Medicine (TCM), with a history of thousands of years of clinical practice, is gaining more and more attention and application worldwide. And TCM-based new drug development, especially for the treatment of complex diseases is promising. However, owing to the TCM’s diverse ingredients and their complex interaction with human body, it is still quite difficult to uncover its molecular mechanism, which greatly hinders the TCM modernization and internationalization. Here we developed the first online Bioinformatics Analysis Tool for Molecular mechANism of TCM (BATMAN-TCM). Its main functions include 1) TCM ingredients’ target prediction; 2) functional analyses of targets including biological pathway, Gene Ontology functional term and disease enrichment analyses; 3) the visualization of ingredient-target-pathway/disease association network and KEGG biological pathway with highlighted targets; 4) comparison analysis of multiple TCMs. Finally, we applied BATMAN-TCM to Qishen Yiqi dripping Pill (QSYQ) and combined with subsequent experimental validation to reveal the functions of renin-angiotensin system responsible for QSYQ’s cardioprotective effects for the first time. BATMAN-TCM will contribute to the understanding of the “multi-component, multi-target and multi-pathway” combinational therapeutic mechanism of TCM, and provide valuable clues for subsequent experimental validation, accelerating the elucidation of TCM’s molecular mechanism. BATMAN-TCM is available at http://bionet.ncpsb.org/batman-tcm.

BATMAN-TCM: a Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine

PubMed Central

Liu, Zhongyang; Guo, Feifei; Wang, Yong; Li, Chun; Zhang, Xinlei; Li, Honglei; Diao, Lihong; Gu, Jiangyong; Wang, Wei; Li, Dong; He, Fuchu

2016-01-01

Traditional Chinese Medicine (TCM), with a history of thousands of years of clinical practice, is gaining more and more attention and application worldwide. And TCM-based new drug development, especially for the treatment of complex diseases is promising. However, owing to the TCM’s diverse ingredients and their complex interaction with human body, it is still quite difficult to uncover its molecular mechanism, which greatly hinders the TCM modernization and internationalization. Here we developed the first online Bioinformatics Analysis Tool for Molecular mechANism of TCM (BATMAN-TCM). Its main functions include 1) TCM ingredients’ target prediction; 2) functional analyses of targets including biological pathway, Gene Ontology functional term and disease enrichment analyses; 3) the visualization of ingredient-target-pathway/disease association network and KEGG biological pathway with highlighted targets; 4) comparison analysis of multiple TCMs. Finally, we applied BATMAN-TCM to Qishen Yiqi dripping Pill (QSYQ) and combined with subsequent experimental validation to reveal the functions of renin-angiotensin system responsible for QSYQ’s cardioprotective effects for the first time. BATMAN-TCM will contribute to the understanding of the “multi-component, multi-target and multi-pathway” combinational therapeutic mechanism of TCM, and provide valuable clues for subsequent experimental validation, accelerating the elucidation of TCM’s molecular mechanism. BATMAN-TCM is available at http://bionet.ncpsb.org/batman-tcm. PMID:26879404

DyNAMiC Workbench: an integrated development environment for dynamic DNA nanotechnology

PubMed Central

Grun, Casey; Werfel, Justin; Zhang, David Yu; Yin, Peng

2015-01-01

Dynamic DNA nanotechnology provides a promising avenue for implementing sophisticated assembly processes, mechanical behaviours, sensing and computation at the nanoscale. However, design of these systems is complex and error-prone, because the need to control the kinetic pathway of a system greatly increases the number of design constraints and possible failure modes for the system. Previous tools have automated some parts of the design workflow, but an integrated solution is lacking. Here, we present software implementing a three ‘tier’ design process: a high-level visual programming language is used to describe systems, a molecular compiler builds a DNA implementation and nucleotide sequences are generated and optimized. Additionally, our software includes tools for analysing and ‘debugging’ the designs in silico, and for importing/exporting designs to other commonly used software systems. The software we present is built on many existing pieces of software, but is integrated into a single package—accessible using a Web-based interface at http://molecular-systems.net/workbench. We hope that the deep integration between tools and the flexibility of this design process will lead to better experimental results, fewer experimental design iterations and the development of more complex DNA nanosystems. PMID:26423437

Nondestructive surface analysis for material research using fiber optic vibrational spectroscopy

NASA Astrophysics Data System (ADS)

Afanasyeva, Natalia I.

2001-11-01

The advanced methods of fiber optical vibrational spectroscopy (FOVS) has been developed in conjunction with interferometer and low-loss, flexible, and nontoxic optical fibers, sensors, and probes. The combination of optical fibers and sensors with Fourier Transform (FT) spectrometer has been used in the range from 2.5 to 12micrometers . This technique serves as an ideal diagnostic tool for surface analysis of numerous and various diverse materials such as complex structured materials, fluids, coatings, implants, living cells, plants, and tissue. Such surfaces as well as living tissue or plants are very difficult to investigate in vivo by traditional FT infrared or Raman spectroscopy methods. The FOVS technique is nondestructive, noninvasive, fast (15 sec) and capable of operating in remote sampling regime (up to a fiber length of 3m). Fourier transform infrared (FTIR) and Raman fiber optic spectroscopy operating with optical fibers has been suggested as a new powerful tool. These techniques are highly sensitive techniques for structural studies in material research and various applications during process analysis to determine molecular composition, chemical bonds, and molecular conformations. These techniques could be developed as a new tool for quality control of numerous materials as well as noninvasive biopsy.

Application of computer-assisted molecular modeling for immunoassay of low molecular weight food contaminants: A review.

PubMed

Xu, Zhen-Lin; Shen, Yu-Dong; Beier, Ross C; Yang, Jin-Yi; Lei, Hong-Tao; Wang, Hong; Sun, Yuan-Ming

2009-08-11

Immunoassay for low molecular weight food contaminants, such as pesticides, veterinary drugs, and mycotoxins is now a well-established technique which meets the demand for a rapid, reliable, and cost-effective analytical method. However, due to limited understanding of the molecular structure of antibody binding sites and antigenic epitopes, as well as the intermolecular binding forces that come into play, the traditional 'trial and error' method used to develop antibodies still remains the method of choice. Therefore, development of enhanced immunochemical techniques for specific- and generic-assays, requires new approaches for antibody design that will improve affinity and specificity of the antibody in a more rapid and economic manner. Computer-assisted molecular modeling (CAMM) has been demonstrated to be a useful tool to help the immunochemist develop immunoassays. CAMM methods can be used to help direct improvements to important antibody features, and can provide insights into the effects of molecular structure on biological activity that are difficult or impossible to obtain in any other way. In this review, we briefly summarize applications of CAMM in immunoassay development, including assisting in hapten design, explaining cross-reactivity, modeling antibody-antigen interactions, and providing insights into the effects of the mouse body temperature on the three-dimensional conformation of a hapten during antibody production. The fundamentals and theory, programs and software, limitations, and prospects of CAMM in immunoassay development were also discussed.

Single Cell Cytochemistry Illustrated by the Demonstration of Glucose-6-Phosphate Dehydrogenase Deficiency in Erythrocytes.

PubMed

Peters, Anna L; van Noorden, Cornelis J F

2017-01-01

Cytochemistry is the discipline that is applied to visualize specific molecules in individual cells and has become an essential tool in life sciences. Immunocytochemistry was developed in the sixties of last century and is the most frequently used cytochemical application. However, metabolic mapping is the oldest cytochemical approach to localize activity of specific enzymes, but in the last decades of the previous century and the first decade of the present century it almost became obsolete. The popularity of this approach revived in the past few years. Metabolism gained interest as player in chronic and complex diseases such as cancer, diabetes, neurodegenerative diseases, and vascular diseases and both enzyme cytochemistry and metabolic mapping have become important tools in life sciences.In this chapter, we present glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most prevalent enzyme deficiency worldwide, to illustrate recent developments in enzyme cytochemistry or metabolic mapping. The first assays which were developed quantified enzyme activity but were unreliable for single cell evaluation. The field has expanded with the development of cytochemical single cell assays and DNA testing. Still, all assays-from the earliest developed tests up to the most recently developed tests-have their place in investigations on G6PD activity. Recently, nanoscopy has become available for light and fluorescence microscopy at the nanoscale. For nanoscopy, cytochemistry is an essential tool to visualize intracellular molecular processes. The ultimate goal in the coming years will be nanoscopy of living cells so that the molecular dynamics can be studied. Cytochemistry will undoubtedly play a critical role in these developments.

Agent-Based Modeling in Molecular Systems Biology.

PubMed

Soheilypour, Mohammad; Mofrad, Mohammad R K

2018-07-01

Molecular systems orchestrating the biology of the cell typically involve a complex web of interactions among various components and span a vast range of spatial and temporal scales. Computational methods have advanced our understanding of the behavior of molecular systems by enabling us to test assumptions and hypotheses, explore the effect of different parameters on the outcome, and eventually guide experiments. While several different mathematical and computational methods are developed to study molecular systems at different spatiotemporal scales, there is still a need for methods that bridge the gap between spatially-detailed and computationally-efficient approaches. In this review, we summarize the capabilities of agent-based modeling (ABM) as an emerging molecular systems biology technique that provides researchers with a new tool in exploring the dynamics of molecular systems/pathways in health and disease. © 2018 WILEY Periodicals, Inc.

Molecular Endpoints and Mixtures of EDCs in Fish

EPA Science Inventory

Microarray technology is a relatively novel tool in ecotoxicology and is beginning to be used for exposure and/or hazard characterization for ecological risk assessment. To develop a basis for this type of analysis, fathead minnows (Pimephales promelas) were treated with two bin...

MULTIVARIATE CURVE RESOLUTION OF NMR SPECTROSCOPY METABONOMIC DATA

EPA Science Inventory

Sandia National Laboratories is working with the EPA to evaluate and develop mathematical tools for analysis of the collected NMR spectroscopy data. Initially, we have focused on the use of Multivariate Curve Resolution (MCR) also known as molecular factor analysis (MFA), a tech...

Realizing the promise of AOPs: A stakeholder-driven roadmap to the future

EPA Science Inventory

The adverse outcome pathway (AOP) framework was developed to serve as a knowledge assembly and communication tool to facilitate translation of mechanistic (e.g., molecular, biochemical, histological) data into adverse apical outcomes meaningful to chemical risk assessment. Althou...

Founder lines for improved citrus biotechnology

USDA-ARS?s Scientific Manuscript database

This article discusses the research needed to develop the RMCE strategy and molecular assays for site-specific recombinases as tools for genome manipulation. Explanation of genetic engineering used to generate transgenic citrus plants to exhibit a novel phenotype, but not to contain the recombinase...

Pinpointing Predation Events: A different molecular approach.

USDA-ARS?s Scientific Manuscript database

A glassy-winged sharpshooter (GWSS), Homalodisca vitripennis, protien marking system has been developed as a diagnostic tool for quantifying predation rates via gut content analysis. A field study was conducted to quantify predation rates on each of the GWSS lifestages. Specifically, two GWSS nymp...

SHAPEMOL: a 3D code for calculating CO line emission in planetary and protoplanetary nebulae. Detailed model-fitting of the complex nebula NGC 6302

NASA Astrophysics Data System (ADS)

Santander-García, M.; Bujarrabal, V.; Koning, N.; Steffen, W.

2015-01-01

Context. Modern instrumentation in radioastronomy constitutes a valuable tool for studying the Universe: ALMA has reached unprecedented sensitivities and spatial resolution, while Herschel/HIFI has opened a new window (most of the sub-mm and far-infrared ranges are only accessible from space) for probing molecular warm gas (~50-1000 K). On the other hand, the software SHAPE has emerged in the past few years as a standard tool for determining the morphology and velocity field of different kinds of gaseous emission nebulae via spatio-kinematical modelling. Standard SHAPE implements radiative transfer solving, but it is only available for atomic species and not for molecules. Aims: Being aware of the growing importance of the development of tools for simplifying the analyses of molecular data from new-era observatories, we introduce the computer code shapemol, a complement to SHAPE, with which we intend to fill the so-far under-developed molecular niche. Methods: shapemol enables user-friendly, spatio-kinematic modelling with accurate non-LTE calculations of excitation and radiative transfer in CO lines. Currently, it allows radiative transfer solving in the 12CO and 13CO J = 1-0 to J = 17-16 lines, but its implementation permits easily extending the code to different transitions and other molecular species, either by the code developers or by the user. Used along SHAPE, shapemol allows easily generating synthetic maps to test against interferometric observations, as well as synthetic line profiles to match single-dish observations. Results: We give a full description of how shapemol works, and we discuss its limitations and the sources of uncertainty to be expected in the final synthetic profiles or maps. As an example of the power and versatility of shapemol, we build a model of the molecular envelope of the planetary nebula NGC 6302 and compare it with 12CO and 13CO J = 2-1 interferometric maps from SMA and high-J transitions from Herschel/HIFI. We find the molecular envelope to have a complex, broken ring-like structure with an inner, hotter region and several "fingers" and high-velocity blobs, emerging outwards from the plane of the ring. We derive a mass of 0.11 M⊙ for the molecular envelope. A copy of the code is only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/573/A56

Cheminformatics Research at the Unilever Centre for Molecular Science Informatics Cambridge.

PubMed

Fuchs, Julian E; Bender, Andreas; Glen, Robert C

2015-09-01

The Centre for Molecular Informatics, formerly Unilever Centre for Molecular Science Informatics (UCMSI), at the University of Cambridge is a world-leading driving force in the field of cheminformatics. Since its opening in 2000 more than 300 scientific articles have fundamentally changed the field of molecular informatics. The Centre has been a key player in promoting open chemical data and semantic access. Though mainly focussing on basic research, close collaborations with industrial partners ensured real world feedback and access to high quality molecular data. A variety of tools and standard protocols have been developed and are ubiquitous in the daily practice of cheminformatics. Here, we present a retrospective of cheminformatics research performed at the UCMSI, thereby highlighting historical and recent trends in the field as well as indicating future directions.

Cheminformatics Research at the Unilever Centre for Molecular Science Informatics Cambridge

PubMed Central

Fuchs, Julian E; Bender, Andreas; Glen, Robert C

2015-01-01

The Centre for Molecular Informatics, formerly Unilever Centre for Molecular Science Informatics (UCMSI), at the University of Cambridge is a world-leading driving force in the field of cheminformatics. Since its opening in 2000 more than 300 scientific articles have fundamentally changed the field of molecular informatics. The Centre has been a key player in promoting open chemical data and semantic access. Though mainly focussing on basic research, close collaborations with industrial partners ensured real world feedback and access to high quality molecular data. A variety of tools and standard protocols have been developed and are ubiquitous in the daily practice of cheminformatics. Here, we present a retrospective of cheminformatics research performed at the UCMSI, thereby highlighting historical and recent trends in the field as well as indicating future directions. PMID:26435758

Molecular Imaging in Synthetic Biology, and Synthetic Biology in Molecular Imaging.

PubMed

Gilad, Assaf A; Shapiro, Mikhail G

2017-06-01

Biomedical synthetic biology is an emerging field in which cells are engineered at the genetic level to carry out novel functions with relevance to biomedical and industrial applications. This approach promises new treatments, imaging tools, and diagnostics for diseases ranging from gastrointestinal inflammatory syndromes to cancer, diabetes, and neurodegeneration. As these cellular technologies undergo pre-clinical and clinical development, it is becoming essential to monitor their location and function in vivo, necessitating appropriate molecular imaging strategies, and therefore, we have created an interest group within the World Molecular Imaging Society focusing on synthetic biology and reporter gene technologies. Here, we highlight recent advances in biomedical synthetic biology, including bacterial therapy, immunotherapy, and regenerative medicine. We then discuss emerging molecular imaging approaches to facilitate in vivo applications, focusing on reporter genes for noninvasive modalities such as magnetic resonance, ultrasound, photoacoustic imaging, bioluminescence, and radionuclear imaging. Because reporter genes can be incorporated directly into engineered genetic circuits, they are particularly well suited to imaging synthetic biological constructs, and developing them provides opportunities for creative molecular and genetic engineering.

WebSat--a web software for microsatellite marker development.

PubMed

Martins, Wellington Santos; Lucas, Divino César Soares; Neves, Kelligton Fabricio de Souza; Bertioli, David John

2009-01-01

Simple sequence repeats (SSR), also known as microsatellites, have been extensively used as molecular markers due to their abundance and high degree of polymorphism. We have developed a simple to use web software, called WebSat, for microsatellite molecular marker prediction and development. WebSat is accessible through the Internet, requiring no program installation. Although a web solution, it makes use of Ajax techniques, providing a rich, responsive user interface. WebSat allows the submission of sequences, visualization of microsatellites and the design of primers suitable for their amplification. The program allows full control of parameters and the easy export of the resulting data, thus facilitating the development of microsatellite markers. The web tool may be accessed at http://purl.oclc.org/NET/websat/

The Biomolecular Interaction Network Database and related tools 2005 update

PubMed Central

Alfarano, C.; Andrade, C. E.; Anthony, K.; Bahroos, N.; Bajec, M.; Bantoft, K.; Betel, D.; Bobechko, B.; Boutilier, K.; Burgess, E.; Buzadzija, K.; Cavero, R.; D'Abreo, C.; Donaldson, I.; Dorairajoo, D.; Dumontier, M. J.; Dumontier, M. R.; Earles, V.; Farrall, R.; Feldman, H.; Garderman, E.; Gong, Y.; Gonzaga, R.; Grytsan, V.; Gryz, E.; Gu, V.; Haldorsen, E.; Halupa, A.; Haw, R.; Hrvojic, A.; Hurrell, L.; Isserlin, R.; Jack, F.; Juma, F.; Khan, A.; Kon, T.; Konopinsky, S.; Le, V.; Lee, E.; Ling, S.; Magidin, M.; Moniakis, J.; Montojo, J.; Moore, S.; Muskat, B.; Ng, I.; Paraiso, J. P.; Parker, B.; Pintilie, G.; Pirone, R.; Salama, J. J.; Sgro, S.; Shan, T.; Shu, Y.; Siew, J.; Skinner, D.; Snyder, K.; Stasiuk, R.; Strumpf, D.; Tuekam, B.; Tao, S.; Wang, Z.; White, M.; Willis, R.; Wolting, C.; Wong, S.; Wrong, A.; Xin, C.; Yao, R.; Yates, B.; Zhang, S.; Zheng, K.; Pawson, T.; Ouellette, B. F. F.; Hogue, C. W. V.

2005-01-01

The Biomolecular Interaction Network Database (BIND) (http://bind.ca) archives biomolecular interaction, reaction, complex and pathway information. Our aim is to curate the details about molecular interactions that arise from published experimental research and to provide this information, as well as tools to enable data analysis, freely to researchers worldwide. BIND data are curated into a comprehensive machine-readable archive of computable information and provides users with methods to discover interactions and molecular mechanisms. BIND has worked to develop new methods for visualization that amplify the underlying annotation of genes and proteins to facilitate the study of molecular interaction networks. BIND has maintained an open database policy since its inception in 1999. Data growth has proceeded at a tremendous rate, approaching over 100 000 records. New services provided include a new BIND Query and Submission interface, a Standard Object Access Protocol service and the Small Molecule Interaction Database (http://smid.blueprint.org) that allows users to determine probable small molecule binding sites of new sequences and examine conserved binding residues. PMID:15608229

Prioritizing therapeutic targets using patient-derived xenograft models

PubMed Central

Lodhia, K.A; Hadley, A; Haluska, P; Scott, C.L

2015-01-01

Effective systemic treatment of cancer relies on the delivery of agents with optimal therapeutic potential. The molecular age of medicine has provided genomic tools that can identify a large number of potential therapeutic targets in individual patients, heralding the promise of personalized treatment. However, determining which potential targets actually drive tumor growth and should be prioritized for therapy is challenging. Indeed, reliable molecular matches of target and therapeutic agent have been stringently validated in the clinic for only a small number of targets. Patient-derived xenografts (PDX) are tumor models developed in immunocompromised mice using tumor procured directly from the patient. As patient surrogates, PDX models represent a powerful tool for addressing individualized therapy. Challenges include humanizing the immune system of PDX models and ensuring high quality molecular annotation, in order to maximise insights for the clinic. Importantly, PDX can be sampled repeatedly and in parallel, to reveal clonal evolution, which may predict mechanisms of drug resistance and inform therapeutic strategy design. PMID:25783201

Rendering the Intractable More Tractable: Tools from Caenorhabditis elegans Ripe for Import into Parasitic Nematodes

PubMed Central

Ward, Jordan D.

2015-01-01

Recent and rapid advances in genetic and molecular tools have brought spectacular tractability to Caenorhabditis elegans, a model that was initially prized because of its simple design and ease of imaging. C. elegans has long been a powerful model in biomedical research, and tools such as RNAi and the CRISPR/Cas9 system allow facile knockdown of genes and genome editing, respectively. These developments have created an additional opportunity to tackle one of the most debilitating burdens on global health and food security: parasitic nematodes. I review how development of nonparasitic nematodes as genetic models informs efforts to import tools into parasitic nematodes. Current tools in three commonly studied parasites (Strongyloides spp., Brugia malayi, and Ascaris suum) are described, as are tools from C. elegans that are ripe for adaptation and the benefits and barriers to doing so. These tools will enable dissection of a huge array of questions that have been all but completely impenetrable to date, allowing investigation into host–parasite and parasite–vector interactions, and the genetic basis of parasitism. PMID:26644478

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.

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

PubMed

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

2017-10-01

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

A novel energy conversion based method for velocity correction in molecular dynamics simulations

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

Jin, Hanhui; Collaborative Innovation Center of Advanced Aero-Engine, Hangzhou 310027; Liu, Ningning

2017-05-01

Molecular dynamics (MD) simulation has become an important tool for studying micro- or nano-scale dynamics and the statistical properties of fluids and solids. In MD simulations, there are mainly two approaches: equilibrium and non-equilibrium molecular dynamics (EMD and NEMD). In this paper, a new energy conversion based correction (ECBC) method for MD is developed. Unlike the traditional systematic correction based on macroscopic parameters, the ECBC method is developed strictly based on the physical interaction processes between the pair of molecules or atoms. The developed ECBC method can apply to EMD and NEMD directly. While using MD with this method, themore » difference between the EMD and NEMD is eliminated, and no macroscopic parameters such as external imposed potentials or coefficients are needed. With this method, many limits of using MD are lifted. The application scope of MD is greatly extended.« less

A Comparative Study of Successful Central Nervous System Drugs Using Molecular Modeling

ERIC Educational Resources Information Center

Kim, Hyosub; Sulaimon, Segun; Menezes, Sandra; Son, Anne; Menezes, Warren J. C.

2011-01-01

Molecular modeling is a powerful tool used for three-dimensional visualization and for exploring electrostatic forces involved in drug transport. This tool enhances student understanding of structure-property relationships, as well as actively engaging them in class. Molecular modeling of several central nervous system (CNS) drugs is used to…

Synthesis of Novel Hydrocarbon Soluble Multifunctional Anionic Initiators: Tools for Synthesis of Novel Dendrimer and Molecular Brush Polymer Architectures

DTIC Science & Technology

2015-02-09

Synthesis of Novel Dendrimer and Molecular Brush Polymer Architectures. Research Area:7.4 The views, opinions and/or findings contained in this report...journals: Final Report: Synthesis of Novel Hydrocarbon Soluble Multifunctional Anionic Initiators: Tools for Synthesis of Novel Dendrimer and Molecular

Rapid molecular diagnostics for multi-drug resistant tuberculosis in India.

PubMed

Ramachandran, Rajeswari; Muniyandi, M

2018-03-01

Rapid molecular diagnostic methods help in the detection of TB and Rifampicin resistance. These methods detect TB early, are accurate and play a crucial role in reducing the burden of drug resistant tuberculosis. Areas covered: This review analyses rapid molecular diagnostic tools used in the diagnosis of MDR-TB in India, such as the Line Probe Assay and GeneXpert. We have discussed the burden of MDR-TB and the impact of recent diagnostic tools on case detection and treatment outcomes. This review also discusses the costs involved in establishing these new techniques in India. Expert commentary: Molecular methods have considerable advantages for the programmatic management of drug resistant TB. These include speed, standardization of testing, potentially high throughput and reduced laboratory biosafety requirements. There is a desperate need for India to adopt modern, rapid, molecular tools with point-of-care tests being currently evaluated. New molecular diagnostic tests appear to be cost effective and also help in detecting missing cases. There is enough evidence to support the scaling up of these new tools in India.

Art Advancing Science: Filmmaking Leads to Molecular Insights at the Nanoscale.

PubMed

Reilly, Charles; Ingber, Donald E

2017-12-26

Many have recognized the potential value of facilitating activities that span the art-science interface for the benefit of society; however, there are few examples that demonstrate how pursuit of an artistic agenda can lead to scientific insights. Here, we describe how we set out to produce an entertaining short film depicting the fertilization of the egg by sperm as a parody of a preview for another Star Wars movie to excite the public about science, but ended up developing a simulation tool for multiscale modeling. To produce an aesthetic that communicates mechanical continuity across spatial scales, we developed custom strategies that integrate physics-based animation software from the entertainment industry with molecular dynamics simulation tools, using experimental data from research publications. Using this approach, we were able to depict biological physicality across multiple spatial scales, from how sperm tails move to collective molecular behavior within the axoneme to how the molecular motor, dynein, produces force at the nanometer scale. The dynein simulations, which were validated by replicating results of past simulations and cryo-electron microscopic studies, also predicted a potential mechanism for how ATP hydrolysis drives dynein motion along the microtubule as well as how dynein changes its conformation when it goes through the power stroke. Thus, pursuit of an artistic work led to insights into biology at the nanoscale as well as the development of a highly generalizable modeling and simulation technology that has utility for nanoscience and any other area of scientific investigation that involves analysis of complex multiscale systems.

Transferability of retrotransposon primers derived from Persimmon (Diospyros kaki Thunb.) across other plant species.

PubMed

Du, X Y; Hu, Q N; Zhang, Q L; Wang, Y B; Luo, Z R

2013-06-06

Retrotransposon-based molecular markers are powerful molecular tools. However, these markers are not readily available due to the difficulty in obtaining species-specific retrotransposon primers. Although recent techniques enabling the rapid isolation of retrotransposon sequences have facilitated primer development, this process nonetheless remains time-consuming and costly. Therefore, research into the transferability of retrotransposon primers developed from one plant species onto others would be of great value. The present study investigated the transferability of retrotransposon primers derived from 'Luotian-tianshi' persimmon (Diospyros kaki Thunb.) across other fruit crops, as well as within the genus using inter-retrotransposon amplified polymorphism molecular marker. Fourteen of the 26 retrotransposon primers tested (53.85%) produced robust and reproducible amplification products across all fruit crops tested, indicating their applicability across plant species. Four of the 13 fruit crops showed the best transferability performances: persimmon, grape, citrus, and peach. Furthermore, similarity coefficients and UPGMA clustering indicated that these primers could further offer a potential tool for germplasm differentiation, parentage identification, genetic diversity assessment, classification, and phylogenetic studies across a variety of plant species. Transferability was further confirmed by examining published primers derived from Rosaceae, Gramineae, and Solanaceae. This study is one of the few currently available studies concerning the transferability of retrotransposon primers across plant species in general, and is the first successful study of the transferability of retrotransposon primers derived from persimmon. The primers presented here will help reduce costs for future retrotransposon primer development and therefore contribute to the popularization of retrotransposon molecular markers.

FlaME: Flash Molecular Editor - a 2D structure input tool for the web.

PubMed

Dallakian, Pavel; Haider, Norbert

2011-02-01

So far, there have been no Flash-based web tools available for chemical structure input. The authors herein present a feasibility study, aiming at the development of a compact and easy-to-use 2D structure editor, using Adobe's Flash technology and its programming language, ActionScript. As a reference model application from the Java world, we selected the Java Molecular Editor (JME). In this feasibility study, we made an attempt to realize a subset of JME's functionality in the Flash Molecular Editor (FlaME) utility. These basic capabilities are: structure input, editing and depiction of single molecules, data import and export in molfile format. The result of molecular diagram sketching in FlaME is accessible in V2000 molfile format. By integrating the molecular editor into a web page, its communication with the HTML elements on this page is established using the two JavaScript functions, getMol() and setMol(). In addition, structures can be copied to the system clipboard. A first attempt was made to create a compact single-file application for 2D molecular structure input/editing on the web, based on Flash technology. With the application examples presented in this article, it could be demonstrated that the Flash methods are principally well-suited to provide the requisite communication between the Flash object (application) and the HTML elements on a web page, using JavaScript functions.

MDTraj: A Modern Open Library for the Analysis of Molecular Dynamics Trajectories.

PubMed

McGibbon, Robert T; Beauchamp, Kyle A; Harrigan, Matthew P; Klein, Christoph; Swails, Jason M; Hernández, Carlos X; Schwantes, Christian R; Wang, Lee-Ping; Lane, Thomas J; Pande, Vijay S

2015-10-20

As molecular dynamics (MD) simulations continue to evolve into powerful computational tools for studying complex biomolecular systems, the necessity of flexible and easy-to-use software tools for the analysis of these simulations is growing. We have developed MDTraj, a modern, lightweight, and fast software package for analyzing MD simulations. MDTraj reads and writes trajectory data in a wide variety of commonly used formats. It provides a large number of trajectory analysis capabilities including minimal root-mean-square-deviation calculations, secondary structure assignment, and the extraction of common order parameters. The package has a strong focus on interoperability with the wider scientific Python ecosystem, bridging the gap between MD data and the rapidly growing collection of industry-standard statistical analysis and visualization tools in Python. MDTraj is a powerful and user-friendly software package that simplifies the analysis of MD data and connects these datasets with the modern interactive data science software ecosystem in Python. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

MDTraj: A Modern Open Library for the Analysis of Molecular Dynamics Trajectories

PubMed Central

McGibbon, Robert T.; Beauchamp, Kyle A.; Harrigan, Matthew P.; Klein, Christoph; Swails, Jason M.; Hernández, Carlos X.; Schwantes, Christian R.; Wang, Lee-Ping; Lane, Thomas J.; Pande, Vijay S.

2015-01-01

As molecular dynamics (MD) simulations continue to evolve into powerful computational tools for studying complex biomolecular systems, the necessity of flexible and easy-to-use software tools for the analysis of these simulations is growing. We have developed MDTraj, a modern, lightweight, and fast software package for analyzing MD simulations. MDTraj reads and writes trajectory data in a wide variety of commonly used formats. It provides a large number of trajectory analysis capabilities including minimal root-mean-square-deviation calculations, secondary structure assignment, and the extraction of common order parameters. The package has a strong focus on interoperability with the wider scientific Python ecosystem, bridging the gap between MD data and the rapidly growing collection of industry-standard statistical analysis and visualization tools in Python. MDTraj is a powerful and user-friendly software package that simplifies the analysis of MD data and connects these datasets with the modern interactive data science software ecosystem in Python. PMID:26488642

Java web tools for PCR, in silico PCR, and oligonucleotide assembly and analysis.

PubMed

Kalendar, Ruslan; Lee, David; Schulman, Alan H

2011-08-01

The polymerase chain reaction is fundamental to molecular biology and is the most important practical molecular technique for the research laboratory. We have developed and tested efficient tools for PCR primer and probe design, which also predict oligonucleotide properties based on experimental studies of PCR efficiency. The tools provide comprehensive facilities for designing primers for most PCR applications and their combinations, including standard, multiplex, long-distance, inverse, real-time, unique, group-specific, bisulphite modification assays, Overlap-Extension PCR Multi-Fragment Assembly, as well as a programme to design oligonucleotide sets for long sequence assembly by ligase chain reaction. The in silico PCR primer or probe search includes comprehensive analyses of individual primers and primer pairs. It calculates the melting temperature for standard and degenerate oligonucleotides including LNA and other modifications, provides analyses for a set of primers with prediction of oligonucleotide properties, dimer and G-quadruplex detection, linguistic complexity, and provides a dilution and resuspension calculator. Copyright © 2011 Elsevier Inc. All rights reserved.

Direct mapping of electrical noise sources in molecular wire-based devices

PubMed Central

Cho, Duckhyung; Lee, Hyungwoo; Shekhar, Shashank; Yang, Myungjae; Park, Jae Yeol; Hong, Seunghun

2017-01-01

We report a noise mapping strategy for the reliable identification and analysis of noise sources in molecular wire junctions. Here, different molecular wires were patterned on a gold substrate, and the current-noise map on the pattern was measured and analyzed, enabling the quantitative study of noise sources in the patterned molecular wires. The frequency spectra of the noise from the molecular wire junctions exhibited characteristic 1/f2 behavior, which was used to identify the electrical signals from molecular wires. This method was applied to analyze the molecular junctions comprising various thiol molecules on a gold substrate, revealing that the noise in the junctions mainly came from the fluctuation of the thiol bonds. Furthermore, we quantitatively compared the frequencies of such bond fluctuations in different molecular wire junctions and identified molecular wires with lower electrical noise, which can provide critical information for designing low-noise molecular electronic devices. Our method provides valuable insights regarding noise phenomena in molecular wires and can be a powerful tool for the development of molecular electronic devices. PMID:28233821

Direct mapping of electrical noise sources in molecular wire-based devices

NASA Astrophysics Data System (ADS)

Cho, Duckhyung; Lee, Hyungwoo; Shekhar, Shashank; Yang, Myungjae; Park, Jae Yeol; Hong, Seunghun

2017-02-01

We report a noise mapping strategy for the reliable identification and analysis of noise sources in molecular wire junctions. Here, different molecular wires were patterned on a gold substrate, and the current-noise map on the pattern was measured and analyzed, enabling the quantitative study of noise sources in the patterned molecular wires. The frequency spectra of the noise from the molecular wire junctions exhibited characteristic 1/f2 behavior, which was used to identify the electrical signals from molecular wires. This method was applied to analyze the molecular junctions comprising various thiol molecules on a gold substrate, revealing that the noise in the junctions mainly came from the fluctuation of the thiol bonds. Furthermore, we quantitatively compared the frequencies of such bond fluctuations in different molecular wire junctions and identified molecular wires with lower electrical noise, which can provide critical information for designing low-noise molecular electronic devices. Our method provides valuable insights regarding noise phenomena in molecular wires and can be a powerful tool for the development of molecular electronic devices.

ballaxy: web services for structural bioinformatics.

PubMed

Hildebrandt, Anna Katharina; Stöckel, Daniel; Fischer, Nina M; de la Garza, Luis; Krüger, Jens; Nickels, Stefan; Röttig, Marc; Schärfe, Charlotta; Schumann, Marcel; Thiel, Philipp; Lenhof, Hans-Peter; Kohlbacher, Oliver; Hildebrandt, Andreas

2015-01-01

Web-based workflow systems have gained considerable momentum in sequence-oriented bioinformatics. In structural bioinformatics, however, such systems are still relatively rare; while commercial stand-alone workflow applications are common in the pharmaceutical industry, academic researchers often still rely on command-line scripting to glue individual tools together. In this work, we address the problem of building a web-based system for workflows in structural bioinformatics. For the underlying molecular modelling engine, we opted for the BALL framework because of its extensive and well-tested functionality in the field of structural bioinformatics. The large number of molecular data structures and algorithms implemented in BALL allows for elegant and sophisticated development of new approaches in the field. We hence connected the versatile BALL library and its visualization and editing front end BALLView with the Galaxy workflow framework. The result, which we call ballaxy, enables the user to simply and intuitively create sophisticated pipelines for applications in structure-based computational biology, integrated into a standard tool for molecular modelling.  ballaxy consists of three parts: some minor modifications to the Galaxy system, a collection of tools and an integration into the BALL framework and the BALLView application for molecular modelling. Modifications to Galaxy will be submitted to the Galaxy project, and the BALL and BALLView integrations will be integrated in the next major BALL release. After acceptance of the modifications into the Galaxy project, we will publish all ballaxy tools via the Galaxy toolshed. In the meantime, all three components are available from http://www.ball-project.org/ballaxy. Also, docker images for ballaxy are available at https://registry.hub.docker.com/u/anhi/ballaxy/dockerfile/. ballaxy is licensed under the terms of the GPL. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Real-time fluorescence loop mediated isothermal amplification for the diagnosis of malaria.

