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

PubMed

Chialvo, Ariel A

2018-05-07

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

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.

A composite molecular phylogeny of living lemuroid primates.

PubMed

DelPero, Massimiliano; Pozzi, Luca; Masters, Judith C

2006-01-01

Lemuroid phylogeny is a source of lively debate among primatologists. Reconstructions based on morphological, physiological, behavioural and molecular data have yielded a diverse array of tree topologies with few nodes in common. In the last decade, molecular phylogenetic studies have grown in popularity, and a wide range of sequences has been brought to bear on the problem, but consensus has remained elusive. We present an analysis based on a composite molecular data set of approx. 6,400 bp assembled from the National Center for Biotechnology Information (NCBI) database, including both mitochondrial and nuclear genes, and diverse analytical methods. Our analysis consolidates some of the nodes that were insecure in previous reconstructions, but is still equivocal on the placement of some taxa. We conducted a similar analysis of a composite data set of approx. 3,600 bp to investigate the controversial relationships within the family Lemuridae. Here our analysis was more successful; only the position of Eulemur coronatus remained uncertain. Copyright 2006 S. Karger AG, Basel.

A Hadoop-based Molecular Docking System

NASA Astrophysics Data System (ADS)

Dong, Yueli; Guo, Quan; Sun, Bin

2017-10-01

Molecular docking always faces the challenge of managing tens of TB datasets. It is necessary to improve the efficiency of the storage and docking. We proposed the molecular docking platform based on Hadoop for virtual screening, it provides the preprocessing of ligand datasets and the analysis function of the docking results. A molecular cloud database that supports mass data management is constructed. Through this platform, the docking time is reduced, the data storage is efficient, and the management of the ligand datasets is convenient.

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

OptoBase: A web platform for molecular optogenetics.

PubMed

Kolar, Katja; Knobloch, Christian; Stork, Hendrik; Žnidarič, Matej; Weber, Wilfried

2018-06-18

OptoBase is an online platform for molecular optogenetics. At its core is a hand-annotated and ontology-supported database that aims to cover all existing optogenetic switches and publications, which is further complemented with a collection of convenient optogenetics-related web tools. OptoBase is meant for both expert optogeneticists, to easily keep track of the field, as well as for all researchers who find optogenetics inviting as a powerful tool to address their biological questions of interest. It is available at https://www.optobase.org. This work also presents OptoBase-based analysis of the trends in molecular optogenetics.

Binding affinity toward human prion protein of some anti-prion compounds - Assessment based on QSAR modeling, molecular docking and non-parametric ranking.

PubMed

Kovačević, Strahinja; Karadžić, Milica; Podunavac-Kuzmanović, Sanja; Jevrić, Lidija

2018-01-01

The present study is based on the quantitative structure-activity relationship (QSAR) analysis of binding affinity toward human prion protein (huPrP C ) of quinacrine, pyridine dicarbonitrile, diphenylthiazole and diphenyloxazole analogs applying different linear and non-linear chemometric regression techniques, including univariate linear regression, multiple linear regression, partial least squares regression and artificial neural networks. The QSAR analysis distinguished molecular lipophilicity as an important factor that contributes to the binding affinity. Principal component analysis was used in order to reveal similarities or dissimilarities among the studied compounds. The analysis of in silico absorption, distribution, metabolism, excretion and toxicity (ADMET) parameters was conducted. The ranking of the studied analogs on the basis of their ADMET parameters was done applying the sum of ranking differences, as a relatively new chemometric method. The main aim of the study was to reveal the most important molecular features whose changes lead to the changes in the binding affinities of the studied compounds. Another point of view on the binding affinity of the most promising analogs was established by application of molecular docking analysis. The results of the molecular docking were proven to be in agreement with the experimental outcome. Copyright © 2017 Elsevier B.V. All rights reserved.

Study on the activity of non-purine xanthine oxidase inhibitor by 3D-QSAR modeling and molecular docking

NASA Astrophysics Data System (ADS)

Li, Peizhen; Tian, Yueli; Zhai, Honglin; Deng, Fangfang; Xie, Meihong; Zhang, Xiaoyun

2013-11-01

Non-purine derivatives have been shown to be promising novel drug candidates as xanthine oxidase inhibitors. Based on three-dimensional quantitative structure-activity relationship (3D-QSAR) methods including comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA), two 3D-QSAR models for a series of non-purine xanthine oxidase (XO) inhibitors were established, and their reliability was supported by statistical parameters. Combined 3D-QSAR modeling and the results of molecular docking between non-purine xanthine oxidase inhibitors and XO, the main factors that influenced activity of inhibitors were investigated, and the obtained results could explain known experimental facts. Furthermore, several new potential inhibitors with higher activity predicted were designed, which based on our analyses, and were supported by the simulation of molecular docking. This study provided some useful information for the development of non-purine xanthine oxidase inhibitors with novel structures.

Experimental design and quantitative analysis of microbial community multiomics.

PubMed

Mallick, Himel; Ma, Siyuan; Franzosa, Eric A; Vatanen, Tommi; Morgan, Xochitl C; Huttenhower, Curtis

2017-11-30

Studies of the microbiome have become increasingly sophisticated, and multiple sequence-based, molecular methods as well as culture-based methods exist for population-scale microbiome profiles. To link the resulting host and microbial data types to human health, several experimental design considerations, data analysis challenges, and statistical epidemiological approaches must be addressed. Here, we survey current best practices for experimental design in microbiome molecular epidemiology, including technologies for generating, analyzing, and integrating microbiome multiomics data. We highlight studies that have identified molecular bioactives that influence human health, and we suggest steps for scaling translational microbiome research to high-throughput target discovery across large populations.

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 design of new aggrecanases-2 inhibitors.

PubMed

Shan, Zhi Jie; Zhai, Hong Lin; Huang, Xiao Yan; Li, Li Na; Zhang, Xiao Yun

2013-10-01

Aggrecanases-2 is a very important potential drug target for the treatment of osteoarthritis. In this study, a series of known aggrecanases-2 inhibitors was analyzed by the technologies of three-dimensional quantitative structure-activity relationships (3D-QSAR) and molecular docking. Two 3D-QSAR models, which based on comparative molecular field analysis (CoMFA) and comparative molecular similarity analysis (CoMSIA) methods, were established. Molecular docking was employed to explore the details of the interaction between inhibitors and aggrecanases-2 protein. According to the analyses for these models, several new potential inhibitors with higher activity predicted were designed, and were supported by the simulation of molecular docking. This work propose the fast and effective approach to design and prediction for new potential inhibitors, and the study of the interaction mechanism provide a better understanding for the inhibitors binding into the target protein, which will be useful for the structure-based drug design and modifications. Copyright © 2013 Elsevier Ltd. All rights reserved.

Quantitative image analysis of cellular heterogeneity in breast tumors complements genomic profiling.

PubMed

Yuan, Yinyin; Failmezger, Henrik; Rueda, Oscar M; Ali, H Raza; Gräf, Stefan; Chin, Suet-Feung; Schwarz, Roland F; Curtis, Christina; Dunning, Mark J; Bardwell, Helen; Johnson, Nicola; Doyle, Sarah; Turashvili, Gulisa; Provenzano, Elena; Aparicio, Sam; Caldas, Carlos; Markowetz, Florian

2012-10-24

Solid tumors are heterogeneous tissues composed of a mixture of cancer and normal cells, which complicates the interpretation of their molecular profiles. Furthermore, tissue architecture is generally not reflected in molecular assays, rendering this rich information underused. To address these challenges, we developed a computational approach based on standard hematoxylin and eosin-stained tissue sections and demonstrated its power in a discovery and validation cohort of 323 and 241 breast tumors, respectively. To deconvolute cellular heterogeneity and detect subtle genomic aberrations, we introduced an algorithm based on tumor cellularity to increase the comparability of copy number profiles between samples. We next devised a predictor for survival in estrogen receptor-negative breast cancer that integrated both image-based and gene expression analyses and significantly outperformed classifiers that use single data types, such as microarray expression signatures. Image processing also allowed us to describe and validate an independent prognostic factor based on quantitative analysis of spatial patterns between stromal cells, which are not detectable by molecular assays. Our quantitative, image-based method could benefit any large-scale cancer study by refining and complementing molecular assays of tumor samples.

Evidence-Based Diagnostic Algorithm for Glioma: Analysis of the Results of Pathology Panel Review and Molecular Parameters of EORTC 26951 and 26882 Trials.

PubMed

Kros, Johan M; Huizer, Karin; Hernández-Laín, Aurelio; Marucci, Gianluca; Michotte, Alex; Pollo, Bianca; Rushing, Elisabeth J; Ribalta, Teresa; French, Pim; Jaminé, David; Bekka, Nawal; Lacombe, Denis; van den Bent, Martin J; Gorlia, Thierry

2015-06-10

With the rapid discovery of prognostic and predictive molecular parameters for glioma, the status of histopathology in the diagnostic process should be scrutinized. Our project aimed to construct a diagnostic algorithm for gliomas based on molecular and histologic parameters with independent prognostic values. The pathology slides of 636 patients with gliomas who had been included in EORTC 26951 and 26882 trials were reviewed using virtual microscopy by a panel of six neuropathologists who independently scored 18 histologic features and provided an overall diagnosis. The molecular data for IDH1, 1p/19q loss, EGFR amplification, loss of chromosome 10 and chromosome arm 10q, gain of chromosome 7, and hypermethylation of the promoter of MGMT were available for some of the cases. The slides were divided in discovery (n = 426) and validation sets (n = 210). The diagnostic algorithm resulting from analysis of the discovery set was validated in the latter. In 66% of cases, consensus of overall diagnosis was present. A diagnostic algorithm consisting of two molecular markers and one consensus histologic feature was created by conditional inference tree analysis. The order of prognostic significance was: 1p/19q loss, EGFR amplification, and astrocytic morphology, which resulted in the identification of four diagnostic nodes. Validation of the nodes in the validation set confirmed the prognostic value (P < .001). We succeeded in the creation of a timely diagnostic algorithm for anaplastic glioma based on multivariable analysis of consensus histopathology and molecular parameters. © 2015 by American Society of Clinical Oncology.

Evaluation of bending modulus of lipid bilayers using undulation and orientation analysis

NASA Astrophysics Data System (ADS)

Chaurasia, Adarsh K.; Rukangu, Andrew M.; Philen, Michael K.; Seidel, Gary D.; Freeman, Eric C.

2018-03-01

In the current paper, phospholipid bilayers are modeled using coarse-grained molecular dynamics simulations with the MARTINI force field. The extracted molecular trajectories are analyzed using Fourier analysis of the undulations and orientation vectors to establish the differences between the two approaches for evaluating the bending modulus. The current work evaluates and extends the implementation of the Fourier analysis for molecular trajectories using a weighted horizon-based averaging approach. The effect of numerical parameters in the analysis of these trajectories is explored by conducting parametric studies. Computational modeling results are validated against experimentally characterized bending modulus of lipid membranes using a shape fluctuation analysis. The computational framework is then used to estimate the bending moduli for different types of lipids (phosphocholine, phosphoethanolamine, and phosphoglycerol). This work provides greater insight into the numerical aspects of evaluating the bilayer bending modulus, provides validation for the orientation analysis technique, and explores differences in bending moduli based on differences in the lipid nanostructures.

Discovering transnosological molecular basis of human brain diseases using biclustering analysis of integrated gene expression data.

PubMed

Cha, Kihoon; Hwang, Taeho; Oh, Kimin; Yi, Gwan-Su

2015-01-01

It has been reported that several brain diseases can be treated as transnosological manner implicating possible common molecular basis under those diseases. However, molecular level commonality among those brain diseases has been largely unexplored. Gene expression analyses of human brain have been used to find genes associated with brain diseases but most of those studies were restricted either to an individual disease or to a couple of diseases. In addition, identifying significant genes in such brain diseases mostly failed when it used typical methods depending on differentially expressed genes. In this study, we used a correlation-based biclustering approach to find coexpressed gene sets in five neurodegenerative diseases and three psychiatric disorders. By using biclustering analysis, we could efficiently and fairly identified various gene sets expressed specifically in both single and multiple brain diseases. We could find 4,307 gene sets correlatively expressed in multiple brain diseases and 3,409 gene sets exclusively specified in individual brain diseases. The function enrichment analysis of those gene sets showed many new possible functional bases as well as neurological processes that are common or specific for those eight diseases. This study introduces possible common molecular bases for several brain diseases, which open the opportunity to clarify the transnosological perspective assumed in brain diseases. It also showed the advantages of correlation-based biclustering analysis and accompanying function enrichment analysis for gene expression data in this type of investigation.