PubMed

Lucchi, Naomi W; Demas, Allison; Narayanan, Jothikumar; Sumari, Deborah; Kabanywanyi, Abdunoor; Kachur, S Patrick; Barnwell, John W; Udhayakumar, Venkatachalam

2010-10-29

Molecular diagnostic methods can complement existing tools to improve the diagnosis of malaria. However, they require good laboratory infrastructure thereby restricting their use to reference laboratories and research studies. Therefore, adopting molecular tools for routine use in malaria endemic countries will require simpler molecular platforms. The recently developed loop-mediated isothermal amplification (LAMP) method is relatively simple and can be improved for better use in endemic countries. In this study, we attempted to improve this method for malaria diagnosis by using a simple and portable device capable of performing both the amplification and detection (by fluorescence) of LAMP in one platform. We refer to this as the RealAmp method. Published genus-specific primers were used to test the utility of this method. DNA derived from different species of malaria parasites was used for the initial characterization. Clinical samples of P. falciparum were used to determine the sensitivity and specificity of this system compared to microscopy and a nested PCR method. Additionally, directly boiled parasite preparations were compared with a conventional DNA isolation method. The RealAmp method was found to be simple and allowed real-time detection of DNA amplification. The time to amplification varied but was generally less than 60 minutes. All human-infecting Plasmodium species were detected. The sensitivity and specificity of RealAmp in detecting P. falciparum was 96.7% and 91.7% respectively, compared to microscopy and 98.9% and 100% respectively, compared to a standard nested PCR method. In addition, this method consistently detected P. falciparum from directly boiled blood samples. This RealAmp method has great potential as a field usable molecular tool for diagnosis of malaria. This tool can provide an alternative to conventional PCR based diagnostic methods for field use in clinical and operational programs.

Integration of EGA secure data access into Galaxy.

PubMed

Hoogstrate, Youri; Zhang, Chao; Senf, Alexander; Bijlard, Jochem; Hiltemann, Saskia; van Enckevort, David; Repo, Susanna; Heringa, Jaap; Jenster, Guido; J A Fijneman, Remond; Boiten, Jan-Willem; A Meijer, Gerrit; Stubbs, Andrew; Rambla, Jordi; Spalding, Dylan; Abeln, Sanne

2016-01-01

High-throughput molecular profiling techniques are routinely generating vast amounts of data for translational medicine studies. Secure access controlled systems are needed to manage, store, transfer and distribute these data due to its personally identifiable nature. The European Genome-phenome Archive (EGA) was created to facilitate access and management to long-term archival of bio-molecular data. Each data provider is responsible for ensuring a Data Access Committee is in place to grant access to data stored in the EGA. Moreover, the transfer of data during upload and download is encrypted. ELIXIR, a European research infrastructure for life-science data, initiated a project (2016 Human Data Implementation Study) to understand and document the ELIXIR requirements for secure management of controlled-access data. As part of this project, a full ecosystem was designed to connect archived raw experimental molecular profiling data with interpreted data and the computational workflows, using the CTMM Translational Research IT (CTMM-TraIT) infrastructure http://www.ctmm-trait.nl as an example. Here we present the first outcomes of this project, a framework to enable the download of EGA data to a Galaxy server in a secure way. Galaxy provides an intuitive user interface for molecular biologists and bioinformaticians to run and design data analysis workflows. More specifically, we developed a tool -- ega_download_streamer - that can download data securely from EGA into a Galaxy server, which can subsequently be further processed. This tool will allow a user within the browser to run an entire analysis containing sensitive data from EGA, and to make this analysis available for other researchers in a reproducible manner, as shown with a proof of concept study.  The tool ega_download_streamer is available in the Galaxy tool shed: https://toolshed.g2.bx.psu.edu/view/yhoogstrate/ega_download_streamer.

Integration of EGA secure data access into Galaxy

PubMed Central

Hoogstrate, Youri; Zhang, Chao; Senf, Alexander; Bijlard, Jochem; Hiltemann, Saskia; van Enckevort, David; Repo, Susanna; Heringa, Jaap; Jenster, Guido; Fijneman, Remond J.A.; Boiten, Jan-Willem; A. Meijer, Gerrit; Stubbs, Andrew; Rambla, Jordi; Spalding, Dylan; Abeln, Sanne

2016-01-01

High-throughput molecular profiling techniques are routinely generating vast amounts of data for translational medicine studies. Secure access controlled systems are needed to manage, store, transfer and distribute these data due to its personally identifiable nature. The European Genome-phenome Archive (EGA) was created to facilitate access and management to long-term archival of bio-molecular data. Each data provider is responsible for ensuring a Data Access Committee is in place to grant access to data stored in the EGA. Moreover, the transfer of data during upload and download is encrypted. ELIXIR, a European research infrastructure for life-science data, initiated a project (2016 Human Data Implementation Study) to understand and document the ELIXIR requirements for secure management of controlled-access data. As part of this project, a full ecosystem was designed to connect archived raw experimental molecular profiling data with interpreted data and the computational workflows, using the CTMM Translational Research IT (CTMM-TraIT) infrastructure http://www.ctmm-trait.nl as an example. Here we present the first outcomes of this project, a framework to enable the download of EGA data to a Galaxy server in a secure way. Galaxy provides an intuitive user interface for molecular biologists and bioinformaticians to run and design data analysis workflows. More specifically, we developed a tool -- ega_download_streamer - that can download data securely from EGA into a Galaxy server, which can subsequently be further processed. This tool will allow a user within the browser to run an entire analysis containing sensitive data from EGA, and to make this analysis available for other researchers in a reproducible manner, as shown with a proof of concept study.  The tool ega_download_streamer is available in the Galaxy tool shed: https://toolshed.g2.bx.psu.edu/view/yhoogstrate/ega_download_streamer. PMID:28232859

Logic integration of mRNA signals by an RNAi-based molecular computer.

PubMed

Xie, Zhen; Liu, Siyuan John; Bleris, Leonidas; Benenson, Yaakov

2010-05-01

Synthetic in vivo molecular 'computers' could rewire biological processes by establishing programmable, non-native pathways between molecular signals and biological responses. Multiple molecular computer prototypes have been shown to work in simple buffered solutions. Many of those prototypes were made of DNA strands and performed computations using cycles of annealing-digestion or strand displacement. We have previously introduced RNA interference (RNAi)-based computing as a way of implementing complex molecular logic in vivo. Because it also relies on nucleic acids for its operation, RNAi computing could benefit from the tools developed for DNA systems. However, these tools must be harnessed to produce bioactive components and be adapted for harsh operating environments that reflect in vivo conditions. In a step toward this goal, we report the construction and implementation of biosensors that 'transduce' mRNA levels into bioactive, small interfering RNA molecules via RNA strand exchange in a cell-free Drosophila embryo lysate, a step beyond simple buffered environments. We further integrate the sensors with our RNAi 'computational' module to evaluate two-input logic functions on mRNA concentrations. Our results show how RNA strand exchange can expand the utility of RNAi computing and point toward the possibility of using strand exchange in a native biological setting.

Logic integration of mRNA signals by an RNAi-based molecular computer

PubMed Central

Xie, Zhen; Liu, Siyuan John; Bleris, Leonidas; Benenson, Yaakov

2010-01-01

Synthetic in vivo molecular ‘computers’ could rewire biological processes by establishing programmable, non-native pathways between molecular signals and biological responses. Multiple molecular computer prototypes have been shown to work in simple buffered solutions. Many of those prototypes were made of DNA strands and performed computations using cycles of annealing-digestion or strand displacement. We have previously introduced RNA interference (RNAi)-based computing as a way of implementing complex molecular logic in vivo. Because it also relies on nucleic acids for its operation, RNAi computing could benefit from the tools developed for DNA systems. However, these tools must be harnessed to produce bioactive components and be adapted for harsh operating environments that reflect in vivo conditions. In a step toward this goal, we report the construction and implementation of biosensors that ‘transduce’ mRNA levels into bioactive, small interfering RNA molecules via RNA strand exchange in a cell-free Drosophila embryo lysate, a step beyond simple buffered environments. We further integrate the sensors with our RNAi ‘computational’ module to evaluate two-input logic functions on mRNA concentrations. Our results show how RNA strand exchange can expand the utility of RNAi computing and point toward the possibility of using strand exchange in a native biological setting. PMID:20194121

AN ECOLOGICAL PERSPECTIVE OF GENOMICS: ASSESSING ECOLOGICAL RISK THROUGH PARTNERSHIPS

EPA Science Inventory

A workshop attended by approximately 60 scientists from around the world met to discuss the application of new molecular biology tools to issues in environmental toxicology and chemistry. With the sequencing of the human genome, development of microarrays and DNA chips, and devel...

Using biotechnology and genomics to improve biotic and abiotic stress in apple

USDA-ARS?s Scientific Manuscript database

Genomic sequencing, molecular biology, and transformation technologies are providing valuable tools to better understand the complexity of how plants develop, function, and respond to biotic and abiotic stress. These approaches should complement but not replace a solid understanding of whole plant ...

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.

A web server for mining Comparative Genomic Hybridization (CGH) data

NASA Astrophysics Data System (ADS)

Liu, Jun; Ranka, Sanjay; Kahveci, Tamer

2007-11-01

Advances in cytogenetics and molecular biology has established that chromosomal alterations are critical in the pathogenesis of human cancer. Recurrent chromosomal alterations provide cytological and molecular markers for the diagnosis and prognosis of disease. They also facilitate the identification of genes that are important in carcinogenesis, which in the future may help in the development of targeted therapy. A large amount of publicly available cancer genetic data is now available and it is growing. There is a need for public domain tools that allow users to analyze their data and visualize the results. This chapter describes a web based software tool that will allow researchers to analyze and visualize Comparative Genomic Hybridization (CGH) datasets. It employs novel data mining methodologies for clustering and classification of CGH datasets as well as algorithms for identifying important markers (small set of genomic intervals with aberrations) that are potentially cancer signatures. The developed software will help in understanding the relationships between genomic aberrations and cancer types.

Designing the molecular future.

PubMed

Schneider, Gisbert

2012-01-01

Approximately 25 years ago the first computer applications were conceived for the purpose of automated 'de novo' drug design, prominent pioneering tools being ALADDIN, CAVEAT, GENOA, and DYLOMMS. Many of these early concepts were enabled by innovative techniques for ligand-receptor interaction modeling like GRID, MCSS, DOCK, and CoMFA, which still provide the theoretical framework for several more recently developed molecular design algorithms. After a first wave of software tools and groundbreaking applications in the 1990s--expressly GROW, GrowMol, LEGEND, and LUDI representing some of the key players--we are currently witnessing a renewed strong interest in this field. Innovative ideas for both receptor and ligand-based drug design have recently been published. We here provide a personal perspective on the evolution of de novo design, highlighting some of the historic achievements as well as possible future developments of this exciting field of research, which combines multiple scientific disciplines and is, like few other areas in chemistry, subject to continuous enthusiastic discussion and compassionate dispute.

Combining medical informatics and bioinformatics toward tools for personalized medicine.

PubMed

Sarachan, B D; Simmons, M K; Subramanian, P; Temkin, J M

2003-01-01

Key bioinformatics and medical informatics research areas need to be identified to advance knowledge and understanding of disease risk factors and molecular disease pathology in the 21 st century toward new diagnoses, prognoses, and treatments. Three high-impact informatics areas are identified: predictive medicine (to identify significant correlations within clinical data using statistical and artificial intelligence methods), along with pathway informatics and cellular simulations (that combine biological knowledge with advanced informatics to elucidate molecular disease pathology). Initial predictive models have been developed for a pilot study in Huntington's disease. An initial bioinformatics platform has been developed for the reconstruction and analysis of pathways, and work has begun on pathway simulation. A bioinformatics research program has been established at GE Global Research Center as an important technology toward next generation medical diagnostics. We anticipate that 21 st century medical research will be a combination of informatics tools with traditional biology wet lab research, and that this will translate to increased use of informatics techniques in the clinic.

DNA microarray technology in nutraceutical and food safety.

PubMed

Liu-Stratton, Yiwen; Roy, Sashwati; Sen, Chandan K

2004-04-15

The quality and quantity of diet is a key determinant of health and disease. Molecular diagnostics may play a key role in food safety related to genetically modified foods, food-borne pathogens and novel nutraceuticals. Functional outcomes in biology are determined, for the most part, by net balance between sets of genes related to the specific outcome in question. The DNA microarray technology offers a new dimension of strength in molecular diagnostics by permitting the simultaneous analysis of large sets of genes. Automation of assay and novel bioinformatics tools make DNA microarrays a robust technology for diagnostics. Since its development a few years ago, this technology has been used for the applications of toxicogenomics, pharmacogenomics, cell biology, and clinical investigations addressing the prevention and intervention of diseases. Optimization of this technology to specifically address food safety is a vast resource that remains to be mined. Efforts to develop diagnostic custom arrays and simplified bioinformatics tools for field use are warranted.

Designing the molecular future

NASA Astrophysics Data System (ADS)

Schneider, Gisbert

2012-01-01

Approximately 25 years ago the first computer applications were conceived for the purpose of automated `de novo' drug design, prominent pioneering tools being ALADDIN, CAVEAT, GENOA, and DYLOMMS. Many of these early concepts were enabled by innovative techniques for ligand-receptor interaction modeling like GRID, MCSS, DOCK, and CoMFA, which still provide the theoretical framework for several more recently developed molecular design algorithms. After a first wave of software tools and groundbreaking applications in the 1990s—expressly GROW, GrowMol, LEGEND, and LUDI representing some of the key players—we are currently witnessing a renewed strong interest in this field. Innovative ideas for both receptor and ligand-based drug design have recently been published. We here provide a personal perspective on the evolution of de novo design, highlighting some of the historic achievements as well as possible future developments of this exciting field of research, which combines multiple scientific disciplines and is, like few other areas in chemistry, subject to continuous enthusiastic discussion and compassionate dispute.

Deconstructing host-pathogen interactions in Drosophila

PubMed Central

Bier, Ethan; Guichard, Annabel

2012-01-01

Many of the cellular mechanisms underlying host responses to pathogens have been well conserved during evolution. As a result, Drosophila can be used to deconstruct many of the key events in host-pathogen interactions by using a wealth of well-developed molecular and genetic tools. In this review, we aim to emphasize the great leverage provided by the suite of genomic and classical genetic approaches available in flies for decoding details of host-pathogen interactions; these findings can then be applied to studies in higher organisms. We first briefly summarize the general strategies by which Drosophila resists and responds to pathogens. We then focus on how recently developed genome-wide RNA interference (RNAi) screens conducted in cells and flies, combined with classical genetic methods, have provided molecular insight into host-pathogen interactions, covering examples of bacteria, fungi and viruses. Finally, we discuss novel strategies for how flies can be used as a tool to examine how specific isolated virulence factors act on an intact host. PMID:21979942

High-throughput strategies for the discovery and engineering of enzymes for biocatalysis.

PubMed

Jacques, Philippe; Béchet, Max; Bigan, Muriel; Caly, Delphine; Chataigné, Gabrielle; Coutte, François; Flahaut, Christophe; Heuson, Egon; Leclère, Valérie; Lecouturier, Didier; Phalip, Vincent; Ravallec, Rozenn; Dhulster, Pascal; Froidevaux, Rénato

2017-02-01

Innovations in novel enzyme discoveries impact upon a wide range of industries for which biocatalysis and biotransformations represent a great challenge, i.e., food industry, polymers and chemical industry. Key tools and technologies, such as bioinformatics tools to guide mutant library design, molecular biology tools to create mutants library, microfluidics/microplates, parallel miniscale bioreactors and mass spectrometry technologies to create high-throughput screening methods and experimental design tools for screening and optimization, allow to evolve the discovery, development and implementation of enzymes and whole cells in (bio)processes. These technological innovations are also accompanied by the development and implementation of clean and sustainable integrated processes to meet the growing needs of chemical, pharmaceutical, environmental and biorefinery industries. This review gives an overview of the benefits of high-throughput screening approach from the discovery and engineering of biocatalysts to cell culture for optimizing their production in integrated processes and their extraction/purification.

The Comprehensive Antibiotic Resistance Database

PubMed Central

McArthur, Andrew G.; Waglechner, Nicholas; Nizam, Fazmin; Yan, Austin; Azad, Marisa A.; Baylay, Alison J.; Bhullar, Kirandeep; Canova, Marc J.; De Pascale, Gianfranco; Ejim, Linda; Kalan, Lindsay; King, Andrew M.; Koteva, Kalinka; Morar, Mariya; Mulvey, Michael R.; O'Brien, Jonathan S.; Pawlowski, Andrew C.; Piddock, Laura J. V.; Spanogiannopoulos, Peter; Sutherland, Arlene D.; Tang, Irene; Taylor, Patricia L.; Thaker, Maulik; Wang, Wenliang; Yan, Marie; Yu, Tennison

2013-01-01

The field of antibiotic drug discovery and the monitoring of new antibiotic resistance elements have yet to fully exploit the power of the genome revolution. Despite the fact that the first genomes sequenced of free living organisms were those of bacteria, there have been few specialized bioinformatic tools developed to mine the growing amount of genomic data associated with pathogens. In particular, there are few tools to study the genetics and genomics of antibiotic resistance and how it impacts bacterial populations, ecology, and the clinic. We have initiated development of such tools in the form of the Comprehensive Antibiotic Research Database (CARD; http://arpcard.mcmaster.ca). The CARD integrates disparate molecular and sequence data, provides a unique organizing principle in the form of the Antibiotic Resistance Ontology (ARO), and can quickly identify putative antibiotic resistance genes in new unannotated genome sequences. This unique platform provides an informatic tool that bridges antibiotic resistance concerns in health care, agriculture, and the environment. PMID:23650175

Public data and open source tools for multi-assay genomic investigation of disease.

PubMed

Kannan, Lavanya; Ramos, Marcel; Re, Angela; El-Hachem, Nehme; Safikhani, Zhaleh; Gendoo, Deena M A; Davis, Sean; Gomez-Cabrero, David; Castelo, Robert; Hansen, Kasper D; Carey, Vincent J; Morgan, Martin; Culhane, Aedín C; Haibe-Kains, Benjamin; Waldron, Levi

2016-07-01

Molecular interrogation of a biological sample through DNA sequencing, RNA and microRNA profiling, proteomics and other assays, has the potential to provide a systems level approach to predicting treatment response and disease progression, and to developing precision therapies. Large publicly funded projects have generated extensive and freely available multi-assay data resources; however, bioinformatic and statistical methods for the analysis of such experiments are still nascent. We review multi-assay genomic data resources in the areas of clinical oncology, pharmacogenomics and other perturbation experiments, population genomics and regulatory genomics and other areas, and tools for data acquisition. Finally, we review bioinformatic tools that are explicitly geared toward integrative genomic data visualization and analysis. This review provides starting points for accessing publicly available data and tools to support development of needed integrative methods. © The Author 2015. Published by Oxford University Press.

Molecular profiling--a tool for addressing emerging gaps in the comparative risk assessment of GMOs.

PubMed

Heinemann, Jack A; Kurenbach, Brigitta; Quist, David

2011-10-01

Assessing the risks of genetically modified organisms (GMOs) is required by both international agreement and domestic legislation. Many view the use of the "omics" tools for profiling classes of molecules as useful in risk assessment, but no consensus has formed on the need or value of these techniques for assessing the risks of all GMOs. In this and many other cases, experts support case-by-case use of molecular profiling techniques for risk assessment. We review the latest research on the applicability and usefulness of molecular profiling techniques for GMO risk assessment. As more and more kinds of GMOs and traits are developed, broader use of molecular profiling in a risk assessment may be required to supplement the comparative approach to risk assessment. The literature-based discussions on the use of profiling appear to have settled on two findings: 1. profiling techniques are reliable and relevant, at least no less so than other techniques used in risk assessment; and 2. although not required routinely, regulators should be aware of when they are needed. The dismissal of routine molecular profiling may be confusing to regulators who then lack guidance on when molecular profiling might be worthwhile. Molecular profiling is an important way to increase confidence in risk assessments if the profiles are properly designed to address relevant risks and are applied at the correct stage of the assessment. Copyright © 2011 Elsevier Ltd. All rights reserved.

Nanoimaging to Prevent and Treat Alzheimer’s and Parkinson’s Diseases. Scientific/Technical report

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

Yuri L. Lyubchenko, PhD, DSc

2012-12-20

This project will develop innovative approaches to characterization of the very early stages of protein aggregation that eventually can be translated to the development of early diagnostic tools and efficient treatments for Alzheimer’s, Parkinson’s and Huntington’s diseases. Funding will be used to acquire nanoimaging technology for nanoscale imaging, manipulation and analysis of biomedical materials to develop treatments that will repair disabled proteins and cure diseases that result from protein malfunction, specifically Alzheimer’s and Parkinson’s diseases. Expected outcomes include tests for early diagnosis and therapeutic treatments for these devastating neurological diseases. To elucidate the mechanisms of protein misfolding, we will establishmore » an extensive program of experimental studies using a broad arsenal of advanced nanoscale and traditional techniques that will be integrated with molecular-scale modeling of protein misfolding and the nucleation of aggregate structures. To identify intracellular machinery or/and multicomponent complexes critically involved in protein misfolding, we will characterize interactions between targeted proteins and specific intracellular components or metabolites that impact on protein conformational pathways leading to protein misfolding accompanied by formation of toxic aggregated morphologies. To design innovative nanotechnology tools for the control of intracellular protein misfolding and aggregation processes, we will develop a predictive molecular scale model for intracellular protein misfolding and the formation of toxic aggregates. Verified through experimental studies, the objective is to establish an enabling foundation for the engineering of novel molecular diagnostics and therapeutics for various cellular pathologies.« less

Unveiling molecular events in the brain by noninvasive imaging.

PubMed

Klohs, Jan; Rudin, Markus

2011-10-01

Neuroimaging allows researchers and clinicians to noninvasively assess structure and function of the brain. With the advances of imaging modalities such as magnetic resonance, nuclear, and optical imaging; the design of target-specific probes; and/or the introduction of reporter gene assays, these technologies are now capable of visualizing cellular and molecular processes in vivo. Undoubtedly, the system biological character of molecular neuroimaging, which allows for the study of molecular events in the intact organism, will enhance our understanding of physiology and pathophysiology of the brain and improve our ability to diagnose and treat diseases more specifically. Technical/scientific challenges to be faced are the development of highly sensitive imaging modalities, the design of specific imaging probe molecules capable of penetrating the CNS and reporting on endogenous cellular and molecular processes, and the development of tools for extracting quantitative, biologically relevant information from imaging data. Today, molecular neuroimaging is still an experimental approach with limited clinical impact; this is expected to change within the next decade. This article provides an overview of molecular neuroimaging approaches with a focus on rodent studies documenting the exploratory state of the field. Concepts are illustrated by discussing applications related to the pathophysiology of Alzheimer's disease.

A methodological overview on molecular preimplantation genetic diagnosis and screening: a genomic future?

PubMed

Vendrell, Xavier; Bautista-Llácer, Rosa

2012-12-01

The genetic diagnosis and screening of preimplantation embryos generated by assisted reproduction technology has been consolidated in the prenatal care framework. The rapid evolution of DNA technologies is tending to molecular approaches. Our intention is to present a detailed methodological view, showing different diagnostic strategies based on molecular techniques that are currently applied in preimplantation genetic diagnosis. The amount of DNA from one single, or a few cells, obtained by embryo biopsy is a limiting factor for the molecular analysis. In this sense, genetic laboratories have developed molecular protocols considering this restrictive condition. Nevertheless, the development of whole-genome amplification methods has allowed preimplantation genetic diagnosis for two or more indications simultaneously, like the selection of histocompatible embryos plus detection of monogenic diseases or aneuploidies. Moreover, molecular techniques have permitted preimplantation genetic screening to progress, by implementing microarray-based comparative genome hybridization. Finally, a future view of the embryo-genetics field based on molecular advances is proposed. The normalization, cost-effectiveness analysis, and new technological tools are the next topics for preimplantation genetic diagnosis and screening. Concomitantly, these additions to assisted reproduction technologies could have a positive effect on the schedules of preimplantation studies.

Genomic Tools in Groundnut Breeding Program: Status and Perspectives

PubMed Central

Janila, P.; Variath, Murali T.; Pandey, Manish K.; Desmae, Haile; Motagi, Babu N.; Okori, Patrick; Manohar, Surendra S.; Rathnakumar, A. L.; Radhakrishnan, T.; Liao, Boshou; Varshney, Rajeev K.

2016-01-01

Groundnut, a nutrient-rich food legume, is cultivated world over. It is valued for its good quality cooking oil, energy and protein rich food, and nutrient-rich fodder. Globally, groundnut improvement programs have developed varieties to meet the preferences of farmers, traders, processors, and consumers. Enhanced yield, tolerance to biotic and abiotic stresses and quality parameters have been the target traits. Spurt in genetic information of groundnut was facilitated by development of molecular markers, genetic, and physical maps, generation of expressed sequence tags (EST), discovery of genes, and identification of quantitative trait loci (QTL) for some important biotic and abiotic stresses and quality traits. The first groundnut variety developed using marker assisted breeding (MAB) was registered in 2003. Since then, USA, China, Japan, and India have begun to use genomic tools in routine groundnut improvement programs. Introgression lines that combine foliar fungal disease resistance and early maturity were developed using MAB. Establishment of marker-trait associations (MTA) paved way to integrate genomic tools in groundnut breeding for accelerated genetic gain. Genomic Selection (GS) tools are employed to improve drought tolerance and pod yield, governed by several minor effect QTLs. Draft genome sequence and low cost genotyping tools such as genotyping by sequencing (GBS) are expected to accelerate use of genomic tools to enhance genetic gains for target traits in groundnut. PMID:27014312

Identifying the Interaction of Vancomycin With Novel pH-Responsive Lipids as Antibacterial Biomaterials Via Accelerated Molecular Dynamics and Binding Free Energy Calculations.

PubMed

Ahmed, Shaimaa; Vepuri, Suresh B; Jadhav, Mahantesh; Kalhapure, Rahul S; Govender, Thirumala

2018-06-01

Nano-drug delivery systems have proven to be an efficient formulation tool to overcome the challenges with current antibiotics therapy and resistance. A series of pH-responsive lipid molecules were designed and synthesized for future liposomal formulation as a nano-drug delivery system for vancomycin at the infection site. The structures of these lipids differ from each other in respect of hydrocarbon tails: Lipid1, 2, 3 and 4 have stearic, oleic, linoleic, and linolenic acid hydrocarbon chains, respectively. The impact of variation in the hydrocarbon chain in the lipid structure on drug encapsulation and release profile, as well as mode of drug interaction, was investigated using molecular modeling analyses. A wide range of computational tools, including accelerated molecular dynamics, normal molecular dynamics, binding free energy calculations and principle component analysis, were applied to provide comprehensive insight into the interaction landscape between vancomycin and the designed lipid molecules. Interestingly, both MM-GBSA and MM-PBSA binding affinity calculations using normal molecular dynamics and accelerated molecular dynamics trajectories showed a very consistent trend, where the order of binding affinity towards vancomycin was lipid4 > lipid1 > lipid2 > lipid3. From both normal molecular dynamics and accelerated molecular dynamics, the interaction of lipid3 with vancomycin is demonstrated to be the weakest (∆G binding  = -2.17 and -11.57, for normal molecular dynamics and accelerated molecular dynamics, respectively) when compared to other complexes. We believe that the degree of unsaturation of the hydrocarbon chain in the lipid molecules may impact on the overall conformational behavior, interaction mode and encapsulation (wrapping) of the lipid molecules around the vancomycin molecule. This thorough computational analysis prior to the experimental investigation is a valuable approach to guide for predicting the encapsulation ability, drug release and further development of novel liposome-based pH-responsive nano-drug delivery system with refined structural and chemical features of potential lipid molecule for formulation development.

Quantitative imaging as cancer biomarker

NASA Astrophysics Data System (ADS)

Mankoff, David A.

2015-03-01

The ability to assay tumor biologic features and the impact of drugs on tumor biology is fundamental to drug development. Advances in our ability to measure genomics, gene expression, protein expression, and cellular biology have led to a host of new targets for anticancer drug therapy. In translating new drugs into clinical trials and clinical practice, these same assays serve to identify patients most likely to benefit from specific anticancer treatments. As cancer therapy becomes more individualized and targeted, there is an increasing need to characterize tumors and identify therapeutic targets to select therapy most likely to be successful in treating the individual patient's cancer. Thus far assays to identify cancer therapeutic targets or anticancer drug pharmacodynamics have been based upon in vitro assay of tissue or blood samples. Advances in molecular imaging, particularly PET, have led to the ability to perform quantitative non-invasive molecular assays. Imaging has traditionally relied on structural and anatomic features to detect cancer and determine its extent. More recently, imaging has expanded to include the ability to image regional biochemistry and molecular biology, often termed molecular imaging. Molecular imaging can be considered an in vivo assay technique, capable of measuring regional tumor biology without perturbing it. This makes molecular imaging a unique tool for cancer drug development, complementary to traditional assay methods, and a potentially powerful method for guiding targeted therapy in clinical trials and clinical practice. The ability to quantify, in absolute measures, regional in vivo biologic parameters strongly supports the use of molecular imaging as a tool to guide therapy. This review summarizes current and future applications of quantitative molecular imaging as a biomarker for cancer therapy, including the use of imaging to (1) identify patients whose tumors express a specific therapeutic target; (2) determine whether the drug reaches the target; (3) identify an early response to treatment; and (4) predict the impact of therapy on long-term outcomes such as survival. The manuscript reviews basic concepts important in the application of molecular imaging to cancer drug therapy, in general, and will discuss specific examples of studies in humans, and highlight future directions, including ongoing multi-center clinical trials using molecular imaging as a cancer biomarker.

The Origins of Molecular Biology: A Pedagogical Tool for the Professional Development of Pre-College Science Teachers

ERIC Educational Resources Information Center

Silverman, Philip M.

2003-01-01

We examine the science and pedagogy behind a historical approach to the professional development of pre-college science (primarily biology) teachers. Our intention is to reach professional scientists, who, as a group, are uniquely qualified to provide experience and insights essential to this approach. The underlying research for this article has…

Assessing Date Palm Genetic Diversity Using Different Molecular Markers.

PubMed

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

2017-01-01

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

Molecular diagnostics of inflammatory disease: New tools and perspectives.

PubMed

Garzorz-Stark, Natalie; Lauffer, Felix

2017-08-01

This essay reviews current approaches to establish novel molecular diagnostic tools for inflammatory skin diseases. Moreover, it highlights the importance of stratifying patients according to molecular signatures and revising current outdated disease classification systems to eventually reach the goal of personalized medicine. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Molecular rheology of branched polymers: decoding and exploring the role of architectural dispersity through a synergy of anionic synthesis, interaction chromatography, rheometry and modeling.

PubMed

van Ruymbeke, E; Lee, H; Chang, T; Nikopoulou, A; Hadjichristidis, N; Snijkers, F; Vlassopoulos, D

2014-07-21

An emerging challenge in polymer physics is the quantitative understanding of the influence of a macromolecular architecture (i.e., branching) on the rheological response of entangled complex polymers. Recent investigations of the rheology of well-defined architecturally complex polymers have determined the composition in the molecular structure and identified the role of side-products in the measured samples. The combination of different characterization techniques, experimental and/or theoretical, represents the current state-of-the-art. Here we review this interdisciplinary approach to molecular rheology of complex polymers, and show the importance of confronting these different tools for ensuring an accurate characterization of a given polymeric sample. We use statistical tools in order to relate the information available from the synthesis protocols of a sample and its experimental molar mass distribution (typically obtained from size exclusion chromatography), and hence obtain precise information about its structural composition, i.e. enhance the existing sensitivity limit. We critically discuss the use of linear rheology as a reliable quantitative characterization tool, along with the recently developed temperature gradient interaction chromatography. The latter, which has emerged as an indispensable characterization tool for branched architectures, offers unprecedented sensitivity in detecting the presence of different molecular structures in a sample. Combining these techniques is imperative in order to quantify the molecular composition of a polymer and its consequences on the macroscopic properties. We validate this approach by means of a new model asymmetric comb polymer which was synthesized anionically. It was thoroughly characterized and its rheology was carefully analyzed. The main result is that the rheological signal reveals fine molecular details, which must be taken into account to fully elucidate the viscoelastic response of entangled branched polymers. It is important to appreciate that, even optimal model systems, i.e., those synthesized with high-vacuum anionic methods, need thorough characterization via a combination of techniques. Besides helping to improve synthetic techniques, this methodology will be significant in fine-tuning mesoscopic tube-based models and addressing outstanding issues such as the quantitative description of the constraint release mechanism.

Molecular entomology and prospects for malaria control.

PubMed Central

Collins, F. H.; Kamau, L.; Ranson, H. A.; Vulule, J. M.

2000-01-01

During the past decade, the techniques of molecular and cell biology have been embraced by many scientists doing research on anopheline vectors of malaria parasites. Some of the most important research advances in molecular entomology have concerned the development of sophisticated molecular tools for procedures such as genetic and physical mapping and germ line transformation. Major advances have also been made in the study of specific biological processes such as insect defence against pathogens and the manner in which malaria parasites and their anopheline hosts interact during sporogony. One of the most important highlights of this research trend has been the emergence during the past year of a formal international Anopheles gambiae genome project, which at present includes investigators in several laboratories in Europe and the USA. Although much of this molecular research is directed towards the development of malaria control strategies that are probably many years from implementation, there are some important areas of molecular entomology that may have a more near-term impact on malaria control. We highlight developments over the past decade in three such areas that we believe can make important contributions to the development of near-term malaria control strategies. These areas are anopheline species identification, the detection and monitoring of insecticide susceptibility/resistance in wild anopheline populations and the determination of the genetic structure of anopheline populations. PMID:11196488

Molecular markers in the epidemiology and diagnosis of coccidioidomycosis.

PubMed

Duarte-Escalante, Esperanza; Frías-De-León, María Guadalupe; Zúñiga, Gerardo; Martínez-Herrera, Erick; Acosta-Altamirano, Gustavo; Reyes-Montes, María Del Rocío

2014-01-01

The prevalence of coccidioidomycosis in endemic areas has been observed to increase daily. To understand the causes of the spread of the disease and design strategies for fungal detection in clinical and environmental samples, scientists have resorted to molecular tools that allow fungal detection in a natural environment, reliable identification in clinical cases and the study of biological characteristics, such as reproductive and genetic structure, demographic history and diversification. We conducted a review of the most important molecular markers in the epidemiology of Coccidioides spp. and the diagnosis of coccidioidomycosis. A literature search was performed for scientific publications concerning the application of molecular tools for the epidemiology and diagnosis of coccidioidomycosis. The use of molecular markers in the epidemiological study and diagnosis of coccidioidomycosis has allowed for the typing of Coccidioides spp. isolates, improved understanding of their mode of reproduction, genetic variation and speciation and resulted in the development specific, rapid and sensitive strategies for detecting the fungus in environmental and clinical samples. Molecular markers have revealed genetic variability in Coccidioides spp. This finding influences changes in the epidemiology of coccidioidomycosis, such as the emergence of more virulent or antifungal resistant genotypes. Furthermore, the molecular markers currently used to identify Coccidioides immitis and Coccidioides posadasii are specific and sensitive. However, they must be validated to determine their application in diagnosis. This manuscript is part of the series of works presented at the "V International Workshop: Molecular genetic approaches to the study of human pathogenic fungi" (Oaxaca, Mexico, 2012). Copyright © 2013 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.

Quantum probability ranking principle for ligand-based virtual screening.

PubMed

Al-Dabbagh, Mohammed Mumtaz; Salim, Naomie; Himmat, Mubarak; Ahmed, Ali; Saeed, Faisal

2017-04-01

Chemical libraries contain thousands of compounds that need screening, which increases the need for computational methods that can rank or prioritize compounds. The tools of virtual screening are widely exploited to enhance the cost effectiveness of lead drug discovery programs by ranking chemical compounds databases in decreasing probability of biological activity based upon probability ranking principle (PRP). In this paper, we developed a novel ranking approach for molecular compounds inspired by quantum mechanics, called quantum probability ranking principle (QPRP). The QPRP ranking criteria would make an attempt to draw an analogy between the physical experiment and molecular structure ranking process for 2D fingerprints in ligand based virtual screening (LBVS). The development of QPRP criteria in LBVS has employed the concepts of quantum at three different levels, firstly at representation level, this model makes an effort to develop a new framework of molecular representation by connecting the molecular compounds with mathematical quantum space. Secondly, estimate the similarity between chemical libraries and references based on quantum-based similarity searching method. Finally, rank the molecules using QPRP approach. Simulated virtual screening experiments with MDL drug data report (MDDR) data sets showed that QPRP outperformed the classical ranking principle (PRP) for molecular chemical compounds.

Quantum probability ranking principle for ligand-based virtual screening

NASA Astrophysics Data System (ADS)

Al-Dabbagh, Mohammed Mumtaz; Salim, Naomie; Himmat, Mubarak; Ahmed, Ali; Saeed, Faisal

2017-04-01

Chemical libraries contain thousands of compounds that need screening, which increases the need for computational methods that can rank or prioritize compounds. The tools of virtual screening are widely exploited to enhance the cost effectiveness of lead drug discovery programs by ranking chemical compounds databases in decreasing probability of biological activity based upon probability ranking principle (PRP). In this paper, we developed a novel ranking approach for molecular compounds inspired by quantum mechanics, called quantum probability ranking principle (QPRP). The QPRP ranking criteria would make an attempt to draw an analogy between the physical experiment and molecular structure ranking process for 2D fingerprints in ligand based virtual screening (LBVS). The development of QPRP criteria in LBVS has employed the concepts of quantum at three different levels, firstly at representation level, this model makes an effort to develop a new framework of molecular representation by connecting the molecular compounds with mathematical quantum space. Secondly, estimate the similarity between chemical libraries and references based on quantum-based similarity searching method. Finally, rank the molecules using QPRP approach. Simulated virtual screening experiments with MDL drug data report (MDDR) data sets showed that QPRP outperformed the classical ranking principle (PRP) for molecular chemical compounds.

Intentions and actions in molecular self-assembly: perspectives on students' language use

NASA Astrophysics Data System (ADS)

Höst, Gunnar E.; Anward, Jan

2017-04-01

Learning to talk science is an important aspect of learning to do science. Given that scientists' language frequently includes intentions and purposes in explanations of unobservable objects and events, teachers must interpret whether learners' use of such language reflects a scientific understanding or inaccurate anthropomorphism and teleology. In the present study, a framework consisting of three 'stances' (Dennett, 1987) - intentional, design and physical - is presented as a powerful tool for analysing students' language use. The aim was to investigate how the framework can be differentiated and used analytically for interpreting students' talk about a molecular process. Semi-structured group discussions and individual interviews about the molecular self-assembly process were conducted with engineering biology/chemistry (n = 15) and biology/chemistry teacher students (n = 6). Qualitative content analysis of transcripts showed that all three stances were employed by students. The analysis also identified subcategories for each stance, and revealed that intentional language with respect to molecular movement and assumptions about design requirements may be potentially problematic areas. Students' exclusion of physical stance explanations may indicate literal anthropomorphic interpretations. Implications for practice include providing teachers with a tool for scaffolding their use of metaphorical language and for supporting students' metacognitive development as scientific language users.

Investigating Novice and Expert Conceptions of Genetically Modified Organisms

PubMed Central

Potter, Lisa M.; Bissonnette, Sarah A.; Knight, Jonathan D.; Tanner, Kimberly D.

2017-01-01

The aspiration of biology education is to give students tools to apply knowledge learned in the classroom to everyday life. Genetic modification is a real-world biological concept that relies on an in-depth understanding of the molecular behavior of DNA and proteins. This study investigated undergraduate biology students’ conceptions of genetically modified organisms (GMOs) when probed with real-world, molecular and cellular, and essentialist cues, and how those conceptions compared across biology expertise. We developed a novel written assessment tool and administered it to 120 non–biology majors, 154 entering biology majors, 120 advanced biology majors (ABM), and nine biology faculty. Results indicated that undergraduate biology majors rarely included molecular and cellular rationales in their initial explanations of GMOs. Despite ABM demonstrating that they have much of the biology knowledge necessary to understand genetic modification, they did not appear to apply this knowledge to explaining GMOs. Further, this study showed that all undergraduate student populations exhibited evidence of essentialist thinking while explaining GMOs, regardless of their level of biology training. Finally, our results suggest an association between scientifically accurate ideas and the application of molecular and cellular rationales, as well as an association between misconceptions and essentialist rationales. PMID:28821537

GlycCompSoft: Software for Automated Comparison of Low Molecular Weight Heparins Using Top-Down LC/MS Data

PubMed Central

Li, Lingyun; Zhang, Fuming; Hu, Min; Ren, Fuji; Chi, Lianli; Linhardt, Robert J.

2016-01-01

Low molecular weight heparins are complex polycomponent drugs that have recently become amenable to top-down analysis using liquid chromatography-mass spectrometry. Even using open source deconvolution software, DeconTools, and automatic structural assignment software, GlycReSoft, the comparison of two or more low molecular weight heparins is extremely time-consuming, taking about a week for an expert analyst and provides no guarantee of accuracy. Efficient data processing tools are required to improve analysis. This study uses the programming language of Microsoft Excel™ Visual Basic for Applications to extend its standard functionality for macro functions and specific mathematical modules for mass spectrometric data processing. The program developed enables the comparison of top-down analytical glycomics data on two or more low molecular weight heparins. The current study describes a new program, GlycCompSoft, which has a low error rate with good time efficiency in the automatic processing of large data sets. The experimental results based on three lots of Lovenox®, Clexane® and three generic enoxaparin samples show that the run time of GlycCompSoft decreases from 11 to 2 seconds when the data processed decreases from 18000 to 1500 rows. PMID:27942011

Call for Standardized Definitions of Osteoarthritis and Risk Stratification for Clinical Trials and Clinical Use

PubMed Central

Kraus, Virginia Byers; Blanco, Francisco J.; Englund, Martin; Karsdal, Morten A.; Lohmander, L. Stefan

2015-01-01

Osteoarthritis is a heterogeneous disorder. The goals of this review are (1) To stimulate use of standardized nomenclature for osteoarthritis (OA) that could serve as building blocks for describing OA and defining OA phenotypes, in short to provide unifying disease concepts for a heterogeneous disorder; and (2) To stimulate establishment of ROAD (Risk of Osteoarthritis Development) and ROAP (Risk of Osteoarthritis Progression) tools analogous to the FRAX™ instrument for predicting risk of fracture in osteoporosis; and (3) To stimulate formulation of tools for identifying disease in its early preradiographic and/or molecular stages -- REDI (Reliable Early Disease Identification). Consensus around more sensitive and specific diagnostic criteria for OA could spur development of disease modifying therapies for this entity that has proved so recalcitrant to date. We fully acknowledge that as we move forward, we expect to develop more sophisticated definitions, terminology and tools. PMID:25865392

DOMINO: development of informative molecular markers for phylogenetic and genome-wide population genetic studies in non-model organisms.

PubMed

Frías-López, Cristina; Sánchez-Herrero, José F; Guirao-Rico, Sara; Mora, Elisa; Arnedo, Miquel A; Sánchez-Gracia, Alejandro; Rozas, Julio

2016-12-15

The development of molecular markers is one of the most important challenges in phylogenetic and genome wide population genetics studies, especially in studies with non-model organisms. A highly promising approach for obtaining suitable markers is the utilization of genomic partitioning strategies for the simultaneous discovery and genotyping of a large number of markers. Unfortunately, not all markers obtained from these strategies provide enough information for solving multiple evolutionary questions at a reasonable taxonomic resolution. We have developed Development Of Molecular markers In Non-model Organisms (DOMINO), a bioinformatics tool for informative marker development from both next generation sequencing (NGS) data and pre-computed sequence alignments. The application implements popular NGS tools with new utilities in a highly versatile pipeline specifically designed to discover or select personalized markers at different levels of taxonomic resolution. These markers can be directly used to study the taxa surveyed for their design, utilized for further downstream PCR amplification in a broader set taxonomic scope, or exploited as suitable templates to bait design for target DNA enrichment techniques. We conducted an exhaustive evaluation of the performance of DOMINO via computer simulations and illustrate its utility to find informative markers in an empirical dataset. DOMINO is freely available from www.ub.edu/softevol/domino CONTACT: elsanchez@ub.edu or jrozas@ub.eduSupplementary information: Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Lessons learned from DNA-based tool development and use in a genebank

USDA-ARS?s Scientific Manuscript database

In 2002, a molecular genetics laboratory was established at the United States Department of Agriculture Agricultural Research Service (USDA-ARS), National Clonal Germplasm Repository (NCGR), in Corvallis, Oregon. This facility houses the US national genebank for strawberry (Fragaria L.). A main obje...

Development and characterization of rice mutants for functional genomic studies and breeding

USDA-ARS?s Scientific Manuscript database

Mutagenesis is a powerful tool for creating genetic materials for studying functional genomics, breeding, and understanding the molecular basis of disease resistance. Approximately 100,000 putative mutants of rice (Oryza sativa L.) have been generated with mutagens. Numerous mutant genes involved in...

Zinc Fingers, TALEs, and CRISPR Systems: A Comparison of Tools for Epigenome Editing.

PubMed

Waryah, Charlene Babra; Moses, Colette; Arooj, Mahira; Blancafort, Pilar

2018-01-01

The completion of genome, epigenome, and transcriptome mapping in multiple cell types has created a demand for precision biomolecular tools that allow researchers to functionally manipulate DNA, reconfigure chromatin structure, and ultimately reshape gene expression patterns. Epigenetic editing tools provide the ability to interrogate the relationship between epigenetic modifications and gene expression. Importantly, this information can be exploited to reprogram cell fate for both basic research and therapeutic applications. Three different molecular platforms for epigenetic editing have been developed: zinc finger proteins (ZFs), transcription activator-like effectors (TALEs), and the system of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-associated (Cas) proteins. These platforms serve as custom DNA-binding domains (DBDs), which are fused to epigenetic modifying domains to manipulate epigenetic marks at specific sites in the genome. The addition and/or removal of epigenetic modifications reconfigures local chromatin structure, with the potential to provoke long-lasting changes in gene transcription. Here we summarize the molecular structure and mechanism of action of ZF, TALE, and CRISPR platforms and describe their applications for the locus-specific manipulation of the epigenome. The advantages and disadvantages of each platform will be discussed with regard to genomic specificity, potency in regulating gene expression, and reprogramming cell phenotypes, as well as ease of design, construction, and delivery. Finally, we outline potential applications for these tools in molecular biology and biomedicine and identify possible barriers to their future clinical implementation.

Guidelines for the analysis of free energy calculations

PubMed Central

Klimovich, Pavel V.; Shirts, Michael R.; Mobley, David L.

2015-01-01

Free energy calculations based on molecular dynamics (MD) simulations show considerable promise for applications ranging from drug discovery to prediction of physical properties and structure-function studies. But these calculations are still difficult and tedious to analyze, and best practices for analysis are not well defined or propagated. Essentially, each group analyzing these calculations needs to decide how to conduct the analysis and, usually, develop its own analysis tools. Here, we review and recommend best practices for analysis yielding reliable free energies from molecular simulations. Additionally, we provide a Python tool, alchemical–analysis.py, freely available on GitHub at https://github.com/choderalab/pymbar–examples, that implements the analysis practices reviewed here for several reference simulation packages, which can be adapted to handle data from other packages. Both this review and the tool covers analysis of alchemical calculations generally, including free energy estimates via both thermodynamic integration and free energy perturbation-based estimators. Our Python tool also handles output from multiple types of free energy calculations, including expanded ensemble and Hamiltonian replica exchange, as well as standard fixed ensemble calculations. We also survey a range of statistical and graphical ways of assessing the quality of the data and free energy estimates, and provide prototypes of these in our tool. We hope these tools and discussion will serve as a foundation for more standardization of and agreement on best practices for analysis of free energy calculations. PMID:25808134

ToxiM: A Toxicity Prediction Tool for Small Molecules Developed Using Machine Learning and Chemoinformatics Approaches.

PubMed

Sharma, Ashok K; Srivastava, Gopal N; Roy, Ankita; Sharma, Vineet K

2017-01-01

The experimental methods for the prediction of molecular toxicity are tedious and time-consuming tasks. Thus, the computational approaches could be used to develop alternative methods for toxicity prediction. We have developed a tool for the prediction of molecular toxicity along with the aqueous solubility and permeability of any molecule/metabolite. Using a comprehensive and curated set of toxin molecules as a training set, the different chemical and structural based features such as descriptors and fingerprints were exploited for feature selection, optimization and development of machine learning based classification and regression models. The compositional differences in the distribution of atoms were apparent between toxins and non-toxins, and hence, the molecular features were used for the classification and regression. On 10-fold cross-validation, the descriptor-based, fingerprint-based and hybrid-based classification models showed similar accuracy (93%) and Matthews's correlation coefficient (0.84). The performances of all the three models were comparable (Matthews's correlation coefficient = 0.84-0.87) on the blind dataset. In addition, the regression-based models using descriptors as input features were also compared and evaluated on the blind dataset. Random forest based regression model for the prediction of solubility performed better ( R 2 = 0.84) than the multi-linear regression (MLR) and partial least square regression (PLSR) models, whereas, the partial least squares based regression model for the prediction of permeability (caco-2) performed better ( R 2 = 0.68) in comparison to the random forest and MLR based regression models. The performance of final classification and regression models was evaluated using the two validation datasets including the known toxins and commonly used constituents of health products, which attests to its accuracy. The ToxiM web server would be a highly useful and reliable tool for the prediction of toxicity, solubility, and permeability of small molecules.

ToxiM: A Toxicity Prediction Tool for Small Molecules Developed Using Machine Learning and Chemoinformatics Approaches

PubMed Central

Sharma, Ashok K.; Srivastava, Gopal N.; Roy, Ankita; Sharma, Vineet K.

2017-01-01

The experimental methods for the prediction of molecular toxicity are tedious and time-consuming tasks. Thus, the computational approaches could be used to develop alternative methods for toxicity prediction. We have developed a tool for the prediction of molecular toxicity along with the aqueous solubility and permeability of any molecule/metabolite. Using a comprehensive and curated set of toxin molecules as a training set, the different chemical and structural based features such as descriptors and fingerprints were exploited for feature selection, optimization and development of machine learning based classification and regression models. The compositional differences in the distribution of atoms were apparent between toxins and non-toxins, and hence, the molecular features were used for the classification and regression. On 10-fold cross-validation, the descriptor-based, fingerprint-based and hybrid-based classification models showed similar accuracy (93%) and Matthews's correlation coefficient (0.84). The performances of all the three models were comparable (Matthews's correlation coefficient = 0.84–0.87) on the blind dataset. In addition, the regression-based models using descriptors as input features were also compared and evaluated on the blind dataset. Random forest based regression model for the prediction of solubility performed better (R2 = 0.84) than the multi-linear regression (MLR) and partial least square regression (PLSR) models, whereas, the partial least squares based regression model for the prediction of permeability (caco-2) performed better (R2 = 0.68) in comparison to the random forest and MLR based regression models. The performance of final classification and regression models was evaluated using the two validation datasets including the known toxins and commonly used constituents of health products, which attests to its accuracy. The ToxiM web server would be a highly useful and reliable tool for the prediction of toxicity, solubility, and permeability of small molecules. PMID:29249969

Laser-induced Fluorescence Spectroscopy (LIFS) for Discrimination of Genetically Close Sweet Orange Accessions ( Citrus sinensis L. Osbeck).

PubMed

Massaiti Kuboyama Kubota, Thiago; Bebeachibuli Magalhães, Aida; Nery da Silva, Marina; Ribeiro Villas Boas, Paulino; Novelli, Valdenice M; Bastianel, Marinês; Sagawa, Cíntia H D; Cristofani-Yaly, Mariângela; Marcondes Bastos Pereira Milori, Débora

2017-02-01

Although there is substantial diversity among cultivated sweet oranges genotypes with respect to morphological, physiological, and agronomic traits, very little variation at DNA level has been observed. It is possible that this low DNA molecular variability is due to a narrow genetic basis commonly observed in this citrus group. The most different morphological characters observed were originated through mutations, which are maintained by vegetative propagation. Despite all molecular tools available for discrimination between these different accessions, in general, low polymorphism has been observed in all groups of sweet oranges and they may not be identified by molecular markers. In this context, this paper describes the results obtained by using laser-induced fluorescent spectroscopy (LIFS) as a tool to discriminate sweet orange accessions ( Citrus sinensis L. Osbeck) including common, low acidity, pigmented, and navel orange groups, with very little variation at DNA level. The findings showed that LIFS combined with statistical methods is capable to discriminate different accessions. The basic idea is that citrus leaves have multiple fluorophores and concentration depends on their genetics and metabolism. Thus, we consider that the optical properties of citrus leaves may be different, depending on variety. The results have shown that the developed method, for the best classification rate, reaches an average sensitivity and specificity of 95% and 97.5%, respectively. An interesting application of this study is the development of an economically viable tool for early identification in seedling certification, in citrus breeding programs, in cultivar protection, or in germplasm core collection.

Molecular Evolution in Historical Perspective.

PubMed

Suárez-Díaz, Edna

2016-12-01

In the 1960s, advances in protein chemistry and molecular genetics provided new means for the study of biological evolution. Amino acid sequencing, nucleic acid hybridization, zone gel electrophoresis, and immunochemistry were some of the experimental techniques that brought about new perspectives to the study of the patterns and mechanisms of evolution. New concepts, such as the molecular evolutionary clock, and the discovery of unexpected molecular phenomena, like the presence of repetitive sequences in eukaryotic genomes, eventually led to the realization that evolution might occur at a different pace at the organismic and the molecular levels, and according to different mechanisms. These developments sparked important debates between defendants of the molecular and organismic approaches. The most vocal confrontations focused on the relation between primates and humans, and the neutral theory of molecular evolution. By the 1980s and 1990s, the construction of large protein and DNA sequences databases, and the development of computer-based statistical tools, facilitated the coming together of molecular and evolutionary biology. Although in its contemporary form the field of molecular evolution can be traced back to the last five decades, the field has deep roots in twentieth century experimental life sciences. For historians of science, the origins and consolidation of molecular evolution provide a privileged field for the study of scientific debates, the relation between technological advances and scientific knowledge, and the connection between science and broader social concerns.

Investigation of type-I interferon dysregulation by arenaviruses : a multidisciplinary approach.

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

Kozina, Carol L.; Moorman, Matthew Wallace; Branda, Catherine

2011-09-01

This report provides a detailed overview of the work performed for project number 130781, 'A Systems Biology Approach to Understanding Viral Hemorrhagic Fever Pathogenesis.' We report progress in five key areas: single cell isolation devices and control systems, fluorescent cytokine and transcription factor reporters, on-chip viral infection assays, molecular virology analysis of Arenavirus nucleoprotein structure-function, and development of computational tools to predict virus-host protein interactions. Although a great deal of work remains from that begun here, we have developed several novel single cell analysis tools and knowledge of Arenavirus biology that will facilitate and inform future publications and funding proposals.

WebSat ‐ A web software for microsatellite marker development

PubMed Central

Martins, Wellington Santos; Soares Lucas, Divino César; de Souza Neves, Kelligton Fabricio; Bertioli, David John

2009-01-01

Simple sequence repeats (SSR), also known as microsatellites, have been extensively used as molecular markers due to their abundance and high degree of polymorphism. We have developed a simple to use web software, called WebSat, for microsatellite molecular marker prediction and development. WebSat is accessible through the Internet, requiring no program installation. Although a web solution, it makes use of Ajax techniques, providing a rich, responsive user interface. WebSat allows the submission of sequences, visualization of microsatellites and the design of primers suitable for their amplification. The program allows full control of parameters and the easy export of the resulting data, thus facilitating the development of microsatellite markers. Availability The web tool may be accessed at http://purl.oclc.org/NET/websat/ PMID:19255650

Molecular and Cellular Biology Animations: Development and Impact on Student Learning

PubMed Central

2005-01-01

Educators often struggle when teaching cellular and molecular processes because typically they have only two-dimensional tools to teach something that plays out in four dimensions. Learning research has demonstrated that visualizing processes in three dimensions aids learning, and animations are effective visualization tools for novice learners and aid with long-term memory retention. The World Wide Web Instructional Committee at North Dakota State University has used these research results as an inspiration to develop a suite of high-quality animations of molecular and cellular processes. Currently, these animations represent transcription, translation, bacterial gene expression, messenger RNA (mRNA) processing, mRNA splicing, protein transport into an organelle, the electron transport chain, and the use of a biological gradient to drive adenosine triphosphate synthesis. These animations are integrated with an educational module that consists of First Look and Advanced Look components that feature captioned stills from the animation representing the key steps in the processes at varying levels of complexity. These animation-based educational modules are available via the World Wide Web at http://vcell.ndsu.edu/animations. An in-class research experiment demonstrated that student retention of content material was significantly better when students received a lecture coupled with the animations and then used the animation as an individual study activity. PMID:15917875

Structural systems pharmacology: a new frontier in discovering novel drug targets.

PubMed

Tan, Hepan; Ge, Xiaoxia; Xie, Lei

2013-08-01

The modern target-based drug discovery process, characterized by the one-drug-one-gene paradigm, has been of limited success. In contrast, phenotype-based screening produces thousands of active compounds but gives no hint as to what their molecular targets are or which ones merit further research. This presents a question: What is a suitable target for an efficient and safe drug? In this paper, we argue that target selection should take into account the proteome-wide energetic and kinetic landscape of drug-target interactions, as well as their cellular and organismal consequences. We propose a new paradigm of structural systems pharmacology to deconvolute the molecular targets of successful drugs as well as to identify druggable targets and their drug-like binders. Here we face two major challenges in structural systems pharmacology: How do we characterize and analyze the structural and energetic origins of drug-target interactions on a proteome scale? How do we correlate the dynamic molecular interactions to their in vivo activity? We will review recent advances in developing new computational tools for biophysics, bioinformatics, chemoinformatics, and systems biology related to the identification of genome-wide target profiles. We believe that the integration of these tools will realize structural systems pharmacology, enabling us to both efficiently develop effective therapeutics for complex diseases and combat drug resistance.

PETROLEUM RESIDUA SOLUBILITY PARAMETER/POLARITY MAP: STABILITY STUDIES OF RESIDUA PYROLYSIS

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

John F. Schabron; A. Troy Pauli; Joseph F. Rovani, Jr.

1999-04-30

A new molecular weight/polarity map based on the Scatchard-Hildebrand solubility equation has been developed for petroleum residua. A series of extractions are performed with solvents of increasing solubility parameter, and the fractions are analyzed by vapor pressure osmometry for number average molecular weight and by analytical-scale size exclusion chromatography for molecular weight spread. Work was performed for a heavy oil material subjected to three increasing severities of thermal treatment prior to and through the onset of coke formation. The results are diagnostic of the layers of solvations by resin-type molecules around a central asphaltene core. Two additional stability diagnostic methodsmore » were also used. These were the Heithaus titration ''P-index'' and Gaestel ''G'' index, which have been applied to paving asphalts for decades. The Heithaus titration involves the titration of three toluene solutions of a residuum at three concentrations with a poor solvent, such as isooctane, to the point of asphaltene flocculation. In the present work, the significance of the data are developed in terms of the Hildebrand solubility parameter. The Heithaus results are combined with data from the new molecular weight/polarity map. The solubility parameters for the toluene-soluble asphaltene components are measured, and the solubility parameters of the maltenes can be calculated. As thermal treatment progresses, the solubility parameters of asphaltene materials increase and the molecular weights decrease. A new coking index is proposed based on Heithaus titration data. Preliminary results suggest that an alternative, simpler coking index may be developed by measuring the weight percent of cyclohexane solubles in heptane asphaltenes. Coking onset appears to coincide with the depletion of these resin-type asphaltene solubilizing components of residua. The objective of the present study was to develop a mapping tool that will enhance understanding of the changes that occur in residua during upgrading and support the industry-sponsored work in which Western Research Institute is engaged. WRI performs proprietary industry-sponsored residua and heavy oil upgrading process development and optimization research. The new mapping tool can be used for evaluating heavy oils and residua in both upstream and downstream operations.« less

Biomass Characterization | Bioenergy | NREL

Science.gov Websites

analytical methods for biomass characterization available for downloading. View the Biomass Compositional Methods Molecular Beam Mass Spectrometry Photo of a man in front of multiple computer screens that present Characterization of Biomass We develop new methods and tools to understand the chemical composition of raw biomass

PREDICTION OF THE SOLUBILITY, ACTIVITY COEFFICIENT AND LIQUID/LIQUID PARTITION COEFFICIENT OF ORGANIC COMPOUNDS

EPA Science Inventory

Solvation models, based on fundamental chemical structure theory, were developed in the SPARC mechanistic tool box to predict a large array of physical properties of organic compounds in water and in non-aqueous solvents strictly from molecular structure. The SPARC self-interact...

Biochemical Visual Literacy with Constructive Alignment: Outcomes, Assessment, and Activities

ERIC Educational Resources Information Center

Herraez, Angel; Costa, Manuel Joao

2013-01-01

Several contributions in "Biochemistry and Molecular Biology Education" have highlighted the role of visualization tools and the importance of developing students' visual literacy in biochemistry education. In this forum, the authors suggest that more focus is needed on the assessment of student learning, and they advance…

Molecular Targeted Viral Nanoparticles as Tools for Imaging Cancer

PubMed Central

Cho, C.F.; Sourabh, S.; Simpson, E.J.; Steinmetz, N.F.; Luyt, L.G.; Lewis, J.D.

2015-01-01

Viral nanoparticles (VNPs) are a novel class of bionanomaterials that harness the natural biocompatibility of viruses for the development of therapeutics, vaccines, and imaging tools. The plant virus, cowpea mosaic virus (CPMV), has been successfully engineered to create novel cancer-targeted imaging agents by incorporating fluorescent dyes, polyethylene glycol (PEG) polymers, and targeting moieties. Using straightforward conjugation strategies, VNPs with high selectivity for cancer-specific molecular targets can be synthesized for in vivo imaging of tumors. Here we describe the synthesis and purification of CPMV-based VNPs, the functionalization of these VNPs using click chemistry, and their use for imaging xenograft tumors in animal models. VNPs decorated with fluorescent dyes, PEG, and targeting ligands can be synthesized in one day, and imaging studies can be performed over hours, days, or weeks, depending on the application. PMID:24243252

'Personalized medicine': what's in a name?

PubMed

Pokorska-Bocci, Anna; Stewart, Alison; Sagoo, Gurdeep S; Hall, Alison; Kroese, Mark; Burton, Hilary

2014-03-01

Over the last decade genomics and other molecular biosciences have enabled new capabilities that, according to many, have the potential to revolutionize medicine and healthcare. These developments have been associated with a range of terminologies, including 'precision', 'personalized', 'individualized' and 'stratified' medicine. In this article, based on a literature review, we examine how the terms have arisen and their various meanings and definitions. We discuss the impact of the new technologies on disease classification, prevention and management. We suggest that although genomics and molecular biosciences will undoubtedly greatly enhance the power of medicine, they will not lead to a conceptually new paradigm of medical care. What is new is the portfolio of modern tools that medicine and healthcare can use for better targeted approaches to health and disease management, and the sociopolitical contexts within which these tools are applied.

Development and Application of Camelid Molecular Cytogenetic Tools

PubMed Central

Avila, Felipe; Das, Pranab J.; Kutzler, Michelle; Owens, Elaine; Perelman, Polina; Rubes, Jiri; Hornak, Miroslav; Johnson, Warren E.

2014-01-01

Cytogenetic chromosome maps offer molecular tools for genome analysis and clinical cytogenetics and are of particular importance for species with difficult karyotypes, such as camelids (2n = 74). Building on the available human–camel zoo-fluorescence in situ hybridization (FISH) data, we developed the first cytogenetic map for the alpaca (Lama pacos, LPA) genome by isolating and identifying 151 alpaca bacterial artificial chromosome (BAC) clones corresponding to 44 specific genes. The genes were mapped by FISH to 31 alpaca autosomes and the sex chromosomes; 11 chromosomes had 2 markers, which were ordered by dual-color FISH. The STS gene mapped to Xpter/Ypter, demarcating the pseudoautosomal region, whereas no markers were assigned to chromosomes 14, 21, 22, 28, and 36. The chromosome-specific markers were applied in clinical cytogenetics to identify LPA20, the major histocompatibility complex (MHC)-carrying chromosome, as a part of an autosomal translocation in a sterile male llama (Lama glama, LGL; 2n = 73,XY). FISH with LPAX BACs and LPA36 paints, as well as comparative genomic hybridization, were also used to investigate the origin of the minute chromosome, an abnormally small LPA36 in infertile female alpacas. This collection of cytogenetically mapped markers represents a new tool for camelid clinical cytogenetics and has applications for the improvement of the alpaca genome map and sequence assembly. PMID:23109720

DOVIS 2.0: An Efficient and Easy to Use Parallel Virtual Screening Tool Based on AutoDock 4.0

DTIC Science & Technology

2008-09-08

under the GNU General Public License. Background Molecular docking is a computational method that pre- dicts how a ligand interacts with a receptor...Hence, it is an important tool in studying receptor-ligand interactions and plays an essential role in drug design. Particularly, molecular docking has...libraries from OpenBabel and setup a molecular data structure as a C++ object in our program. This makes handling of molecular structures (e.g., atoms

Molecular karyotyping of the 2La inversion in Anopheles gambiae.

PubMed

White, Bradley J; Santolamazza, Federica; Kamau, Luna; Pombi, Marco; Grushko, Olga; Mouline, Karine; Brengues, Cecile; Guelbeogo, Wamdaogo; Coulibaly, Mamadou; Kayondo, Jonathan K; Sharakhov, Igor; Simard, Frederic; Petrarca, Vincenzo; Della Torre, Alessandra; Besansky, Nora J

2007-02-01

The African malaria vector Anopheles gambiae is polymorphic for alternative arrangements on the left arm of chromosome 2 (2La and 2L+(a)) that are non-randomly distributed with respect to degree of aridity. Detailed studies on the ecological role of inversion 2La have been hindered by the technical demands of traditional karyotype analysis and by sex- and stage-specific limitations on the availability of polytene chromosomes favorable for analysis. Recent molecular characterization of both inversion breakpoints presented the opportunity to develop a polymerase chain reaction (PCR)-based method for karyotype analysis. Here we report the development of this molecular diagnostic assay and the results of extensive field validation. When tested on 765 An. gambiae specimens sampled across Africa, the molecular approach compared favorably with traditional cytologic methods, correctly scoring > 94% of these specimens. By providing ready access to the 2La karyotype, this tool lays groundwork for future studies of the ecological genomics of this medically important species.

Inside a VAMDC data node—putting standards into practical software

NASA Astrophysics Data System (ADS)

Regandell, Samuel; Marquart, Thomas; Piskunov, Nikolai

2018-03-01

Access to molecular and atomic data is critical for many forms of remote sensing analysis across different fields. Many atomic and molecular databases are however highly specialised for their intended application, complicating querying and combination data between sources. The Virtual Atomic and Molecular Data Centre, VAMDC, is an electronic infrastructure that allows each database to register as a ‘node’. Through services such as VAMDC’s portal website, users can then access and query all nodes in a homogenised way. Today all major Atomic and Molecular databases are attached to VAMDC This article describes the software tools we developed to help data providers create and manage a VAMDC node. It gives an overview of the VAMDC infrastructure and of the various standards it uses. The article then discusses the development choices made and how the standards are implemented in practice. It concludes with a full example of implementing a VAMDC node using a real-life case as well as future plans for the node software.

Molecular and biological diagnostic tests for monitoring benzimidazole resistance in human soil-transmitted helminths.

PubMed

Diawara, Aïssatou; Schwenkenbecher, Jan M; Kaplan, Ray M; Prichard, Roger K

2013-06-01

In endemic countries with soil-transmitted helminths mass drug administration with albendazole or mebendazole are being implemented as a control strategy. However, it is well known in veterinary helminths that the use of the same benzimidazole drugs can place selection on the β-tubulin gene, leading to resistance. Given the concern that resistance could arise in human soil-transmitted helminths, there is an urgent need to develop accurate diagnostic tools for monitoring resistance. In this study, we developed molecular assays to detect putative resistance genetic changes in Ascaris lumbricoides, Trichuris trichiura, and hookworms, and we optimized an egg hatch assay for the canine hookworm Ancylostoma caninum and applied it to Necator americanus. Both assays were tested on field samples. The molecular assays demonstrated their reproducibility and capacity to detect the presence of worms carrying putative resistance-associated genetic changes. However, further investigations are needed to validate our molecular and biological tests on additional field isolates.

Imaging and Force Recognition of Single Molecular Behaviors Using Atomic Force Microscopy

PubMed Central

Li, Mi; Dang, Dan; Liu, Lianqing; Xi, Ning; Wang, Yuechao

2017-01-01

The advent of atomic force microscopy (AFM) has provided a powerful tool for investigating the behaviors of single native biological molecules under physiological conditions. AFM can not only image the conformational changes of single biological molecules at work with sub-nanometer resolution, but also sense the specific interactions of individual molecular pair with piconewton force sensitivity. In the past decade, the performance of AFM has been greatly improved, which makes it widely used in biology to address diverse biomedical issues. Characterizing the behaviors of single molecules by AFM provides considerable novel insights into the underlying mechanisms guiding life activities, contributing much to cell and molecular biology. In this article, we review the recent developments of AFM studies in single-molecule assay. The related techniques involved in AFM single-molecule assay were firstly presented, and then the progress in several aspects (including molecular imaging, molecular mechanics, molecular recognition, and molecular activities on cell surface) was summarized. The challenges and future directions were also discussed. PMID:28117741

Ambient Ionization Mass Spectrometry for Cancer Diagnosis and Surgical Margin Evaluation

PubMed Central

Ifa, Demian R.; Eberlin, Livia S.

2017-01-01

Background There is a clinical need for new technologies that would enable rapid disease diagnosis based on diagnostic molecular signatures. Ambient ionization mass spectrometry has revolutionized the means by which molecular information can be obtained from tissue samples in real time and with minimal sample pretreatment. New developments in ambient ionization techniques applied to clinical research suggest that ambient ionization mass spectrometry will soon become a routine medical tool for tissue diagnosis. Content This review summarizes the main developments in ambient ionization techniques applied to tissue analysis, with focus on desorption electrospray ionization mass spectrometry, probe electrospray ionization, touch spray, and rapid evaporative ionization mass spectrometry. We describe their applications to human cancer research and surgical margin evaluation, highlighting integrated approaches tested for ex vivo and in vivo human cancer tissue analysis. We also discuss the challenges for clinical implementation of these tools and offer perspectives on the future of the field. Summary A variety of studies have showcased the value of ambient ionization mass spectrometry for rapid and accurate cancer diagnosis. Small molecules have been identified as potential diagnostic biomarkers, including metabolites, fatty acids, and glycerophospholipids. Statistical analysis allows tissue discrimination with high accuracy rates (>95%) being common. This young field has challenges to overcome before it is ready to be broadly accepted as a medical tool for cancer diagnosis. Growing research in new, integrated ambient ionization mass spectrometry technologies and the ongoing improvements in the existing tools make this field very promising for future translation into the clinic. PMID:26555455

Diagnosis of In Situ Metabolic State and Rates of Microbial Metabolism During In Situ Uranium Bioremediation with Molecular Techniques

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

Lovley, Derek R.

2012-11-28

The goal of these projects was to develop molecule tools to tract the metabolic activity and physiological status of microorganisms during in situ uranium bioremediation. Such information is important in able to design improved bioremediation strategies. As summarized below, the research was highly successful with new strategies developed for estimating in situ rates of metabolism and diagnosing the physiological status of the predominant subsurface microorganisms. This is a first not only for groundwater bioremediation studies, but also for subsurface microbiology in general. The tools and approaches developed in these studies should be applicable to the study of microbial communities inmore » a diversity of soils and sediments.« less

Molecular Approaches to Thyroid Cancer Diagnosis

PubMed Central

Hsiao, Susan J.; Nikiforov, Yuri E.

2014-01-01

Thyroid nodules are common, and the accurate diagnosis of cancer or benign disease is important for the effective clinical management of these patients. Molecular markers are a helpful diagnostic tool, particularly for cytologically indeterminate thyroid nodules. In the past few years, significant progress has been made in developing molecular markers for clinical use in fine needle aspiration (FNA) specimens, including gene mutation panels and gene expression classifiers. With the availability of next generation sequencing technology, gene mutation panels can be expanded to interrogate multiple genes simultaneously and to provide yet more accurate diagnostic information. In addition, recently several new molecular markers in thyroid cancer have been identified that offer diagnostic, prognostic, and therapeutic information that could potentially be of value in guiding individualized management of patients with thyroid nodules. PMID:24829266

Molecular pathogenesis of American Foulbrood: how Paenibacillus larvae kills honey bee larvae.

PubMed

Poppinga, Lena; Genersch, Elke

2015-08-01

American Foulbrood caused by Paenibacillus larvae is one of the unsolved health problems honey bee colonies are suffering from. In the recent past, considerable progress has been achieved in understanding molecular details of P. larvae infections of honey bee larvae. This was facilitated by the development of molecular tools for manipulating P. larvae and by the availability of complete genome sequences of different P. larvae genotypes. We here report on several peptides and proteins that have recently been identified, biochemically analyzed, and proposed to act as virulence factors of P. larvae. For some of them, experimental proof for their role as virulence factor has been provided allowing presenting a preliminary model for the molecular pathogenesis of American Foulbrood. Copyright © 2015 Elsevier Inc. All rights reserved.