Discovering transnosological molecular basis of human brain diseases using biclustering analysis of integrated gene expression data

PubMed Central

2015-01-01

Background It has been reported that several brain diseases can be treated as transnosological manner implicating possible common molecular basis under those diseases. However, molecular level commonality among those brain diseases has been largely unexplored. Gene expression analyses of human brain have been used to find genes associated with brain diseases but most of those studies were restricted either to an individual disease or to a couple of diseases. In addition, identifying significant genes in such brain diseases mostly failed when it used typical methods depending on differentially expressed genes. Results In this study, we used a correlation-based biclustering approach to find coexpressed gene sets in five neurodegenerative diseases and three psychiatric disorders. By using biclustering analysis, we could efficiently and fairly identified various gene sets expressed specifically in both single and multiple brain diseases. We could find 4,307 gene sets correlatively expressed in multiple brain diseases and 3,409 gene sets exclusively specified in individual brain diseases. The function enrichment analysis of those gene sets showed many new possible functional bases as well as neurological processes that are common or specific for those eight diseases. Conclusions This study introduces possible common molecular bases for several brain diseases, which open the opportunity to clarify the transnosological perspective assumed in brain diseases. It also showed the advantages of correlation-based biclustering analysis and accompanying function enrichment analysis for gene expression data in this type of investigation. PMID:26043779

Enrichment of low molecular weight serum proteins using acetonitrile precipitation for mass spectrometry based proteomic analysis.

PubMed

Kay, Richard; Barton, Chris; Ratcliffe, Lucy; Matharoo-Ball, Balwir; Brown, Pamela; Roberts, Jane; Teale, Phil; Creaser, Colin

2008-10-01

A rapid acetonitrile (ACN)-based extraction method has been developed that reproducibly depletes high abundance and high molecular weight proteins from serum prior to mass spectrometric analysis. A nanoflow liquid chromatography/tandem mass spectrometry (nano-LC/MS/MS) multiple reaction monitoring (MRM) method for 57 high to medium abundance serum proteins was used to characterise the ACN-depleted fraction after tryptic digestion. Of the 57 targeted proteins 29 were detected and albumin, the most abundant protein in serum and plasma, was identified as the 20th most abundant protein in the extract. The combination of ACN depletion and one-dimensional nano-LC/MS/MS enabled the detection of the low abundance serum protein, insulin-like growth factor-I (IGF-I), which has a serum concentration in the region of 100 ng/mL. One-dimensional sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS-PAGE) analysis of the depleted serum showed no bands corresponding to proteins of molecular mass over 75 kDa after extraction, demonstrating the efficiency of the method for the depletion of high molecular weight proteins. Total protein analysis of the ACN extracts showed that approximately 99.6% of all protein is removed from the serum. The ACN-depletion strategy offers a viable alternative to the immunochemistry-based protein-depletion techniques commonly used for removing high abundance proteins from serum prior to MS-based proteomic analyses.

3D-quantitative structure-activity relationship studies on benzothiadiazepine hydroxamates as inhibitors of tumor necrosis factor-alpha converting enzyme.

PubMed

Murumkar, Prashant R; Giridhar, Rajani; Yadav, Mange Ram

2008-04-01

A set of 29 benzothiadiazepine hydroxamates having selective tumor necrosis factor-alpha converting enzyme inhibitory activity were used to compare the quality and predictive power of 3D-quantitative structure-activity relationship, comparative molecular field analysis, and comparative molecular similarity indices models for the atom-based, centroid/atom-based, data-based, and docked conformer-based alignment. Removal of two outliers from the initial training set of molecules improved the predictivity of models. Among the 3D-quantitative structure-activity relationship models developed using the above four alignments, the database alignment provided the optimal predictive comparative molecular field analysis model for the training set with cross-validated r(2) (q(2)) = 0.510, non-cross-validated r(2) = 0.972, standard error of estimates (s) = 0.098, and F = 215.44 and the optimal comparative molecular similarity indices model with cross-validated r(2) (q(2)) = 0.556, non-cross-validated r(2) = 0.946, standard error of estimates (s) = 0.163, and F = 99.785. These models also showed the best test set prediction for six compounds with predictive r(2) values of 0.460 and 0.535, respectively. The contour maps obtained from 3D-quantitative structure-activity relationship studies were appraised for activity trends for the molecules analyzed. The comparative molecular similarity indices models exhibited good external predictivity as compared with that of comparative molecular field analysis models. The data generated from the present study helped us to further design and report some novel and potent tumor necrosis factor-alpha converting enzyme inhibitors.

Atomic and molecular data for space astronomy - Needs, analysis, and availability; 21st IAU General Assembly, Buenos Aires, Argentina, July 23-Aug. 1, 1991, Selected Papers

NASA Technical Reports Server (NTRS)

Smith, Peter L. (Editor); Wiese, Wolfgang L. (Editor)

1992-01-01

The present volume on atomic and molecular spectroscopic data for space astrophysics discusses scientific problems and laboratory data needs associated with the Hubble Space Telescope, atomic data needed for far ultraviolet astronomy with HUT and FUSE and for analysis of EUV and X-ray spectra, and data for observations of interstellar medium with the Hubble Space Telescope. Attention is also given to atomic and molecular data for analysis of IR spectra from ISO and SIRTF, atomic data from the opacity project, sources of atomic spectroscopic data for astrophysics, and summary of current molecular data bases.

The role of molecular genetic analysis in the diagnosis of primary ciliary dyskinesia.

PubMed

Kim, Raymond H; A Hall, David; Cutz, Ernest; Knowles, Michael R; Nelligan, Kathleen A; Nykamp, Keith; Zariwala, Maimoona A; Dell, Sharon D

2014-03-01

Primary ciliary dyskinesia (PCD) is an autosomal recessive genetic disorder of motile cilia. The diagnosis of PCD has previously relied on ciliary analysis with transmission electron microscopy or video microscopy. However, patients with PCD may have normal ultrastructural appearance, and ciliary analysis has limited accessibility. Alternatively, PCD can be diagnosed by demonstrating biallelic mutations in known PCD genes. Genetic testing is emerging as a diagnostic tool to complement ciliary analysis where interpretation and access may delay diagnosis. To determine the diagnostic yield of genetic testing of patients with a confirmed or suspected diagnosis of PCD in a multiethnic urban center. Twenty-eight individuals with confirmed PCD on transmission electron microscopy of ciliary ultrastructure and 24 individuals with a probable diagnosis of PCD based on a classical PCD phenotype and low nasal nitric oxide had molecular analysis of 12 genes associated with PCD. Of 49 subjects who underwent ciliary biopsy, 28 (57%) were diagnosed with PCD through an ultrastructural defect. Of the 52 individuals who underwent molecular genetic analysis, 22 (42%) individuals had two mutations in known PCD genes. Twenty-four previously unreported mutations in known PCD genes were observed. Combining both diagnostic modalities of biopsy and molecular genetics, the diagnostic yield increased to 69% compared with 57% based on biopsy alone. The diagnosis of PCD is challenging and has traditionally relied on ciliary biopsy, which is unreliable as the sole criterion for a definitive diagnosis. Molecular genetic analysis can be used as a complementary test to increase the diagnostic yield.

Integrative pathway knowledge bases as a tool for systems molecular medicine.

PubMed

Liang, Mingyu

2007-08-20

There exists a sense of urgency to begin to generate a cohesive assembly of biomedical knowledge as the pace of knowledge accumulation accelerates. The urgency is in part driven by the emergence of systems molecular medicine that emphasizes the combination of systems analysis and molecular dissection in the future of medical practice and research. A potentially powerful approach is to build integrative pathway knowledge bases that link organ systems function with molecules.

Vibrational, spectroscopic, molecular docking and density functional theory studies on N-(5-aminopyridin-2-yl)acetamide

NASA Astrophysics Data System (ADS)

Asath, R. Mohamed; Rekha, T. N.; Premkumar, S.; Mathavan, T.; Benial, A. Milton Franklin

2016-12-01

Conformational analysis was carried out for N-(5-aminopyridin-2-yl)acetamide (APA) molecule. The most stable, optimized structure was predicted by the density functional theory calculations using the B3LYP functional with cc-pVQZ basis set. The optimized structural parameters and vibrational frequencies were calculated. The experimental and theoretical vibrational frequencies were assigned and compared. Ultraviolet-visible spectrum was simulated and validated experimentally. The molecular electrostatic potential surface was simulated. Frontier molecular orbitals and related molecular properties were computed, which reveals that the higher molecular reactivity and stability of the APA molecule and further density of states spectrum was simulated. The natural bond orbital analysis was also performed to confirm the bioactivity of the APA molecule. Antidiabetic activity was studied based on the molecular docking analysis and the APA molecule was identified that it can act as a good inhibitor against diabetic nephropathy.

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

NASA Astrophysics Data System (ADS)

Abe, Takahiro; Matsubara, Ryosuke; Hayakawa, Munetaka; Shimoyama, Akifumi; Tanaka, Takaaki; Tsuji, Akira; Takahashi, Yoshikazu; Kubono, Atsushi

2018-03-01

To investigate the effects of incident molecular temperature on organic-thin-film growth by vacuum evaporation, quantitative analysis of molecular temperature is required. In this study, we propose a method of determining molecular temperature based on the heat exchange between a platinum filament and molecular vapor. Molecular temperature is estimated from filament temperature, which remains unchanged even under molecular vapor supply. The results indicate that our method has sufficient sensitivity to evaluate the molecular temperature under the typical growth rate used for fabrication of functional organic thin films.

Identifying molecular features for prostate cancer with Gleason 7 based on microarray gene expression profiles.

PubMed

Bălăcescu, Loredana; Bălăcescu, O; Crişan, N; Fetica, B; Petruţ, B; Bungărdean, Cătălina; Rus, Meda; Tudoran, Oana; Meurice, G; Irimie, Al; Dragoş, N; Berindan-Neagoe, Ioana

2011-01-01

Prostate cancer represents the first leading cause of cancer among western male population, with different clinical behavior ranging from indolent to metastatic disease. Although many molecules and deregulated pathways are known, the molecular mechanisms involved in the development of prostate cancer are not fully understood. The aim of this study was to explore the molecular variation underlying the prostate cancer, based on microarray analysis and bioinformatics approaches. Normal and prostate cancer tissues were collected by macrodissection from prostatectomy pieces. All prostate cancer specimens used in our study were Gleason score 7. Gene expression microarray (Agilent Technologies) was used for Whole Human Genome evaluation. The bioinformatics and functional analysis were based on Limma and Ingenuity software. The microarray analysis identified 1119 differentially expressed genes between prostate cancer and normal prostate, which were up- or down-regulated at least 2-fold. P-values were adjusted for multiple testing using Benjamini-Hochberg method with a false discovery rate of 0.01. These genes were analyzed with Ingenuity Pathway Analysis software and were established 23 genetic networks. Our microarray results provide new information regarding the molecular networks in prostate cancer stratified as Gleason 7. These data highlighted gene expression profiles for better understanding of prostate cancer progression.

First morphological and molecular analysis of Eucoleus boehmi like eggs in dogs from Argentina.

PubMed

Lavallén, Carla Mariela; Petrigh, Romina Sandra; Fugassa, Martín Horacio; Denegri, Guillermo María; Dopchiz, Marcela Cecilia

2018-07-01

The canid parasites Eucoleus aerophilus (syn. Capillaria aerophila) and Eucoleus boehmi (syn. Capillaria boehmi) parasitize the lower and the upper respiratory tract, respectively. Reports and descriptions of these nematodes are scarce in Argentina, possibly due to misdiagnosis of morphologically similar trichuroids eggs, and the lack of knowledge about the species of Eucoleus in this geographical area. Scanning electron microscopy is a useful tool for identification of E. boehmi eggs based on the characteristics of the shell structure which differentiate between species. Molecular analysis complements morphological identification. Until now, there are no studies based on the analysis of E. boehmi eggs in Argentina. The aim of the present work was to study by morphological, morphometric, and molecular analysis, eggs attributable to E. boehmi isolated from dogs naturally infected in Mar del Plata city, Argentina. Eggs isolated from two dog fecal samples were analyzed by light and scanning electron microscopy. A fragment of mitochondrial DNA (mtDNA) of the cytochrome c oxidase subunit I gene (cox1) from eggs was sequenced, and phylogenetic analysis was performed in this study. According to morphological results based on the wall surface ultrastructure, the eggs studied were assigned to E. boehmi. Molecular analysis supported the morphological identification. The divergence of 9-12% with the European isolated could suggest a new geographical genetic variation of E. boehmi, but also question the possible existence of cryptic species. This is the first characterization of E. boehmi eggs in dogs from Argentina.

Molecular phylogeny, pathogenicity and toxigenicity of Fusarium oxysporum f. sp. lycopersici

PubMed Central

Nirmaladevi, D.; Venkataramana, M.; Srivastava, Rakesh K.; Uppalapati, S. R.; Gupta, Vijai Kumar; Yli-Mattila, T.; Clement Tsui, K. M.; Srinivas, C.; Niranjana, S. R.; Chandra, Nayaka S.