FlaME: Flash Molecular Editor - a 2D structure input tool for the web

PubMed Central

2011-01-01

Background So far, there have been no Flash-based web tools available for chemical structure input. The authors herein present a feasibility study, aiming at the development of a compact and easy-to-use 2D structure editor, using Adobe's Flash technology and its programming language, ActionScript. As a reference model application from the Java world, we selected the Java Molecular Editor (JME). In this feasibility study, we made an attempt to realize a subset of JME's functionality in the Flash Molecular Editor (FlaME) utility. These basic capabilities are: structure input, editing and depiction of single molecules, data import and export in molfile format. Implementation The result of molecular diagram sketching in FlaME is accessible in V2000 molfile format. By integrating the molecular editor into a web page, its communication with the HTML elements on this page is established using the two JavaScript functions, getMol() and setMol(). In addition, structures can be copied to the system clipboard. Conclusion A first attempt was made to create a compact single-file application for 2D molecular structure input/editing on the web, based on Flash technology. With the application examples presented in this article, it could be demonstrated that the Flash methods are principally well-suited to provide the requisite communication between the Flash object (application) and the HTML elements on a web page, using JavaScript functions. PMID:21284863

Molecular profiling and commercial predication assays in ovarian cancer: still not ready for prime time?

PubMed

Kohn, Elise C

2014-01-01

Short of early detection to allow curative primary intervention, the other major barrier to further success in treatment of ovarian cancers is matching the best treatment to the proper ovarian cancer type and to the individual patient. There are several decades of experience applying in vitro chemoresponse testing for solid tumors including ovarian cancer. This concept, first described in 1979, has yet to receive level one evidence supporting its application, despite the testing of numerous assays commercially as well as in academic centers and its use for tens of thousands of patients at a significant cost. The approach-rather than undergoing rigorous scientific examination-is now being muddied by the development of commercial molecular profiling assays from which treatment suggestions are provided. Molecular profiling as a research tool has added value to our understanding and treatment of patients with ovarian cancer. Morphologic and histochemical characterizations coupled now with increasing knowledge of ovarian cancer type-specific molecular patterns is improving our ability to properly diagnosis ovarian cancer type and thus guide therapy. With the exception of the role of germ-line and possibly somatic BRCA1 and BRCA2 mutations and their true predictiveness for probable response to poly(ADP-ribose) polymerase inhibition, molecular typing and profiling has yet to identify druggable molecular targets in ovarian cancer. Its use should be continued as a research and learning tool, and its results should be subjected to clinical trial validation. For very different reasons, neither chemoresponse assays nor molecular profiling are ready for prime time, yet.

Mammalian synthetic biology for studying the cell

PubMed Central

Mathur, Melina; Xiang, Joy S.

2017-01-01

Synthetic biology is advancing the design of genetic devices that enable the study of cellular and molecular biology in mammalian cells. These genetic devices use diverse regulatory mechanisms to both examine cellular processes and achieve precise and dynamic control of cellular phenotype. Synthetic biology tools provide novel functionality to complement the examination of natural cell systems, including engineered molecules with specific activities and model systems that mimic complex regulatory processes. Continued development of quantitative standards and computational tools will expand capacities to probe cellular mechanisms with genetic devices to achieve a more comprehensive understanding of the cell. In this study, we review synthetic biology tools that are being applied to effectively investigate diverse cellular processes, regulatory networks, and multicellular interactions. We also discuss current challenges and future developments in the field that may transform the types of investigation possible in cell biology. PMID:27932576

The Virtual Cell Animation Collection: Tools for Teaching Molecular and Cellular Biology

PubMed Central

Reindl, Katie M.; White, Alan R.; Johnson, Christina; Vender, Bradley; Slator, Brian M.; McClean, Phillip

2015-01-01

A cell is a minifactory in which structures and molecules are assembled, rearranged, disassembled, packaged, sorted, and transported. Because cellular structures and molecules are invisible to the human eye, students often have difficulty conceptualizing the dynamic nature of cells that function at multiple scales across time and space. To represent these dynamic cellular processes, the Virtual Cell Productions team at North Dakota State University develops freely available multimedia materials to support molecular and cellular biology learning inside and outside the high school and university classroom. PMID:25856580

Molecular mechanisms of action of bacterial exotoxins.

PubMed

Balfanz, J; Rautenberg, P; Ullmann, U

1996-07-01

Toxins are one of the inventive strategies that bacteria have developed in order to survive. As virulence factors, they play a major role in the pathogenesis of infectious diseases. Recent discoveries have once more highlighted the effectiveness of these precisely adjusted bacterial weapons. Furthermore, toxins have become an invaluable tool in the investigation of fundamental cell processes, including regulation of cellular functions by various G proteins, cytoskeletal dynamics and neural transmission. In this review, the bacterial toxins are presented in a rational classification based on the molecular mechanisms of action.

An Integrated Molecular Database on Indian Insects.

PubMed

Pratheepa, Maria; Venkatesan, Thiruvengadam; Gracy, Gandhi; Jalali, Sushil Kumar; Rangheswaran, Rajagopal; Antony, Jomin Cruz; Rai, Anil

2018-01-01

MOlecular Database on Indian Insects (MODII) is an online database linking several databases like Insect Pest Info, Insect Barcode Information System (IBIn), Insect Whole Genome sequence, Other Genomic Resources of National Bureau of Agricultural Insect Resources (NBAIR), Whole Genome sequencing of Honey bee viruses, Insecticide resistance gene database and Genomic tools. This database was developed with a holistic approach for collecting information about phenomic and genomic information of agriculturally important insects. This insect resource database is available online for free at http://cib.res.in. http://cib.res.in/.

Fundamental Limits:. Developing New Tools for a Better Understanding of Second-Order Molecular Nonlinear Optics

NASA Astrophysics Data System (ADS)

Pérez-Moreno, Javier; Clays, Koen

The generalized Thomas-Kuhn sum rules are used to characterize the nonlinear optical response of organic chromophores in terms of fundamental parameters that can be measured experimentally. The nonlinear optical performance of organic molecules is evaluated from the combination of hyper-Rayleigh scattering measurements and the analysis in terms of the fundamental limits. Different strategies for the enhancement of nonlinear optical behavior at the molecular and supramolecular level are evaluated and new paradigms for the design of more efficient nonlinear optical molecules are proposed and investigated.

Basket Studies: Redefining Clinical Trials in the Era of Genome-Driven Oncology.

PubMed

Tao, Jessica J; Schram, Alison M; Hyman, David M

2018-01-29

Understanding a tumor's detailed molecular profile has become increasingly necessary to deliver the standard of care for patients with advanced cancer. Innovations in both tumor genomic sequencing technology and the development of drugs that target molecular alterations have fueled recent gains in genome-driven oncology care. "Basket studies," or histology-agnostic clinical trials in genomically selected patients, represent one important research tool to continue making progress in this field. We review key aspects of genome-driven oncology care, including the purpose and utility of basket studies, biostatistical considerations in trial design, genomic knowledgebase development, and patient matching and enrollment models, which are critical for translating our genomic knowledge into clinically meaningful outcomes.

Key Developments in Ionic Liquid Crystals.

PubMed

Alvarez Fernandez, Alexandra; Kouwer, Paul H J

2016-05-16

Ionic liquid crystals are materials that combine the classes of liquid crystals and ionic liquids. The first one is based on the multi-billion-dollar flat panel display industry, whilst the latter quickly developed in the past decades into a family of highly-tunable non-volatile solvents. The combination yields materials with a unique set of properties, but also with many challenges ahead. In this review, we provide an overview of the key concepts in ionic liquid crystals, particularly from a molecular perspective. What are the important molecular parameters that determine the phase behavior? How should they be introduced into the molecules? Finally, which other tools does one have to realize specific properties in the material?

Key Developments in Ionic Liquid Crystals

PubMed Central

Alvarez Fernandez, Alexandra; Kouwer, Paul H. J.

2016-01-01

Ionic liquid crystals are materials that combine the classes of liquid crystals and ionic liquids. The first one is based on the multi-billion-dollar flat panel display industry, whilst the latter quickly developed in the past decades into a family of highly-tunable non-volatile solvents. The combination yields materials with a unique set of properties, but also with many challenges ahead. In this review, we provide an overview of the key concepts in ionic liquid crystals, particularly from a molecular perspective. What are the important molecular parameters that determine the phase behavior? How should they be introduced into the molecules? Finally, which other tools does one have to realize specific properties in the material? PMID:27196890

The evolving field of prognostication and risk stratification in MDS: Recent developments and future directions.

PubMed

Lee, Eun-Ju; Podoltsev, Nikolai; Gore, Steven D; Zeidan, Amer M

2016-01-01

The clinical course of patients with myelodysplastic syndromes (MDS) is characterized by wide variability reflecting the underlying genetic and biological heterogeneity of the disease. Accurate prediction of outcomes for individual patients is an integral part of the evidence-based risk/benefit calculations that are necessary for tailoring the aggressiveness of therapeutic interventions. While several prognostication tools have been developed and validated for risk stratification, each of these systems has limitations. The recent progress in genomic sequencing techniques has led to discoveries of recurrent molecular mutations in MDS patients with independent impact on relevant clinical outcomes. Reliable assays of these mutations have already entered the clinic and efforts are currently ongoing to formally incorporate mutational analysis into the existing clinicopathologic risk stratification tools. Additionally, mutational analysis holds promise for going beyond prognostication to therapeutic selection and individualized treatment-specific prediction of outcomes; abilities that would revolutionize MDS patient care. Despite these exciting developments, the best way of incorporating molecular testing for use in prognostication and prediction of outcomes in clinical practice remains undefined and further research is warranted. Copyright © 2015 Elsevier Ltd. All rights reserved.

Optimising molecular diagnostic capacity for effective control of tuberculosis in high-burden settings.

PubMed

Sabiiti, W; Mtafya, B; Kuchaka, D; Azam, K; Viegas, S; Mdolo, A; Farmer, E C W; Khonga, M; Evangelopoulos, D; Honeyborne, I; Rachow, A; Heinrich, N; Ntinginya, N E; Bhatt, N; Davies, G R; Jani, I V; McHugh, T D; Kibiki, G; Hoelscher, M; Gillespie, S H

2016-08-01

The World Health Organization's 2035 vision is to reduce tuberculosis (TB) associated mortality by 95%. While low-burden, well-equipped industrialised economies can expect to see this goal achieved, it is challenging in the low- and middle-income countries that bear the highest burden of TB. Inadequate diagnosis leads to inappropriate treatment and poor clinical outcomes. The roll-out of the Xpert(®) MTB/RIF assay has demonstrated that molecular diagnostics can produce rapid diagnosis and treatment initiation. Strong molecular services are still limited to regional or national centres. The delay in implementation is due partly to resources, and partly to the suggestion that such techniques are too challenging for widespread implementation. We have successfully implemented a molecular tool for rapid monitoring of patient treatment response to anti-tuberculosis treatment in three high TB burden countries in Africa. We discuss here the challenges facing TB diagnosis and treatment monitoring, and draw from our experience in establishing molecular treatment monitoring platforms to provide practical insights into successful optimisation of molecular diagnostic capacity in resource-constrained, high TB burden settings. We recommend a holistic health system-wide approach for molecular diagnostic capacity development, addressing human resource training, institutional capacity development, streamlined procurement systems, and engagement with the public, policy makers and implementers of TB control programmes.

Quantitative molecular analysis in mantle cell lymphoma.

PubMed

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

2011-07-01

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

Advances in Molecular Rotational Spectroscopy for Applied Science

NASA Astrophysics Data System (ADS)

Harris, Brent; Fields, Shelby S.; Pulliam, Robin; Muckle, Matt; Neill, Justin L.

2017-06-01

Advances in chemical sensitivity and robust, solid-state designs for microwave/millimeter-wave instrumentation compel the expansion of molecular rotational spectroscopy as research tool into applied science. It is familiar to consider molecular rotational spectroscopy for air analysis. Those techniques for molecular rotational spectroscopy are included in our presentation of a more broad application space for materials analysis using Fourier Transform Molecular Rotational Resonance (FT-MRR) spectrometers. There are potentially transformative advantages for direct gas analysis of complex mixtures, determination of unknown evolved gases with parts per trillion detection limits in solid materials, and unambiguous chiral determination. The introduction of FT-MRR as an alternative detection principle for analytical chemistry has created a ripe research space for the development of new analytical methods and sampling equipment to fully enable FT-MRR. We present the current state of purpose-built FT-MRR instrumentation and the latest application measurements that make use of new sampling methods.

Zebrafish for the Study of the Biological Effects of Nicotine

PubMed Central

Klee, Eric W.; Schneider, Henning; Hurt, Richard D.; Ekker, Stephen C.

2011-01-01

Introduction: Zebrafish are emerging as a powerful animal model for studying the molecular and physiological effects of nicotine exposure. The zebrafish have many advantageous physical characteristics, including small size, high fecundity rates, and externally developing transparent embryos. When combined with a battery of molecular–genetic tools and behavioral assays, these attributes enable studies to be conducted that are not practical using traditional animal models. Methods: We reviewed the literature on the application of the zebrafish model as a preclinical model to study the biological effects of nicotine exposure. Results: The identified studies used zebrafish to examine the effects of nicotine exposure on early development, addiction, anxiety, and learning. The methods used included green fluorescent protein–labeled proteins to track in vivo nicotine-altered neuron development, nicotine-conditioned place preference, and locomotive sensitization linked with high-throughput molecular and genetic screens and behavioral models of learning and stress response to nicotine. Data are presented on the complete homology of all known human neural nicotinic acetylcholine receptors in zebrafish and on the biological similarity of human and zebrafish dopaminergic signaling. Conclusions: Tobacco dependence remains a major health problem worldwide. Further understanding of the molecular effects of nicotine exposure and genetic contributions to dependence may lead to improvement in patient treatment strategies. While there are limitations to the use of zebrafish as a preclinical model, it should provide a valuable tool to complement existing model systems. The reviewed studies demonstrate the enormous opportunity zebrafish have to advance the science of nicotine and tobacco research. PMID:21385906

Modelling the molecular mechanisms of aging

PubMed Central

Mc Auley, Mark T.; Guimera, Alvaro Martinez; Hodgson, David; Mcdonald, Neil; Mooney, Kathleen M.; Morgan, Amy E.

2017-01-01

The aging process is driven at the cellular level by random molecular damage that slowly accumulates with age. Although cells possess mechanisms to repair or remove damage, they are not 100% efficient and their efficiency declines with age. There are many molecular mechanisms involved and exogenous factors such as stress also contribute to the aging process. The complexity of the aging process has stimulated the use of computational modelling in order to increase our understanding of the system, test hypotheses and make testable predictions. As many different mechanisms are involved, a wide range of models have been developed. This paper gives an overview of the types of models that have been developed, the range of tools used, modelling standards and discusses many specific examples of models that have been grouped according to the main mechanisms that they address. We conclude by discussing the opportunities and challenges for future modelling in this field. PMID:28096317

Laser desorption ionization mass spectrometry: Recent progress in matrix-free and label-assisted techniques.

PubMed

Mandal, Arundhoti; Singha, Monisha; Addy, Partha Sarathi; Basak, Amit

2017-10-13

The MALDI-based mass spectrometry, over the last three decades, has become an important analytical tool. It is a gentle ionization technique, usually applicable to detect and characterize analytes with high molecular weights like proteins and other macromolecules. The earlier difficulty of detection of analytes with low molecular weights like small organic molecules and metal ion complexes with this technique arose due to the cluster of peaks in the low molecular weight region generated from the matrix. To detect such molecules and metal ion complexes, a four-prong strategy has been developed. These include use of alternate matrix materials, employment of new surface materials that require no matrix, use of metabolites that directly absorb the laser light, and the laser-absorbing label-assisted LDI-MS (popularly known as LALDI-MS). This review will highlight the developments with all these strategies with a special emphasis on LALDI-MS. © 2017 Wiley Periodicals, Inc.

Planting molecular functions in an ecological context with Arabidopsis thaliana.

PubMed

Krämer, Ute

2015-03-25

The vascular plant Arabidopsis thaliana is a central genetic model and universal reference organism in plant and crop science. The successful integration of different fields of research in the study of A. thaliana has made a large contribution to our molecular understanding of key concepts in biology. The availability and active development of experimental tools and resources, in combination with the accessibility of a wealth of cumulatively acquired knowledge about this plant, support the most advanced systems biology approaches among all land plants. Research in molecular ecology and evolution has also brought the natural history of A. thaliana into the limelight. This article showcases our current knowledge of the natural history of A. thaliana from the perspective of the most closely related plant species, providing an evolutionary framework for interpreting novel findings and for developing new hypotheses based on our knowledge of this plant.

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

Molecular dynamics simulations and docking enable to explore the biophysical factors controlling the yields of engineered nanobodies.

PubMed

Soler, Miguel A; de Marco, Ario; Fortuna, Sara

2016-10-10

Nanobodies (VHHs) have proved to be valuable substitutes of conventional antibodies for molecular recognition. Their small size represents a precious advantage for rational mutagenesis based on modelling. Here we address the problem of predicting how Camelidae nanobody sequences can tolerate mutations by developing a simulation protocol based on all-atom molecular dynamics and whole-molecule docking. The method was tested on two sets of nanobodies characterized experimentally for their biophysical features. One set contained point mutations introduced to humanize a wild type sequence, in the second the CDRs were swapped between single-domain frameworks with Camelidae and human hallmarks. The method resulted in accurate scoring approaches to predict experimental yields and enabled to identify the structural modifications induced by mutations. This work is a promising tool for the in silico development of single-domain antibodies and opens the opportunity to customize single functional domains of larger macromolecules.

Molecular dynamics simulations and docking enable to explore the biophysical factors controlling the yields of engineered nanobodies

NASA Astrophysics Data System (ADS)

Soler, Miguel A.; De Marco, Ario; Fortuna, Sara

2016-10-01

Nanobodies (VHHs) have proved to be valuable substitutes of conventional antibodies for molecular recognition. Their small size represents a precious advantage for rational mutagenesis based on modelling. Here we address the problem of predicting how Camelidae nanobody sequences can tolerate mutations by developing a simulation protocol based on all-atom molecular dynamics and whole-molecule docking. The method was tested on two sets of nanobodies characterized experimentally for their biophysical features. One set contained point mutations introduced to humanize a wild type sequence, in the second the CDRs were swapped between single-domain frameworks with Camelidae and human hallmarks. The method resulted in accurate scoring approaches to predict experimental yields and enabled to identify the structural modifications induced by mutations. This work is a promising tool for the in silico development of single-domain antibodies and opens the opportunity to customize single functional domains of larger macromolecules.

CAST: a new program package for the accurate characterization of large and flexible molecular systems.

PubMed

Grebner, Christoph; Becker, Johannes; Weber, Daniel; Bellinger, Daniel; Tafipolski, Maxim; Brückner, Charlotte; Engels, Bernd

2014-09-15

The presented program package, Conformational Analysis and Search Tool (CAST) allows the accurate treatment of large and flexible (macro) molecular systems. For the determination of thermally accessible minima CAST offers the newly developed TabuSearch algorithm, but algorithms such as Monte Carlo (MC), MC with minimization, and molecular dynamics are implemented as well. For the determination of reaction paths, CAST provides the PathOpt, the Nudge Elastic band, and the umbrella sampling approach. Access to free energies is possible through the free energy perturbation approach. Along with a number of standard force fields, a newly developed symmetry-adapted perturbation theory-based force field is included. Semiempirical computations are possible through DFTB+ and MOPAC interfaces. For calculations based on density functional theory, a Message Passing Interface (MPI) interface to the Graphics Processing Unit (GPU)-accelerated TeraChem program is available. The program is available on request. Copyright © 2014 Wiley Periodicals, Inc.

Application of whole genome re-sequencing data in the development of diagnostic DNA markers tightly linked to a disease-resistance locus for marker-assisted selection in lupin (Lupinus angustifolius).

PubMed

Yang, Huaan; Jian, Jianbo; Li, Xuan; Renshaw, Daniel; Clements, Jonathan; Sweetingham, Mark W; Tan, Cong; Li, Chengdao

2015-09-02

Molecular marker-assisted breeding provides an efficient tool to develop improved crop varieties. A major challenge for the broad application of markers in marker-assisted selection is that the marker phenotypes must match plant phenotypes in a wide range of breeding germplasm. In this study, we used the legume crop species Lupinus angustifolius (lupin) to demonstrate the utility of whole genome sequencing and re-sequencing on the development of diagnostic markers for molecular plant breeding. Nine lupin cultivars released in Australia from 1973 to 2007 were subjected to whole genome re-sequencing. The re-sequencing data together with the reference genome sequence data were used in marker development, which revealed 180,596 to 795,735 SNP markers from pairwise comparisons among the cultivars. A total of 207,887 markers were anchored on the lupin genetic linkage map. Marker mining obtained an average of 387 SNP markers and 87 InDel markers for each of the 24 genome sequence assembly scaffolds bearing markers linked to 11 genes of agronomic interest. Using the R gene PhtjR conferring resistance to phomopsis stem blight disease as a test case, we discovered 17 candidate diagnostic markers by genotyping and selecting markers on a genetic linkage map. A further 243 candidate diagnostic markers were discovered by marker mining on a scaffold bearing non-diagnostic markers linked to the PhtjR gene. Nine out from the ten tested candidate diagnostic markers were confirmed as truly diagnostic on a broad range of commercial cultivars. Markers developed using these strategies meet the requirements for broad application in molecular plant breeding. We demonstrated that low-cost genome sequencing and re-sequencing data were sufficient and very effective in the development of diagnostic markers for marker-assisted selection. The strategies used in this study may be applied to any trait or plant species. Whole genome sequencing and re-sequencing provides a powerful tool to overcome current limitations in molecular plant breeding, which will enable plant breeders to precisely pyramid favourable genes to develop super crop varieties to meet future food demands.

Broadening the horizon – level 2.5 of the HUPO-PSI format for molecular interactions

PubMed Central

Kerrien, Samuel; Orchard, Sandra; Montecchi-Palazzi, Luisa; Aranda, Bruno; Quinn, Antony F; Vinod, Nisha; Bader, Gary D; Xenarios, Ioannis; Wojcik, Jérôme; Sherman, David; Tyers, Mike; Salama, John J; Moore, Susan; Ceol, Arnaud; Chatr-aryamontri, Andrew; Oesterheld, Matthias; Stümpflen, Volker; Salwinski, Lukasz; Nerothin, Jason; Cerami, Ethan; Cusick, Michael E; Vidal, Marc; Gilson, Michael; Armstrong, John; Woollard, Peter; Hogue, Christopher; Eisenberg, David; Cesareni, Gianni; Apweiler, Rolf; Hermjakob, Henning

2007-01-01

Background Molecular interaction Information is a key resource in modern biomedical research. Publicly available data have previously been provided in a broad array of diverse formats, making access to this very difficult. The publication and wide implementation of the Human Proteome Organisation Proteomics Standards Initiative Molecular Interactions (HUPO PSI-MI) format in 2004 was a major step towards the establishment of a single, unified format by which molecular interactions should be presented, but focused purely on protein-protein interactions. Results The HUPO-PSI has further developed the PSI-MI XML schema to enable the description of interactions between a wider range of molecular types, for example nucleic acids, chemical entities, and molecular complexes. Extensive details about each supported molecular interaction can now be captured, including the biological role of each molecule within that interaction, detailed description of interacting domains, and the kinetic parameters of the interaction. The format is supported by data management and analysis tools and has been adopted by major interaction data providers. Additionally, a simpler, tab-delimited format MITAB2.5 has been developed for the benefit of users who require only minimal information in an easy to access configuration. Conclusion The PSI-MI XML2.5 and MITAB2.5 formats have been jointly developed by interaction data producers and providers from both the academic and commercial sector, and are already widely implemented and well supported by an active development community. PSI-MI XML2.5 enables the description of highly detailed molecular interaction data and facilitates data exchange between databases and users without loss of information. MITAB2.5 is a simpler format appropriate for fast Perl parsing or loading into Microsoft Excel. PMID:17925023

The Amber Biomolecular Simulation Programs

PubMed Central

CASE, DAVID A.; CHEATHAM, THOMAS E.; DARDEN, TOM; GOHLKE, HOLGER; LUO, RAY; MERZ, KENNETH M.; ONUFRIEV, ALEXEY; SIMMERLING, CARLOS; WANG, BING; WOODS, ROBERT J.

2006-01-01

We describe the development, current features, and some directions for future development of the Amber package of computer programs. This package evolved from a program that was constructed in the late 1970s to do Assisted Model Building with Energy Refinement, and now contains a group of programs embodying a number of powerful tools of modern computational chemistry, focused on molecular dynamics and free energy calculations of proteins, nucleic acids, and carbohydrates. PMID:16200636

Advances in DNA metabarcoding for food and wildlife forensic species identification.

PubMed

Staats, Martijn; Arulandhu, Alfred J; Gravendeel, Barbara; Holst-Jensen, Arne; Scholtens, Ingrid; Peelen, Tamara; Prins, Theo W; Kok, Esther

2016-07-01

Species identification using DNA barcodes has been widely adopted by forensic scientists as an effective molecular tool for tracking adulterations in food and for analysing samples from alleged wildlife crime incidents. DNA barcoding is an approach that involves sequencing of short DNA sequences from standardized regions and comparison to a reference database as a molecular diagnostic tool in species identification. In recent years, remarkable progress has been made towards developing DNA metabarcoding strategies, which involves next-generation sequencing of DNA barcodes for the simultaneous detection of multiple species in complex samples. Metabarcoding strategies can be used in processed materials containing highly degraded DNA e.g. for the identification of endangered and hazardous species in traditional medicine. This review aims to provide insight into advances of plant and animal DNA barcoding and highlights current practices and recent developments for DNA metabarcoding of food and wildlife forensic samples from a practical point of view. Special emphasis is placed on new developments for identifying species listed in the Convention on International Trade of Endangered Species (CITES) appendices for which reliable methods for species identification may signal and/or prevent illegal trade. Current technological developments and challenges of DNA metabarcoding for forensic scientists will be assessed in the light of stakeholders' needs.

Advances in Maize Genomics and Their Value for Enhancing Genetic Gains from Breeding

PubMed Central

Xu, Yunbi; Skinner, Debra J.; Wu, Huixia; Palacios-Rojas, Natalia; Araus, Jose Luis; Yan, Jianbing; Gao, Shibin; Warburton, Marilyn L.; Crouch, Jonathan H.

2009-01-01

Maize is an important crop for food, feed, forage, and fuel across tropical and temperate areas of the world. Diversity studies at genetic, molecular, and functional levels have revealed that, tropical maize germplasm, landraces, and wild relatives harbor a significantly wider range of genetic variation. Among all types of markers, SNP markers are increasingly the marker-of-choice for all genomics applications in maize breeding. Genetic mapping has been developed through conventional linkage mapping and more recently through linkage disequilibrium-based association analyses. Maize genome sequencing, initially focused on gene-rich regions, now aims for the availability of complete genome sequence. Conventional insertion mutation-based cloning has been complemented recently by EST- and map-based cloning. Transgenics and nutritional genomics are rapidly advancing fields targeting important agronomic traits including pest resistance and grain quality. Substantial advances have been made in methodologies for genomics-assisted breeding, enhancing progress in yield as well as abiotic and biotic stress resistances. Various genomic databases and informatics tools have been developed, among which MaizeGDB is the most developed and widely used by the maize research community. In the future, more emphasis should be given to the development of tools and strategic germplasm resources for more effective molecular breeding of tropical maize products. PMID:19688107

Wide interguild relationships among entomopathogenic and free-living nematodes in soil as measured by real time qPCR.

PubMed

Campos-Herrera, Raquel; El-Borai, Fahiem E; Duncan, Larry W

2012-10-01

Entomopathogenic nematodes (EPNs) are promising biological control agents of soil-dwelling insect pests of many crops. These nematodes are ubiquitous in both natural and agricultural areas. Their efficacy against arthropods is affected directly and indirectly by food webs and edaphic conditions. It has long been suggested that a greater understanding of EPN ecology is needed to achieve consistent biological control by these nematodes and the development of molecular tools is helping to overcome obstacles to the study of cryptic organisms and complex interactions. Here we extend the repertoire of molecular tools to characterize soil food webs by describing primers/probe set to quantify certain free-living, bactivorous nematodes (FLBNs) that interact with EPNs in soil. Three FLBN isolates were recovered from soil baited with insect larvae. Morphological and molecular characterization confirmed their identities as Acrobeloides maximum (RT-1-R15C and RT-2-R25A) and Rhabditis rainai (PT-R14B). Laboratory experiments demonstrated the ability of these FLBNs to interfere with the development of Steinernema diaprepesi, Steinernema riobrave and Heterorhabditis indica parasitizing the weevil Diaprepes abbreviatus (P<0.001), perhaps due to resource competition. A molecular probe was developed for the strongest competitor, A. maximum. We selected the highly conserved SSU rDNA sequence to design the primers/probe, because these sequences are more abundantly available for free-living nematodes than ITS sequences that can likely provide better taxonomic resolution. Our molecular probe can identify organisms that share ⩾98% similarity at this locus. The use of this molecular probe to characterize soil communities from samples of nematode DNA collected within a citrus orchard revealed positive correlations (P<0.01) between Acrobeloides-group nematodes and total numbers of EPNs (S. diaprepesi, H. indica and Heterorhabditis zealandica) as well as a complex of nematophagous fungi comprising Catenaria sp. and Monachrosporium gephyropagum that are natural enemies of EPNs. These relationships can be broadly interpreted as supporting Linford's hypothesis, i.e., decomposition of organic matter (here, insect cadavers) greatly increases bactivorous nematodes and their natural enemies. Copyright © 2012 Elsevier Inc. All rights reserved.

Investigating Evolutionary Questions Using Online Molecular Databases.

ERIC Educational Resources Information Center

Puterbaugh, Mary N.; Burleigh, J. Gordon

2001-01-01

Recommends using online molecular databases as teaching tools to illustrate evolutionary questions and concepts while introducing students to public molecular databases. Provides activities in which students make molecular comparisons between species. (YDS)

Development of computationally predicted Adverse Outcome Pathway (AOP) networks through data mining and integration of publicly available in vivo, in vitro, phenotype, and biological pathway data

EPA Science Inventory

The Adverse Outcome Pathway (AOP) framework is increasingly being adopted as a tool for organizing and summarizing the mechanistic information connecting molecular perturbations by environmental stressors with adverse outcomes relevant for ecological and human health outcomes. Ho...

Transferability of SSR and RGA markers developed in Cynodon spp. to Zoysia spp.

USDA-ARS?s Scientific Manuscript database

Bermudagrass (Cynodon spp.) and zoysiagrass (Zoysia spp.), which are both used as warm-season turfgrasses in the United States, are members of subfamily Chloridoideae and are reported to be at least 55% genetically similar. To assess if molecular tools between the two species can be interchanged, 93...

Integrating molecular tools and conventional approaches in the Oregon State University hazelnut breeding program

Treesearch

Shawn A. Mehlenbacher

2012-01-01

The Oregon State University (OSU) hazelnut breeding program, initiated in 1969, continues to develop new cultivars for the hazelnut industry that combine suitability to the blanched kernel market with resistance to eastern filbert blight (EFB) caused by Anisogramma anomala. Oregon's hazelnut growers support the program through the Oregon...

A new approach for detecting fungal and oomycete plant pathogens in next generation sequencing metagenome data utilising electronic probes

USDA-ARS?s Scientific Manuscript database

Early stage infections caused by fungal/oomycete spores can remain undetected until signs or symptoms develop. Serological and molecular techniques are currently used for detecting these pathogens. Next-generation sequencing (NGS) has potential as a diagnostic tool, due to the capacity to target mul...

An Integrated, Statistical Molecular Approach to the Physical Chemistry Curriculum

ERIC Educational Resources Information Center

Cartier, Stephen F.

2009-01-01

As an alternative to the "thermodynamics first" or "quantum first" approaches to the physical chemistry curriculum, the statistical definition of entropy and the Boltzmann distribution are introduced in the first days of the course and the entire two-semester curriculum is then developed from these concepts. Once the tools of statistical mechanics…

DanceChemistry: Helping Students Visualize Chemistry Concepts through Dance Videos

ERIC Educational Resources Information Center

Tay, Gidget C.; Edwards, Kimberly D.

2015-01-01

A visual aid teaching tool, the DanceChemistry video series, has been developed to teach fundamental chemistry concepts through dance. These educational videos portray chemical interactions at the molecular level using dancers to represent chemical species. Students reported that the DanceChemistry videos helped them visualize chemistry ideas in a…

Guidelines for the analysis of free energy calculations.

PubMed

Klimovich, Pavel V; Shirts, Michael R; Mobley, David L

2015-05-01

Free energy calculations based on molecular dynamics simulations show considerable promise for applications ranging from drug discovery to prediction of physical properties and structure-function studies. But these calculations are still difficult and tedious to analyze, and best practices for analysis are not well defined or propagated. Essentially, each group analyzing these calculations needs to decide how to conduct the analysis and, usually, develop its own analysis tools. Here, we review and recommend best practices for analysis yielding reliable free energies from molecular simulations. Additionally, we provide a Python tool, alchemical-analysis.py, freely available on GitHub as part of the pymbar package (located at http://github.com/choderalab/pymbar), that implements the analysis practices reviewed here for several reference simulation packages, which can be adapted to handle data from other packages. Both this review and the tool covers analysis of alchemical calculations generally, including free energy estimates via both thermodynamic integration and free energy perturbation-based estimators. Our Python tool also handles output from multiple types of free energy calculations, including expanded ensemble and Hamiltonian replica exchange, as well as standard fixed ensemble calculations. We also survey a range of statistical and graphical ways of assessing the quality of the data and free energy estimates, and provide prototypes of these in our tool. We hope this tool and discussion will serve as a foundation for more standardization of and agreement on best practices for analysis of free energy calculations.

Perspectives of ruthenium(ii) polyazaaromatic photo-oxidizing complexes photoreactive towards tryptophan-containing peptides and derivatives.

PubMed

Estalayo-Adrián, S; Garnir, K; Moucheron, C

2018-01-04

Ru II polyazaaromatic complexes have been studied with the aim of developing molecular tools for DNA and oligonucleotides. In this context, Ru II -TAP (TAP = 1,4,5,8-tetraazaphenanthrene) complexes have been developed as specific photoreagents targeting the genetic material. The advantage of such compounds is due to the formation of photo-addition products between the Ru-TAP complex and the biomolecule, originating from a photo-induced electron transfer process that takes place between the excited Ru-TAP complex and guanine (G) bases of DNA. This photo-addition has been more recently extended to amino acids in view of applications involving peptides, such as inhibition or photocontrol of proteins. More particularly, tryptophan (Trp) and Trp-containing peptides are also able to be photo-oxidized by Ru II -TAP complexes, leading to the formation of photo-addition products. This mini review focuses on recent advances in the search for Ru II polyazaaromatic photo-oxidizing complexes of interest as molecular tools and photoreagents for Trp-containing peptides and proteins. Different possible future directions in this field are also discussed.

The MIntAct project—IntAct as a common curation platform for 11 molecular interaction databases

PubMed Central

Orchard, Sandra; Ammari, Mais; Aranda, Bruno; Breuza, Lionel; Briganti, Leonardo; Broackes-Carter, Fiona; Campbell, Nancy H.; Chavali, Gayatri; Chen, Carol; del-Toro, Noemi; Duesbury, Margaret; Dumousseau, Marine; Galeota, Eugenia; Hinz, Ursula; Iannuccelli, Marta; Jagannathan, Sruthi; Jimenez, Rafael; Khadake, Jyoti; Lagreid, Astrid; Licata, Luana; Lovering, Ruth C.; Meldal, Birgit; Melidoni, Anna N.; Milagros, Mila; Peluso, Daniele; Perfetto, Livia; Porras, Pablo; Raghunath, Arathi; Ricard-Blum, Sylvie; Roechert, Bernd; Stutz, Andre; Tognolli, Michael; van Roey, Kim; Cesareni, Gianni; Hermjakob, Henning

2014-01-01

IntAct (freely available at http://www.ebi.ac.uk/intact) is an open-source, open data molecular interaction database populated by data either curated from the literature or from direct data depositions. IntAct has developed a sophisticated web-based curation tool, capable of supporting both IMEx- and MIMIx-level curation. This tool is now utilized by multiple additional curation teams, all of whom annotate data directly into the IntAct database. Members of the IntAct team supply appropriate levels of training, perform quality control on entries and take responsibility for long-term data maintenance. Recently, the MINT and IntAct databases decided to merge their separate efforts to make optimal use of limited developer resources and maximize the curation output. All data manually curated by the MINT curators have been moved into the IntAct database at EMBL-EBI and are merged with the existing IntAct dataset. Both IntAct and MINT are active contributors to the IMEx consortium (http://www.imexconsortium.org). PMID:24234451

The European Bioinformatics Institute's data resources: towards systems biology.