2016-01-01

The present study aimed at the molecular characterization of pathogenic and non pathogenic F. oxysporum f. sp. lycopersici strains isolated from tomato. The causal agent isolated from symptomatic plants and soil samples was identified based on morphological and molecular analyses. Pathogenicity testing of 69 strains on five susceptible tomato varieties showed 45% of the strains were highly virulent and 30% were moderately virulent. Molecular analysis based on the fingerprints obtained through ISSR indicated the presence of wide genetic diversity among the strains. Phylogenetic analysis based on ITS sequences showed the presence of at least four evolutionary lineages of the pathogen. The clustering of F. oxysporum with non pathogenic isolates and with the members of other formae speciales indicated polyphyletic origin of F. oxysporum f. sp. lycopersici. Further analysis revealed intraspecies variability and nucleotide insertions or deletions in the ITS region among the strains in the study and the observed variations were found to be clade specific. The high genetic diversity in the pathogen population demands for development of effective resistance breeding programs in tomato. Among the pathogenic strains tested, toxigenic strains harbored the Fum1 gene clearly indicating that the strains infecting tomato crops have the potential to produce Fumonisin. PMID:26883288

Analysis of Physical and Numerical Factors for Prediction of UV Radiation from High Altitude Two-Phase Plumes

DTIC Science & Technology

2008-05-30

varies from continuum inside the nozzle, to transitional in the near field, to free molecular in the far field of the plume. The scales of interest vary...unity based on the rocket length. This results in the formation of a viscous shock layer characterized by a bimodal molecular velocity distribution. The...transfer model. Previous analysis21 have shown that the heat transfer model implemented in CFD++ is reproduced closely by the free molecular model

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 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.

Molecular Isotopic Distribution Analysis (MIDAs) with Adjustable Mass Accuracy

NASA Astrophysics Data System (ADS)

Alves, Gelio; Ogurtsov, Aleksey Y.; Yu, Yi-Kuo

2014-01-01

In this paper, we present Molecular Isotopic Distribution Analysis (MIDAs), a new software tool designed to compute molecular isotopic distributions with adjustable accuracies. MIDAs offers two algorithms, one polynomial-based and one Fourier-transform-based, both of which compute molecular isotopic distributions accurately and efficiently. The polynomial-based algorithm contains few novel aspects, whereas the Fourier-transform-based algorithm consists mainly of improvements to other existing Fourier-transform-based algorithms. We have benchmarked the performance of the two algorithms implemented in MIDAs with that of eight software packages (BRAIN, Emass, Mercury, Mercury5, NeutronCluster, Qmass, JFC, IC) using a consensus set of benchmark molecules. Under the proposed evaluation criteria, MIDAs's algorithms, JFC, and Emass compute with comparable accuracy the coarse-grained (low-resolution) isotopic distributions and are more accurate than the other software packages. For fine-grained isotopic distributions, we compared IC, MIDAs's polynomial algorithm, and MIDAs's Fourier transform algorithm. Among the three, IC and MIDAs's polynomial algorithm compute isotopic distributions that better resemble their corresponding exact fine-grained (high-resolution) isotopic distributions. MIDAs can be accessed freely through a user-friendly web-interface at http://www.ncbi.nlm.nih.gov/CBBresearch/Yu/midas/index.html.

Molecular Isotopic Distribution Analysis (MIDAs) with adjustable mass accuracy.

PubMed

Alves, Gelio; Ogurtsov, Aleksey Y; Yu, Yi-Kuo

2014-01-01

In this paper, we present Molecular Isotopic Distribution Analysis (MIDAs), a new software tool designed to compute molecular isotopic distributions with adjustable accuracies. MIDAs offers two algorithms, one polynomial-based and one Fourier-transform-based, both of which compute molecular isotopic distributions accurately and efficiently. The polynomial-based algorithm contains few novel aspects, whereas the Fourier-transform-based algorithm consists mainly of improvements to other existing Fourier-transform-based algorithms. We have benchmarked the performance of the two algorithms implemented in MIDAs with that of eight software packages (BRAIN, Emass, Mercury, Mercury5, NeutronCluster, Qmass, JFC, IC) using a consensus set of benchmark molecules. Under the proposed evaluation criteria, MIDAs's algorithms, JFC, and Emass compute with comparable accuracy the coarse-grained (low-resolution) isotopic distributions and are more accurate than the other software packages. For fine-grained isotopic distributions, we compared IC, MIDAs's polynomial algorithm, and MIDAs's Fourier transform algorithm. Among the three, IC and MIDAs's polynomial algorithm compute isotopic distributions that better resemble their corresponding exact fine-grained (high-resolution) isotopic distributions. MIDAs can be accessed freely through a user-friendly web-interface at http://www.ncbi.nlm.nih.gov/CBBresearch/Yu/midas/index.html.

MOLECULAR MARKER ANALYSIS OF DEARS SAMPLES

EPA Science Inventory

Source apportionment based on organic molecular markers provides a promising approach for meeting the Detroit Exposure and Aerosol Research Study (DEARS) objective of comparing source contributions between community air monitoring stations and various neighborhoods. Source appor...

(ISEA) MOLECULAR MARKER ANALYSIS OF DEARS SAMPLES

EPA Science Inventory

Source apportionment based on organic molecular markers provides a promising approach for meeting the Detroit Exposure and Aerosol Research Study (DEARS) objective of comparing source contributions between community air monitoring stations and various neighborhoods. Source appor...

Boolean logic tree of graphene-based chemical system for molecular computation and intelligent molecular search query.

PubMed

Huang, Wei Tao; Luo, Hong Qun; Li, Nian Bing

2014-05-06

The most serious, and yet unsolved, problem of constructing molecular computing devices consists in connecting all of these molecular events into a usable device. This report demonstrates the use of Boolean logic tree for analyzing the chemical event network based on graphene, organic dye, thrombin aptamer, and Fenton reaction, organizing and connecting these basic chemical events. And this chemical event network can be utilized to implement fluorescent combinatorial logic (including basic logic gates and complex integrated logic circuits) and fuzzy logic computing. On the basis of the Boolean logic tree analysis and logic computing, these basic chemical events can be considered as programmable "words" and chemical interactions as "syntax" logic rules to construct molecular search engine for performing intelligent molecular search query. Our approach is helpful in developing the advanced logic program based on molecules for application in biosensing, nanotechnology, and drug delivery.

Formalizing the definition of meta-analysis in Molecular Ecology.

PubMed

ArchMiller, Althea A; Bauer, Eric F; Koch, Rebecca E; Wijayawardena, Bhagya K; Anil, Ammu; Kottwitz, Jack J; Munsterman, Amelia S; Wilson, Alan E

2015-08-01

Meta-analysis, the statistical synthesis of pertinent literature to develop evidence-based conclusions, is relatively new to the field of molecular ecology, with the first meta-analysis published in the journal Molecular Ecology in 2003 (Slate & Phua 2003). The goal of this article is to formalize the definition of meta-analysis for the authors, editors, reviewers and readers of Molecular Ecology by completing a review of the meta-analyses previously published in this journal. We also provide a brief overview of the many components required for meta-analysis with a more specific discussion of the issues related to the field of molecular ecology, including the use and statistical considerations of Wright's FST and its related analogues as effect sizes in meta-analysis. We performed a literature review to identify articles published as 'meta-analyses' in Molecular Ecology, which were then evaluated by at least two reviewers. We specifically targeted Molecular Ecology publications because as a flagship journal in this field, meta-analyses published in Molecular Ecology have the potential to set the standard for meta-analyses in other journals. We found that while many of these reviewed articles were strong meta-analyses, others failed to follow standard meta-analytical techniques. One of these unsatisfactory meta-analyses was in fact a secondary analysis. Other studies attempted meta-analyses but lacked the fundamental statistics that are considered necessary for an effective and powerful meta-analysis. By drawing attention to the inconsistency of studies labelled as meta-analyses, we emphasize the importance of understanding the components of traditional meta-analyses to fully embrace the strengths of quantitative data synthesis in the field of molecular ecology. © 2015 John Wiley & Sons Ltd.

Molecular genetic analysis of activation-tagged transcription factors thought to be involved in photomorphogenesis

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

Neff, Michael M.

This is a final report for Department of Energy Grant No. DE-FG02-08ER15927 entitled “Molecular Genetic Analysis of Activation-Tagged Transcription Factors Thought to be Involved in Photomorphogenesis”. Based on our preliminary photobiological and genetic analysis of the sob1-D mutant, we hypothesized that OBP3 is a transcription factor involved in both phytochrome and cryptochrome-mediated signal transduction. In addition, we hypothesized that OBP3 is involved in auxin signaling and root development. Based on our preliminary photobiological and genetic analysis of the sob2-D mutant, we also hypothesized that a related gene, LEP, is involved in hormone signaling and seedling development.

Massively Parallel, Molecular Analysis Platform Developed Using a CMOS Integrated Circuit With Biological Nanopores

PubMed Central

Roever, Stefan

2012-01-01

A massively parallel, low cost molecular analysis platform will dramatically change the nature of protein, molecular and genomics research, DNA sequencing, and ultimately, molecular diagnostics. An integrated circuit (IC) with 264 sensors was fabricated using standard CMOS semiconductor processing technology. Each of these sensors is individually controlled with precision analog circuitry and is capable of single molecule measurements. Under electronic and software control, the IC was used to demonstrate the feasibility of creating and detecting lipid bilayers and biological nanopores using wild type α-hemolysin. The ability to dynamically create bilayers over each of the sensors will greatly accelerate pore development and pore mutation analysis. In addition, the noise performance of the IC was measured to be 30fA(rms). With this noise performance, single base detection of DNA was demonstrated using α-hemolysin. The data shows that a single molecule, electrical detection platform using biological nanopores can be operationalized and can ultimately scale to millions of sensors. Such a massively parallel platform will revolutionize molecular analysis and will completely change the field of molecular diagnostics in the future.

Grid-based Continual Analysis of Molecular Interior for Drug Discovery, QSAR and QSPR.

PubMed

Potemkin, Andrey V; Grishina, Maria A; Potemkin, Vladimir A

2017-01-01

In 1979, R.D.Cramer and M.Milne made a first realization of 3D comparison of molecules by aligning them in space and by mapping their molecular fields to a 3D grid. Further, this approach was developed as the DYLOMMS (Dynamic Lattice- Oriented Molecular Modelling System) approach. In 1984, H.Wold and S.Wold proposed the use of partial least squares (PLS) analysis, instead of principal component analysis, to correlate the field values with biological activities. Then, in 1988, the method which was called CoMFA (Comparative Molecular Field Analysis) was introduced and the appropriate software became commercially available. Since 1988, a lot of 3D QSAR methods, algorithms and their modifications are introduced for solving of virtual drug discovery problems (e.g., CoMSIA, CoMMA, HINT, HASL, GOLPE, GRID, PARM, Raptor, BiS, CiS, ConGO,). All the methods can be divided into two groups (classes):1. Methods studying the exterior of molecules; 2) Methods studying the interior of molecules. A series of grid-based computational technologies for Continual Molecular Interior analysis (CoMIn) are invented in the current paper. The grid-based analysis is fulfilled by means of a lattice construction analogously to many other grid-based methods. The further continual elucidation of molecular structure is performed in various ways. (i) In terms of intermolecular interactions potentials. This can be represented as a superposition of Coulomb, Van der Waals interactions and hydrogen bonds. All the potentials are well known continual functions and their values can be determined in all lattice points for a molecule. (ii) In the terms of quantum functions such as electron density distribution, Laplacian and Hamiltonian of electron density distribution, potential energy distribution, the highest occupied and the lowest unoccupied molecular orbitals distribution and their superposition. To reduce time of calculations using quantum methods based on the first principles, an original quantum free-orbital approach AlteQ is proposed. All the functions can be calculated using a quantum approach at a sufficient level of theory and their values can be determined in all lattice points for a molecule. Then, the molecules of a dataset can be superimposed in the lattice for the maximal coincidence (or minimal deviations) of the potentials (i) or the quantum functions (ii). The methods and criteria of the superimposition are discussed. After that a functional relationship between biological activity or property and characteristics of potentials (i) or functions (ii) is created. The methods of the quantitative relationship construction are discussed. New approaches for rational virtual drug design based on the intermolecular potentials and quantum functions are invented. All the invented methods are realized at www.chemosophia.com web page. Therefore, a set of 3D QSAR approaches for continual molecular interior study giving a lot of opportunities for virtual drug discovery, virtual screening and ligand-based drug design are invented. The continual elucidation of molecular structure is performed in the terms of intermolecular interactions potentials and in the terms of quantum functions such as electron density distribution, Laplacian and Hamiltonian of electron density distribution, potential energy distribution, the highest occupied and the lowest unoccupied molecular orbitals distribution and their superposition. To reduce time of calculations using quantum methods based on the first principles, an original quantum free-orbital approach AlteQ is proposed. The methods of the quantitative relationship construction are discussed. New approaches for rational virtual drug design based on the intermolecular potentials and quantum functions are invented. All the invented methods are realized at www.chemosophia.com web page. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Molecular activity prediction by means of supervised subspace projection based ensembles of classifiers.

PubMed

Cerruela García, G; García-Pedrajas, N; Luque Ruiz, I; Gómez-Nieto, M Á

2018-03-01

This paper proposes a method for molecular activity prediction in QSAR studies using ensembles of classifiers constructed by means of two supervised subspace projection methods, namely nonparametric discriminant analysis (NDA) and hybrid discriminant analysis (HDA). We studied the performance of the proposed ensembles compared to classical ensemble methods using four molecular datasets and eight different models for the representation of the molecular structure. Using several measures and statistical tests for classifier comparison, we observe that our proposal improves the classification results with respect to classical ensemble methods. Therefore, we show that ensembles constructed using supervised subspace projections offer an effective way of creating classifiers in cheminformatics.

"Mini-Array" Transcriptional Analysis of the "Listeria Monocytogenes" Lecithinase Operon as a Class Project: A Student Investigative Molecular Biology Laboratory Experience

ERIC Educational Resources Information Center

Christensen, Douglas; Jovic, Marko

2006-01-01

This report describes a molecular biotechnology-based laboratory curriculum developed to accompany an undergraduate genetics course. During the course of a semester, students researched the pathogen, developed a research question, designed experiments, and performed transcriptional analysis of a set of genes that confer virulence to the food-borne…

`Inter-Arrival Time' Inspired Algorithm and its Application in Clustering and Molecular Phylogeny

NASA Astrophysics Data System (ADS)

Kolekar, Pandurang S.; Kale, Mohan M.; Kulkarni-Kale, Urmila

2010-10-01

Bioinformatics, being multidisciplinary field, involves applications of various methods from allied areas of Science for data mining using computational approaches. Clustering and molecular phylogeny is one of the key areas in Bioinformatics, which help in study of classification and evolution of organisms. Molecular phylogeny algorithms can be divided into distance based and character based methods. But most of these methods are dependent on pre-alignment of sequences and become computationally intensive with increase in size of data and hence demand alternative efficient approaches. `Inter arrival time distribution' (IATD) is a popular concept in the theory of stochastic system modeling but its potential in molecular data analysis has not been fully explored. The present study reports application of IATD in Bioinformatics for clustering and molecular phylogeny. The proposed method provides IATDs of nucleotides in genomic sequences. The distance function based on statistical parameters of IATDs is proposed and distance matrix thus obtained is used for the purpose of clustering and molecular phylogeny. The method is applied on a dataset of 3' non-coding region sequences (NCR) of Dengue virus type 3 (DENV-3), subtype III, reported in 2008. The phylogram thus obtained revealed the geographical distribution of DENV-3 isolates. Sri Lankan DENV-3 isolates were further observed to be clustered in two sub-clades corresponding to pre and post Dengue hemorrhagic fever emergence groups. These results are consistent with those reported earlier, which are obtained using pre-aligned sequence data as an input. These findings encourage applications of the IATD based method in molecular phylogenetic analysis in particular and data mining in general.

A survey of the 2001 to 2005 quartz crystal microbalance biosensor literature: applications of acoustic physics to the analysis of biomolecular interactions.

PubMed

Cooper, Matthew A; Singleton, Victoria T

2007-01-01

The widespread exploitation of biosensors in the analysis of molecular recognition has its origins in the mid-1990s following the release of commercial systems based on surface plasmon resonance (SPR). More recently, platforms based on piezoelectric acoustic sensors (principally 'bulk acoustic wave' (BAW), 'thickness shear mode' (TSM) sensors or 'quartz crystal microbalances' (QCM)), have been released that are driving the publication of a large number of papers analysing binding specificities, affinities, kinetics and conformational changes associated with a molecular recognition event. This article highlights salient theoretical and practical aspects of the technologies that underpin acoustic analysis, then reviews exemplary papers in key application areas involving small molecular weight ligands, carbohydrates, proteins, nucleic acids, viruses, bacteria, cells and lipidic and polymeric interfaces. Key differentiators between optical and acoustic sensing modalities are also reviewed. Copyright (c) 2007 John Wiley & Sons, Ltd.

The spa typing of methicillin-resistant Staphylococcus aureus isolates by High Resolution Melting (HRM) analysis.

PubMed

Fasihi, Yasser; Fooladi, Saba; Mohammadi, Mohammad Ali; Emaneini, Mohammad; Kalantar-Neyestanaki, Davood

2017-09-06

Molecular typing is an important tool for control and prevention of infection. A suitable molecular typing method for epidemiological investigation must be easy to perform, highly reproducible, inexpensive, rapid and easy to interpret. In this study, two molecular typing methods including the conventional PCR-sequencing method and high resolution melting (HRM) analysis were used for staphylococcal protein A (spa) typing of 30 Methicillin-resistant Staphylococcus aureus (MRSA) isolates recovered from clinical samples. Based on PCR-sequencing method results, 16 different spa types were identified among the 30 MRSA isolates. Among the 16 different spa types, 14 spa types separated by HRM method. Two spa types including t4718 and t2894 were not separated from each other. According to our results, spa typing based on HRM analysis method is very rapid, easy to perform and cost-effective, but this method must be standardized for different regions, spa types, and real-time machinery.

Dielectrophoresis-Based Sample Handling in General-Purpose Programmable Diagnostic Instruments

PubMed Central

Gascoyne, Peter R. C.; Vykoukal, Jody V.

2009-01-01

As the molecular origins of disease are better understood, the need for affordable, rapid, and automated technologies that enable microscale molecular diagnostics has become apparent. Widespread use of microsystems that perform sample preparation and molecular analysis could ensure that the benefits of new biomedical discoveries are realized by a maximum number of people, even those in environments lacking any infrastructure. While progress has been made in developing miniaturized diagnostic systems, samples are generally processed off-device using labor-intensive and time-consuming traditional sample preparation methods. We present the concept of an integrated programmable general-purpose sample analysis processor (GSAP) architecture where raw samples are routed to separation and analysis functional blocks contained within a single device. Several dielectrophoresis-based methods that could serve as the foundation for building GSAP functional blocks are reviewed including methods for cell and particle sorting, cell focusing, cell ac impedance analysis, cell lysis, and the manipulation of molecules and reagent droplets. PMID:19684877

GraphSAW: a web-based system for graphical analysis of drug interactions and side effects using pharmaceutical and molecular data.

PubMed

Shoshi, Alban; Hoppe, Tobias; Kormeier, Benjamin; Ogultarhan, Venus; Hofestädt, Ralf

2015-02-28

Adverse drug reactions are one of the most common causes of death in industrialized Western countries. Nowadays, empirical data from clinical studies for the approval and monitoring of drugs and molecular databases is available. The integration of database information is a promising method for providing well-based knowledge to avoid adverse drug reactions. This paper presents our web-based decision support system GraphSAW which analyzes and evaluates drug interactions and side effects based on data from two commercial and two freely available molecular databases. The system is able to analyze single and combined drug-drug interactions, drug-molecule interactions as well as single and cumulative side effects. In addition, it allows exploring associative networks of drugs, molecules, metabolic pathways, and diseases in an intuitive way. The molecular medication analysis includes the capabilities of the upper features. A statistical evaluation of the integrated data and top 20 drugs concerning drug interactions and side effects is performed. The results of the data analysis give an overview of all theoretically possible drug interactions and side effects. The evaluation shows a mismatch between pharmaceutical and molecular databases. The concordance of drug interactions was about 12% and 9% of drug side effects. An application case with prescribed data of 11 patients is presented in order to demonstrate the functionality of the system under real conditions. For each patient at least two interactions occured in every medication and about 8% of total diseases were possibly induced by drug therapy. GraphSAW (http://tunicata.techfak.uni-bielefeld.de/graphsaw/) is meant to be a web-based system for health professionals and researchers. GraphSAW provides comprehensive drug-related knowledge and an improved medication analysis which may support efforts to reduce the risk of medication errors and numerous drastic side effects.

Exploring the molecular mechanisms of Traditional Chinese Medicine components using gene expression signatures and connectivity map.

PubMed

Yoo, Minjae; Shin, Jimin; Kim, Hyunmin; Kim, Jihye; Kang, Jaewoo; Tan, Aik Choon

2018-04-04

Traditional Chinese Medicine (TCM) has been practiced over thousands of years in China and other Asian countries for treating various symptoms and diseases. However, the underlying molecular mechanisms of TCM are poorly understood, partly due to the "multi-component, multi-target" nature of TCM. To uncover the molecular mechanisms of TCM, we perform comprehensive gene expression analysis using connectivity map. We interrogated gene expression signatures obtained 102 TCM components using the next generation Connectivity Map (CMap) resource. We performed systematic data mining and analysis on the mechanism of action (MoA) of these TCM components based on the CMap results. We clustered the 102 TCM components into four groups based on their MoAs using next generation CMap resource. We performed gene set enrichment analysis on these components to provide additional supports for explaining these molecular mechanisms. We also provided literature evidence to validate the MoAs identified through this bioinformatics analysis. Finally, we developed the Traditional Chinese Medicine Drug Repurposing Hub (TCM Hub) - a connectivity map resource to facilitate the elucidation of TCM MoA for drug repurposing research. TCMHub is freely available in http://tanlab.ucdenver.edu/TCMHub. Molecular mechanisms of TCM could be uncovered by using gene expression signatures and connectivity map. Through this analysis, we identified many of the TCM components possess diverse MoAs, this may explain the applications of TCM in treating various symptoms and diseases. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

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

PubMed

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

2014-03-28

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

Serrated colorectal cancer: Molecular classification, prognosis, and response to chemotherapy

PubMed Central

Murcia, Oscar; Juárez, Miriam; Hernández-Illán, Eva; Egoavil, Cecilia; Giner-Calabuig, Mar; Rodríguez-Soler, María; Jover, Rodrigo

2016-01-01

Molecular advances support the existence of an alternative pathway of colorectal carcinogenesis that is based on the hypermethylation of specific DNA regions that silences tumor suppressor genes. This alternative pathway has been called the serrated pathway due to the serrated appearance of tumors in histological analysis. New classifications for colorectal cancer (CRC) were proposed recently based on genetic profiles that show four types of molecular alterations: BRAF gene mutations, KRAS gene mutations, microsatellite instability, and hypermethylation of CpG islands. This review summarizes what is known about the serrated pathway of CRC, including CRC molecular and clinical features, prognosis, and response to chemotherapy. PMID:27053844

Tracking and Motion Analysis of Crack Propagations in Crystals for Molecular Dynamics

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

Tsap, L V; Duchaineau, M; Goldgof, D B

2001-05-14

This paper presents a quantitative analysis for a discovery in molecular dynamics. Recent simulations have shown that velocities of crack propagations in crystals under certain conditions can become supersonic, which is contrary to classical physics. In this research, they present a framework for tracking and motion analysis of crack propagations in crystals. It includes line segment extraction based on Canny edge maps, feature selection based on physical properties, and subsequent tracking of primary and secondary wavefronts. This tracking is completely automated; it runs in real time on three 834-image sequences using forty 250 MHZ processors. Results supporting physical observations aremore » presented in terms of both feature tracking and velocity analysis.« less

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

NASA Astrophysics Data System (ADS)

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

2018-04-01

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

Molecular imaging in neuroendocrine tumors: molecular uptake mechanisms and clinical results.

PubMed

Koopmans, Klaas P; Neels, Oliver N; Kema, Ido P; Elsinga, Philip H; Links, Thera P; de Vries, Elisabeth G E; Jager, Pieter L

2009-09-01

Neuroendocrine tumors can originate almost everywhere in the body and consist of a great variety of subtypes. This paper focuses on molecular imaging methods using nuclear medicine techniques in neuroendocrine tumors, coupling molecular uptake mechanisms of radiotracers with clinical results. A non-systematic review is presented on receptor based and metabolic imaging methods. Receptor-based imaging covers the molecular backgrounds of somatostatin, vaso-intestinal peptide (VIP), bombesin and cholecystokinin (CCK) receptors and their link with nuclear imaging. Imaging methods based on specific metabolic properties include meta-iodo-benzylguanide (MIBG) and dimercapto-sulphuric acid (DMSA-V) scintigraphy as well as more modern positron emission tomography (PET)-based methods using radio-labeled analogues of amino acids, glucose, dihydroxyphenylalanine (DOPA), dopamine and tryptophan. Diagnostic sensitivities are presented for each imaging method and for each neuroendocrine tumor subtype. Finally, a Forest plot analysis of diagnostic performance is presented for each tumor type in order to provide a comprehensive overview for clinical use.

Application of comprehensive NMR-based analysis strategy in annotation, isolation and structure elucidation of low molecular weight metabolites of Ricinus communis seeds.