PubMed

Brooksbank, Catherine; Cameron, Graham; Thornton, Janet

2005-01-01

Genomic and post-genomic biological research has provided fine-grain insights into the molecular processes of life, but also threatens to drown biomedical researchers in data. Moreover, as new high-throughput technologies are developed, the types of data that are gathered en masse are diversifying. The need to collect, store and curate all this information in ways that allow its efficient retrieval and exploitation is greater than ever. The European Bioinformatics Institute's (EBI's) databases and tools have evolved to meet the changing needs of molecular biologists: since we last wrote about our services in the 2003 issue of Nucleic Acids Research, we have launched new databases covering protein-protein interactions (IntAct), pathways (Reactome) and small molecules (ChEBI). Our existing core databases have continued to evolve to meet the changing needs of biomedical researchers, and we have developed new data-access tools that help biologists to move intuitively through the different data types, thereby helping them to put the parts together to understand biology at the systems level. The EBI's data resources are all available on our website at http://www.ebi.ac.uk.

The European Bioinformatics Institute's data resources: towards systems biology

PubMed Central

Brooksbank, Catherine; Cameron, Graham; Thornton, Janet

2005-01-01

Genomic and post-genomic biological research has provided fine-grain insights into the molecular processes of life, but also threatens to drown biomedical researchers in data. Moreover, as new high-throughput technologies are developed, the types of data that are gathered en masse are diversifying. The need to collect, store and curate all this information in ways that allow its efficient retrieval and exploitation is greater than ever. The European Bioinformatics Institute's (EBI's) databases and tools have evolved to meet the changing needs of molecular biologists: since we last wrote about our services in the 2003 issue of Nucleic Acids Research, we have launched new databases covering protein–protein interactions (IntAct), pathways (Reactome) and small molecules (ChEBI). Our existing core databases have continued to evolve to meet the changing needs of biomedical researchers, and we have developed new data-access tools that help biologists to move intuitively through the different data types, thereby helping them to put the parts together to understand biology at the systems level. The EBI's data resources are all available on our website at http://www.ebi.ac.uk. PMID:15608238

Combined distribution functions: A powerful tool to identify cation coordination geometries in liquid systems

NASA Astrophysics Data System (ADS)

Sessa, Francesco; D'Angelo, Paola; Migliorati, Valentina

2018-01-01

In this work we have developed an analytical procedure to identify metal ion coordination geometries in liquid media based on the calculation of Combined Distribution Functions (CDFs) starting from Molecular Dynamics (MD) simulations. CDFs provide a fingerprint which can be easily and unambiguously assigned to a reference polyhedron. The CDF analysis has been tested on five systems and has proven to reliably identify the correct geometries of several ion coordination complexes. This tool is simple and general and can be efficiently applied to different MD simulations of liquid systems.

Patent protection for microbial technologies.

PubMed

Sherkow, Jacob S

2017-11-01

Microbial technologies often serve as the basis of fundamental research tools in molecular biology. These present a variety of ethical, legal and social issues concerning their patenting. This commentary presents several case studies of these issues across three major microbiological tools: CRISPR, viral vectors and antimicrobial resistance drugs. It concludes that the development of these technologies-both scientifically and commercially-depend, in part, on the patent regime available for each, and researchers' willingness to enforce those patents against others. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

MLP Tools: a PyMOL plugin for using the molecular lipophilicity potential in computer-aided drug design

NASA Astrophysics Data System (ADS)

Oberhauser, Nils; Nurisso, Alessandra; Carrupt, Pierre-Alain

2014-05-01

The molecular lipophilicity potential (MLP) is a well-established method to calculate and visualize lipophilicity on molecules. We are here introducing a new computational tool named MLP Tools, written in the programming language Python, and conceived as a free plugin for the popular open source molecular viewer PyMOL. The plugin is divided into several sub-programs which allow the visualization of the MLP on molecular surfaces, as well as in three-dimensional space in order to analyze lipophilic properties of binding pockets. The sub-program Log MLP also implements the virtual log P which allows the prediction of the octanol/water partition coefficients on multiple three-dimensional conformations of the same molecule. An implementation on the recently introduced MLP GOLD procedure, improving the GOLD docking performance in hydrophobic pockets, is also part of the plugin. In this article, all functions of the MLP Tools will be described through a few chosen examples.

Conservation of the introgressed European water frog complex using molecular tools.

PubMed

Holsbeek, G; Maes, G E; De Meester, L; Volckaert, F A M

2009-03-01

In Belgium, the Pelophylax esculentus complex has recently been subjected to multiple introductions of non-native water frogs, increasing the occurrence of hybridisation events. In the present study, we tested the reliability of morphometric and recently developed microsatellite tools to identify introgression and to determine the origin of exotic Belgian water frogs. By analysing 150 individuals of each taxon of the P. esculentus complex and an additional 60 specimens of the introduced P. cf. bedriagae, we show that neither of the currently available tools appears to have sufficient power to reliably distinguish all Belgian water frog species. We therefore aimed at increasing the discriminatory power of a microsatellite identification tool by developing a new marker panel with additional microsatellite loci. By adding only two new microsatellite loci (RlCA5 and RlCA1b20), all taxa of the P. esculentus complex could be distinguished from each other with high confidence. Three more loci (Res3, Res5 and Res17) provided a powerful discrimination of the exotic species.

Cas9-based tools for targeted genome editing and transcriptional control.

PubMed

Xu, Tao; Li, Yongchao; Van Nostrand, Joy D; He, Zhili; Zhou, Jizhong

2014-03-01

Development of tools for targeted genome editing and regulation of gene expression has significantly expanded our ability to elucidate the mechanisms of interesting biological phenomena and to engineer desirable biological systems. Recent rapid progress in the study of a clustered, regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated (Cas) protein system in bacteria has facilitated the development of newly facile and programmable platforms for genome editing and transcriptional control in a sequence-specific manner. The core RNA-guided Cas9 endonuclease in the type II CRISPR system has been harnessed to realize gene mutation and DNA deletion and insertion, as well as transcriptional activation and repression, with multiplex targeting ability, just by customizing 20-nucleotide RNA components. Here we describe the molecular basis of the type II CRISPR/Cas system and summarize applications and factors affecting its utilization in model organisms. We also discuss the advantages and disadvantages of Cas9-based tools in comparison with widely used customizable tools, such as Zinc finger nucleases and transcription activator-like effector nucleases.

[Caenorhabditis elegans: a powerful tool for drug discovery].

PubMed

Jia, Xi-Hua; Cao, Cheng

2009-07-01

A simple model organism Caenorhabditis elegans has contributed substantially to the fundamental researches in biology. In an era of functional genomics, nematode worm has been developed into a multi-purpose tool that can be exploited to identify disease-causing or disease-associated genes, validate potential drug targets. This, coupled with its genetic amenability, low cost experimental manipulation and compatibility with high throughput screening in an intact physiological condition, makes the model organism into an effective toolbox for drug discovery. This review shows the unique features of C. elegans, how it can play a valuable role in our understanding of the molecular mechanism of human diseases and finding drug leads in drug development process.

In-Line Detection and Measurement of Molecular Contamination in Semiconductor Process Solutions

NASA Astrophysics Data System (ADS)

Wang, Jason; West, Michael; Han, Ye; McDonald, Robert C.; Yang, Wenjing; Ormond, Bob; Saini, Harmesh

2005-09-01

This paper discusses a fully automated metrology tool for detection and quantitative measurement of contamination, including cationic, anionic, metallic, organic, and molecular species present in semiconductor process solutions. The instrument is based on an electrospray ionization time-of-flight mass spectrometer (ESI-TOF/MS) platform. The tool can be used in diagnostic or analytical modes to understand process problems in addition to enabling routine metrology functions. Metrology functions include in-line contamination measurement with near real-time trend analysis. This paper discusses representative organic and molecular contamination measurement results in production process problem solving efforts. The examples include the analysis and identification of organic compounds in SC-1 pre-gate clean solution; urea, NMP (N-Methyl-2-pyrrolidone) and phosphoric acid contamination in UPW; and plasticizer and an organic sulfur-containing compound found in isopropyl alcohol (IPA). It is expected that these unique analytical and metrology capabilities will improve the understanding of the effect of organic and molecular contamination on device performance and yield. This will permit the development of quantitative correlations between contamination levels and process degradation. It is also expected that the ability to perform routine process chemistry metrology will lead to corresponding improvements in manufacturing process control and yield, the ability to avoid excursions and will improve the overall cost effectiveness of the semiconductor manufacturing process.

TopoGromacs: Automated Topology Conversion from CHARMM to GROMACS within VMD.

PubMed

Vermaas, Josh V; Hardy, David J; Stone, John E; Tajkhorshid, Emad; Kohlmeyer, Axel

2016-06-27

Molecular dynamics (MD) simulation engines use a variety of different approaches for modeling molecular systems with force fields that govern their dynamics and describe their topology. These different approaches introduce incompatibilities between engines, and previously published software bridges the gaps between many popular MD packages, such as between CHARMM and AMBER or GROMACS and LAMMPS. While there are many structure building tools available that generate topologies and structures in CHARMM format, only recently have mechanisms been developed to convert their results into GROMACS input. We present an approach to convert CHARMM-formatted topology and parameters into a format suitable for simulation with GROMACS by expanding the functionality of TopoTools, a plugin integrated within the widely used molecular visualization and analysis software VMD. The conversion process was diligently tested on a comprehensive set of biological molecules in vacuo. The resulting comparison between energy terms shows that the translation performed was lossless as the energies were unchanged for identical starting configurations. By applying the conversion process to conventional benchmark systems that mimic typical modestly sized MD systems, we explore the effect of the implementation choices made in CHARMM, NAMD, and GROMACS. The newly available automatic conversion capability breaks down barriers between simulation tools and user communities and allows users to easily compare simulation programs and leverage their unique features without the tedium of constructing a topology twice.

Final Report for Department of Energy Project DE-SC0012198

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

Lucchese, Robert; Poliakoff, Erwin; Trallero-Herrero, Carlos

The study of the motion of atoms in molecules is important to understanding many areas of physical and life sciences. Such motion occurs on many different times scales, with electronic motion occurring on a sub-femtosecond time scale, and simple vibrational motion in tens to hundreds of femtoseconds. One way to follow such processes in real time is by the use of short-pulsed lasers, and in particular by studying time-resolved photoionization and the related process of high-harmonic generation (HHG). Thus there has been much effort to develop the tools necessary to probe molecular systems using short pulse lasers and understanding themore » sensitivity of the different possible probes to the time dependent geometric structure as well as the electronic structure of molecules. Our research has particularly focused on the connection between high-field processes and the more traditional weak field photoionization processes. Strong field and weak field processes can be connected through models that involve the same matrix elements. We have demonstrated in our study of HHG from SF6 that the spectrum is sensitive to the interplay between the angular dependence of the ionization step and recombination step. In our study of rescattering spectroscopy, we have shown that with a combination of experiment and theory, we can use this high-field spectroscopy to determine molecular structure in molecules such as C2H4. We have also developed new computational tools based on overset grids to enable studies on larger molecular systems which use much more robust numerical approaches so that the resulting code can be a tool that non-specialists can use to study related systems.« less

Early detection of gastric cancer using global, genome-wide and IRF4, ELMO1, CLIP4 and MSC DNA methylation in endoscopic biopsies

PubMed Central

Rodriguez-Torres, Sebastian; Friess, Leah; Michailidi, Christina; Cok, Jaime; Combe, Juan; Vargas, Gloria; Prado, William; Soudry, Ethan; Pérez, Jimena; Yudin, Tikki; Mancinelli, Andrea; Unger, Helen; Ili-Gangas, Carmen; Brebi-Mieville, Priscilla; Berg, Douglas E.; Hayashi, Masamichi; Sidransky, David; Gilman, Robert H.; Guerrero-Preston, Rafael

2017-01-01

Clinically useful molecular tools to triage gastric cancer patients are not currently available. We aimed to develop a molecular tool to predict gastric cancer risk in endoscopy-driven biopsies obtained from high-risk gastric cancer clinics in low resource settings. We discovered and validated a DNA methylation biomarker panel in endoscopic samples obtained from 362 patients seen between 2004 and 2009 in three high-risk gastric cancer clinics in Lima, Perú, and validated it in 306 samples from the Cancer Genome Atlas project (“TCGA”). Global, epigenome wide and gene-specific DNA methylation analyses were used in a Phase I Biomarker Development Trial to identify a continuous biomarker panel that combines a Global DNA Methylation Index (GDMI) and promoter DNA methylation levels of IRF4, ELMO1, CLIP4 and MSC. We observed an inverse association between the GDMI and histological progression to gastric cancer, when comparing gastritis patients without metaplasia (mean = 5.74, 95% CI, 4.97−6.50), gastritis patients with metaplasia (mean = 4.81, 95% CI, 3.77−5.84), and gastric cancer cases (mean = 3.38, 95% CI, 2.82−3.94), respectively (p < 0.0001). Promoter methylation of IRF4 (p < 0.0001), ELMO1 (p < 0.0001), CLIP4 (p < 0.0001), and MSC (p < 0.0001), is also associated with increasing severity from gastritis with no metaplasia to gastritis with metaplasia and gastric cancer. Our findings suggest that IRF4, ELMO1, CLIP4 and MSC promoter methylation coupled with a GDMI>4 are useful molecular tools for gastric cancer risk stratification in endoscopic biopsies. PMID:28418867

Mergeomics: a web server for identifying pathological pathways, networks, and key regulators via multidimensional data integration.

PubMed

Arneson, Douglas; Bhattacharya, Anindya; Shu, Le; Mäkinen, Ville-Petteri; Yang, Xia

2016-09-09

Human diseases are commonly the result of multidimensional changes at molecular, cellular, and systemic levels. Recent advances in genomic technologies have enabled an outpour of omics datasets that capture these changes. However, separate analyses of these various data only provide fragmented understanding and do not capture the holistic view of disease mechanisms. To meet the urgent needs for tools that effectively integrate multiple types of omics data to derive biological insights, we have developed Mergeomics, a computational pipeline that integrates multidimensional disease association data with functional genomics and molecular networks to retrieve biological pathways, gene networks, and central regulators critical for disease development. To make the Mergeomics pipeline available to a wider research community, we have implemented an online, user-friendly web server ( http://mergeomics. idre.ucla.edu/ ). The web server features a modular implementation of the Mergeomics pipeline with detailed tutorials. Additionally, it provides curated genomic resources including tissue-specific expression quantitative trait loci, ENCODE functional annotations, biological pathways, and molecular networks, and offers interactive visualization of analytical results. Multiple computational tools including Marker Dependency Filtering (MDF), Marker Set Enrichment Analysis (MSEA), Meta-MSEA, and Weighted Key Driver Analysis (wKDA) can be used separately or in flexible combinations. User-defined summary-level genomic association datasets (e.g., genetic, transcriptomic, epigenomic) related to a particular disease or phenotype can be uploaded and computed real-time to yield biologically interpretable results, which can be viewed online and downloaded for later use. Our Mergeomics web server offers researchers flexible and user-friendly tools to facilitate integration of multidimensional data into holistic views of disease mechanisms in the form of tissue-specific key regulators, biological pathways, and gene networks.

Bioanalytical applications of SERS (surface-enhanced Raman spectroscopy).

PubMed

Hudson, Stephen D; Chumanov, George

2009-06-01

Surface-enhanced Raman scattering (SERS) is a powerful technique for analyzing biological samples as it can rapidly and nondestructively provide chemical and, in some cases, structural information about molecules in aqueous environments. In the Raman scattering process, both visible and near-infrared (NIR) wavelengths of light can be used to induce polarization of Raman-active molecules, leading to inelastic light scattering that yields specific molecular vibrational information. The development of surface enhancement has enabled Raman scattering to be an effective tool for qualitative as well as quantitative measurements with high sensitivity and specificity. Recent advances have led to many novel applications of SERS for biological analyses, resulting in new insights for biochemistry and molecular biology, the detection of biological warfare agents, and medical diagnostics for cancer, diabetes, and other diseases. This trend article highlights many of these recent investigations and provides a brief outlook in order to assess possible future directions of SERS as a bioanalytical tool.

The application of genome-wide 5-hydroxymethylcytosine studies in cancer research.

PubMed

Thomson, John P; Meehan, Richard R

2017-01-01

Early detection and characterization of molecular events associated with tumorgenesis remain high priorities. Genome-wide epigenetic assays are promising diagnostic tools, as aberrant epigenetic events are frequent and often cancer specific. The deposition and analysis of multiple patient-derived cancer epigenomic profiles contributes to our appreciation of the underlying biology; aiding the detection of novel identifiers for cancer subtypes. Modifying enzymes and co-factors regulating these epigenetic marks are frequently mutated in cancers, and as epigenetic modifications themselves are reversible, this makes their study very attractive with respect to pharmaceutical intervention. Here we focus on the novel modified base, 5-hydoxymethylcytosine, and discuss how genome-wide 5-hydoxymethylcytosine profiling expedites our molecular understanding of cancer, serves as a lineage tracer, classifies the mode of action of potentially carcinogenic agents and clarifies the roles of potential novel cancer drug targets; thus assisting the development of new diagnostic/prognostic tools.

Molecular identification tools for sibling species of Scedosporium and Pseudallescheria.

PubMed

Lackner, M; Klaassen, C H; Meis, J F; van den Ende, A H G Gerrits; de Hoog, G S

2012-07-01

The aim of this study was to develop molecular identification tools for currently recognized species of Pseudallescheria and Scedosporium through the use of species-specific primers and RFLP, so as to enhance rapid differentiation of clinically relevant species. The variability of species was established in a set of 681 Internal Transcribed Spacer (ITS) and 349 ß-tubulin (BT2) sequences. Amplified Fragment Length Polymorphism profile clustering matched with BT2 results, whereas ITS grouping was less detailed. ITS was sufficient for the differentiation of most haplotypes of clinically relevant species (P. apiosperma, P. boydii, S. aurantiacum, S. dehoogii, and S. prolificans) and of environmental species (P. minutispora and Lophotrichus fimeti) when Restriction Fragment Length Polymorphism (RFLP) were applied. For the identification of P. apiosperma and P. boydii species-specific BT2 primers were needed. Pseudallescheria fusoidea, P. ellipsoidea and P. angusta remained difficult to distinguish from P. boydii.

A Fruitful Endeavor: Modeling ALS in the Fruit Fly

PubMed Central

Casci, Ian; Pandey, Udai Bhan

2014-01-01

For over a century Drosophila melanogaster, commonly known as the fruit fly, has been instrumental in genetics research and disease modeling. In more recent years, it has been a powerful tool for modeling and studying neurodegenerative diseases, including the devastating and fatal amyotrophic lateral sclerosis (ALS). The success of this model organism in ALS research comes from the availability of tools to manipulate gene/protein expression in a number of desired cell-types, and the subsequent recapitulation of cellular and molecular phenotypic features of the disease. Several Drosophila models have now been developed for studying the roles of ALS-associated genes in disease pathogenesis that allowed us to understand the molecular pathways that lead to motor neuron degeneration in ALS patients. Our primary goal in this review is to highlight the lessons we have learned using Drosophila models pertaining to ALS research. PMID:25289585

PBxplore: a tool to analyze local protein structure and deformability with Protein Blocks

PubMed Central

Craveur, Pierrick; Joseph, Agnel Praveen; Jallu, Vincent

2017-01-01

This paper describes the development and application of a suite of tools, called PBxplore, to analyze the dynamics and deformability of protein structures using Protein Blocks (PBs). Proteins are highly dynamic macromolecules, and a classical way to analyze their inherent flexibility is to perform molecular dynamics simulations. The advantage of using small structural prototypes such as PBs is to give a good approximation of the local structure of the protein backbone. More importantly, by reducing the conformational complexity of protein structures, PBs allow analysis of local protein deformability which cannot be done with other methods and had been used efficiently in different applications. PBxplore is able to process large amounts of data such as those produced by molecular dynamics simulations. It produces frequencies, entropy and information logo outputs as text and graphics. PBxplore is available at https://github.com/pierrepo/PBxplore and is released under the open-source MIT license. PMID:29177113

Microbial ecology to manage processes in environmental biotechnology.

PubMed

Rittmann, Bruce E

2006-06-01

Microbial ecology and environmental biotechnology are inherently tied to each other. The concepts and tools of microbial ecology are the basis for managing processes in environmental biotechnology; and these processes provide interesting ecosystems to advance the concepts and tools of microbial ecology. Revolutionary advancements in molecular tools to understand the structure and function of microbial communities are bolstering the power of microbial ecology. A push from advances in modern materials along with a pull from a societal need to become more sustainable is enabling environmental biotechnology to create novel processes. How do these two fields work together? Five principles illuminate the way: (i) aim for big benefits; (ii) develop and apply more powerful tools to understand microbial communities; (iii) follow the electrons; (iv) retain slow-growing biomass; and (v) integrate, integrate, integrate.

3D-Lab: a collaborative web-based platform for molecular modeling.

PubMed

Grebner, Christoph; Norrby, Magnus; Enström, Jonatan; Nilsson, Ingemar; Hogner, Anders; Henriksson, Jonas; Westin, Johan; Faramarzi, Farzad; Werner, Philip; Boström, Jonas

2016-09-01

The use of 3D information has shown impact in numerous applications in drug design. However, it is often under-utilized and traditionally limited to specialists. We want to change that, and present an approach making 3D information and molecular modeling accessible and easy-to-use 'for the people'. A user-friendly and collaborative web-based platform (3D-Lab) for 3D modeling, including a blazingly fast virtual screening capability, was developed. 3D-Lab provides an interface to automatic molecular modeling, like conformer generation, ligand alignments, molecular dockings and simple quantum chemistry protocols. 3D-Lab is designed to be modular, and to facilitate sharing of 3D-information to promote interactions between drug designers. Recent enhancements to our open-source virtual reality tool Molecular Rift are described. The integrated drug-design platform allows drug designers to instantaneously access 3D information and readily apply advanced and automated 3D molecular modeling tasks, with the aim to improve decision-making in drug design projects.

Developmental origins of cardiovascular disease: Impact of early life stress in humans and rodents.

PubMed

Murphy, M O; Cohn, D M; Loria, A S

2017-03-01

The Developmental Origins of Health and Disease (DOHaD) hypothesizes that environmental insults during childhood programs the individual to develop chronic disease in adulthood. Emerging epidemiological data strongly supports that early life stress (ELS) given by the exposure to adverse childhood experiences is regarded as an independent risk factor capable of predicting future risk of cardiovascular disease. Experimental animal models utilizing chronic behavioral stress during postnatal life, specifically maternal separation (MatSep) provides a suitable tool to elucidate molecular mechanisms by which ELS increases the risk to develop cardiovascular disease, including hypertension. The purpose of this review is to highlight current epidemiological studies linking ELS to the development of cardiovascular disease and to discuss the potential molecular mechanisms identified from animal studies. Overall, this review reveals the need for future investigations to further clarify the molecular mechanisms of ELS in order to develop more personalized therapeutics to mitigate the long-term consequences of chronic behavioral stress including cardiovascular and heart disease in adulthood. Copyright © 2016 Elsevier Ltd. All rights reserved.

Recent advances in molecular medicine techniques for the diagnosis, prevention, and control of infectious diseases.

PubMed

França, R F O; da Silva, C C; De Paula, S O

2013-06-01

In recent years we have observed great advances in our ability to combat infectious diseases. Through the development of novel genetic methodologies, including a better understanding of pathogen biology, pathogenic mechanisms, advances in vaccine development, designing new therapeutic drugs, and optimization of diagnostic tools, significant infectious diseases are now better controlled. Here, we briefly describe recent reports in the literature concentrating on infectious disease control. The focus of this review is to describe the molecular methods widely used in the diagnosis, prevention, and control of infectious diseases with regard to the innovation of molecular techniques. Since the list of pathogenic microorganisms is extensive, we emphasize some of the major human infectious diseases (AIDS, tuberculosis, malaria, rotavirus, herpes virus, viral hepatitis, and dengue fever). As a consequence of these developments, infectious diseases will be more accurately and effectively treated; safe and effective vaccines are being developed and rapid detection of infectious agents now permits countermeasures to avoid potential outbreaks and epidemics. But, despite considerable progress, infectious diseases remain a strong challenge to human survival.

Molecular gastronomy, a scientific look at cooking.

PubMed

This, Hervé

2009-05-19

Food preparation is such a routine activity that we often do not question the process. For example, why do we cook as we do? Why do we eat certain foods and avoid other perfectly edible ingredients? To help answer these questions, it is extremely important to study the chemical changes that food undergoes during preparation; even simply cutting a vegetable can lead to enzymatic reactions. For many years, these molecular transformations were neglected by the food science field. In 1988, the scientific discipline called "molecular gastronomy" was created, and the field is now developing in many countries. Its many applications fall into two categories. First, there are technology applications for restaurants, for homes, or even for the food industry. In particular, molecular gastronomy has led to "molecular cooking", a way of food preparation that uses "new" tools, ingredients, and methods. According to a British culinary magazine, the three "top chefs" of the world employ elements of molecular cooking. Second, there are educational applications of molecular gastronomy: new insights into the culinary processes have led to new culinary curricula for chefs in many countries such as France, Canada, Italy, and Finland, as well as educational programs in schools. In this Account, we focus on science, explain why molecular gastronomy had to be created, and consider its tools, concepts, and results. Within the field, conceptual tools have been developed in order to make the necessary studies. The emphasis is on two important parts of recipes: culinary definitions (describing the objective of recipes) and culinary "precisions" (information that includes old wives' tales, methods, tips, and proverbs, for example). As for any science, the main objective of molecular gastronomy is, of course, the discovery of new phenomena and new mechanisms. This explains why culinary precisions are so important: cooks of the past could see, but not interpret, phenomena that awaited scientific studies. For French cuisine alone, more than 25,000 culinary precisions have been collected since 1980. The study of the organization of dishes was improved by the introduction of a formalism called "complex disperse systems/nonperiodical organization of space" (CDS/NPOS). CDS describes the colloidal materials from which the parts of a dish are made; NPOS provides an overall description of a dish. This formalism has proven useful for the study of both scientific (examining phenomena to arrive at a mechanism) and technological (using the results of science to improve technique) applications. For example, it can be used to describe the physical structure of dishes (science) but also to examine the characteristics of classical French sauces (technology). Many questions still remain in the field of molecular gastronomy. For example, one "Holy Grail" of the field is the prediction of physical, biological, chemical, and organoleptic properties of systems from their CDS/NPOS formula. Another issue to be worked out is the relationship between compound migration in food and chemical modifications of those migrating compounds. These questions will likely keep scientists busy in the near future.

Molecular biomimetics: nanotechnology through biology.

PubMed

Sarikaya, Mehmet; Tamerler, Candan; Jen, Alex K-Y; Schulten, Klaus; Baneyx, François

2003-09-01

Proteins, through their unique and specific interactions with other macromolecules and inorganics, control structures and functions of all biological hard and soft tissues in organisms. Molecular biomimetics is an emerging field in which hybrid technologies are developed by using the tools of molecular biology and nanotechnology. Taking lessons from biology, polypeptides can now be genetically engineered to specifically bind to selected inorganic compounds for applications in nano- and biotechnology. This review discusses combinatorial biological protocols, that is, bacterial cell surface and phage-display technologies, in the selection of short sequences that have affinity to (noble) metals, semiconducting oxides and other technological compounds. These genetically engineered proteins for inorganics (GEPIs) can be used in the assembly of functional nanostructures. Based on the three fundamental principles of molecular recognition, self-assembly and DNA manipulation, we highlight successful uses of GEPI in nanotechnology.

NGL Viewer: Web-based molecular graphics for large complexes.

PubMed

Rose, Alexander S; Bradley, Anthony R; Valasatava, Yana; Duarte, Jose M; Prlic, Andreas; Rose, Peter W

2018-05-29

The interactive visualization of very large macromolecular complexes on the web is becoming a challenging problem as experimental techniques advance at an unprecedented rate and deliver structures of increasing size. We have tackled this problem by developing highly memory-efficient and scalable extensions for the NGL WebGL-based molecular viewer and by using MMTF, a binary and compressed Macromolecular Transmission Format. These enable NGL to download and render molecular complexes with millions of atoms interactively on desktop computers and smartphones alike, making it a tool of choice for web-based molecular visualization in research and education. The source code is freely available under the MIT license at github.com/arose/ngl and distributed on NPM (npmjs.com/package/ngl). MMTF-JavaScript encoders and decoders are available at github.com/rcsb/mmtf-javascript. asr.moin@gmail.com.

Using Domestic and Free-Ranging Arctic Canid Models for Environmental Molecular Toxicology Research.

PubMed

Harley, John R; Bammler, Theo K; Farin, Federico M; Beyer, Richard P; Kavanagh, Terrance J; Dunlap, Kriya L; Knott, Katrina K; Ylitalo, Gina M; O'Hara, Todd M

2016-02-16

The use of sentinel species for population and ecosystem health assessments has been advocated as part of a One Health perspective. The Arctic is experiencing rapid change, including climate and environmental shifts, as well as increased resource development, which will alter exposure of biota to environmental agents of disease. Arctic canid species have wide geographic ranges and feeding ecologies and are often exposed to high concentrations of both terrestrial and marine-based contaminants. The domestic dog (Canis lupus familiaris) has been used in biomedical research for a number of years and has been advocated as a sentinel for human health due to its proximity to humans and, in some instances, similar diet. Exploiting the potential of molecular tools for describing the toxicogenomics of Arctic canids is critical for their development as biomedical models as well as environmental sentinels. Here, we present three approaches analyzing toxicogenomics of Arctic contaminants in both domestic and free-ranging canids (Arctic fox, Vulpes lagopus). We describe a number of confounding variables that must be addressed when conducting toxicogenomics studies in canid and other mammalian models. The ability for canids to act as models for Arctic molecular toxicology research is unique and significant for advancing our understanding and expanding the tool box for assessing the changing landscape of environmental agents of disease in the Arctic.

The role of standards in the development and implementation of clinical laboratory tests: a domestic and global perspective.

PubMed

Michaud, Ginette Y

2005-01-01

In the field of clinical laboratory medicine, standardization is aimed at increasing the trueness and reliability of measured values. Standardization relies on the use of written standards, reference measurement procedures and reference materials. These are important tools for the design and validation of new tests, and for establishing the metrological traceability of diagnostic assays. Their use supports the translation of research technologies into new diagnostic assays and leads to more rapid advances in science and medicine, as well as improvements in the quality of patient care. The various standardization tools are described, as are the procedures by which written standards, reference procedures and reference materials are developed. Recent efforts to develop standards for use in the field of molecular diagnostics are discussed. The recognition of standardization tools by the FDA and other regulatory authorities is noted as evidence of their important role in ensuring the safety and performance of in vitro diagnostic devices.

MEvoLib v1.0: the first molecular evolution library for Python.

PubMed

Álvarez-Jarreta, Jorge; Ruiz-Pesini, Eduardo

2016-10-28

Molecular evolution studies involve many different hard computational problems solved, in most cases, with heuristic algorithms that provide a nearly optimal solution. Hence, diverse software tools exist for the different stages involved in a molecular evolution workflow. We present MEvoLib, the first molecular evolution library for Python, providing a framework to work with different tools and methods involved in the common tasks of molecular evolution workflows. In contrast with already existing bioinformatics libraries, MEvoLib is focused on the stages involved in molecular evolution studies, enclosing the set of tools with a common purpose in a single high-level interface with fast access to their frequent parameterizations. The gene clustering from partial or complete sequences has been improved with a new method that integrates accessible external information (e.g. GenBank's features data). Moreover, MEvoLib adjusts the fetching process from NCBI databases to optimize the download bandwidth usage. In addition, it has been implemented using parallelization techniques to cope with even large-case scenarios. MEvoLib is the first library for Python designed to facilitate molecular evolution researches both for expert and novel users. Its unique interface for each common task comprises several tools with their most used parameterizations. It has also included a method to take advantage of biological knowledge to improve the gene partition of sequence datasets. Additionally, its implementation incorporates parallelization techniques to enhance computational costs when handling very large input datasets.

Combating mutations in genetic disease and drug resistance: understanding molecular mechanisms to guide drug design.

PubMed

Albanaz, Amanda T S; Rodrigues, Carlos H M; Pires, Douglas E V; Ascher, David B

2017-06-01

Mutations introduce diversity into genomes, leading to selective changes and driving evolution. These changes have contributed to the emergence of many of the current major health concerns of the 21st century, from the development of genetic diseases and cancers to the rise and spread of drug resistance. The experimental systematic testing of all mutations in a system of interest is impractical and not cost-effective, which has created interest in the development of computational tools to understand the molecular consequences of mutations to aid and guide rational experimentation. Areas covered: Here, the authors discuss the recent development of computational methods to understand the effects of coding mutations to protein function and interactions, particularly in the context of the 3D structure of the protein. Expert opinion: While significant progress has been made in terms of innovative tools to understand and quantify the different range of effects in which a mutation or a set of mutations can give rise to a phenotype, a great gap still exists when integrating these predictions and drawing causality conclusions linking variants. This often requires a detailed understanding of the system being perturbed. However, as part of the drug development process it can be used preemptively in a similar fashion to pharmacokinetics predictions, to guide development of therapeutics to help guide the design and analysis of clinical trials, patient treatment and public health policy strategies.

Evolution of egg coats: linking molecular biology and ecology.

PubMed

Shu, Longfei; Suter, Marc J-F; Räsänen, Katja

2015-08-01

One central goal of evolutionary biology is to explain how biological diversity emerges and is maintained in nature. Given the complexity of the phenotype and the multifaceted nature of inheritance, modern evolutionary ecological studies rely heavily on the use of molecular tools. Here, we show how molecular tools help to gain insight into the role of egg coats (i.e. the extracellular structures surrounding eggs and embryos) in evolutionary diversification. Egg coats are maternally derived structures that have many biological functions from mediating fertilization to protecting the embryo from environmental hazards. They show great molecular, structural and functional diversity across species, but intraspecific variability and the role of ecology in egg coat evolution have largely been overlooked. Given that much of the variation that influences egg coat function is ultimately determined by their molecular phenotype, cutting-edge molecular tools (e.g. proteomics, glycomics and transcriptomics), combined with functional assays, are needed for rigorous inferences on their evolutionary ecology. Here, we identify key research areas and highlight emerging molecular techniques that can increase our understanding of the role of egg coats in the evolution of biological diversity, from adaptation to speciation. © 2015 John Wiley & Sons Ltd.

MIMO: an efficient tool for molecular interaction maps overlap

PubMed Central

2013-01-01

Background Molecular pathways represent an ensemble of interactions occurring among molecules within the cell and between cells. The identification of similarities between molecular pathways across organisms and functions has a critical role in understanding complex biological processes. For the inference of such novel information, the comparison of molecular pathways requires to account for imperfect matches (flexibility) and to efficiently handle complex network topologies. To date, these characteristics are only partially available in tools designed to compare molecular interaction maps. Results Our approach MIMO (Molecular Interaction Maps Overlap) addresses the first problem by allowing the introduction of gaps and mismatches between query and template pathways and permits -when necessary- supervised queries incorporating a priori biological information. It then addresses the second issue by relying directly on the rich graph topology described in the Systems Biology Markup Language (SBML) standard, and uses multidigraphs to efficiently handle multiple queries on biological graph databases. The algorithm has been here successfully used to highlight the contact point between various human pathways in the Reactome database. Conclusions MIMO offers a flexible and efficient graph-matching tool for comparing complex biological pathways. PMID:23672344

Probing biological redox chemistry with large amplitude Fourier transformed ac voltammetry

PubMed Central

Adamson, Hope

2017-01-01

Biological electron-exchange reactions are fundamental to life on earth. Redox reactions underpin respiration, photosynthesis, molecular biosynthesis, cell signalling and protein folding. Chemical, biomedical and future energy technology developments are also inspired by these natural electron transfer processes. Further developments in techniques and data analysis are required to gain a deeper understanding of the redox biochemistry processes that power Nature. This review outlines the new insights gained from developing Fourier transformed ac voltammetry as a tool for protein film electrochemistry. PMID:28804798

Mammalian synthetic biology for studying the cell.