PubMed

Vučković, Ivan; Rapinoja, Marja-Leena; Vaismaa, Matti; Vanninen, Paula; Koskela, Harri

2016-01-01

Powder-like extract of Ricinus communis seeds contain a toxic protein, ricin, which has a history of military, criminal and terroristic use. As the detection of ricin in this "terrorist powder" is difficult and time-consuming, related low mass metabolites have been suggested to be useful for screening as biomarkers of ricin. To apply a comprehensive NMR-based analysis strategy for annotation, isolation and structure elucidation of low molecular weight plant metabolites of Ricinus communis seeds. The seed extract was prepared with a well-known acetone extraction approach. The common metabolites were annotated from seed extract dissolved in acidic solution using (1)H NMR spectroscopy with spectrum library comparison and standard addition, whereas unconfirmed metabolites were identified using multi-step off-line HPLC-DAD-NMR approach. In addition to the common plant metabolites, two previously unreported compounds, 1,3-digalactoinositol and ricinyl-alanine, were identified with support of MS analyses. The applied comprehensive NMR-based analysis strategy provided identification of the prominent low molecular weight metabolites with high confidence. Copyright © 2015 John Wiley & Sons, Ltd.

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

Xia, Guanguang; Chen, Baowei; Zhang, Rui

In this work, new strategies involving organic bases were evaluated to depolymerize lignin to reduced molecular fragments in aqueous medium. NaOH as an inorganic base was also investigated as a reference. Full nature lignin samples are used for the study. As research tools to unravel the complexity of the macro lignin structure and bulky molecular size under this study, size exclusion chromatography and high resolution mass spectrometric analysis, typically used for protein characterizations, were used to follow the progress of lignin depolymerisation by measuring the molecular weight distribution of the products and determining the key molecular fingerprints, respectively. The resultsmore » show that sodium phenoxide and guanidine carbonate are effective catalysts for lignin depolymerization. It is observed that there exists a synergism between H2O2 and the organic base, which is strongest with guanidine carbonate.« less

Peptidylation for the determination of low-molecular-weight compounds by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

PubMed

Tang, Feng; Cen, Si-Ying; He, Huan; Liu, Yi; Yuan, Bi-Feng; Feng, Yu-Qi

2016-05-23

Determination of low-molecular-weight compounds by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) has been a great challenge in the analytical research field. Here we developed a universal peptide-based derivatization (peptidylation) strategy for the sensitive analysis of low-molecular-weight compounds by MALDI-TOF-MS. Upon peptidylation, the molecular weights of target analytes increase, thus avoiding serious matrix ion interference in the low-molecular-weight region in MALDI-TOF-MS. Since peptides typically exhibit good signal response during MALDI-TOF-MS analysis, peptidylation endows high detection sensitivities of low-molecular-weight analytes. As a proof-of-concept, we analyzed low-molecular-weight compounds of aldehydes and thiols by the developed peptidylation strategy. Our results showed that aldehydes and thiols can be readily determined upon peptidylation, thus realizing the sensitive and efficient determination of low-molecular-weight compounds by MALDI-TOF-MS. Moreover, target analytes also can be unambiguously detected in biological samples using the peptidylation strategy. The established peptidylation strategy is a universal strategy and can be extended to the sensitive analysis of various low-molecular-weight compounds by MALDI-TOF-MS, which may be potentially used in areas such as metabolomics.

Molecular effective coverage surface area of optical clearing agents for predicting optical clearing potential

NASA Astrophysics Data System (ADS)

Feng, Wei; Ma, Ning; Zhu, Dan

2015-03-01

The improvement of methods for optical clearing agent prediction exerts an important impact on tissue optical clearing technique. The molecular dynamic simulation is one of the most convincing and simplest approaches to predict the optical clearing potential of agents by analyzing the hydrogen bonds, hydrogen bridges and hydrogen bridges type forming between agents and collagen. However, the above analysis methods still suffer from some problem such as analysis of cyclic molecule by reason of molecular conformation. In this study, a molecular effective coverage surface area based on the molecular dynamic simulation was proposed to predict the potential of optical clearing agents. Several typical cyclic molecules, fructose, glucose and chain molecules, sorbitol, xylitol were analyzed by calculating their molecular effective coverage surface area, hydrogen bonds, hydrogen bridges and hydrogen bridges type, respectively. In order to verify this analysis methods, in vitro skin samples optical clearing efficacy were measured after 25 min immersing in the solutions, fructose, glucose, sorbitol and xylitol at concentration of 3.5 M using 1951 USAF resolution test target. The experimental results show accordance with prediction of molecular effective coverage surface area. Further to compare molecular effective coverage surface area with other parameters, it can show that molecular effective coverage surface area has a better performance in predicting OCP of agents.

Molecular Phylogenetics: Concepts for a Newcomer.

PubMed

Ajawatanawong, Pravech

Molecular phylogenetics is the study of evolutionary relationships among organisms using molecular sequence data. The aim of this review is to introduce the important terminology and general concepts of tree reconstruction to biologists who lack a strong background in the field of molecular evolution. Some modern phylogenetic programs are easy to use because of their user-friendly interfaces, but understanding the phylogenetic algorithms and substitution models, which are based on advanced statistics, is still important for the analysis and interpretation without a guide. Briefly, there are five general steps in carrying out a phylogenetic analysis: (1) sequence data preparation, (2) sequence alignment, (3) choosing a phylogenetic reconstruction method, (4) identification of the best tree, and (5) evaluating the tree. Concepts in this review enable biologists to grasp the basic ideas behind phylogenetic analysis and also help provide a sound basis for discussions with expert phylogeneticists.

Contrasting results from molecular and pedigree-based population diversity measures in captive zebra highlight challenges facing genetic management of zoo populations.

PubMed

Ito, Hideyuki; Ogden, Rob; Langenhorst, Tanya; Inoue-Murayama, Miho

2017-01-01

Zoo conservation breeding programs manage the retention of population genetic diversity through analysis of pedigree records. The range of demographic and genetic indices determined through pedigree analysis programs allows the conservation of diversity to be monitored relative to the particular founder population for a species. Such approaches are based on a number of well-documented founder assumptions, however without knowledge of actual molecular genetic diversity there is a risk that pedigree-based measures will be misinterpreted and population genetic diversity misunderstood. We examined the genetic diversity of the captive populations of Grevy's zebra, Hartmann's mountain zebra and plains zebra in Japan and the United Kingdom through analysis of mitochondrial DNA sequences. Very low nucleotide variability was observed in Grevy's zebra. The results were evaluated with respect to current and historic diversity in the wild, and indicate that low genetic diversity in the captive population is likely a result of low founder diversity, which in turn suggests relatively low wild genetic diversity prior to recent population declines. Comparison of molecular genetic diversity measures with analogous diversity indices generated from the studbook data for Grevy's zebra and Hartmann's mountain zebra show contrasting patterns, with Grevy's zebra displaying markedly less molecular diversity than mountain zebra, despite studbook analysis indicating that the Grevy's zebra population has substantially more founders, greater effective population size, lower mean kinship, and has suffered less loss of gene diversity. These findings emphasize the need to validate theoretical estimates of genetic diversity in captive breeding programs with empirical molecular genetic data. Zoo Biol. 36:87-94, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Web-TCGA: an online platform for integrated analysis of molecular cancer data sets.

PubMed

Deng, Mario; Brägelmann, Johannes; Schultze, Joachim L; Perner, Sven

2016-02-06

The Cancer Genome Atlas (TCGA) is a pool of molecular data sets publicly accessible and freely available to cancer researchers anywhere around the world. However, wide spread use is limited since an advanced knowledge of statistics and statistical software is required. In order to improve accessibility we created Web-TCGA, a web based, freely accessible online tool, which can also be run in a private instance, for integrated analysis of molecular cancer data sets provided by TCGA. In contrast to already available tools, Web-TCGA utilizes different methods for analysis and visualization of TCGA data, allowing users to generate global molecular profiles across different cancer entities simultaneously. In addition to global molecular profiles, Web-TCGA offers highly detailed gene and tumor entity centric analysis by providing interactive tables and views. As a supplement to other already available tools, such as cBioPortal (Sci Signal 6:pl1, 2013, Cancer Discov 2:401-4, 2012), Web-TCGA is offering an analysis service, which does not require any installation or configuration, for molecular data sets available at the TCGA. Individual processing requests (queries) are generated by the user for mutation, methylation, expression and copy number variation (CNV) analyses. The user can focus analyses on results from single genes and cancer entities or perform a global analysis (multiple cancer entities and genes simultaneously).

Systematic RH genotyping and variant identification in French donors of African origin

PubMed Central

Kappler-Gratias, Sandrine; Auxerre, Carine; Dubeaux, Isabelle; Beolet, Marylise; Ripaux, Maryline; Le Pennec, Pierre-Yves; Pham, Bach-Nga

2014-01-01

Background RH molecular analysis has enabled the documentation of numerous variants of RHD and RHCE alleles, especially in individuals of African origin. The aim of the present study was to determine the type and frequency of D and/or RhCE variants among blood donors of African origin in France, by performing a systematic RH molecular analysis, in order to evaluate the implications for blood transfusion of patients of African origin. Materials and methods Samples from 316 African blood donors, whose origin was established by their Fy(a−b−) phenotype, were first analysed using the RHD and RHCE BeadChips Kit (BioArray Solutions, Immucor, Warren, NJ, USA). Sequencing was performed when necessary. Results RHD molecular analysis showed that 26.2% of donors had a variant RHD allele. It allowed the prediction of a partial D in 11% of cases. RHCE molecular analysis showed that 14.2% of donors had a variant RHCE allele or RH [RN or (C)ces] haplotype. A rare Rh phenotype associated with the loss of a high-prevalence antigen or partial RhCE antigens were predicted from RHCE molecular analysis in 1 (0.3%) and 17 (5%) cases, respectively. Discussion Systematic RHD and RHCE molecular analysis performed in blood donors of African origin provides transfusion-relevant information for individuals of African origin because of the frequency of variant RH alleles. RH molecular analysis may improve transfusion therapy of patients by allowing better donor and recipient matching, based not only on phenotypically matched red blood cell units, but also on units that are genetically matched with regards to RhCE variants. PMID:23867180

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

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

P Yu

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

Molecular phylogeny and evolutionary timescale for the family of mammalian herpesviruses.

PubMed

McGeoch, D J; Cook, S; Dolan, A; Jamieson, F E; Telford, E A

1995-03-31

A detailed phylogenetic analysis for mammalian members of the family Herpesviridae, based on molecular sequences is reported. Sets of encoded amino acid sequences were collected for eight well conserved genes that are common to mammalian herpesviruses. Phylogenetic trees were inferred from alignments of these sequence sets using both maximum parsimony and distance methods, and evaluated by bootstrap analysis. In all cases the three recognised subfamilies (Alpha-, Beta- and Gammaherpesvirinae), and major sublineages in each subfamily, were clearly distinguished, but within sublineages some finer details of branching were incompletely resolved. Multiple-gene sets were assembled to give a broadly based tree. The root position of the tree was estimated by assuming a constant molecular clock and also by analysis of one herpesviral gene set (that encoding uracil-DNA glycosylase) using cellular homologues as outgroups. Both procedures placed the root between the Alphaherpesvirinae and the other two subfamilies. Substitution rates were calculated for the combined gene sets based on a previous estimate for alphaherpesviral UL27 genes, where the time base had been obtained according to the hypothesis of cospeciation of virus and host lineages. Assuming a constant molecular clock, it was then estimated that the three subfamilies arose approximately 180 to 220 million years ago, that major sublineages within subfamilies were probably generated before the mammalian radiation of 80 to 60 million years ago, and that speciations within sublineages took place in the last 80 million years, probably with a major component of cospeciation with host lineages.

First molecular characterisation of a Brazilian Burkholderia mallei strain isolated from a mule in 2016.

PubMed

Laroucau, K; Lucia de Assis Santana, V; Girault, G; Martin, B; Miranda da Silveira, P P; Brasil Machado, M; Joseph, M; Wernery, R; Wernery, U; Zientara, S; Madani, N

2018-01-01

We present the first molecular characterisation based on MLVA and SNP analysis of a strain of Burkholderia mallei isolated from a mule found dead in Brazil in 2016. Copyright © 2017 Elsevier B.V. All rights reserved.