PubMed

Mathur, Melina; Xiang, Joy S; Smolke, Christina D

2017-01-02

Synthetic biology is advancing the design of genetic devices that enable the study of cellular and molecular biology in mammalian cells. These genetic devices use diverse regulatory mechanisms to both examine cellular processes and achieve precise and dynamic control of cellular phenotype. Synthetic biology tools provide novel functionality to complement the examination of natural cell systems, including engineered molecules with specific activities and model systems that mimic complex regulatory processes. Continued development of quantitative standards and computational tools will expand capacities to probe cellular mechanisms with genetic devices to achieve a more comprehensive understanding of the cell. In this study, we review synthetic biology tools that are being applied to effectively investigate diverse cellular processes, regulatory networks, and multicellular interactions. We also discuss current challenges and future developments in the field that may transform the types of investigation possible in cell biology. © 2017 Mathur et al.

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.

Genetic testing for patients with renal disease: procedures, pitfalls, and ethical considerations.

PubMed

Korf, B R

1999-07-01

The Human Genome Project is rapidly producing insights into the molecular basis of human genetic disorders. The most immediate clinical benefit is the advent of new diagnostic methods. Molecular diagnostic tools are available for several genetic renal disorders and are in development for many more. Two general approaches to molecular diagnosis are linkage-based testing and direct mutation detection. The former is used when the gene has not been cloned but has been mapped in relation to polymorphic loci. Linkage-based testing is also helpful when a large diversity of mutations makes direct detection difficult. Limitations include the need to study multiple family members, the need for informative polymorphisms, and genetic heterogeneity. Direct mutation detection is limited by genetic heterogeneity and the need to distinguish nonpathogenic allelic variants from pathogenic mutations. Molecular testing raises a number of complex ethical issues, including those associated with prenatal or presymptomatic diagnosis. In addition, there are concerns about informed consent, privacy, genetic discrimination, and technology transfer for newly developed tests. Health professionals need to be aware of the technical and ethical implications of these new methods of testing, as well as the complexities in test interpretation, as molecular approaches are increasingly integrated into medical practice.

Coupled binding-bending-folding: The complex conformational dynamics of protein-DNA binding studied by atomistic molecular dynamics simulations.

PubMed

van der Vaart, Arjan

2015-05-01

Protein-DNA binding often involves dramatic conformational changes such as protein folding and DNA bending. While thermodynamic aspects of this behavior are understood, and its biological function is often known, the mechanism by which the conformational changes occur is generally unclear. By providing detailed structural and energetic data, molecular dynamics simulations have been helpful in elucidating and rationalizing protein-DNA binding. This review will summarize recent atomistic molecular dynamics simulations of the conformational dynamics of DNA and protein-DNA binding. A brief overview of recent developments in DNA force fields is given as well. Simulations have been crucial in rationalizing the intrinsic flexibility of DNA, and have been instrumental in identifying the sequence of binding events, the triggers for the conformational motion, and the mechanism of binding for a number of important DNA-binding proteins. Molecular dynamics simulations are an important tool for understanding the complex binding behavior of DNA-binding proteins. With recent advances in force fields and rapid increases in simulation time scales, simulations will become even more important for future studies. This article is part of a Special Issue entitled Recent developments of molecular dynamics. Copyright © 2014. Published by Elsevier B.V.

Individual human cell responses to low doses of chemicals studied by synchrotron infrared spectromicroscopy

NASA Astrophysics Data System (ADS)

Holman, Hoi-Ying N.; Goth-Goldstein, Regine; Blakely, Elanor A.; Bjornstad, Kathy; Martin, Michael C.; McKinney, Wayne R.

2000-05-01

Vibrational spectroscopy, when combined with synchrotron radiation-based (SR) microscopy, is a powerful new analytical tool with high spatial resolution for detecting biochemical changes in the individual living cells. In contrast to other microscopy methods that require fixing, drying, staining or labeling, SR-FTIR microscopy probes intact living cells providing a composite view of all of the molecular response and the ability to monitor the response over time in the same cell. Observed spectral changes include all types of lesions induced in that cell as well as cellular responses to external and internal stresses. These spectral changes combined with other analytical tools may provide a fundamental understanding of the key molecular mechanisms induced in response to stresses created by low- doses of chemicals. In this study we used the high spatial - resolution SR-FTIR vibrational spectromicroscopy as a sensitive analytical tool to detect chemical- and radiation- induced changes in individual human cells. Our preliminary spectral measurements indicate that this technique is sensitive enough to detect changes in nucleic acids and proteins of cells treated with environmentally relevant concentrations of dioxin. This technique has the potential to distinguish changes from exogenous or endogenous oxidative processes. Future development of this technique will allow rapid monitoring of cellular processes such as drug metabolism, early detection of disease, bio- compatibility of implant materials, cellular repair mechanisms, self assembly of cellular apparatus, cell differentiation and fetal development.

Molecular mechanism of the sweet taste enhancers.

PubMed

Zhang, Feng; Klebansky, Boris; Fine, Richard M; Liu, Haitian; Xu, Hong; Servant, Guy; Zoller, Mark; Tachdjian, Catherine; Li, Xiaodong

2010-03-09

Positive allosteric modulators of the human sweet taste receptor have been developed as a new way of reducing dietary sugar intake. Besides their potential health benefit, the sweet taste enhancers are also valuable tool molecules to study the general mechanism of positive allosteric modulations of T1R taste receptors. Using chimeric receptors, mutagenesis, and molecular modeling, we reveal how these sweet enhancers work at the molecular level. Our data argue that the sweet enhancers follow a similar mechanism as the natural umami taste enhancer molecules. Whereas the sweeteners bind to the hinge region and induce the closure of the Venus flytrap domain of T1R2, the enhancers bind close to the opening and further stabilize the closed and active conformation of the receptor.

Molecular determinants of Pichinde virus infection of guinea pigs--a small animal model system for arenaviral hemorrhagic fevers.

PubMed

Liang, Yuying; Lan, Shuiyun; Ly, Hinh

2009-09-01

Arenaviruses are enveloped single-strand RNA viruses that mostly have natural hosts in rodents. Upon infection of humans, several arenaviruses can cause severe hemorrhagic fever diseases, including Lassa fever that is endemic in West Africa. The virulence mechanism of these deadly arenaviruses can be studied in a safe and economical small animal model-guinea pigs infected by a nonpathogenic arenavirus Pichinde virus (PICV), a virulent strain of which can cause similar disease syndromes in guinea pigs as arenaviral hemorrhagic fevers in humans. We have recently developed molecular clones for both the virulent and avirulent strains of PICV. Using the available reverse genetics tools, we are characterizing the molecular determinants of virulent arenavirus infections in vivo.

Prognostic factors, predictive markers and cancer biology: the triad for successful oral cancer chemoprevention.

PubMed

Monteiro de Oliveira Novaes, Jose Augusto; William, William N

2016-10-01

Oral squamous cell carcinomas represent a significant cancer burden worldwide. Unfortunately, chemoprevention strategies investigated to date have failed to produce an agent considered standard of care to prevent oral cancers. Nonetheless, recent advances in clinical trial design may streamline drug development in this setting. In this manuscript, we review some of these improvements, including risk prediction tools based on molecular markers that help select patients most suitable for chemoprevention. We also discuss the opportunities that novel preclinical models and modern molecular profiling techniques will bring to the prevention field in the near future, and propose a clinical trials framework that incorporates molecular prognostic factors, predictive markers and cancer biology as a roadmap to improve chemoprevention strategies for oral cancers.

The fabulous destiny of the Drosophila heart.

PubMed

Medioni, Caroline; Sénatore, Sébastien; Salmand, Pierre-Adrien; Lalevée, Nathalie; Perrin, Laurent; Sémériva, Michel

2009-10-01

For the last 15 years the fly cardiovascular system has attracted developmental geneticists for its potential as a model system of organogenesis. Heart development in Drosophila indeed provides a remarkable system for elucidating the basic molecular and cellular mechanisms of morphogenesis and, more recently, for understanding the genetic control of cardiac physiology. The success of these studies can in part be attributed to multidisciplinary approaches, the multiplicity of existing genetic tools, and a detailed knowledge of the system. Striking similarities with vertebrate cardiogenesis have long been stressed, in particular concerning the conservation of key molecular regulators of cardiogenesis and the new data presented here confirm Drosophila cardiogenesis as a model not only for organogenesis but also for the study of molecular mechanisms of human cardiac disease.

Drug repositioning: playing dirty to kill pain.

PubMed

Bastos, Leandro Francisco Silva; Coelho, Márcio Matos

2014-01-01

The number of approved new molecular entity drugs has been decreasing as the pharmaceutical company investment in research and development is increasing. As we face this painful crisis, called an innovation gap, there is increasing awareness that development of new uses of existing drugs may be a powerful tool to help overcome this obstacle because it takes too long, costs too much and can be risky to release drugs developed de novo. Consequently, drug repositioning is emerging in different therapeutic areas, including the pain research area. Worldwide, pain is the main reason for seeking healthcare, and pain relief represents an unmet global clinical need. Therefore, development of analgesics with better efficacy, safety and cost effectiveness is of paramount importance. Despite the remarkable advancement in research on cellular and molecular mechanisms underlying pain pathophysiology over the past three decades, target-based therapeutic opportunities have not been pursued to the same extent. Phenotypic screening remains a more powerful tool for drug development than target-based screening so far. It sounds somewhat heretical, but some multi-action drugs, rather than very selective ones, have been developed intentionally. In the present review, we first critically discuss the utility of drug repositioning for analgesic drug development and then show examples of 'old' drugs that have been successfully repositioned or that are under investigation for their analgesic actions. We conclude that drug repositioning should be more strongly encouraged to help build a bridge between basic research and pain relief worldwide.

Geochemical Reaction Mechanism Discovery from Molecular Simulation

DOE PAGES

Stack, Andrew G.; Kent, Paul R. C.

2014-11-10

Methods to explore reactions using computer simulation are becoming increasingly quantitative, versatile, and robust. In this review, a rationale for how molecular simulation can help build better geochemical kinetics models is first given. We summarize some common methods that geochemists use to simulate reaction mechanisms, specifically classical molecular dynamics and quantum chemical methods and discuss their strengths and weaknesses. Useful tools such as umbrella sampling and metadynamics that enable one to explore reactions are discussed. Several case studies wherein geochemists have used these tools to understand reaction mechanisms are presented, including water exchange and sorption on aqueous species and mineralmore » surfaces, surface charging, crystal growth and dissolution, and electron transfer. The impact that molecular simulation has had on our understanding of geochemical reactivity are highlighted in each case. In the future, it is anticipated that molecular simulation of geochemical reaction mechanisms will become more commonplace as a tool to validate and interpret experimental data, and provide a check on the plausibility of geochemical kinetic models.« less

OpenMM 7: Rapid development of high performance algorithms for molecular dynamics

PubMed Central

Swails, Jason; Zhao, Yutong; Beauchamp, Kyle A.; Wang, Lee-Ping; Stern, Chaya D.; Brooks, Bernard R.; Pande, Vijay S.

2017-01-01

OpenMM is a molecular dynamics simulation toolkit with a unique focus on extensibility. It allows users to easily add new features, including forces with novel functional forms, new integration algorithms, and new simulation protocols. Those features automatically work on all supported hardware types (including both CPUs and GPUs) and perform well on all of them. In many cases they require minimal coding, just a mathematical description of the desired function. They also require no modification to OpenMM itself and can be distributed independently of OpenMM. This makes it an ideal tool for researchers developing new simulation methods, and also allows those new methods to be immediately available to the larger community. PMID:28746339

Development and application of an algorithm to compute weighted multiple glycan alignments.

PubMed

Hosoda, Masae; Akune, Yukie; Aoki-Kinoshita, Kiyoko F

2017-05-01

A glycan consists of monosaccharides linked by glycosidic bonds, has branches and forms complex molecular structures. Databases have been developed to store large amounts of glycan-binding experiments, including glycan arrays with glycan-binding proteins. However, there are few bioinformatics techniques to analyze large amounts of data for glycans because there are few tools that can handle the complexity of glycan structures. Thus, we have developed the MCAW (Multiple Carbohydrate Alignment with Weights) tool that can align multiple glycan structures, to aid in the understanding of their function as binding recognition molecules. We have described in detail the first algorithm to perform multiple glycan alignments by modeling glycans as trees. To test our tool, we prepared several data sets, and as a result, we found that the glycan motif could be successfully aligned without any prior knowledge applied to the tool, and the known recognition binding sites of glycans could be aligned at a high rate amongst all our datasets tested. We thus claim that our tool is able to find meaningful glycan recognition and binding patterns using data obtained by glycan-binding experiments. The development and availability of an effective multiple glycan alignment tool opens possibilities for many other glycoinformatics analysis, making this work a big step towards furthering glycomics analysis. http://www.rings.t.soka.ac.jp. kkiyoko@soka.ac.jp. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press.

Double strand RNA-mediated RNA interference through feeding in larval gypsy moth, Lymantria dispar (Lepidoptera: Erebidae)

USDA-ARS?s Scientific Manuscript database

RNA interference (RNAi) has gained popularity in several fields of research, silencing targeted genes by degradation of RNA. The objective of this study was to develop RNAi for use as a molecular tool in the control of the invasive pest Lymantria dispar (Lepidoptera: Erebidae), gypsy moth, which ha...

Real-Time Imaging of Plant Cell Wall Structure at Nanometer Scale, with Respect to Cellulase Accessibility and Degradation Kinetics (Presentation)

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

Ding, S. Y.

Presentation on real-time imaging of plant cell wall structure at nanometer scale. Objectives are to develop tools to measure biomass at the nanometer scale; elucidate the molecular bases of biomass deconstruction; and identify factors that affect the conversion efficiency of biomass-to-biofuels.

Early cellular evolution.

NASA Technical Reports Server (NTRS)

Margulis, L.

1972-01-01

Study of the evolutionary developments that occurred subsequent to the origin of ancestral cells. Microbial physiology and ecology are potential sharp tools for shaping concepts of microbial evolution. Some popular unjustified assumptions are discussed. It is considered that certain principles derived mainly from the advances of molecular biology can be used to order the natural groups (genera) of extant prokaryotes and their patterns phylogenetically.

Plant Tissue Culture Development and Biotechnology, Chapter 10: Molecular Tools for Studying Plant Genetic Diversity

USDA-ARS?s Scientific Manuscript database

The ubiquitous nature of DNA is a central theme for all biology. The nucleus of each cell that makes up an organism contains genomic DNA, which is the blueprint for life. The differential expression of genes within each cell gives rise to different tissues, organs and, ultimately, different organism...

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

ERIC Educational Resources Information Center

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

2008-01-01

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

Molecular typing of Sarcocystis neurona: current status and future trends.

PubMed

Elsheikha, Hany M; Mansfield, Linda S

2007-10-21

Sarcocystis neurona is an important protozoal pathogen because it causes the serious neurological disease equine protozoal myeloencephalitis (EPM). The capacity of this organism to cause a wide spectrum of neurological signs in horses and the broad geographic distribution of observed cases in the Americas drive the need for sensitive, reliable and rapid typing methods to characterize strains. Various molecular methods have been developed and used to diagnose EPM due to S. neurona, to identify S. neurona isolates and to determine the heterogeneity and evolutionary relatedness within this species and related Sarcocystis spp. These methods included sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), immuno-fluorescent assay (IFA), slide agglutination test (SAT), SnSAG-specific ELISA, random amplified polymorphic DNA (RAPD), PCR-based restriction fragment length polymorphism (RFLP), amplified fragment length polymorphism (AFLP) fingerprinting, and sequence analysis of surface protein genes, ribosomal genes, microsatellite alleles and other molecular markers. Here, the utility of these molecular methods is reviewed and evaluated with respect to the need for molecular approaches that utilize well-characterized polymorphic, simple, independent, and stable genetic markers. These tools have the potential to add to knowledge of the genetic population structure of S. neurona and to provide new insights into the pathogenesis of EPM and S. neurona epidemiology. In particular, these methods provide new tools to address the hypothesis that particular genetic variants are associated with adverse clinical outcomes (severe pathotypes). The ultimate goal is to utilize them in future studies to improve treatment and prevention strategies.

Pediatric tuberculosis-human immunodeficiency virus co-infection in the United Kingdom highlights the need for better therapy monitoring tools: a case report.

PubMed

Evangelopoulos, Dimitrios; Whittaker, Elizabeth; Honeyborne, Isobella; McHugh, Timothy D; Klein, Nigel; Shingadia, Delane

2017-02-26

Tuberculosis is an infection that requires at least 6 months of chemotherapy in order to clear the bacteria from the patient's lungs. Usually, therapeutic monitoring is dependent on smear microscopy where a decline in acid-fast bacilli is observed. However, this might not be indicative of the actual decline of bacterial load and thus other tools such as culture and molecular assays are required for patient management. Here, we report the case of a 12-year-old Black African boy co-infected with tuberculosis and human immunodeficiency virus who remained smear culture positive and liquid culture negative for a prolonged period of time following chemotherapy. In order to determine whether there was any live bacteria present in his specimens, we applied the newly developed molecular bacterial load assay that detects the presence of 16S ribosomal ribonucleic acid derived from the bacteria. Using this methodology, we were able to quantify his bacterial load and inform the management of his treatment in order to reduce the disease burden. Following this intervention he went on to make a complete recovery. This case report highlights the value of improved biomarkers for monitoring the treatment of tuberculosis and the role of molecular assays such as the molecular bacterial load assay applied here. The molecular bacterial load assay detects bacterial ribonucleic acid which corresponds closely with the number of live bacilli as compared with polymerase chain reaction that detects deoxyribonucleic acid and may include dead bacteria.

Molecular imaging of rheumatoid arthritis: emerging markers, tools, and techniques

PubMed Central

2014-01-01

Early diagnosis and effective monitoring of rheumatoid arthritis (RA) are important for a positive outcome. Instant treatment often results in faster reduction of inflammation and, as a consequence, less structural damage. Anatomical imaging techniques have been in use for a long time, facilitating diagnosis and monitoring of RA. However, mere imaging of anatomical structures provides little information on the processes preceding changes in synovial tissue, cartilage, and bone. Molecular imaging might facilitate more effective diagnosis and monitoring in addition to providing new information on the disease pathogenesis. A limiting factor in the development of new molecular imaging techniques is the availability of suitable probes. Here, we review which cells and molecules can be targeted in the RA joint and discuss the advances that have been made in imaging of arthritis with a focus on such molecular targets as folate receptor, F4/80, macrophage mannose receptor, E-selectin, intercellular adhesion molecule-1, phosphatidylserine, and matrix metalloproteinases. In addition, we discuss a new tool that is being introduced in the field, namely the use of nanobodies as tracers. Finally, we describe additional molecules displaying specific features in joint inflammation and propose these as potential new molecular imaging targets, more specifically receptor activator of nuclear factor κB and its ligand, chemokine receptors, vascular cell adhesion molecule-1, αVβ3 integrin, P2X7 receptor, suppression of tumorigenicity 2, dendritic cell-specific transmembrane protein, and osteoclast-stimulatory transmembrane protein. PMID:25099015

Gonadal and Sex Differentiation Abnormalities of Dogs and Cats

PubMed Central

Meyers-Wallen, V.N.

2012-01-01

The molecular steps in normal sexual development were largely discovered by studying patients and animal models with disorders of sexual development (DSD). Although several types of DSD have been reported in the cat and dog, which are often strikingly similar to human DSD, these have been infrequently utilized to contribute to our knowledge of mammalian sexual development. Canine and feline cases of DSD with sufficient evidence to be considered as potential models are summarized in this report. The consensus DSD terminology, and reference to previous terminology, is used to foster adoption of a common nomenclature that will facilitate communication and collaboration between veterinarians, physicians, and researchers. To efficiently utilize these unique resources as molecular tools continue to improve, it will be helpful to deposit samples from valuable cases into repositories where they are available to contribute to our understanding of sexual development, and thus improve human and animal health. PMID:22005097

CHARMM: The Biomolecular Simulation Program

PubMed Central

Brooks, B.R.; Brooks, C.L.; MacKerell, A.D.; Nilsson, L.; Petrella, R.J.; Roux, B.; Won, Y.; Archontis, G.; Bartels, C.; Boresch, S.; Caflisch, A.; Caves, L.; Cui, Q.; Dinner, A.R.; Feig, M.; Fischer, S.; Gao, J.; Hodoscek, M.; Im, W.; Kuczera, K.; Lazaridis, T.; Ma, J.; Ovchinnikov, V.; Paci, E.; Pastor, R.W.; Post, C.B.; Pu, J.Z.; Schaefer, M.; Tidor, B.; Venable, R. M.; Woodcock, H. L.; Wu, X.; Yang, W.; York, D.M.; Karplus, M.

2009-01-01

CHARMM (Chemistry at HARvard Molecular Mechanics) is a highly versatile and widely used molecular simulation program. It has been developed over the last three decades with a primary focus on molecules of biological interest, including proteins, peptides, lipids, nucleic acids, carbohydrates and small molecule ligands, as they occur in solution, crystals, and membrane environments. For the study of such systems, the program provides a large suite of computational tools that include numerous conformational and path sampling methods, free energy estimators, molecular minimization, dynamics, and analysis techniques, and model-building capabilities. In addition, the CHARMM program is applicable to problems involving a much broader class of many-particle systems. Calculations with CHARMM can be performed using a number of different energy functions and models, from mixed quantum mechanical-molecular mechanical force fields, to all-atom classical potential energy functions with explicit solvent and various boundary conditions, to implicit solvent and membrane models. The program has been ported to numerous platforms in both serial and parallel architectures. This paper provides an overview of the program as it exists today with an emphasis on developments since the publication of the original CHARMM paper in 1983. PMID:19444816

Development and use of molecular markers: past and present.

PubMed

Grover, Atul; Sharma, P C

2016-01-01

Molecular markers, due to their stability, cost-effectiveness and ease of use provide an immensely popular tool for a variety of applications including genome mapping, gene tagging, genetic diversity diversity, phylogenetic analysis and forensic investigations. In the last three decades, a number of molecular marker techniques have been developed and exploited worldwide in different systems. However, only a handful of these techniques, namely RFLPs, RAPDs, AFLPs, ISSRs, SSRs and SNPs have received global acceptance. A recent revolution in DNA sequencing techniques has taken the discovery and application of molecular markers to high-throughput and ultrahigh-throughput levels. Although, the choice of marker will obviously depend on the targeted use, microsatellites, SNPs and genotyping by sequencing (GBS) largely fulfill most of the user requirements. Further, modern transcriptomic and functional markers will lead the ventures onto high-density genetic map construction, identification of QTLs, breeding and conservation strategies in times to come in combination with other high throughput techniques. This review presents an overview of different marker technologies and their variants with a comparative account of their characteristic features and applications.

MaMiCo: Software design for parallel molecular-continuum flow simulations

NASA Astrophysics Data System (ADS)

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

2016-03-01

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

[Progress in porky genes and transcriptome and discussion of relative issues].

PubMed

Zhu, Meng-Jin; Liu, Bang; Li, Kui

2005-01-01

To date, research on molecular base of porky molecular development was mainly involved in muscle growth and meat quality. Some functional genes including Hal gene and RN gene and some QTLs controlling or associated with porky growth and quality were detected through candidate gene approach and genome-wide scanning. Genic transcriptome pertinent to porcine muscle and adipose also came into study. At the same time, these researches have befallen some shortcomings to some extent. Research from molecular quantitative genetics showed shortcomings that single gene was devilishly emphasized and co-expression pattern of multi-genes was ignored. Research applying transcriptome analysis tool also met two of limitations, one was the singleness of type of molecular experimental techniques, and another was that genes of muscle and adipose were artificially divided into unattached two parts. Thus, porky genes were explored by parallel genetics based on systemic views and techniques to specially reveal the interactional mechanism of porky genes respectively controlling muscle and adipose, which would be important issues of genes and genome researches on porky development in the near future.

Integration of genomic and medical data into a 3D atlas of human anatomy.

PubMed

Turinsky, Andrei L; Fanea, Elena; Trinh, Quang; Dong, Xiaoli; Stromer, Julie N; Shu, Xueling; Wat, Stephen; Hallgrímsson, Benedikt; Hill, Jonathan W; Edwards, Carol; Grosenick, Brenda; Yajima, Masumi; Sensen, Christoph W

2008-01-01

We have developed a framework for the visual integration and exploration of multi-scale biomedical data, which includes anatomical and molecular components. We have also created a Java-based software system that integrates molecular information, such as gene expression data, into a three-dimensional digital atlas of the male adult human anatomy. Our atlas is structured according to the Terminologia Anatomica. The underlying data-indexing mechanism uses open standards and semantic ontology-processing tools to establish the associations between heterogeneous data types. The software system makes an extensive use of virtual reality visualization.

Engineering molecularly imprinted polymers (MIPs) for the selective extraction and quantification of the novel psychoactive substance (NPS) methoxphenidine and its regioisomers.

PubMed

Lowdon, J W; Alkirkit, S M O; Mewis, R E; Fulton, D; Banks, C E; Sutcliffe, O B; Peeters, M

2018-04-30

In this communication, we present the first developed Molecularly Imprinted Polymers (MIPs) for the specific detection of a New Psychoactive Substance (NPS); namely, methoxphenidine (MXP) and its regioisomers. Selectivity of the MIP towards MXP is studied by analysing mixtures and an acquired street sample with High Performance Liquid Chromatography coupled to UV detection. The study demonstrates that the engineered polymers selectively extract MXP from heterogeneous samples, which makes for a very powerful diagnostic tool that can detect traces of MXP in complicated NPS samples.

Improving molecular tools for global surveillance of measles virus.

PubMed

Bankamp, Bettina; Byrd-Leotis, Lauren A; Lopareva, Elena N; Woo, Gibson K S; Liu, Chunyu; Jee, Youngmee; Ahmed, Hinda; Lim, Wilina W; Ramamurty, Nalini; Mulders, Mick N; Featherstone, David; Bellini, William J; Rota, Paul A

2013-09-01

The genetic characterization of wild-type measles viruses plays an important role in the description of viral transmission pathways and the verification of measles elimination. The 450 nucleotides that encode the carboxyl-terminus of the nucleoprotein (N-450) are routinely sequenced for genotype analysis. The objectives of this study were to develop improved primers and controls for RT-PCR reactions used for genotyping of measles samples and to develop a method to provide a convenient, safe, and inexpensive means to distribute measles RNA for RT-PCR assays and practice panels. A newly designed, genetically defined synthetic RNA and RNA isolated from cells infected with currently circulating genotypes were used to compare the sensitivity of primer pairs in RT-PCR and nested PCR. FTA® cards loaded with lysates of measles infected cells were tested for their ability to preserve viral RNA and destroy virus infectivity. A new primer pair, MeV216/MeV214, was able to amplify N-450 from viruses representing 10 currently circulating genotypes and a genotype A vaccine strain and demonstrated 100-fold increased sensitivity compared to the previously used primer set. A nested PCR assay further increased the sensitivity of detection from patient samples. A synthetic positive control RNA was developed that produced PCR products that are distinguishable by size from PCR products amplified from clinical samples. FTA® cards completely inactivated measles virus and stabilized RNA for at least six months. These improved molecular tools will advance molecular characterization of circulating measles viruses globally and provide enhanced quality control measures. Published by Elsevier B.V.

Genetic dissection of GABAergic neural circuits in mouse neocortex

PubMed Central

Taniguchi, Hiroki

2014-01-01

Diverse and flexible cortical functions rely on the ability of neural circuits to perform multiple types of neuronal computations. GABAergic inhibitory interneurons significantly contribute to this task by regulating the balance of activity, synaptic integration, spiking, synchrony, and oscillation in a neural ensemble. GABAergic interneurons display a high degree of cellular diversity in morphology, physiology, connectivity, and gene expression. A considerable number of subtypes of GABAergic interneurons diversify modes of cortical inhibition, enabling various types of information processing in the cortex. Thus, comprehensively understanding fate specification, circuit assembly, and physiological function of GABAergic interneurons is a key to elucidate the principles of cortical wiring and function. Recent advances in genetically encoded molecular tools have made a breakthrough to systematically study cortical circuitry at the molecular, cellular, circuit, and whole animal levels. However, the biggest obstacle to fully applying the power of these to analysis of GABAergic circuits was that there were no efficient and reliable methods to express them in subtypes of GABAergic interneurons. Here, I first summarize cortical interneuron diversity and current understanding of mechanisms, by which distinct classes of GABAergic interneurons are generated. I then review recent development in genetically encoded molecular tools for neural circuit research, and genetic targeting of GABAergic interneuron subtypes, particularly focusing on our recent effort to develop and characterize Cre/CreER knockin lines. Finally, I highlight recent success in genetic targeting of chandelier cells, the most unique and distinct GABAergic interneuron subtype, and discuss what kind of questions need to be addressed to understand development and function of cortical inhibitory circuits. PMID:24478631

Improving molecular tools for global surveillance of measles virus⋆

PubMed Central

Bankamp, Bettina; Byrd-Leotis, Lauren A.; Lopareva, Elena N.; Woo, Gibson K.S.; Liu, Chunyu; Jee, Youngmee; Ahmed, Hinda; Lim, Wilina W.; Ramamurty, Nalini; Mulders, Mick N.; Featherstone, David; Bellini, William J.; Rota, Paul A.

2017-01-01

Background The genetic characterization of wild-type measles viruses plays an important role in the description of viral transmission pathways and the verification of measles elimination. The 450 nucleotides that encode the carboxyl-terminus of the nucleoprotein (N-450) are routinely sequenced for genotype analysis. Objectives The objectives of this study were to develop improved primers and controls for RT-PCR reactions used for genotyping of measles samples and to develop a method to provide a convenient, safe, and inexpensive means to distribute measles RNA for RT-PCR assays and practice panels. Study design A newly designed, genetically defined synthetic RNA and RNA isolated from cells infected with currently circulating genotypes were used to compare the sensitivity of primer pairs in RT-PCR and nested PCR. FTA® cards loaded with lysates of measles infected cells were tested for their ability to preserve viral RNA and destroy virus infectivity. Results A new primer pair, MeV216/MeV214, was able to amplify N-450 from viruses representing 10 currently circulating genotypes and a genotype A vaccine strain and demonstrated 100-fold increased sensitivity compared to the previously used primer set. A nested PCR assay further increased the sensitivity of detection from patient samples. A synthetic positive control RNA was developed that produced PCR products that are distinguishable by size from PCR products amplified from clinical samples. FTA® cards completely inactivated measles virus and stabilized RNA for at least six months. Conclusions These improved molecular tools will advance molecular characterization of circulating measles viruses globally and provide enhanced quality control measures. PMID:23806666

Application of high level wavefunction methods in quantum mechanics/molecular mechanics hybrid schemes.

PubMed

Mata, Ricardo A

2010-05-21

In this Perspective, several developments in the field of quantum mechanics/molecular mechanics (QM/MM) approaches are reviewed. Emphasis is placed on the use of correlated wavefunction theory and new state of the art methods for the treatment of large quantum systems. Until recently, computational chemistry approaches to large/complex chemical problems have seldom been considered as tools for quantitative predictions. However, due to the tremendous development of computational resources and new quantum chemical methods, it is nowadays possible to describe the electronic structure of biomolecules at levels of theory which a decade ago were only possible for system sizes of up to 20 atoms. These advances are here outlined in the context of QM/MM. The article concludes with a short outlook on upcoming developments and possible bottlenecks for future applications.

Understanding the chemistry of the development of latent fingerprints by superglue fuming.

PubMed

Wargacki, Stephen P; Lewis, Linda A; Dadmun, Mark D

2007-09-01

Cyanoacrylate fuming is a widely used forensic tool for the development of latent fingerprints, however the mechanistic details of the reaction between the fingerprint residue and the cyanoacrylate vapor are not well understood. Here the polymerization of ethyl-cyanoacrylate vapor by sodium lactate or alanine solutions, two of the major components in fingerprint residue, has been examined by monitoring the time dependence of the mass uptake and resultant polymer molecular weight characteristics. This data provides insight into the molecular level actions in the efficient development of latent fingerprints by superglue fuming. The results show that the carboxylate moiety is the primary initiator of the polymerization process and that a basic environment inhibits chain termination while an acidic environment promotes it. The results also indicate that water cannot be the primary initiator in this forensic technique.

Fully anharmonic IR and Raman spectra of medium-size molecular systems: accuracy and interpretation†

PubMed Central

Barone, Vincenzo; Biczysko, Malgorzata; Bloino, Julien

2015-01-01

Computation of full infrared (IR) and Raman spectra (including absolute intensities and transition energies) for medium- and large-sized molecular systems beyond the harmonic approximation is one of the most interesting challenges of contemporary computational chemistry. Contrary to common beliefs, low-order perturbation theory is able to deliver results of high accuracy (actually often better than those issuing from current direct dynamics approaches) provided that anharmonic resonances are properly managed. This perspective sketches the recent developments in our research group toward the development a robust and user-friendly virtual spectrometer rooted into the second-order vibrational perturbation theory (VPT2) and usable also by non-specialists essentially as a black-box procedure. Several examples are explicitly worked out in order to illustrate the features of our computational tool together with the most important ongoing developments. PMID:24346191

Screening of multiple potential control genes for use in caste and body region comparisons using RT-qPCR in Coptotermes formosanus

USDA-ARS?s Scientific Manuscript database

Formosan subterranean termites, Coptotermes formosanus, are an important world wide pest. Molecular gene expression is an important tool for understanding the physiology of organisms. The recent advancement of molecular tools for Coptotermes formosanus is leading to advancement of the understanding ...

Dual Functional Roles of Molecular Beacon as a MicroRNA Detector and Inhibitor*

PubMed Central

Li, Wai Ming; Chan, Ching-Man; Miller, Andrew L.; Lee, Chow H.

2017-01-01

MicroRNAs are essential in many cellular processes. The ability to detect microRNAs is important for understanding its function and biogenesis. This study is aimed at using a molecular beacon to detect miR-430 in developing zebrafish embryos as a proof of principle. miR-430 is crucial for the clearance of maternal mRNA during maternal zygotic transition in embryonic development. Despite its known function, the temporal and spatial expression of miR-430 remains unclear. We used various imaging techniques, including laser scanning confocal microscopy, spinning disk, and lightsheet microscopy, to study the localization of miR-430 and any developmental defects possibly caused by the molecular beacon. Our results show that miR-430 is expressed early in development and is localized in distinct cytoplasmic granules where its target mRNA can be detected. We also show that the designed molecular beacon can inhibit the function of miR-430 and cause developmental defect in the brain, notochord, heart, and kidney, depending on the delivery site within the embryo, suggesting that miR-430 plays a diverse role in embryonic morphogenesis. When compared with morpholino, molecular beacon is 2 orders of magnitude more potent in inhibiting miR-430. Thus, our results reveal that in addition to being used as a valuable tool for the detection of microRNAs in vivo, molecular beacons can also be employed to inhibit microRNAs in a specific manner. PMID:28100783

Molecular identification of livestock breeds: a tool for modern conservation biology.

PubMed

Yaro, Mohammed; Munyard, Kylie A; Stear, Michael J; Groth, David M

2017-05-01

Global livestock genetic diversity includes all of the species, breeds and strains of domestic animals, and their variations. Although a recent census indicated that there were 40 species and over 8000 breeds of domestic animals; for the purpose of conservation biology the diversity between and within breeds rather than species is regarded to be of crucial importance. This domestic animal genetic diversity has developed through three main evolutionary events, from speciation (about 3 million years ago) through domestication (about 12000 years ago) to specialised breeding (starting about 200 years ago). These events and their impacts on global animal genetic resources have been well documented in the literature. The key importance of global domestic animal resources in terms of economic, scientific and cultural heritage has also been addressed. In spite of their importance, there is a growing number of reports on the alarming erosion of domestic animal genetic resources. This erosion of is happening in spite of several global conservation initiatives designed to mitigate it. Herein we discuss these conservation interventions and highlight their strengths and weaknesses. However, pivotal to the success of these conservation initiatives is the reliability of the genetic assignment of individual members to a target breed. Finally, we discuss the prospect of using improved breed identification methodologies to develop a reliable breed-specific molecular identification tool that is easily applicable to populations of livestock breeds in various ecosystems. These identification tools, when developed, will not only facilitate the regular monitoring of threatened or endangered breed populations, but also enhance the development of more efficient and sustainable livestock production systems. © 2016 Cambridge Philosophical Society.

Dual Functional Roles of Molecular Beacon as a MicroRNA Detector and Inhibitor.

PubMed

Li, Wai Ming; Chan, Ching-Man; Miller, Andrew L; Lee, Chow H

2017-03-03

MicroRNAs are essential in many cellular processes. The ability to detect microRNAs is important for understanding its function and biogenesis. This study is aimed at using a molecular beacon to detect miR-430 in developing zebrafish embryos as a proof of principle. miR-430 is crucial for the clearance of maternal mRNA during maternal zygotic transition in embryonic development. Despite its known function, the temporal and spatial expression of miR-430 remains unclear. We used various imaging techniques, including laser scanning confocal microscopy, spinning disk, and lightsheet microscopy, to study the localization of miR-430 and any developmental defects possibly caused by the molecular beacon. Our results show that miR-430 is expressed early in development and is localized in distinct cytoplasmic granules where its target mRNA can be detected. We also show that the designed molecular beacon can inhibit the function of miR-430 and cause developmental defect in the brain, notochord, heart, and kidney, depending on the delivery site within the embryo, suggesting that miR-430 plays a diverse role in embryonic morphogenesis. When compared with morpholino, molecular beacon is 2 orders of magnitude more potent in inhibiting miR-430. Thus, our results reveal that in addition to being used as a valuable tool for the detection of microRNAs in vivo , molecular beacons can also be employed to inhibit microRNAs in a specific manner. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Recent Advances in Cardiac Computed Tomography: Dual Energy, Spectral and Molecular CT Imaging

PubMed Central

Danad, Ibrahim; Fayad, Zahi A.; Willemink, Martin J.; Min, James K.

2015-01-01

Computed tomography (CT) evolved into a powerful diagnostic tool and it is impossible to imagine current clinical practice without CT imaging. Due to its widespread availability, ease of clinical application, superb sensitivity for detection of CAD, and non-invasive nature, CT has become a valuable tool within the armamentarium of the cardiologist. In the last few years, numerous technological advances in CT have occurred—including dual energy CT (DECT), spectral CT and CT-based molecular imaging. By harnessing the advances in technology, cardiac CT has advanced beyond the mere evaluation of coronary stenosis to an imaging modality tool that permits accurate plaque characterization, assessment of myocardial perfusion and even probing of molecular processes that are involved in coronary atherosclerosis. Novel innovations in CT contrast agents and pre-clinical spectral CT devices have paved the way for CT-based molecular imaging. PMID:26068288

Engineering Yarrowia lipolytica for Use in Biotechnological Applications: A Review of Major Achievements and Recent Innovations.

PubMed

Madzak, Catherine

2018-06-25

Yarrowia lipolytica is an oleaginous saccharomycetous yeast with a long history of industrial use. It aroused interest several decades ago as host for heterologous protein production. Thanks to the development of numerous molecular and genetic tools, Y. lipolytica is now a recognized system for expressing heterologous genes and secreting the corresponding proteins of interest. As genomic and transcriptomic tools increased our basic knowledge on this yeast, we can now envision engineering its metabolic pathways for use as whole-cell factory in various bioconversion processes. Y. lipolytica is currently being developed as a workhorse for biotechnology, notably for single-cell oil production and upgrading of industrial wastes into valuable products. As it becomes more and more difficult to keep up with an ever-increasing literature on Y. lipolytica engineering technology, this article aims to provide basic and actualized knowledge on this research area. The most useful reviews on Y. lipolytica biology, use, and safety will be evoked, together with a resume of the engineering tools available in this yeast. This mini-review will then focus on recently developed tools and engineering strategies, with a particular emphasis on promoter tuning, metabolic pathways assembly, and genome editing technologies.

Visualization for Molecular Dynamics Simulation of Gas and Metal Surface Interaction

NASA Astrophysics Data System (ADS)

Puzyrkov, D.; Polyakov, S.; Podryga, V.

2016-02-01

The development of methods, algorithms and applications for visualization of molecular dynamics simulation outputs is discussed. The visual analysis of the results of such calculations is a complex and actual problem especially in case of the large scale simulations. To solve this challenging task it is necessary to decide on: 1) what data parameters to render, 2) what type of visualization to choose, 3) what development tools to use. In the present work an attempt to answer these questions was made. For visualization it was offered to draw particles in the corresponding 3D coordinates and also their velocity vectors, trajectories and volume density in the form of isosurfaces or fog. We tested the way of post-processing and visualization based on the Python language with use of additional libraries. Also parallel software was developed that allows processing large volumes of data in the 3D regions of the examined system. This software gives the opportunity to achieve desired results that are obtained in parallel with the calculations, and at the end to collect discrete received frames into a video file. The software package "Enthought Mayavi2" was used as the tool for visualization. This visualization application gave us the opportunity to study the interaction of a gas with a metal surface and to closely observe the adsorption effect.

PopSc: Computing Toolkit for Basic Statistics of Molecular Population Genetics Simultaneously Implemented in Web-Based Calculator, Python and R

PubMed Central

Huang, Ying; Li, Cao; Liu, Linhai; Jia, Xianbo; Lai, Song-Jia

2016-01-01

Although various computer tools have been elaborately developed to calculate a series of statistics in molecular population genetics for both small- and large-scale DNA data, there is no efficient and easy-to-use toolkit available yet for exclusively focusing on the steps of mathematical calculation. Here, we present PopSc, a bioinformatic toolkit for calculating 45 basic statistics in molecular population genetics, which could be categorized into three classes, including (i) genetic diversity of DNA sequences, (ii) statistical tests for neutral evolution, and (iii) measures of genetic differentiation among populations. In contrast to the existing computer tools, PopSc was designed to directly accept the intermediate metadata, such as allele frequencies, rather than the raw DNA sequences or genotyping results. PopSc is first implemented as the web-based calculator with user-friendly interface, which greatly facilitates the teaching of population genetics in class and also promotes the convenient and straightforward calculation of statistics in research. Additionally, we also provide the Python library and R package of PopSc, which can be flexibly integrated into other advanced bioinformatic packages of population genetics analysis. PMID:27792763

The IBD interactome: an integrated view of aetiology, pathogenesis and therapy.

PubMed

de Souza, Heitor S P; Fiocchi, Claudio; Iliopoulos, Dimitrios

2017-12-01

Crohn's disease and ulcerative colitis are prototypical complex diseases characterized by chronic and heterogeneous manifestations, induced by interacting environmental, genomic, microbial and immunological factors. These interactions result in an overwhelming complexity that cannot be tackled by studying the totality of each pathological component (an '-ome') in isolation without consideration of the interaction among all relevant -omes that yield an overall 'network effect'. The outcome of this effect is the 'IBD interactome', defined as a disease network in which dysregulation of individual -omes causes intestinal inflammation mediated by dysfunctional molecular modules. To define the IBD interactome, new concepts and tools are needed to implement a systems approach; an unbiased data-driven integration strategy that reveals key players of the system, pinpoints the central drivers of inflammation and enables development of targeted therapies. Powerful bioinformatics tools able to query and integrate multiple -omes are available, enabling the integration of genomic, epigenomic, transcriptomic, proteomic, metabolomic and microbiome information to build a comprehensive molecular map of IBD. This approach will enable identification of IBD molecular subtypes, correlations with clinical phenotypes and elucidation of the central hubs of the IBD interactome that will aid discovery of compounds that can specifically target the hubs that control the disease.

PopSc: Computing Toolkit for Basic Statistics of Molecular Population Genetics Simultaneously Implemented in Web-Based Calculator, Python and R.

PubMed

Chen, Shi-Yi; Deng, Feilong; Huang, Ying; Li, Cao; Liu, Linhai; Jia, Xianbo; Lai, Song-Jia

2016-01-01

Although various computer tools have been elaborately developed to calculate a series of statistics in molecular population genetics for both small- and large-scale DNA data, there is no efficient and easy-to-use toolkit available yet for exclusively focusing on the steps of mathematical calculation. Here, we present PopSc, a bioinformatic toolkit for calculating 45 basic statistics in molecular population genetics, which could be categorized into three classes, including (i) genetic diversity of DNA sequences, (ii) statistical tests for neutral evolution, and (iii) measures of genetic differentiation among populations. In contrast to the existing computer tools, PopSc was designed to directly accept the intermediate metadata, such as allele frequencies, rather than the raw DNA sequences or genotyping results. PopSc is first implemented as the web-based calculator with user-friendly interface, which greatly facilitates the teaching of population genetics in class and also promotes the convenient and straightforward calculation of statistics in research. Additionally, we also provide the Python library and R package of PopSc, which can be flexibly integrated into other advanced bioinformatic packages of population genetics analysis.

Discovery of simian virus 40 (SV40) and its relationship to poliomyelitis virus vaccines.

PubMed

Hilleman, M R

1998-01-01

Simian Virus 40 (SV40) was discovered in 1959 as a covert contaminant of poliovirus vaccines prepared using Macacus monkey renal cell cultures. This inapparent polyoma virus of monkeys was detected using Cercopithecus renal cell cultures and was eliminated from poliovaccines. There has been no evidence to implicate SV40 virus of vaccine origin in long- or short-term consequences in human subjects. Of importance, SV40 virus provided a new model for basic studies of viral pathogenesis and for cell transformation and neoplasia. Neoplastic transformation is fixed on the promiscuous binding of SV40 large T antigen to anti-oncogene cellular protein elements. SV40 also served as a valuable model for defining the immunology of virus-induced cancer and in its prevention and cure. Further, it has been a prime tool for elucidating the molecular details of eukaryotic cell processes. Numerous techniques now used in molecular biology were pioneered in the SV40 system. The SV40 promoter is commonly used in vector expression constructs and it has continued to be a model to develop new tools for site-specific mutagenesis. The virus has been critically important to studies in modern genetics and in molecular biology.

Development of the Central Dogma Concept Inventory (CDCI) Assessment Tool.

PubMed

Newman, Dina L; Snyder, Christopher W; Fisk, J Nick; Wright, L Kate

2016-01-01

Scientific teaching requires scientifically constructed, field-tested instruments to accurately evaluate student thinking and gauge teacher effectiveness. We have developed a 23-question, multiple select-format assessment of student understanding of the essential concepts of the central dogma of molecular biology that is appropriate for all levels of undergraduate biology. Questions for the Central Dogma Concept Inventory (CDCI) tool were developed and iteratively revised based on student language and review by experts. The ability of the CDCI to discriminate between levels of understanding of the central dogma is supported by field testing (N= 54), and large-scale beta testing (N= 1733). Performance on the assessment increased with experience in biology; scores covered a broad range and showed no ceiling effect, even with senior biology majors, and pre/posttesting of a single class focused on the central dogma showed significant improvement. The multiple-select format reduces the chances of correct answers by random guessing, allows students at different levels to exhibit the extent of their knowledge, and provides deeper insight into the complexity of student thinking on each theme. To date, the CDCI is the first tool dedicated to measuring student thinking about the central dogma of molecular biology, and version 5 is ready to use. © 2016 D. L. Newman 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).

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

PubMed

Doiron, Kevin J; Yu, Peiqiang

2017-01-02

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

Analyte-Triggered DNA-Probe Release from a Triplex Molecular Beacon for Nanopore Sensing.

PubMed

Guo, Bingyuan; Sheng, Yingying; Zhou, Ke; Liu, Quansheng; Liu, Lei; Wu, Hai-Chen

2018-03-26

A new nanopore sensing strategy based on triplex molecular beacon was developed for the detection of specific DNA or multivalent proteins. The sensor is composed of a triplex-forming molecular beacon and a stem-forming DNA component that is modified with a host-guest complex. Upon target DNA hybridizing with the molecular beacon loop or multivalent proteins binding to the recognition elements on the stem, the DNA probe is released and produces highly characteristic current signals when translocated through α-hemolysin. The frequency of current signatures can be used to quantify the concentrations of the target molecules. This sensing approach provides a simple, quick, and modular tool for the detection of specific macromolecules with high sensitivity and excellent selectivity. It may find useful applications in point-of-care diagnostics with a portable nanopore kit in the future. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Internal force corrections with machine learning for quantum mechanics/molecular mechanics simulations.

PubMed

Wu, Jingheng; Shen, Lin; Yang, Weitao

2017-10-28

Ab initio quantum mechanics/molecular mechanics (QM/MM) molecular dynamics simulation is a useful tool to calculate thermodynamic properties such as potential of mean force for chemical reactions but intensely time consuming. In this paper, we developed a new method using the internal force correction for low-level semiempirical QM/MM molecular dynamics samplings with a predefined reaction coordinate. As a correction term, the internal force was predicted with a machine learning scheme, which provides a sophisticated force field, and added to the atomic forces on the reaction coordinate related atoms at each integration step. We applied this method to two reactions in aqueous solution and reproduced potentials of mean force at the ab initio QM/MM level. The saving in computational cost is about 2 orders of magnitude. The present work reveals great potentials for machine learning in QM/MM simulations to study complex chemical processes.

LAMMPS integrated materials engine (LIME) for efficient automation of particle-based simulations: application to equation of state generation

NASA Astrophysics Data System (ADS)

Barnes, Brian C.; Leiter, Kenneth W.; Becker, Richard; Knap, Jaroslaw; Brennan, John K.

2017-07-01

We describe the development, accuracy, and efficiency of an automation package for molecular simulation, the large-scale atomic/molecular massively parallel simulator (LAMMPS) integrated materials engine (LIME). Heuristics and algorithms employed for equation of state (EOS) calculation using a particle-based model of a molecular crystal, hexahydro-1,3,5-trinitro-s-triazine (RDX), are described in detail. The simulation method for the particle-based model is energy-conserving dissipative particle dynamics, but the techniques used in LIME are generally applicable to molecular dynamics simulations with a variety of particle-based models. The newly created tool set is tested through use of its EOS data in plate impact and Taylor anvil impact continuum simulations of solid RDX. The coarse-grain model results from LIME provide an approach to bridge the scales from atomistic simulations to continuum simulations.

Design tools for complex dynamic security systems.

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

Byrne, Raymond Harry; Rigdon, James Brian; Rohrer, Brandon Robinson

2007-01-01

The development of tools for complex dynamic security systems is not a straight forward engineering task but, rather, a scientific task where discovery of new scientific principles and math is necessary. For years, scientists have observed complex behavior but have had difficulty understanding it. Prominent examples include: insect colony organization, the stock market, molecular interactions, fractals, and emergent behavior. Engineering such systems will be an even greater challenge. This report explores four tools for engineered complex dynamic security systems: Partially Observable Markov Decision Process, Percolation Theory, Graph Theory, and Exergy/Entropy Theory. Additionally, enabling hardware technology for next generation security systemsmore » are described: a 100 node wireless sensor network, unmanned ground vehicle and unmanned aerial vehicle.« less

The 'right' size in nanobiotechnology.

PubMed

Whitesides, George M

2003-10-01

The biological and physical sciences share a common interest in small structures (the definition of 'small' depends on the application, but can range from 1 nm to 1 mm). A vigorous trade across the borders of these areas of science is developing around new materials and tools (largely from the physical sciences) and new phenomena (largely from the biological sciences). The physical sciences offer tools for synthesis and fabrication of devices for measuring the characteristics of cells and sub-cellular components, and of materials useful in cell and molecular biology; biology offers a window into the most sophisticated collection of functional nanostructures that exists.

Recent science and its exploration: the case of molecular biology.

PubMed

Rheinberger, Hans-Jörg

2009-03-01

This paper is about the interaction and the intertwinement between history of science as a historical process and history of science as the historiography of this process, taking molecular biology as an example. In the first part, two historical shifts are briefly characterized that appear to have punctuated the emergence of molecular biology between the 1930s and the 1980s, one connected to a new generation of analytical apparatus, the other to properly molecular tools. The second part concentrates on the historiography of this development. Basically, it distinguishes three phases. The first phase was largely dominated by accounts of the actors themselves. The second coincided with the general 'practical turn' in history of science at large, and today's historical appropriations of the molecularization of the life sciences appear to be marked by the changing disciplinary status of the science under review. In a closing remark, an argument is made for differentiating between long-range, middle-range and short-range perspectives in dealing with the history of the sciences.

Structure simulation with calculated NMR parameters - integrating COSMOS into the CCPN framework.

PubMed

Schneider, Olaf; Fogh, Rasmus H; Sternberg, Ulrich; Klenin, Konstantin; Kondov, Ivan

2012-01-01

The Collaborative Computing Project for NMR (CCPN) has build a software framework consisting of the CCPN data model (with APIs) for NMR related data, the CcpNmr Analysis program and additional tools like CcpNmr FormatConverter. The open architecture allows for the integration of external software to extend the abilities of the CCPN framework with additional calculation methods. Recently, we have carried out the first steps for integrating our software Computer Simulation of Molecular Structures (COSMOS) into the CCPN framework. The COSMOS-NMR force field unites quantum chemical routines for the calculation of molecular properties with a molecular mechanics force field yielding the relative molecular energies. COSMOS-NMR allows introducing NMR parameters as constraints into molecular mechanics calculations. The resulting infrastructure will be made available for the NMR community. As a first application we have tested the evaluation of calculated protein structures using COSMOS-derived 13C Cα and Cβ chemical shifts. In this paper we give an overview of the methodology and a roadmap for future developments and applications.

Molecular anions.

PubMed

Simons, Jack

2008-07-24

The experimental and theoretical study of molecular anions has undergone explosive growth over the past 40 years. Advances in techniques used to generate anions in appreciable numbers as well as new ion-storage, ion-optics, and laser spectroscopic tools have been key on the experimental front. Theoretical developments on the electronic structure and molecular dynamics fronts now allow one to achieve higher accuracy and to study electronically metastable states, thus bringing theory in close collaboration with experiment in this field. In this article, many of the experimental and theoretical challenges specific to studying molecular anions are discussed. Results from many research groups on several classes of molecular anions are overviewed, and both literature citations and active (in online html and pdf versions) links to numerous contributing scientists' Web sites are provided. Specific focus is made on the following families of anions: dipole-bound, zwitterion-bound, double-Rydberg, multiply charged, metastable, cluster-based, and biological anions. In discussing each kind of anion, emphasis is placed on the structural, energetic, spectroscopic, and chemical-reactivity characteristics that make these anions novel, interesting, and important.

Detection and Characterization of Viral Species/Subspecies Using Isothermal Recombinase Polymerase Amplification (RPA) Assays.

PubMed

Glais, Laurent; Jacquot, Emmanuel

2015-01-01

Numerous molecular-based detection protocols include an amplification step of the targeted nucleic acids. This step is important to reach the expected sensitive detection of pathogens in diagnostic procedures. Amplifications of nucleic acid sequences are generally performed, in the presence of appropriate primers, using thermocyclers. However, the time requested to amplify molecular targets and the cost of the thermocycler machines could impair the use of these methods in routine diagnostics. Recombinase polymerase amplification (RPA) technique allows rapid (short-term incubation of sample and primers in an enzymatic mixture) and simple (isothermal) amplification of molecular targets. RPA protocol requires only basic molecular steps such as extraction procedures and agarose gel electrophoresis. Thus, RPA can be considered as an interesting alternative to standard molecular-based diagnostic tools. In this paper, the complete procedures to set up an RPA assay, applied to detection of RNA (Potato virus Y, Potyvirus) and DNA (Wheat dwarf virus, Mastrevirus) viruses, are described. The proposed procedure allows developing species- or subspecies-specific detection assay.

Development of diet-induced insulin resistance in adult Drosophila melanogaster

PubMed Central

Morris, Siti Nur Sarah; Coogan, Claire; Chamseddin, Khalil; Fernandez-Kim, Sun Ok; Kolli, Santharam; Keller, Jeffrey N.; Bauer, Johannes H.

2013-01-01

The fruit fly Drosophila melanogaster is increasingly utilized as an alternative to costly rodent models to study human diseases. Fly models exist for a wide variety of human conditions, such as Alzheimer's and Parkinson’s Disease, or cardiac function. Advantages of the fly system are its rapid generation time and its low cost. However, the greatest strength of the fly system are the powerful genetic tools that allow for rapid dissection of molecular disease mechanisms. Here, we describe the diet-dependent development of metabolic phenotypes in adult fruit flies. Depending on the specific type of nutrient, as well as its relative quantity in the diet, flies show weight gain and changes in the levels of storage macromolecules. Furthermore, the activity of insulin-signaling in the major metabolic organ of the fly, the fat body, decreases upon overfeeding. This decrease in insulin-signaling activity in overfed flies is moreover observed when flies are challenged with an acute food stimulus, suggesting that overfeeding leads to insulin resistance. Similar changes were observed in aging flies, with the development of the insulin resistance-like phenotype beginning at early middle ages. Taken together, these data demonstrate that imbalanced diet disrupts metabolic homeostasis in adult D. melanogaster and promotes insulin-resistant phenotypes. Therefore, the fly system may be a useful alternative tool in the investigation of molecular mechanisms of insulin resistance and the development of pharmacologic treatment options. PMID:22542511

Novel findings about management of gastric cancer: a summary from 10th IGCC.

PubMed

Penon, Danila; Cito, Letizia; Giordano, Antonio

2014-07-21

The Tenth International Gastric Cancer Congress (IGCC) was held in Verona, Italy, from June 19 to 22, 2013. The meeting enclosed various aspects of stomach tumor management, including both tightly clinical approaches, and topics more related to basic research. Moreover, an overview on gastrointestinal stromal tumors was provided too, although here not discussed. Here we will discuss some topics related to molecular biology of gastric cancer (GC), inherent to prognostic, diagnostic and therapeutic tools shown at the conference. Results about well known subjects, such as E-cadherin loss of expression/function, were presented. They revealed that other mutations of the gene were identified, showing a continuous research to improve diagnosis and prognosis of stomach tumor. Simultaneously, new possible molecular markers with an established role for other neoplasms, were discussed, such as mesothelin, stomatin-like protein 2 and Notch-1. Hence, a wide overview including both old and new diagnostic/prognostic tools was offered. Great attention was also dedicated to possible drugs to be used against GC. They included monoclonal antibodies, such as MS57-2.1, drugs used in other pathologies, such as maraviroc, and natural extracts from plants such as biflorin. We would like to contribute to summarize the most impressive studies presented at the IGCC, concerning novel findings about molecular biology of gastric cancer. Although further investigations will be necessary, it can be inferred that more and more tools were developed, so as to better face stomach neoplasms.

Novel findings about management of gastric cancer: A summary from 10th IGCC

PubMed Central

Penon, Danila; Cito, Letizia; Giordano, Antonio

2014-01-01

The Tenth International Gastric Cancer Congress (IGCC) was held in Verona, Italy, from June 19 to 22, 2013. The meeting enclosed various aspects of stomach tumor management, including both tightly clinical approaches, and topics more related to basic research. Moreover, an overview on gastrointestinal stromal tumors was provided too, although here not discussed. Here we will discuss some topics related to molecular biology of gastric cancer (GC), inherent to prognostic, diagnostic and therapeutic tools shown at the conference. Results about well known subjects, such as E-cadherin loss of expression/function, were presented. They revealed that other mutations of the gene were identified, showing a continuous research to improve diagnosis and prognosis of stomach tumor. Simultaneously, new possible molecular markers with an established role for other neoplasms, were discussed, such as mesothelin, stomatin-like protein 2 and Notch-1. Hence, a wide overview including both old and new diagnostic/prognostic tools was offered. Great attention was also dedicated to possible drugs to be used against GC. They included monoclonal antibodies, such as MS57-2.1, drugs used in other pathologies, such as maraviroc, and natural extracts from plants such as biflorin. We would like to contribute to summarize the most impressive studies presented at the IGCC, concerning novel findings about molecular biology of gastric cancer. Although further investigations will be necessary, it can be inferred that more and more tools were developed, so as to better face stomach neoplasms. PMID:25083072

Leveraging Modeling Approaches: Reaction Networks and Rules

PubMed Central

Blinov, Michael L.; Moraru, Ion I.

2012-01-01

We have witnessed an explosive growth in research involving mathematical models and computer simulations of intracellular molecular interactions, ranging from metabolic pathways to signaling and gene regulatory networks. Many software tools have been developed to aid in the study of such biological systems, some of which have a wealth of features for model building and visualization, and powerful capabilities for simulation and data analysis. Novel high resolution and/or high throughput experimental techniques have led to an abundance of qualitative and quantitative data related to the spatio-temporal distribution of molecules and complexes, their interactions kinetics, and functional modifications. Based on this information, computational biology researchers are attempting to build larger and more detailed models. However, this has proved to be a major challenge. Traditionally, modeling tools require the explicit specification of all molecular species and interactions in a model, which can quickly become a major limitation in the case of complex networks – the number of ways biomolecules can combine to form multimolecular complexes can be combinatorially large. Recently, a new breed of software tools has been created to address the problems faced when building models marked by combinatorial complexity. These have a different approach for model specification, using reaction rules and species patterns. Here we compare the traditional modeling approach with the new rule-based methods. We make a case for combining the capabilities of conventional simulation software with the unique features and flexibility of a rule-based approach in a single software platform for building models of molecular interaction networks. PMID:22161349

Leveraging modeling approaches: reaction networks and rules.

PubMed

Blinov, Michael L; Moraru, Ion I

2012-01-01

We have witnessed an explosive growth in research involving mathematical models and computer simulations of intracellular molecular interactions, ranging from metabolic pathways to signaling and gene regulatory networks. Many software tools have been developed to aid in the study of such biological systems, some of which have a wealth of features for model building and visualization, and powerful capabilities for simulation and data analysis. Novel high-resolution and/or high-throughput experimental techniques have led to an abundance of qualitative and quantitative data related to the spatiotemporal distribution of molecules and complexes, their interactions kinetics, and functional modifications. Based on this information, computational biology researchers are attempting to build larger and more detailed models. However, this has proved to be a major challenge. Traditionally, modeling tools require the explicit specification of all molecular species and interactions in a model, which can quickly become a major limitation in the case of complex networks - the number of ways biomolecules can combine to form multimolecular complexes can be combinatorially large. Recently, a new breed of software tools has been created to address the problems faced when building models marked by combinatorial complexity. These have a different approach for model specification, using reaction rules and species patterns. Here we compare the traditional modeling approach with the new rule-based methods. We make a case for combining the capabilities of conventional simulation software with the unique features and flexibility of a rule-based approach in a single software platform for building models of molecular interaction networks.

Biotechnology of temperate fruit trees and grapevines.

PubMed

Laimer, Margit; Mendonça, Duarte; Maghuly, Fatemeh; Marzban, Gorji; Leopold, Stephan; Khan, Mahmood; Balla, Ildiko; Katinger, Hermann

2005-01-01

Challenges concerning fruit trees and grapevines as long lived woody perennial crops require adapted biotechnological approaches, if solutions are to be found within a reasonable time frame. These challenges are represented by the need for correct identification of genetic resources, with the foreseen use either in conservation or in breeding programmes. Molecular markers provide most accurate information and will be the major solution for questions about plant breeders rights. Providing healthy planting material and rapid detection of newly introduced pathogens by reliable methods involving serological and molecular biological tools will be a future challenge of increases importance, given the fact that plant material travels freely in the entire European Union. But also new breeding goals and transgenic solutions are part of the biotechnological benefits, e.g. resistance against biotic and abiotic stress factors, modified growth habits, modified nutritional properties and altered processing and storage qualities. The successful characterization of transgenic grapevines and stone fruit trees carrying genes of viral origin in different vectors constructed under ecological consideration, will be presented. Beyond technical feasibility, efficiency of resistance, environmental safety and Intellectual Property Rights, also public acceptance needs consideration and has been addressed in a specific project. The molecular determination of internal quality parameters of food can also be addressed by the use of biotechnological tools. Patient independent detection tools for apple allergens have been developed and should allow to compare fruits from different production systems, sites, and genotypes for their content of health threatening compounds.

Molecular Markers for Breast Cancer: Prediction on Tumor Behavior

PubMed Central

Banin Hirata, Bruna Karina; Oda, Julie Massayo Maeda; Losi Guembarovski, Roberta; Ariza, Carolina Batista; de Oliveira, Carlos Eduardo Coral; Watanabe, Maria Angelica Ehara

2014-01-01

Breast cancer is one of the most common cancers with greater than 1,300,000 cases and 450,000 deaths each year worldwide. The development of breast cancer involves a progression through intermediate stages until the invasive carcinoma and finally into metastatic disease. Given the variability in clinical progression, the identification of markers that could predict the tumor behavior is particularly important in breast cancer. The determination of tumor markers is a useful tool for clinical management in cancer patients, assisting in diagnostic, staging, evaluation of therapeutic response, detection of recurrence and metastasis, and development of new treatment modalities. In this context, this review aims to discuss the main tumor markers in breast carcinogenesis. The most well-established breast molecular markers with prognostic and/or therapeutic value like hormone receptors, HER-2 oncogene, Ki-67, and p53 proteins, and the genes for hereditary breast cancer will be presented. Furthermore, this review shows the new molecular targets in breast cancer: CXCR4, caveolin, miRNA, and FOXP3, as promising candidates for future development of effective and targeted therapies, also with lower toxicity. PMID:24591761

Molecular typing of methicillin-resistant Staphylococcus aureus: Comparison of PCR-based open reading frame typing, multilocus sequence typing, and Staphylococcus protein A gene typing.

PubMed

Ogihara, Shinji; Saito, Ryoichi; Sawabe, Etsuko; Kozakai, Takahiro; Shima, Mari; Aiso, Yoshibumi; Fujie, Toshihide; Nukui, Yoko; Koike, Ryuji; Hagihara, Michio; Tohda, Shuji

2018-04-01

The recently developed PCR-based open reading frame typing (POT) method is a useful molecular typing tool. Here, we evaluated the performance of POT for molecular typing of methicillin-resistant Staphylococcus aureus (MRSA) isolates and compared its performance to those of multilocus sequence typing (MLST) and Staphylococcus protein A gene typing (spa typing). Thirty-seven MRSA isolates were collected between July 2012 and May 2015. MLST, spa typing, and POT were performed, and their discriminatory powers were evaluated using Simpson's index analysis. The MRSA isolates were classified into 11, 18, and 33 types by MLST, spa typing, and POT, respectively. The predominant strains identified by MLST, spa typing, and POT were ST8 and ST764, t002, and 93-191-127, respectively. The discriminatory power of MLST, spa typing, and POT was 0.853, 0.875, and 0.992, respectively, indicating that POT had the highest discriminatory power. Moreover, the results of MLST and spa were available after 2 days, whereas that of POT was available in 5 h. Furthermore, POT is rapid and easy to perform and interpret. Therefore, POT is a superior molecular typing tool for monitoring nosocomial transmission of MRSA. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

The application of HIV molecular epidemiology to public health.

PubMed

Paraskevis, D; Nikolopoulos, G K; Magiorkinis, G; Hodges-Mameletzis, I; Hatzakis, A

2016-12-01

HIV is responsible for one of the largest viral pandemics in human history. Despite a concerted global response for prevention and treatment, the virus persists. Thus, urgent public health action, utilizing novel interventions, is needed to prevent future transmission events, critical to eliminating HIV. For public health planning to prove effective and successful, we need to understand the dynamics of regional epidemics and to intervene appropriately. HIV molecular epidemiology tools as implemented in phylogenetic, phylodynamic and phylogeographic analyses have proven to be powerful tools in public health planning across many studies. Numerous applications with HIV suggest that molecular methods alone or in combination with mathematical modelling can provide inferences about the transmission dynamics, critical epidemiological parameters (prevalence, incidence, effective number of infections, Re, generation times, time between infection and diagnosis), or the spatiotemporal characteristics of epidemics. Molecular tools have been used to assess the impact of an intervention and outbreak investigation which are of great public health relevance. In some settings, molecular sequence data may be more readily available than HIV surveillance data, and can therefore allow for molecular analyses to be conducted more easily. Nonetheless, classic methods have an integral role in monitoring and evaluation of public health programmes, and should supplement emerging techniques from the field of molecular epidemiology. Importantly, molecular epidemiology remains a promising approach in responding to viral diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

Geometric Morphometrics on Gene Expression Patterns Within Phenotypes: A Case Example on Limb Development

PubMed Central

Martínez-Abadías, Neus; Mateu, Roger; Niksic, Martina; Russo, Lucia; Sharpe, James

2016-01-01

How the genotype translates into the phenotype through development is critical to fully understand the evolution of phenotypes. We propose a novel approach to directly assess how changes in gene expression patterns are associated with changes in morphology using the limb as a case example. Our method combines molecular biology techniques, such as whole-mount in situ hybridization, with image and shape analysis, extending the use of Geometric Morphometrics to the analysis of nonanatomical shapes, such as gene expression domains. Elliptical Fourier and Procrustes-based semilandmark analyses were used to analyze the variation and covariation patterns of the limb bud shape with the expression patterns of two relevant genes for limb morphogenesis, Hoxa11 and Hoxa13. We devised a multiple thresholding method to semiautomatically segment gene domains at several expression levels in large samples of limb buds from C57Bl6 mouse embryos between 10 and 12 postfertilization days. Besides providing an accurate phenotyping tool to quantify the spatiotemporal dynamics of gene expression patterns within developing structures, our morphometric analyses revealed high, non-random, and gene-specific variation undergoing canalization during limb development. Our results demonstrate that Hoxa11 and Hoxa13, despite being paralogs with analogous functions in limb patterning, show clearly distinct dynamic patterns, both in shape and size, and are associated differently with the limb bud shape. The correspondence between our results and already well-established molecular processes underlying limb development confirms that this morphometric approach is a powerful tool to extract features of development regulating morphogenesis. Such multilevel analyses are promising in systems where not so much molecular information is available and will advance our understanding of the genotype–phenotype map. In systematics, this knowledge will increase our ability to infer how evolution modified a common developmental pattern to generate a wide diversity of morphologies, as in the vertebrate limb. PMID:26377442

eMovie: a storyboard-based tool for making molecular movies.

PubMed

Hodis, Eran; Schreiber, Gideon; Rother, Kristian; Sussman, Joel L

2007-05-01

The 3D structures of macromolecules are difficult to grasp and also to communicate. By their nature, movies or animations are particularly useful for highlighting key features by offering a 'guided tour' of structures and conformation changes. However, high-quality movies are rarely seen because they are currently difficult and time consuming to make. By adopting the traditional movie 'storyboard' concept, which gives guidance and direction to filming, eMovie makes the creation of lengthy molecular animations much easier. This tool is a plug-in for the open-source molecular graphics program PyMOL, and enables experts and novices alike to produce informative and high-quality molecular animations.

Exploring molecular networks using MONET ontology.

PubMed

Silva, João Paulo Müller da; Lemke, Ney; Mombach, José Carlos; Souza, José Guilherme Camargo de; Sinigaglia, Marialva; Vieira, Renata

2006-03-31

The description of the complex molecular network responsible for cell behavior requires new tools to integrate large quantities of experimental data in the design of biological information systems. These tools could be used in the characterization of these networks and in the formulation of relevant biological hypotheses. The building of an ontology is a crucial step because it integrates in a coherent framework the concepts necessary to accomplish such a task. We present MONET (molecular network), an extensible ontology and an architecture designed to facilitate the integration of data originating from different public databases in a single- and well-documented relational database, that is compatible with MONET formal definition. We also present an example of an application that can easily be implemented using these tools.

[Non-viral gene therapy approach for regenerative recovery of skin wounds in mammals].

PubMed

Efremov, A M; Dukhovlinov, I V; Dizhe, E B; Burov, S V; Leko, M V; Akif'ev, B N; Mogilenko, D A; Ivanov, I A; Perevozchikov, A P; Orlov, S V

2010-01-01

The rate and character of skin tissue regeneration after wounds, burns and other traumas depend on the cell proliferation within damaged area. Acceleration of healing by stimulation of cell proliferation and extracellular matrix synthesis is one of the most important tasks of modern medicine. There are gene therapy approaches to wound treatment consisting in the transfer of genes encoding mitogenic growth factors to wound area. The most important step in the development of gene therapy approaches is the design of gene delivery tools. In spite of high efficacy of viral vectors, the non-viral means have some preferences (low toxicity, low immunogenity, safety and the absence of backside effects). Among non-viral gene delivery tools, molecular conjugates are the most popular because of their efficacy, simplicity, and the capacity to the targeted gene transfer. In the present work we have developed two molecular conjugates--NLS-TSF7 and NLS-TSF12 consisting of the modified signal of nuclear localization of T-antigen of SV40 virus (cationic part) and the peptide ligands of mammalian transferrin receptor (ligand part). These conjugates bind to plasmid DNA with formation of polyelectrolytic complexes and are capable to deliver plasmid DNA into cells expressing transferrin receptors by receptor-mediated endocytosis. Transfer of the expression vector of luciferase gene in the complex with molecular conjugate NLS-TSF7 to murine surface tissues led to about 100 fold increasing of luciferase activity in comparison with the transfer of free expression vector. Treatment of slash wounds in mice with the complexes of expression vector of synthetic human gene encoding insulin-like growth factor 1 with molecular conjugates NLS-TSF7 led to acceleration of healing in comparison with mice treated with free expression vector. The results obtained confirm the high efficiency of the developed regenerative gene therapy approach for the treatment of damaged skin tissues in mammals.