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

PubMed Central

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

2012-01-01

Background Rab GTPases constitute the largest subfamily of the Ras protein superfamily. Rab proteins regulate organelle biogenesis and transport, and display distinct binding preferences for effector and activator proteins, many of which have not been elucidated yet. The underlying molecular recognition motifs, binding partner preferences and selectivities are not well understood. Methodology/Principal Findings Comparative analysis of the amino acid sequences and the three-dimensional electrostatic and hydrophobic molecular interaction fields of 62 human Rab proteins revealed a wide range of binding properties with large differences between some Rab proteins. This analysis assists the functional annotation of Rab proteins 12, 14, 26, 37 and 41 and provided an explanation for the shared function of Rab3 and 27. Rab7a and 7b have very different electrostatic potentials, indicating that they may bind to different effector proteins and thus, exert different functions. The subfamily V Rab GTPases which are associated with endosome differ subtly in the interaction properties of their switch regions, and this may explain exchange factor specificity and exchange kinetics. Conclusions/Significance We have analysed conservation of sequence and of molecular interaction fields to cluster and annotate the human Rab proteins. The analysis of three dimensional molecular interaction fields provides detailed insight that is not available from a sequence-based approach alone. Based on our results, we predict novel functions for some Rab proteins and provide insights into their divergent functions and the determinants of their binding partner selectivity. PMID:22523562

Evaluation of Contamination Inspection and Analysis Methods through Modeling System Performance

NASA Technical Reports Server (NTRS)

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

2016-01-01

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

Determination and Quantification of Molecular Interactions in Protein Films: A Review.

PubMed

Hammann, Felicia; Schmid, Markus

2014-12-10

Protein based films are nowadays also prepared with the aim of replacing expensive, crude oil-based polymers as environmentally friendly and renewable alternatives. The protein structure determines the ability of protein chains to form intra- and intermolecular bonds, whereas the degree of cross-linking depends on the amino acid composition and molecular weight of the protein, besides the conditions used in film preparation and processing. The functionality varies significantly depending on the type of protein and affects the resulting film quality and properties. This paper reviews the methods used in examination of molecular interactions in protein films and discusses how these intermolecular interactions can be quantified. The qualitative determination methods can be distinguished by structural analysis of solutions (electrophoretic analysis, size exclusion chromatography) and analysis of solid films (spectroscopy techniques, X-ray scattering methods). To quantify molecular interactions involved, two methods were found to be the most suitable: protein film swelling and solubility. The importance of non-covalent and covalent interactions in protein films can be investigated using different solvents. The research was focused on whey protein, whereas soy protein and wheat gluten were included as further examples of proteins.

Determination Quantification of Molecular Interactions in Protein Films: A Review

PubMed Central

Hammann, Felicia; Schmid, Markus

2014-01-01

Protein based films are nowadays also prepared with the aim of replacing expensive, crude oil-based polymers as environmentally friendly and renewable alternatives. The protein structure determines the ability of protein chains to form intra- and intermolecular bonds, whereas the degree of cross-linking depends on the amino acid composition and molecular weight of the protein, besides the conditions used in film preparation and processing. The functionality varies significantly depending on the type of protein and affects the resulting film quality and properties. This paper reviews the methods used in examination of molecular interactions in protein films and discusses how these intermolecular interactions can be quantified. The qualitative determination methods can be distinguished by structural analysis of solutions (electrophoretic analysis, size exclusion chromatography) and analysis of solid films (spectroscopy techniques, X-ray scattering methods). To quantify molecular interactions involved, two methods were found to be the most suitable: protein film swelling and solubility. The importance of non-covalent and covalent interactions in protein films can be investigated using different solvents. The research was focused on whey protein, whereas soy protein and wheat gluten were included as further examples of proteins. PMID:28788285

Systematic understanding the mechanisms of vitiligo pathogenesis and its treatment by Qubaibabuqi formula.

PubMed

Pei, Tianli; Zheng, Chunli; Huang, Chao; Chen, Xuetong; Guo, Zihu; Fu, Yingxue; Liu, Jianling; Wang, Yonghua

2016-08-22

Vitiligo is a depigmentation disorder, which results in substantial cosmetic disfigurement and poses a detriment to patients' physical as well as mental. Now the molecular pathogenesis of vitiligo still remains unclear, which leads to a daunting challenge for vitiligo therapy in modern medicine. Herbal medicines, characterized by multi-compound and multi-target, have long been shown effective in treating vitiligo, but their molecular mechanisms of action also remain ambiguous. Here we proposed a systems pharmacology approach using a clinically effective herb formula as a tool to detect the molecular pathogenesis of vitiligo. This study provided an integrative analysis of active chemicals, drug targets and interacting pathways of the Uygur medicine Qubaibabuqi formula for curing Vitiligo. The results show that 56 active ingredients of Qubaibabuqi interacting with 83 therapeutic proteins were identified. And Qubaibabuqi probably participate in immunomodulation, neuromodulation and keratinocytes apoptosis inhibition in treatment of vitiligo by a synergistic/cooperative way. The drug-target network-based analysis and pathway-based analysis can provide a new approach for understanding the pathogenesis of vitiligo and uncovering the molecular mechanisms of Qubaibabuqi, which will also facilitate the application of traditional Chinese herbs in modern medicine. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Transcriptome-wide analysis of WRKY transcription factors in wheat and their leaf rust responsive expression profiling.

PubMed

Satapathy, Lopamudra; Singh, Dharmendra; Ranjan, Prashant; Kumar, Dhananjay; Kumar, Manish; Prabhu, Kumble Vinod; Mukhopadhyay, Kunal

2014-12-01

WRKY, a plant-specific transcription factor family, has important roles in pathogen defense, abiotic cues and phytohormone signaling, yet little is known about their roles and molecular mechanism of function in response to rust diseases in wheat. We identified 100 TaWRKY sequences using wheat Expressed Sequence Tag database of which 22 WRKY sequences were novel. Identified proteins were characterized based on their zinc finger motifs and phylogenetic analysis clustered them into six clades consisting of class IIc and class III WRKY proteins. Functional annotation revealed major functions in metabolic and cellular processes in control plants; whereas response to stimuli, signaling and defense in pathogen inoculated plants, their major molecular function being binding to DNA. Tag-based expression analysis of the identified genes revealed differential expression between mock and Puccinia triticina inoculated wheat near isogenic lines. Gene expression was also performed with six rust-related microarray experiments at Gene Expression Omnibus database. TaWRKY10, 15, 17 and 56 were common in both tag-based and microarray-based differential expression analysis and could be representing rust specific WRKY genes. The obtained results will bestow insight into the functional characterization of WRKY transcription factors responsive to leaf rust pathogenesis that can be used as candidate genes in molecular breeding programs to improve biotic stress tolerance in wheat.

Comparison between rpoB and 16S rRNA Gene Sequencing for Molecular Identification of 168 Clinical Isolates of Corynebacterium

PubMed Central

Khamis, Atieh; Raoult, Didier; La Scola, Bernard

2005-01-01

Higher proportions (91%) of 168 corynebacterial isolates were positively identified by partial rpoB gene determination than by that based on 16S rRNA gene sequences. This method is thus a simple, molecular-analysis-based method for identification of corynebacteria, but it should be used in conjunction with other tests for definitive identification. PMID:15815024

Network-based machine learning and graph theory algorithms for precision oncology.

PubMed

Zhang, Wei; Chien, Jeremy; Yong, Jeongsik; Kuang, Rui

2017-01-01

Network-based analytics plays an increasingly important role in precision oncology. Growing evidence in recent studies suggests that cancer can be better understood through mutated or dysregulated pathways or networks rather than individual mutations and that the efficacy of repositioned drugs can be inferred from disease modules in molecular networks. This article reviews network-based machine learning and graph theory algorithms for integrative analysis of personal genomic data and biomedical knowledge bases to identify tumor-specific molecular mechanisms, candidate targets and repositioned drugs for personalized treatment. The review focuses on the algorithmic design and mathematical formulation of these methods to facilitate applications and implementations of network-based analysis in the practice of precision oncology. We review the methods applied in three scenarios to integrate genomic data and network models in different analysis pipelines, and we examine three categories of network-based approaches for repositioning drugs in drug-disease-gene networks. In addition, we perform a comprehensive subnetwork/pathway analysis of mutations in 31 cancer genome projects in the Cancer Genome Atlas and present a detailed case study on ovarian cancer. Finally, we discuss interesting observations, potential pitfalls and future directions in network-based precision oncology.

Analysis of low molecular weight compounds by MALDI-FTICR-MS.

PubMed

Wang, Hao-Yang; Chu, Xu; Zhao, Zhi-Xiong; He, Xiao-Shuang; Guo, Yin-Long

2011-05-15

This review focuses on recent applications of matrix-assisted laser desorption ionization-Fourier-transform ion cyclotron resonance mass spectrometry (MALDI-FTICR-MS) in qualitative and quantitative analysis of low molecular weight compounds. The scope of the work includes amino acids, small peptides, mono and oligosaccharides, lipids, metabolic compounds, small molecule phytochemicals from medicinal herbs and even the volatile organic compounds from tobacco. We discuss both direct analysis and analysis following derivatization. In addition we review sample preparation strategies to reduce interferences in the low m/z range and to improve sensitivities by derivatization with charge tags. We also present coupling of head space techniques with MALDI-FTICR-MS. Furthermore, omics analyses based on MALDI-FTICR-MS were also discussed, including proteomics, metabolomics and lipidomics, as well as the relative MS imaging for bio-active low molecular weight compounds. Finally, we discussed the investigations on dissociation/rearrangement processes of low molecular weight compounds by MALDI-FTICR-MS. Copyright © 2011 Elsevier B.V. All rights reserved.

Comparative Investigation of Normal Modes and Molecular Dynamics of Hepatitis C NS5B Protein

NASA Astrophysics Data System (ADS)

Asafi, M. S.; Yildirim, A.; Tekpinar, M.

2016-04-01

Understanding dynamics of proteins has many practical implications in terms of finding a cure for many protein related diseases. Normal mode analysis and molecular dynamics methods are widely used physics-based computational methods for investigating dynamics of proteins. In this work, we studied dynamics of Hepatitis C NS5B protein with molecular dynamics and normal mode analysis. Principal components obtained from a 100 nanoseconds molecular dynamics simulation show good overlaps with normal modes calculated with a coarse-grained elastic network model. Coarse-grained normal mode analysis takes at least an order of magnitude shorter time. Encouraged by this good overlaps and short computation times, we analyzed further low frequency normal modes of Hepatitis C NS5B. Motion directions and average spatial fluctuations have been analyzed in detail. Finally, biological implications of these motions in drug design efforts against Hepatitis C infections have been elaborated.

A communication theoretical analysis of FRET-based mobile ad hoc molecular nanonetworks.

PubMed

Kuscu, Murat; Akan, Ozgur B

2014-09-01

Nanonetworks refer to a group of nanosized machines with very basic operational capabilities communicating to each other in order to accomplish more complex tasks such as in-body drug delivery, or chemical defense. Realizing reliable and high-rate communication between these nanomachines is a fundamental problem for the practicality of these nanonetworks. Recently, we have proposed a molecular communication method based on Förster Resonance Energy Transfer (FRET) which is a nonradiative excited state energy transfer phenomenon observed among fluorescent molecules, i.e., fluorophores. We have modeled the FRET-based communication channel considering the fluorophores as single-molecular immobile nanomachines, and shown its reliability at high rates, and practicality at the current stage of nanotechnology. In this study, for the first time in the literature, we investigate the network of mobile nanomachines communicating through FRET. We introduce two novel mobile molecular nanonetworks: FRET-based mobile molecular sensor/actor nanonetwork (FRET-MSAN) which is a distributed system of mobile fluorophores acting as sensor or actor node; and FRET-based mobile ad hoc molecular nanonetwork (FRET-MAMNET) which consists of fluorophore-based nanotransmitter, nanoreceivers and nanorelays. We model the single message propagation based on birth-death processes with continuous time Markov chains. We evaluate the performance of FRET-MSAN and FRET-MAMNET in terms of successful transmission probability and mean extinction time of the messages, system throughput, channel capacity and achievable communication rates.

Research on golden-winged warblers: recent progress and current needs

Treesearch

Henry M. Streby; Ronald W. Rohrbaugh; David A. Buehler; David E. Andersen; Rachel Vallender; David I. King; Tom Will

2016-01-01

Considerable advances have been made in knowledge about Golden-winged Warblers (Vermivora chrysoptera) in the past decade. Recent employment of molecular analysis, stable-isotope analysis, telemetry-based monitoring of survival and behavior, and spatially explicit modeling techniques have added to, and revised, an already broad base of published...

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.

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

PubMed

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

2015-08-19

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

Morphoagronomic and molecular profiling of Capsicum spp from southwest Mato Grosso, Brazil.