De novo transcriptome sequencing and customized abscission zone-specific microarray as a new molecular tool for analysis of tomato organ abscission

USDA-ARS?s Scientific Manuscript database

Abscission, which is the process of organ separation, is a highly regulated process occurring as a final stage of organ development. In the tomato (Solanum lycopersicum) system, flower and leaf abscission was induced by flower removal or leaf deblading, leading to auxin depletion which results in in...

Genome-wide analysis of gene expression of EMS-induced short fiber mutant Ligon lintless-y (liy) in cotton (Gossypium hirsutum L.)

USDA-ARS?s Scientific Manuscript database

The length of cotton fiber is an important agronomic trait characteristic that directly affects the quality of yarn and fabric. Cotton fiber mutants have been useful tools to study the molecular processes of fiber development. In this work we describe a chemically-induced short fiber mutant Ligon-li...

ProGeRF: Proteome and Genome Repeat Finder Utilizing a Fast Parallel Hash Function

PubMed Central

Moraes, Walas Jhony Lopes; Rodrigues, Thiago de Souza; Bartholomeu, Daniella Castanheira

2015-01-01

Repetitive element sequences are adjacent, repeating patterns, also called motifs, and can be of different lengths; repetitions can involve their exact or approximate copies. They have been widely used as molecular markers in population biology. Given the sizes of sequenced genomes, various bioinformatics tools have been developed for the extraction of repetitive elements from DNA sequences. However, currently available tools do not provide options for identifying repetitive elements in the genome or proteome, displaying a user-friendly web interface, and performing-exhaustive searches. ProGeRF is a web site for extracting repetitive regions from genome and proteome sequences. It was designed to be efficient, fast, and accurate and primarily user-friendly web tool allowing many ways to view and analyse the results. ProGeRF (Proteome and Genome Repeat Finder) is freely available as a stand-alone program, from which the users can download the source code, and as a web tool. It was developed using the hash table approach to extract perfect and imperfect repetitive regions in a (multi)FASTA file, while allowing a linear time complexity. PMID:25811026

Neurophotonics: optical methods to study and control the brain

NASA Astrophysics Data System (ADS)

Doronina-Amitonova, L. V.; Fedotov, I. V.; Fedotov, A. B.; Anokhin, K. V.; Zheltikov, A. M.

2015-04-01

Methods of optical physics offer unique opportunities for the investigation of brain and higher nervous activity. The integration of cutting-edge laser technologies and advanced neurobiology opens a new cross-disciplinary area of natural sciences - neurophotonics - focusing on the development of a vast arsenal of tools for functional brain diagnostics, stimulation of individual neurons and neural networks, and the molecular engineering of brain cells aimed at the diagnosis and therapy of neurodegenerative and psychic diseases. Optical fibers help to confront the most challenging problems in brain research, including the analysis of molecular-cellular mechanisms of the formation of memory and behavior. New generation optical fibers provide new solutions for the development of fundamentally new, unique tools for neurophotonics and laser neuroengineering - fiber-optic neuroendoscopes and neurointerfaces. These instruments broaden research horizons when investigating the most complex brain functions, enabling a long-term multiplex detection of fluorescent protein markers, as well as photostimulation of neuronal activity in deep brain areas in living, freely moving animals with an unprecedented spatial resolution and minimal invasiveness. This emerging technology opens new horizons for understanding learning and long-term memory through experiments with living, freely moving mammals. Here, we present a brief review of this rapidly growing field of research.

From molecular biology to nanotechnology and nanomedicine.

PubMed

Bogunia-Kubik, Katarzyna; Sugisaka, Masanori

2002-01-01

Great progress in the development of molecular biology techniques has been seen since the discovery of the structure of deoxyribonucleic acid (DNA) and the implementation of a polymerase chain reaction (PCR) method. This started a new era of research on the structure of nucleic acids molecules, the development of new analytical tools, and DNA-based analyses. The latter included not only diagnostic procedures but also, for example, DNA-based computational approaches. On the other hand, people have started to be more interested in mimicking real life, and modeling the structures and organisms that already exist in nature for the further evaluation and insight into their behavior and evolution. These factors, among others, have led to the description of artificial organelles or cells, and the construction of nanoscale devices. These nanomachines and nanoobjects might soon find a practical implementation, especially in the field of medical research and diagnostics. The paper presents some examples, illustrating the progress in multidisciplinary research in the nanoscale area. It is focused especially on immunogenetics-related aspects and the wide usage of DNA molecules in various fields of science. In addition, some proposals for nanoparticles and nanoscale tools and their applications in medicine are reviewed and discussed.

Hard Sphere Simulation by Event-Driven Molecular Dynamics: Breakthrough, Numerical Difficulty, and Overcoming the issues

NASA Astrophysics Data System (ADS)

Isobe, Masaharu

Hard sphere/disk systems are among the simplest models and have been used to address numerous fundamental problems in the field of statistical physics. The pioneering numerical works on the solid-fluid phase transition based on Monte Carlo (MC) and molecular dynamics (MD) methods published in 1957 represent historical milestones, which have had a significant influence on the development of computer algorithms and novel tools to obtain physical insights. This chapter addresses the works of Alder's breakthrough regarding hard sphere/disk simulation: (i) event-driven molecular dynamics, (ii) long-time tail, (iii) molasses tail, and (iv) two-dimensional melting/crystallization. From a numerical viewpoint, there are serious issues that must be overcome for further breakthrough. Here, we present a brief review of recent progress in this area.

The biochemistry and molecular biology of xenobiotic polymer degradation by microorganisms.

PubMed

Kawai, Fusako

2010-01-01

Research on microbial degradation of xenobiotic polymers has been underway for more than 40 years. It has exploited a new field not only in applied microbiology but also in environmental microbiology, and has greatly contributed to polymer science by initiating the design of biodegradable polymers. Owing to the development of analytical tools and technology, molecular biological and biochemical advances have made it possible to prospect for degrading microorganisms in the environment and to determine the mechanisms involved in biodegradation when xenobiotic polymers are introduced into the environment and are exposed to microbial attack. In this review, the molecular biological and biochemical aspects of the microbial degradation of xenobiotic polymers are summarized, and possible applications of potent microorganisms, enzymes, and genes in environmental biotechnology are suggested.

MDANSE: An Interactive Analysis Environment for Molecular Dynamics Simulations.

PubMed

Goret, G; Aoun, B; Pellegrini, E

2017-01-23

The MDANSE software-Molecular Dynamics Analysis of Neutron Scattering Experiments-is presented. It is an interactive application for postprocessing molecular dynamics (MD) simulations. Given the widespread use of MD simulations in material and biomolecular sciences to get a better insight for experimental techniques such as thermal neutron scattering (TNS), the development of MDANSE has focused on providing a user-friendly, interactive, graphical user interface for analyzing many trajectories in the same session and running several analyses simultaneously independently of the interface. This first version of MDANSE already proposes a broad range of analyses, and the application has been designed to facilitate the introduction of new analyses in the framework. All this makes MDANSE a valuable tool for extracting useful information from trajectories resulting from a wide range of MD codes.

Open discovery: An integrated live Linux platform of Bioinformatics tools.

PubMed

Vetrivel, Umashankar; Pilla, Kalabharath

2008-01-01

Historically, live linux distributions for Bioinformatics have paved way for portability of Bioinformatics workbench in a platform independent manner. Moreover, most of the existing live Linux distributions limit their usage to sequence analysis and basic molecular visualization programs and are devoid of data persistence. Hence, open discovery - a live linux distribution has been developed with the capability to perform complex tasks like molecular modeling, docking and molecular dynamics in a swift manner. Furthermore, it is also equipped with complete sequence analysis environment and is capable of running windows executable programs in Linux environment. Open discovery portrays the advanced customizable configuration of fedora, with data persistency accessible via USB drive or DVD. The Open Discovery is distributed free under Academic Free License (AFL) and can be downloaded from http://www.OpenDiscovery.org.in.

Molecular epidemiology, and possible real-world applications in breast cancer.

PubMed

Ito, Hidemi; Matsuo, Keitaro

2016-01-01

Gene-environment interaction, a key idea in molecular epidemiology, has enabled the development of personalized medicine. This concept includes personalized prevention. While genome-wide association studies have identified a number of genetic susceptibility loci in breast cancer risk, however, the application of this knowledge to practical prevention is still underway. Here, we briefly review the history of molecular epidemiology and its progress in breast cancer epidemiology. We then introduce our experience with the trial combination of GWAS-identified loci and well-established lifestyle and reproductive risk factors in the risk prediction of breast cancer. Finally, we report our exploration of the cumulative risk of breast cancer based on this risk prediction model as a potential tool for individual risk communication, including genetic risk factors and gene-environment interaction with obesity.

Screening the receptorome to discover the molecular targets for plant-derived psychoactive compounds: a novel approach for CNS drug discovery.

PubMed

Roth, Bryan L; Lopez, Estela; Beischel, Scott; Westkaemper, Richard B; Evans, Jon M

2004-05-01

Because psychoactive plants exert profound effects on human perception, emotion, and cognition, discovering the molecular mechanisms responsible for psychoactive plant actions will likely yield insights into the molecular underpinnings of human consciousness. Additionally, it is likely that elucidation of the molecular targets responsible for psychoactive drug actions will yield validated targets for CNS drug discovery. This review article focuses on an unbiased, discovery-based approach aimed at uncovering the molecular targets responsible for psychoactive drug actions wherein the main active ingredients of psychoactive plants are screened at the "receptorome" (that portion of the proteome encoding receptors). An overview of the receptorome is given and various in silico, public-domain resources are described. Newly developed tools for the in silico mining of data derived from the National Institute of Mental Health Psychoactive Drug Screening Program's (NIMH-PDSP) K(i) Database (K(i) DB) are described in detail. Additionally, three case studies aimed at discovering the molecular targets responsible for Hypericum perforatum, Salvia divinorum, and Ephedra sinica actions are presented. Finally, recommendations are made for future studies.

Just working with the cellular machine: A high school game for teaching molecular biology.

PubMed

Cardoso, Fernanda Serpa; Dumpel, Renata; da Silva, Luisa B Gomes; Rodrigues, Carlos R; Santos, Dilvani O; Cabral, Lucio Mendes; Castro, Helena C

2008-03-01

Molecular biology is a difficult comprehension subject due to its high complexity, thus requiring new teaching approaches. Herein, we developed an interdisciplinary board game involving the human immune system response against a bacterial infection for teaching molecular biology at high school. Initially, we created a database with several questions and a game story that invites the students for helping the human immunological system to produce antibodies (IgG) and fight back a pathogenic bacterium second-time invasion. The game involves answering questions completing the game board in which the antibodies "are synthesized" through the molecular biology process. At the end, a problem-based learning approach is used, and a last question is raised about proteins. Biology teachers and high school students evaluated the game and considered it an easy and interesting tool for teaching the theme. An increase of about 5-30% in answering molecular biology questions revealed that the game improves learning and induced a more engaged and proactive learning profile in the high school students. Copyright © 2008 International Union of Biochemistry and Molecular Biology, Inc.

Simulation of carbohydrates, from molecular docking to dynamics in water.

PubMed

Sapay, Nicolas; Nurisso, Alessandra; Imberty, Anne

2013-01-01

Modeling of carbohydrates is particularly challenging because of the variety of structures resulting for the high number of monosaccharides and possible linkages and also because of their intrinsic flexibility. The development of carbohydrate parameters for molecular modeling is still an active field. Nowadays, main carbohydrates force fields are GLYCAM06, CHARMM36, and GROMOS 45A4. GLYCAM06 includes the largest choice of compounds and is compatible with the AMBER force fields and associated. Furthermore, AMBER includes tools for the implementation of new parameters. When looking at protein-carbohydrate interaction, the choice of the starting structure is of importance. Such complex can be sometimes obtained from the Protein Data Bank-although the stereochemistry of sugars may require some corrections. When no experimental data is available, molecular docking simulation is generally used to the obtain protein-carbohydrate complex coordinates. As molecular docking parameters are not specifically dedicated to carbohydrates, inaccuracies should be expected, especially for the docking of polysaccharides. This issue can be addressed at least partially by combining molecular docking with molecular dynamics simulation in water.

In silico quantitative structure-toxicity relationship study of aromatic nitro compounds.

PubMed

Pasha, Farhan Ahmad; Neaz, Mohammad Morshed; Cho, Seung Joo; Ansari, Mohiuddin; Mishra, Sunil Kumar; Tiwari, Sharvan

2009-05-01

Small molecules often have toxicities that are a function of molecular structural features. Minor variations in structural features can make large difference in such toxicity. Consequently, in silico techniques may be used to correlate such molecular toxicities with their structural features. Relative to nine different sets of aromatic nitro compounds having known observed toxicities against different targets, we developed ligand-based 2D quantitative structure-toxicity relationship models using 20 selected topological descriptors. The topological descriptors have several advantages such as conformational independency, facile and less time-consuming computation to yield good results. Multiple linear regression analysis was used to correlate variations of toxicity with molecular properties. The information index on molecular size, lopping centric index and Kier flexibility index were identified as fundamental descriptors for different kinds of toxicity, and further showed that molecular size, branching and molecular flexibility might be particularly important factors in quantitative structure-toxicity relationship analysis. This study revealed that topological descriptor-guided quantitative structure-toxicity relationship provided a very useful, cost and time-efficient, in silico tool for describing small-molecule toxicities.

Rapid Molecular Identification of Human Taeniid Cestodes by Pyrosequencing Approach

PubMed Central

Thanchomnang, Tongjit; Tantrawatpan, Chairat; Intapan, Pewpan M.; Sanpool, Oranuch; Janwan, Penchom; Lulitanond, Viraphong; Tourtip, Somjintana; Yamasaki, Hiroshi; Maleewong, Wanchai

2014-01-01

Taenia saginata, T. solium, and T. asiatica are causative agents of taeniasis in humans. The difficulty of morphological identification of human taeniids can lead to misdiagnosis or confusion. To overcome this problem, several molecular methods have been developed, but use of these tends to be time-consuming. Here, a rapid and high-throughput pyrosequencing approach was developed for the identification of three human taeniids originating from various countries. Primers targeting the mitochondrial cytochrome c oxidase subunit 1 (cox1) gene of the three Taenia species were designed. Variations in a 26-nucleotide target region were used for identification. The reproducibility and accuracy of the pyrosequencing technology was confirmed by Sanger sequencing. This technique will be a valuable tool to distinguish between sympatric human taeniids that occur in Thailand, Asia and Pacific countries. This method could potentially be used for the molecular identification of the taeniid species that might be associated with suspicious cysts and lesions, or cyst residues in humans or livestock at the slaughterhouse. PMID:24945530

Characterization and Amplification of Gene-Based Simple Sequence Repeat (SSR) Markers in Date Palm.

PubMed

Zhao, Yongli; Keremane, Manjunath; Prakash, Channapatna S; He, Guohao

2017-01-01

The paucity of molecular markers limits the application of genetic and genomic research in date palm (Phoenix dactylifera L.). Availability of expressed sequence tag (EST) sequences in date palm may provide a good resource for developing gene-based markers. This study characterizes a substantial fraction of transcriptome sequences containing simple sequence repeats (SSRs) from the EST sequences in date palm. The EST sequences studied are mainly homologous to those of Elaeis guineensis and Musa acuminata. A total of 911 gene-based SSR markers, characterized with functional annotations, have provided a useful basis not only for discovering candidate genes and understanding genetic basis of traits of interest but also for developing genetic and genomic tools for molecular research in date palm, such as diversity study, quantitative trait locus (QTL) mapping, and molecular breeding. The procedures of DNA extraction, polymerase chain reaction (PCR) amplification of these gene-based SSR markers, and gel electrophoresis of PCR products are described in this chapter.

Application of Molecular Adsorber Coatings in Chamber A for the James Webb Space Telescope

NASA Technical Reports Server (NTRS)

Abraham, Nithin S.

2017-01-01

As a coating made of highly porous zeolite materials, the Molecular Adsorber Coating (MAC) was developed to capture outgassed molecular contaminants, such as hydrocarbons and silicones. For spaceflight applications, the adsorptive capabilities of the coating can alleviate on-orbit outgassing concerns on or near sensitive surfaces and instruments within the spacecraft. Similarly, this sprayable paint technology has proven to be significantly beneficial for ground-based space applications, in particular, for vacuum chamber environments. This presentation describes the application of the MAC technology for the James Webb Space Telescope (JWST) at NASA Johnson Space Center (JSC). The coating was used as a mitigation tool to entrap outgassed contaminants, specifically silicone-based diffusion pump oil, from within JSCs cryogenic optical vacuum chamber test facility called Chamber A. This presentation summarizes the background, fabrication, installation, chemical analysis test results, and future plans for the MAC technology, which was effectively used to protect the JWST test equipment from vacuum chamber contamination. As a coating made of highly porous zeolite materials, the Molecular Adsorber Coating (MAC) was developed to capture outgassed molecular contaminants, such as hydrocarbons and silicones. For spaceflight applications, the adsorptive capabilities of the coating can alleviate on-orbit outgassing concerns on or near sensitive surfaces and instruments within the spacecraft. Similarly, this sprayable paint technology has proven to be significantly beneficial for ground-based space applications, in particular, for vacuum chamber environments. This presentation describes the application of the MAC technology for the James Webb Space Telescope (JWST) at NASA Johnson Space Center (JSC). The coating was used as a mitigation tool to entrap outgassed contaminants, specifically silicone-based diffusion pump oil, from within JSCs cryogenic optical vacuum chamber test facility called Chamber A. This presentation summarizes the background, fabrication, installation, chemical analysis test results, and future plans for the MAC technology, which was effectively used to protect the JWST test equipment from vacuum chamber contamination.

Information management to enable personalized medicine: stakeholder roles in building clinical decision support.

PubMed

Downing, Gregory J; Boyle, Scott N; Brinner, Kristin M; Osheroff, Jerome A

2009-10-08

Advances in technology and the scientific understanding of disease processes are presenting new opportunities to improve health through individualized approaches to patient management referred to as personalized medicine. Future health care strategies that deploy genomic technologies and molecular therapies will bring opportunities to prevent, predict, and pre-empt disease processes but will be dependent on knowledge management capabilities for health care providers that are not currently available. A key cornerstone to the potential application of this knowledge will be effective use of electronic health records. In particular, appropriate clinical use of genomic test results and molecularly-targeted therapies present important challenges in patient management that can be effectively addressed using electronic clinical decision support technologies. Approaches to shaping future health information needs for personalized medicine were undertaken by a work group of the American Health Information Community. A needs assessment for clinical decision support in electronic health record systems to support personalized medical practices was conducted to guide health future development activities. Further, a suggested action plan was developed for government, researchers and research institutions, developers of electronic information tools (including clinical guidelines, and quality measures), and standards development organizations to meet the needs for personalized approaches to medical practice. In this article, we focus these activities on stakeholder organizations as an operational framework to help identify and coordinate needs and opportunities for clinical decision support tools to enable personalized medicine. This perspective addresses conceptual approaches that can be undertaken to develop and apply clinical decision support in electronic health record systems to achieve personalized medical care. In addition, to represent meaningful benefits to personalized decision-making, a comparison of current and future applications of clinical decision support to enable individualized medical treatment plans is presented. If clinical decision support tools are to impact outcomes in a clear and positive manner, their development and deployment must therefore consider the needs of the providers, including specific practice needs, information workflow, and practice environment.

Information management to enable personalized medicine: stakeholder roles in building clinical decision support

PubMed Central

2009-01-01

Background Advances in technology and the scientific understanding of disease processes are presenting new opportunities to improve health through individualized approaches to patient management referred to as personalized medicine. Future health care strategies that deploy genomic technologies and molecular therapies will bring opportunities to prevent, predict, and pre-empt disease processes but will be dependent on knowledge management capabilities for health care providers that are not currently available. A key cornerstone to the potential application of this knowledge will be effective use of electronic health records. In particular, appropriate clinical use of genomic test results and molecularly-targeted therapies present important challenges in patient management that can be effectively addressed using electronic clinical decision support technologies. Discussion Approaches to shaping future health information needs for personalized medicine were undertaken by a work group of the American Health Information Community. A needs assessment for clinical decision support in electronic health record systems to support personalized medical practices was conducted to guide health future development activities. Further, a suggested action plan was developed for government, researchers and research institutions, developers of electronic information tools (including clinical guidelines, and quality measures), and standards development organizations to meet the needs for personalized approaches to medical practice. In this article, we focus these activities on stakeholder organizations as an operational framework to help identify and coordinate needs and opportunities for clinical decision support tools to enable personalized medicine. Summary This perspective addresses conceptual approaches that can be undertaken to develop and apply clinical decision support in electronic health record systems to achieve personalized medical care. In addition, to represent meaningful benefits to personalized decision-making, a comparison of current and future applications of clinical decision support to enable individualized medical treatment plans is presented. If clinical decision support tools are to impact outcomes in a clear and positive manner, their development and deployment must therefore consider the needs of the providers, including specific practice needs, information workflow, and practice environment. PMID:19814826

Emerging applications of label-free optical biosensors

NASA Astrophysics Data System (ADS)

Zanchetta, Giuliano; Lanfranco, Roberta; Giavazzi, Fabio; Bellini, Tommaso; Buscaglia, Marco

2017-01-01

Innovative technical solutions to realize optical biosensors with improved performance are continuously proposed. Progress in material fabrication enables developing novel substrates with enhanced optical responses. At the same time, the increased spectrum of available biomolecular tools, ranging from highly specific receptors to engineered bioconjugated polymers, facilitates the preparation of sensing surfaces with controlled functionality. What remains often unclear is to which extent this continuous innovation provides effective breakthroughs for specific applications. In this review, we address this challenging question for the class of label-free optical biosensors, which can provide a direct signal upon molecular binding without using secondary probes. Label-free biosensors have become a consolidated approach for the characterization and screening of molecular interactions in research laboratories. However, in the last decade, several examples of other applications with high potential impact have been proposed. We review the recent advances in label-free optical biosensing technology by focusing on the potential competitive advantage provided in selected emerging applications, grouped on the basis of the target type. In particular, direct and real-time detection allows the development of simpler, compact, and rapid analytical methods for different kinds of targets, from proteins to DNA and viruses. The lack of secondary interactions facilitates the binding of small-molecule targets and minimizes the perturbation in single-molecule detection. Moreover, the intrinsic versatility of label-free sensing makes it an ideal platform to be integrated with biomolecular machinery with innovative functionality, as in case of the molecular tools provided by DNA nanotechnology.

Molecular characterization of multidrug-resistant Mycobacterium tuberculosis isolated in Nepal.

PubMed

Poudel, Ajay; Nakajima, Chie; Fukushima, Yukari; Suzuki, Haruka; Pandey, Basu Dev; Maharjan, Bhagwan; Suzuki, Yasuhiko

2012-06-01

Despite the fact that Nepal is one of the first countries globally to introduce multidrug-resistant tuberculosis (MDR-TB) case management, the number of MDR-TB cases is continuing to rise in Nepal. Rapid molecular tests applicable in this setting to identify resistant organisms would be an effective tool in reversing this trend. To develop such tools, information about the frequency and distribution of mutations that are associated with phenotypic drug resistance in Mycobacterium tuberculosis is required. In the present study, we investigated the prevalence of mutations in rpoB and katG genes and the inhA promoter region in 158 M. tuberculosis isolates (109 phenotypically MDR and 49 non-MDR isolates collected in Nepal) by DNA sequencing. Mutations affecting the 81-bp rifampin (RIF) resistance-determining region (RRDR) of rpoB were identified in 106 of 109 (97.3%) RIF-resistant isolates. Codons 531, 526, and 516 were the most commonly affected, at percentages of 58.7, 15.6, and 15.6%, respectively. Of 113 isoniazid (INH)-resistant isolates, 99 (87.6%) had mutations in the katG gene, with Ser315Thr being the most prevalent (81.4%) substitution. Mutations in the inhA promoter region were detected in 14 (12.4%) INH-resistant isolates. The results from this study provide an overview of the current situation of RIF and INH resistance in M. tuberculosis in Nepal and can serve as a basis for developing or improving rapid molecular tests to monitor drug-resistant strains in this country.

Resist development status for immersion lithography

NASA Astrophysics Data System (ADS)

Tsuji, Hiromitsu; Yoshida, Masaaki; Ishizuka, Keita; Hirano, Tomoyuki; Endo, Kotaro; Sato, Mitsuru

2005-05-01

Immersion lithography has already demonstrated superior performance for next generation semiconductor manufacturing, while some challenges with contact immersion fluids and resist still remain. There are many interactions to be considered with regards to the solid and liquid interface. Resist elusion in particular requires very careful attention since the impact on the lens and fluid supply system in exposure tool could pose a significant risk at the manufacturing stage. TOK developed a screening procedure to detect resist elution of ion species down to ppb levels during non and post exposure steps. It was found that the PAG cation elution is affected by molecular weight and structure while the PAG anion elution was dependent on the molecular structure and mobility. In this paper, lithographic performance is also discussed with the low elution type resist.

Molecular dynamics-driven drug discovery: leaping forward with confidence.

PubMed

Ganesan, Aravindhan; Coote, Michelle L; Barakat, Khaled

2017-02-01

Given the significant time and financial costs of developing a commercial drug, it remains important to constantly reform the drug discovery pipeline with novel technologies that can narrow the candidates down to the most promising lead compounds for clinical testing. The past decade has witnessed tremendous growth in computational capabilities that enable in silico approaches to expedite drug discovery processes. Molecular dynamics (MD) has become a particularly important tool in drug design and discovery. From classical MD methods to more sophisticated hybrid classical/quantum mechanical (QM) approaches, MD simulations are now able to offer extraordinary insights into ligand-receptor interactions. In this review, we discuss how the applications of MD approaches are significantly transforming current drug discovery and development efforts. Copyright © 2016 Elsevier Ltd. All rights reserved.

Challenges in breeding for yield increase for drought.

PubMed

Sinclair, Thomas R

2011-06-01

Crop genetic improvement for environmental stress at the molecular and physiological level is very complex and challenging. Unlike the example of the current major commercial transgenic crops for which biotic stress tolerance is based on chemicals alien to plants, the complex, redundant and homeostatic molecular and physiological systems existing in plants must be altered for drought tolerance improvement. Sophisticated tools must be developed to monitor phenotype expression at the crop level to characterize variation among genotypes across a range of environments. Once stress-tolerant cultivars are developed, regional probability distributions describing yield response across years will be necessary. This information can then aid in identifying environmental conditions for positive and negative responses to genetic modification to guide farmer selection of stress-tolerant cultivars. Copyright © 2011 Elsevier Ltd. All rights reserved.

Recent developments in structural proteomics for protein structure determination.

PubMed

Liu, Hsuan-Liang; Hsu, Jyh-Ping

2005-05-01

The major challenges in structural proteomics include identifying all the proteins on the genome-wide scale, determining their structure-function relationships, and outlining the precise three-dimensional structures of the proteins. Protein structures are typically determined by experimental approaches such as X-ray crystallography or nuclear magnetic resonance (NMR) spectroscopy. However, the knowledge of three-dimensional space by these techniques is still limited. Thus, computational methods such as comparative and de novo approaches and molecular dynamic simulations are intensively used as alternative tools to predict the three-dimensional structures and dynamic behavior of proteins. This review summarizes recent developments in structural proteomics for protein structure determination; including instrumental methods such as X-ray crystallography and NMR spectroscopy, and computational methods such as comparative and de novo structure prediction and molecular dynamics simulations.

Morphological and Molecular Descriptors of the Developmental Cycle of Babesia divergens Parasites in Human Erythrocytes.

PubMed

Rossouw, Ingrid; Maritz-Olivier, Christine; Niemand, Jandeli; van Biljon, Riette; Smit, Annel; Olivier, Nicholas A; Birkholtz, Lyn-Marie

2015-05-01

Human babesiosis, especially caused by the cattle derived Babesia divergens parasite, is on the increase, resulting in renewed attentiveness to this potentially life threatening emerging zoonotic disease. The molecular mechanisms underlying the pathophysiology and intra-erythrocytic development of these parasites are poorly understood. This impedes concerted efforts aimed at the discovery of novel anti-babesiacidal agents. By applying sensitive cell biological and molecular functional genomics tools, we describe the intra-erythrocytic development cycle of B. divergens parasites from immature, mono-nucleated ring forms to bi-nucleated paired piriforms and ultimately multi-nucleated tetrads that characterizes zoonotic Babesia spp. This is further correlated for the first time to nuclear content increases during intra-erythrocytic development progression, providing insight into the part of the life cycle that occurs during human infection. High-content temporal evaluation elucidated the contribution of the different stages to life cycle progression. Moreover, molecular descriptors indicate that B. divergens parasites employ physiological adaptation to in vitro cultivation. Additionally, differential expression is observed as the parasite equilibrates its developmental stages during its life cycle. Together, this information provides the first temporal evaluation of the functional transcriptome of B. divergens parasites, information that could be useful in identifying biological processes essential to parasite survival for future anti-babesiacidal discoveries.

Imaging mass spectrometry in drug development and toxicology.

PubMed

Karlsson, Oskar; Hanrieder, Jörg

2017-06-01

During the last decades, imaging mass spectrometry has gained significant relevance in biomedical research. Recent advances in imaging mass spectrometry have paved the way for in situ studies on drug development, metabolism and toxicology. In contrast to whole-body autoradiography that images the localization of radiolabeled compounds, imaging mass spectrometry provides the possibility to simultaneously determine the discrete tissue distribution of the parent compound and its metabolites. In addition, imaging mass spectrometry features high molecular specificity and allows comprehensive, multiplexed detection and localization of hundreds of proteins, peptides and lipids directly in tissues. Toxicologists traditionally screen for adverse findings by histopathological examination. However, studies of the molecular and cellular processes underpinning toxicological and pathologic findings induced by candidate drugs or toxins are important to reach a mechanistic understanding and an effective risk assessment strategy. One of IMS strengths is the ability to directly overlay the molecular information from the mass spectrometric analysis with the tissue section and allow correlative comparisons of molecular and histologic information. Imaging mass spectrometry could therefore be a powerful tool for omics profiling of pharmacological/toxicological effects of drug candidates and toxicants in discrete tissue regions. The aim of the present review is to provide an overview of imaging mass spectrometry, with particular focus on MALDI imaging mass spectrometry, and its use in drug development and toxicology in general.

Molecular-genetic imaging based on reporter gene expression.

PubMed

Kang, Joo Hyun; Chung, June-Key

2008-06-01

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

[Development of a Fluorescence Probe for Live Cell Imaging].

PubMed

Shibata, Aya

2017-01-01

 Probes that detect specific biological materials are indispensable tools for deepening our understanding of various cellular phenomena. In live cell imaging, the probe must emit fluorescence only when a specific substance is detected. In this paper, we introduce a new probe we developed for live cell imaging. Glutathione S-transferase (GST) activity is higher in tumor cells than in normal cells and is involved in the development of resistance to various anticancer drugs. We previously reported the development of a general strategy for the synthesis of probes for detection of GST enzymes, including fluorogenic, bioluminogenic, and 19 F-NMR probes. Arylsulfonyl groups were used as caging groups during probe design. The fluorogenic probes were successfully used to quantitate very low levels of GST activity in cell extracts and were also successfully applied to the imaging of microsomal MGST1 activity in living cells. The bioluminogenic and 19 F-NMR probes were able to detect GST activity in Escherichia coli cells. Oligonucleotide-templated reactions are powerful tools for nucleic acid sensing. This strategy exploits the target strand as a template for two functionalized probes and provides a simple molecular mechanism for multiple turnover reactions. We developed a nucleophilic aromatic substitution reaction-triggered fluorescent probe. The probe completed its reaction within 30 s of initiation and amplified the fluorescence signal from 0.5 pM target oligonucleotide by 1500 fold under isothermal conditions. Additionally, we applied the oligonucleotide-templated reaction for molecular releasing and peptide detection.

Preparation of Conjugates of Cytotoxic Lupane Triterpenes with Biotin.

PubMed

Soural, Miroslav; Hodon, Jiri; Dickinson, Niall J; Sidova, Veronika; Gurska, Sona; Dzubak, Petr; Hajduch, Marian; Sarek, Jan; Urban, Milan

2015-12-16

To better understand the mechanism of action of antitumor triterpenes, we are developing methods to identify their molecular targets. A promising method is based on combination of quantitative proteomics with SILAC and uses active compounds anchored to magnetic beads via biotin-streptavidin interaction. We developed a simple and fast solid-phase synthetic technique to connect terpenes to biotin through a linker. Betulinic acid was biotinylated from three different conjugation sites for use as a standard validation tool since many molecular targets of this triterpene are already known. Then, a set of four other cytotoxic triterpenoids was biotinylated. Biotinylated terpenes were similarly cytotoxic to their nonbiotinylated parents, which suggests that the target identification should not be influenced by linker or biotin. The developed solid-phase synthetic approach is the first attempt to use solid-phase synthesis to connect active triterpenes to biotin and is applicable as a general procedure for routine conjugation of triterpenes with other molecules of choice.

Synthetic biology platform technologies for antimicrobial applications.

PubMed

Braff, Dana; Shis, David; Collins, James J

2016-10-01

The growing prevalence of antibiotic resistance calls for new approaches in the development of antimicrobial therapeutics. Likewise, improved diagnostic measures are essential in guiding the application of targeted therapies and preventing the evolution of therapeutic resistance. Discovery platforms are also needed to form new treatment strategies and identify novel antimicrobial agents. By applying engineering principles to molecular biology, synthetic biologists have developed platforms that improve upon, supplement, and will perhaps supplant traditional broad-spectrum antibiotics. Efforts in engineering bacteriophages and synthetic probiotics demonstrate targeted antimicrobial approaches that can be fine-tuned using synthetic biology-derived principles. Further, the development of paper-based, cell-free expression systems holds promise in promoting the clinical translation of molecular biology tools for diagnostic purposes. In this review, we highlight emerging synthetic biology platform technologies that are geared toward the generation of new antimicrobial therapies, diagnostics, and discovery channels. Copyright © 2016 Elsevier B.V. All rights reserved.

Development of a miRNA-based diagnostic assay for pancreatic ductal adenocarcinoma.

PubMed

Szafranska-Schwarzbach, Anna E; Adai, Alex T; Lee, Linda S; Conwell, Darwin L; Andruss, Bernard F

2011-04-01

Diagnosis of pancreatic cancer remains a clinical challenge. Both chronic pancreatitis and pancreatic cancer may present with similar symptoms and similar imaging features, often leading to incorrect interpretation. Thus, the use of an objective molecular test that can discriminate between chronic pancreatitis and pancreatic cancer will be a valuable asset in obtaining a definitive diagnosis of pancreatic cancer. Following Clinical Laboratory Improvement Amendments and College of American Pathologists guidelines, Asuragen Clinical Services Laboratory has developed and validated a laboratory-developed test, miRInform(®) Pancreas, to aid in the identification of pancreatic ductal adenocarcinoma. This molecular diagnostic tool uses reverse-transcription quantitative PCR to measure the expression difference between two miRNAs, miR-196a and miR-217, in fixed tissue specimens. This article describes the test validation process as well as determination of performance parameters of miRInform Pancreas.

Nano-sized Contrast Agents to Non-Invasively Detect Renal Inflammation by Magnetic Resonance Imaging

PubMed Central

Thurman, Joshua M.; Serkova, Natalie J.

2013-01-01

Several molecular imaging methods have been developed that employ nano-sized contrast agents to detect markers of inflammation within tissues. Renal inflammation contributes to disease progression in a wide range of autoimmune and inflammatory diseases, and a biopsy is currently the only method of definitively diagnosing active renal inflammation. However, the development of new molecular imaging methods that employ contrast agents capable of detecting particular immune cells or protein biomarkers will allow clinicians to evaluate inflammation throughout the kidneys, and to assess a patient's response to immunomodulatory drugs. These imaging tools will improve our ability to validate new therapies and to optimize the treatment of individual patients with existing therapies. This review describes the clinical need for new methods of monitoring renal inflammation, and recent advances in the development of nano-sized contrast agents for detection of inflammatory markers of renal disease. PMID:24206601