PubMed

Campos, A L; Marostega, T N; Cabral, N S S; Araújo, K L; Serafim, M E; Seabra-Júnior, S; Sudré, C P; Rodrigues, R; Neves, L G

2016-07-15

The genus Capsicum ranks as the second most exported vegetable in Brazil, which is also considered to be a center of diversity for this genus. The aim of this study was to rescue genetic variability in the genus Capsicum in the southwest region of Mato Grosso, and to characterize and estimate the genetic diversity of accessions based on morphoagronomic descriptors and inter-simple sequence repeat molecular markers. Data were obtained following the criteria of the International Plant Genetic Resources Institute, renamed Bioversity International for Capsicum. Data were analyzed using different multivariate statistical techniques. An array of binary data was used to analyze molecular data, and the arithmetic complement of the Jaccard index was used to estimate the genetic dissimilarity among accessions. Six well-defined groups were formed based on the morphological characterization. The most divergent accessions were 142 and 126, with 125 and 126 being the most similar. The groups formed following agronomic characterization differed from those formed by morphological characterization, and there was a need to subdivide the groups for better distinction of accessions. Based on molecular analysis, accessions were divided into two groups, and there was also a need to subdivide the groups. Based on joint analysis (morphological + agronomic + molecular), six groups were formed with no duplicates. For all groups, the cophenetic correlation coefficient was higher than 0.8. These results provide useful information for the better management of the work collection. All correlations between the combined distance matrix were significant by the Mantel test.

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

PubMed

Tamer, Ömer; Avcı, Davut; Atalay, Yusuf

2014-01-03

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

Conformation of phylogenetic relationship of Penaeidae shrimp based on morphometric and molecular investigations.

PubMed

Rajakumaran, P; Vaseeharan, B; Jayakumar, R; Chidambara, R

2014-01-01

Understanding of accurate phylogenetic relationship among Penaeidae shrimp is important for academic and fisheries industry. The Morphometric and Randomly amplified polymorphic DNA (RAPD) analysis was used to make the phylogenetic relationsip among 13 Penaeidae shrimp. For morphometric analysis forty variables and total lengths of shrimp were measured for each species, and removed the effect of size variation. The size normalized values obtained was subjected to UPGMA (Unweighted Pair-Group Method with Arithmetic Mean) cluster analysis. For RAPD analysis, the four primers showed reliable differentiation between species, and used correlation coefficient between the DNA banding patterns of 13 Penaeidae species to construct UPGMA dendrogram. Phylogenetic relationship from morphometric and molecular analysis for Penaeidae species found to be congruent. We concluded that as the results from morphometry investigations concur with molecular one, phylogenetic relationship obtained for the studied Penaeidae are considered to be reliable.

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

PubMed

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

2018-06-06

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

Genome-wide molecular dissection of serotype M3 group A Streptococcus strains causing two epidemics of invasive infections.

PubMed

Beres, Stephen B; Sylva, Gail L; Sturdevant, Daniel E; Granville, Chanel N; Liu, Mengyao; Ricklefs, Stacy M; Whitney, Adeline R; Parkins, Larye D; Hoe, Nancy P; Adams, Gerald J; Low, Donald E; DeLeo, Frank R; McGeer, Allison; Musser, James M

2004-08-10

Molecular factors that contribute to the emergence of new virulent bacterial subclones and epidemics are poorly understood. We hypothesized that analysis of a population-based strain sample of serotype M3 group A Streptococcus (GAS) recovered from patients with invasive infection by using genome-wide investigative methods would provide new insight into this fundamental infectious disease problem. Serotype M3 GAS strains (n = 255) cultured from patients in Ontario, Canada, over 11 years and representing two distinct infection peaks were studied. Genetic diversity was indexed by pulsed-field gel electrophoresis, DNA-DNA microarray, whole-genome PCR scanning, prophage genotyping, targeted gene sequencing, and single-nucleotide polymorphism genotyping. All variation in gene content was attributable to acquisition or loss of prophages, a molecular process that generated unique combinations of proven or putative virulence genes. Distinct serotype M3 genotypes experienced rapid population expansion and caused infections that differed significantly in character and severity. Molecular genetic analysis, combined with immunologic studies, implicated a 4-aa duplication in the extreme N terminus of M protein as a factor contributing to an epidemic wave of serotype M3 invasive infections. This finding has implications for GAS vaccine research. Genome-wide analysis of population-based strain samples cultured from clinically well defined patients is crucial for understanding the molecular events underlying bacterial epidemics.

Design and development of radioactive xenon gas purification and analysis system based on molecular sieves.

PubMed

Sabzian, M; Nasrabadi, M N; Haji-Hosseini, M

2018-10-01

The dynamic adsorption of xenon on molecular sieve packed columns was investigated. The modified Wheeler-Jonas equation was used to describe adsorption parameters such as adsorption capacity and adsorption rate coefficient. Different experimental conditions were accomplished to study their effects and to touch appropriate adsorbing circumstances. Respectable consistency was reached between experimental and modeled values. A purification and analysis setup was developed for radioactive xenon gas determination. Standard sample analysis results approved acceptable quantification accuracy. Copyright © 2018. Published by Elsevier Ltd.

NANOSTRUCTURED PLANAR WAVEGUIDE DEVICE FOR MOLECULAR IDENTIFICATION OF HAZARDOUS COMPOUNDS IN WATER BY EVANESCENT SURFACE ENHANCED RAMAN SPECTROSCOPY - PHASE I

EPA Science Inventory

Senspex, Inc. proposes to investigate a novel diagnostic tool based upon evanescent field planar waveguide sensing and complementary nanostructured mediated molecular vibration spectroscopy methods for rapid detection and analysis of hazardous biological and chemical targets i...

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

EPA Science Inventory

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

Learning Molecular Behaviour May Improve Student Explanatory Models of the Greenhouse Effect

ERIC Educational Resources Information Center

Harris, Sara E.; Gold, Anne U.

2018-01-01

We assessed undergraduates' representations of the greenhouse effect, based on student-generated concept sketches, before and after a 30-min constructivist lesson. Principal component analysis of features in student sketches revealed seven distinct and coherent explanatory models including a new "Molecular Details" model. After the…

A Streamlined Molecular Biology Module for Undergraduate Biochemistry Labs

ERIC Educational Resources Information Center

Muth, Gregory W.; Chihade, Joseph W.

2008-01-01

Site-directed mutagenesis and other molecular biology techniques, including plasmid manipulation and restriction analysis, are commonly used tools in the biochemistry research laboratory. In redesigning our biochemistry lab curricula, we sought to integrate these techniques into a term-long, project-based course. In the module presented here,…

Molecular tools for cryptic Candida species identification with applications in a clinical laboratory.

PubMed

Gamarra, Soledad; Dudiuk, Catiana; Mancilla, Estefanía; Vera Garate, María Verónica; Guerrero, Sergio; Garcia-Effron, Guillermo

2013-01-01

Candida spp. includes more than 160 species but only 20 species pose clinical problems. C. albicans and C. parapsilosis account for more than 75% of all the fungemias worldwide. In 1995 and 2005, one C. albicans and two C. parapsilosis-related species were described, respectively. Using phenotypic traits, the identification of these newly described species is inconclusive or impossible. Thus, molecular-based procedures are mandatory. In the proposed educational experiment we have adapted different basic molecular biology techniques designed to identify these species including PCR, multiplex PCR, PCR-based restriction endonuclease analysis and nuclear ribosomal RNA amplification. During the classes, students acquired the ability to search and align gene sequences, design primers, and use bioinformatics software. Also, in the performed experiments, fungal molecular taxonomy concepts were introduced and the obtained results demonstrated that classic identification (phenotypic) in some cases needs to be complemented with molecular-based techniques. As a conclusion we can state that we present an inexpensive and well accepted group of classes involving important concepts that can be recreated in any laboratory. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.

Molecular Epidemiology of Human Intestinal Amoebas in Iran

PubMed Central

Hooshyar, H; Rostamkhani, P; Rezaian, M

2012-01-01

Many microscopic-based epidemiological surveys on the prevalence of human intestinal pathogenic and non-pathogenic protozoa including intestinal amoeba performed in Iran show a high prevalence of human intestinal amoeba in different parts of Iran. Such epidemiological studies on amoebiasis are confusing, mainly due to recently appreciated distinction between the Entamoeba histolytica, E. dispar and E. moshkovskii. Differential diagnosis can be done by some methods such as PCR-based methods, monoclonal antibodies and the analysis of isoenzyme typing, however the molecular study of these protozoa in Iran is low. Based on molecular studies, it seems that E. dispar is predominant species especially in the central and northern areas of Iran and amoebiasis due to E. histolytica is a rare infection in the country. It is suggested that infection with E. moshkovskii may be common among Iranians. Considering the importance of molecular epidemiology of amoeba in Iran and also the current data, the present study reviews the data currently available on the molecular distribution of intestinal human amoeba in Iran. PMID:23193500

Computer-aided molecular modeling techniques for predicting the stability of drug cyclodextrin inclusion complexes in aqueous solutions

NASA Astrophysics Data System (ADS)

Faucci, Maria Teresa; Melani, Fabrizio; Mura, Paola

2002-06-01

Molecular modeling was used to investigate factors influencing complex formation between cyclodextrins and guest molecules and predict their stability through a theoretical model based on the search for a correlation between experimental stability constants ( Ks) and some theoretical parameters describing complexation (docking energy, host-guest contact surfaces, intermolecular interaction fields) calculated from complex structures at a minimum conformational energy, obtained through stochastic methods based on molecular dynamic simulations. Naproxen, ibuprofen, ketoprofen and ibuproxam were used as model drug molecules. Multiple Regression Analysis allowed identification of the significant factors for the complex stability. A mathematical model ( r=0.897) related log Ks with complex docking energy and lipophilic molecular fields of cyclodextrin and drug.

Analysis of hydrophobic interactions of antagonists with the beta2-adrenergic receptor.

PubMed

Novoseletsky, V N; Pyrkov, T V; Efremov, R G

2010-01-01

The adrenergic receptors mediate a wide variety of physiological responses, including vasodilatation and vasoconstriction, heart rate modulation, and others. Beta-adrenergic antagonists ('beta-blockers') thus constitute a widely used class of drugs in cardiovascular medicine as well as in management of anxiety, migraine, and glaucoma. The importance of the hydrophobic effect has been evidenced for a wide range of beta-blocker properties. To better understand the role of the hydrophobic effect in recognition of beta-blockers by their receptor, we carried out a molecular docking study combined with an original approach to estimate receptor-ligand hydrophobic interactions. The proposed method is based on automatic detection of molecular fragments in ligands and the analysis of their interactions with receptors separately. A series of beta-blockers, based on phenylethanolamines and phenoxypropanolamines, were docked to the beta2-adrenoceptor binding site in the crystal structure. Hydrophobic complementarity between the ligand and the receptor was calculated using the PLATINUM web-server (http://model.nmr.ru/platinum). Based on the analysis of the hydrophobic match for molecular fragments of beta-blockers, we have developed a new scoring function which efficiently predicts dissociation constant (pKd) with strong correlations (r(2) approximately 0.8) with experimental data.

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

PubMed Central

2013-01-01

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

Improving the accuracy of hyaluronic acid molecular weight estimation by conventional size exclusion chromatography.

PubMed

Shanmuga Doss, Sreeja; Bhatt, Nirav Pravinbhai; Jayaraman, Guhan

2017-08-15

There is an unreasonably high variation in the literature reports on molecular weight of hyaluronic acid (HA) estimated using conventional size exclusion chromatography (SEC). This variation is most likely due to errors in estimation. Working with commercially available HA molecular weight standards, this work examines the extent of error in molecular weight estimation due to two factors: use of non-HA based calibration and concentration of sample injected into the SEC column. We develop a multivariate regression correlation to correct for concentration effect. Our analysis showed that, SEC calibration based on non-HA standards like polyethylene oxide and pullulan led to approximately 2 and 10 times overestimation, respectively, when compared to HA-based calibration. Further, we found that injected sample concentration has an effect on molecular weight estimation. Even at 1g/l injected sample concentration, HA molecular weight standards of 0.7 and 1.64MDa showed appreciable underestimation of 11-24%. The multivariate correlation developed was found to reduce error in estimations at 1g/l to <4%. The correlation was also successfully applied to accurately estimate the molecular weight of HA produced by a recombinant Lactococcus lactis fermentation. Copyright © 2017 Elsevier B.V. All rights reserved.

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

PubMed

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

2017-01-01

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

Differential proteomics analysis to identify proteins and pathways associated with male sterility of soybean using iTRAQ-based strategy.

PubMed

Li, Jiajia; Ding, Xianlong; Han, Shaohuai; He, Tingting; Zhang, Hao; Yang, Longshu; Yang, Shouping; Gai, Junyi

2016-04-14

To further elucidate the molecular mechanism of cytoplasmic male sterility (CMS) in soybean, a differential proteomic analysis was completed between the CMS line NJCMS1A and its maintainer NJCMS1B using iTRAQ-based strategy. As a result, 180 differential abundance proteins (DAPs) were identified, of which, 60 were down-regulated and 120 were up-regulated in NJCMS1A compared with NJCMS1B. Bioinformatic analysis showed that 167 DAPs were annotated in 41 Gene Ontology functional groups, 106 DAPs were classified into 20 clusters of orthologous groups of protein categories, and 128 DAPs were enrichment in 53 KEGG pathways. Fifteen differential level proteins/genes with the same expression pattern were identified in the further conjoint analysis of DAPs and the previously reported differential expression genes. Moreover, multiple reaction monitoring test, qRT-PCR analysis and enzyme activity assay validated that the iTRAQ results were reliable. Based on functional analysis of DAPs, we concluded that male sterility in NJCMS1A might be related to insufficiencies in energy supply, unbalance of protein synthesis and degradation, disruption of flavonoid synthesis, programmed cell death, abnormalities of substance metabolism, etc. These results might facilitate our understanding of the molecular mechanisms behind CMS in soybean. Soybean is an important global crop that provides protein and oil. Heterosis is a significantly potential approach to increase the yield of soybean. Cytoplasmic male sterility (CMS) plays a vital role in the production of hybrid seeds. However, the genetic and molecular mechanisms of male sterility in soybean still need to be further elucidated. In the present paper, a differential proteomic analysis was carried out and the results showed that several key proteins involved in key pathways were associated with male sterility in soybean. This work provides a new insight to understand the genetic and molecular mechanisms underlying CMS in soybean. Copyright © 2016 Elsevier B.V. All rights reserved.

Insight into the molecular genetics of myopia

PubMed Central

Li, Jiali

2017-01-01

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

Insight into the molecular genetics of myopia.

PubMed

Li, Jiali; Zhang, Qingjiong

2017-01-01

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

Recent Progress of Microfluidics in Translational Applications

PubMed Central

Liu, Zongbin; Han, Xin

2016-01-01

Microfluidics, featuring microfabricated structures, is a technology for manipulating fluids at the micrometer scale. The small dimension and flexibility of microfluidic systems are ideal for mimicking molecular and cellular microenvironment, and show great potential in translational research and development. Here, the recent progress of microfluidics in biological and biomedical applications, including molecular analysis, cellular analysis, and chip-based material delivery and biomimetic design is presented. The potential future developments in the translational microfluidics field are also discussed. PMID:27091777

Relaxation estimation of RMSD in molecular dynamics immunosimulations.

PubMed

Schreiner, Wolfgang; Karch, Rudolf; Knapp, Bernhard; Ilieva, Nevena

2012-01-01

Molecular dynamics simulations have to be sufficiently long to draw reliable conclusions. However, no method exists to prove that a simulation has converged. We suggest the method of "lagged RMSD-analysis" as a tool to judge if an MD simulation has not yet run long enough. The analysis is based on RMSD values between pairs of configurations separated by variable time intervals Δt. Unless RMSD(Δt) has reached a stationary shape, the simulation has not yet converged.

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

PubMed

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

2012-04-01

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

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

PubMed Central

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

2012-01-01

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

Partial least squares based gene expression analysis in estrogen receptor positive and negative breast tumors.

PubMed

Ma, W; Zhang, T-F; Lu, P; Lu, S H

2014-01-01

Breast cancer is categorized into two broad groups: estrogen receptor positive (ER+) and ER negative (ER-) groups. Previous study proposed that under trastuzumab-based neoadjuvant chemotherapy, tumor initiating cell (TIC) featured ER- tumors response better than ER+ tumors. Exploration of the molecular difference of these two groups may help developing new therapeutic strategies, especially for ER- patients. With gene expression profile from the Gene Expression Omnibus (GEO) database, we performed partial least squares (PLS) based analysis, which is more sensitive than common variance/regression analysis. We acquired 512 differentially expressed genes. Four pathways were found to be enriched with differentially expressed genes, involving immune system, metabolism and genetic information processing process. Network analysis identified five hub genes with degrees higher than 10, including APP, ESR1, SMAD3, HDAC2, and PRKAA1. Our findings provide new understanding for the molecular difference between TIC featured ER- and ER+ breast tumors with the hope offer supports for therapeutic studies.

Effect of substituents on prediction of TLC retention of tetra-dentate Schiff bases and their Copper(II) and Nickel(II) complexes.

PubMed

Stevanović, Nikola R; Perušković, Danica S; Gašić, Uroš M; Antunović, Vesna R; Lolić, Aleksandar Đ; Baošić, Rada M

2017-03-01

The objectives of this study were to gain insights into structure-retention relationships and to propose the model to estimating their retention. Chromatographic investigation of series of 36 Schiff bases and their copper(II) and nickel(II) complexes was performed under both normal- and reverse-phase conditions. Chemical structures of the compounds were characterized by molecular descriptors which are calculated from the structure and related to the chromatographic retention parameters by multiple linear regression analysis. Effects of chelation on retention parameters of investigated compounds, under normal- and reverse-phase chromatographic conditions, were analyzed by principal component analysis, quantitative structure-retention relationship and quantitative structure-activity relationship models were developed on the basis of theoretical molecular descriptors, calculated exclusively from molecular structure, and parameters of retention and lipophilicity. Copyright © 2016 John Wiley & Sons, Ltd.

Homology and the optimization of DNA sequence data

NASA Technical Reports Server (NTRS)

Wheeler, W.

2001-01-01

Three methods of nucleotide character analysis are discussed. Their implications for molecular sequence homology and phylogenetic analysis are compared. The criterion of inter-data set congruence, both character based and topological, are applied to two data sets to elucidate and potentially discriminate among these parsimony-based ideas. c2001 The Willi Hennig Society.

Phylogeny of Kinorhyncha Based on Morphology and Two Molecular Loci

PubMed Central

Sørensen, Martin V.; Dal Zotto, Matteo; Rho, Hyun Soo; Herranz, Maria; Sánchez, Nuria; Pardos, Fernando; Yamasaki, Hiroshi

2015-01-01

The phylogeny of Kinorhyncha was analyzed using morphology and the molecular loci 18S rRNA and 28S rRNA. The different datasets were analyzed separately and in combination, using maximum likelihood and Bayesian Inference. Bayesian inference of molecular sequence data in combination with morphology supported the division of Kinorhyncha into two major clades: Cyclorhagida comb. nov. and Allomalorhagida nom. nov. The latter clade represents a new kinorhynch class, and accommodates Dracoderes, Franciscideres, a yet undescribed genus which is closely related with Franciscideres, and the traditional homalorhagid genera. Homalorhagid monophyly was not supported by any analyses with molecular sequence data included. Analysis of the combined molecular and morphological data furthermore supported a cyclorhagid clade which included all traditional cyclorhagid taxa, except Dracoderes that no longer should be considered a cyclorhagid genus. Accordingly, Cyclorhagida is divided into three main lineages: Echinoderidae, Campyloderidae, and a large clade, ‘Kentrorhagata’, which except for species of Campyloderes, includes all species with a midterminal spine present in adult individuals. Maximum likelihood analysis of the combined datasets produced a rather unresolved tree that was not regarded in the following discussion. Results of the analyses with only molecular sequence data included were incongruent at different points. However, common for all analyses was the support of several major clades, i.e., Campyloderidae, Kentrorhagata, Echinoderidae, Dracoderidae, Pycnophyidae, and a clade with Paracentrophyes + New Genus and Franciscideres (in those analyses where the latter was included). All molecular analyses including 18S rRNA sequence data furthermore supported monophyly of Allomalorhagida. Cyclorhagid monophyly was only supported in analyses of combined 18S rRNA and 28S rRNA (both ML and BI), and only in a restricted dataset where taxa with incomplete information from 28S rRNA had been omitted. Analysis of the morphological data produced results that were similar with those from the combined molecular and morphological analysis. E.g., the morphological data also supported exclusion of Dracoderes from Cyclorhagida. The main differences between the morphological analysis and analyses based on the combined datasets include: 1) Homalorhagida appears as monophyletic in the morphological tree only, 2) the morphological analyses position Franciscideres and the new genus within Cyclorhagida near Zelinkaderidae and Cateriidae, whereas analyses including molecular data place the two genera inside Allomalorhagida, and 3) species of Campyloderes appear in a basal trichotomy within Kentrorhagata in the morphological tree, whereas analysis of the combined datasets places species of Campyloderes as a sister clade to Echinoderidae and Kentrorhagata. PMID:26200115

Insight into the interaction mechanism of human SGLT2 with its inhibitors: 3D-QSAR studies, homology modeling, and molecular docking and molecular dynamics simulations.

PubMed

Dong, Lili; Feng, Ruirui; Bi, Jiawei; Shen, Shengqiang; Lu, Huizhe; Zhang, Jianjun

2018-03-06

Human sodium-dependent glucose co-transporter 2 (hSGLT2) is a crucial therapeutic target in the treatment of type 2 diabetes. In this study, both comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were applied to generate three-dimensional quantitative structure-activity relationship (3D-QSAR) models. In the most accurate CoMFA-based and CoMSIA-based QSAR models, the cross-validated coefficients (r 2 cv ) were 0.646 and 0.577, respectively, while the non-cross-validated coefficients (r 2 ) were 0.997 and 0.991, respectively, indicating that both models were reliable. In addition, we constructed a homology model of hSGLT2 in the absence of a crystal structure. Molecular docking was performed to explore the bonding mode of inhibitors to the active site of hSGLT2. Molecular dynamics (MD) simulations and binding free energy calculations using MM-PBSA and MM-GBSA were carried out to further elucidate the interaction mechanism. With regards to binding affinity, we found that hydrogen-bond interactions of Asn51 and Glu75, located in the active site of hSGLT2, with compound 40 were critical. Hydrophobic and electrostatic interactions were shown to enhance activity, in agreement with the results obtained from docking and 3D-QSAR analysis. Our study results shed light on the interaction mode between inhibitors and hSGLT2 and may aid in the development of C-aryl glucoside SGLT2 inhibitors.

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

NASA Astrophysics Data System (ADS)

Xia, Hua

2012-06-01

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

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.

First report on 3D-QSAR and molecular dynamics based docking studies of GCPII inhibitors for targeted drug delivery applications

NASA Astrophysics Data System (ADS)

Pandit, Amit; Sengupta, Sagnik; Krishnan, Mena Asha; Reddy, Ramesh B.; Sharma, Rajesh; Venkatesh, Chelvam

2018-05-01

Prostate Specific Membrane Antigen (PSMA) or Glutamate carboxypeptidase II (GCPII) has been identified as an important target in diagnosis and therapy of prostate cancer. Among several types of inhibitors, urea based inhibitors are the most common and widely employed in preclinical and clinical studies. Computational studies have been carried out to uncover active sites and interaction of PSMA inhibitors with the protein by modifying the core structure of the ligand. Analysis of the literature, however, show lack of 3-D quantitative structure activity relationship (QSAR) and molecular dynamics based molecular docking study to identify structural modifications responsible for better GCPII inhibitory activity. The present study aims to fulfil this gap by analysing well known PSMA inhibitors reported in the literature with known experimental PSMA inhibition constants. Also in order to validate the in silico study, a new GCPII inhibitor 7 was designed, synthesized and experimental PSMA enzyme inhibition was evaluated by using freshly isolated PSMA protein from human cancer cell line derived from lymph node, LNCaP. 3D-QSAR CoMFA models on 58 urea based GCPII inhibitors were generated, and the best correlation was obtained in Gast-Huck charge assigning method with q2, r2 and predictive r2 values as 0.592, 0.995 and 0.842 respectively. Moreover, steric, electrostatic, and hydrogen bond donor field contribution analysis provided best statistical values from CoMSIA model (q2, r2 and predictive r2 as 0.527, 0.981 and 0.713 respectively). Contour maps study revealed that electrostatic field contribution is the major factor for discovering better binding affinity ligands. Further molecular dynamic assisted molecular docking was also performed on GCPII receptor (PDB ID 4NGM) and most active GCPII inhibitor, DCIBzL. 4NGM co-crystallised ligand, JB7 was used to validate the docking procedure and the amino acid interactions present in JB7 are compared with DCIBzL. The results suggest that Arg210, Asn257, Gly518, Tyr552, Lys699, and Tyr700 amino acid residues may play a crucial role in GCPII inhibition. Molecular Dynamics Simulation provides information about docked pose stability of DCIBzL. By combination of CoMFA-CoMSIA field analysis and docking interaction analysis studies, conclusive SAR was generated for urea based derivatives based on which GCPII inhibitor 7 was designed and chemically synthesized in our laboratory. Evaluation of GCPII inhibitory activity of 7 by performing NAALADase assay provided IC50 value of 113 nM which is in close agreement with in silico predicted value (119 nM). Thus we have successfully validated our 3D-QSAR and molecular docking based designing of GCPII inhibitors methodology through biological experiments. This conclusive SAR would be helpful to generate novel and more potent GCPII inhibitors for drug delivery applications.

Molecular Bases of Enantioselectivity of Haloalkane Dehalogenase DbjA

NASA Astrophysics Data System (ADS)

Sato, Yukari; Natsume, Ryo; Prokop, Zbynek; Brezovsky, Jan; Chaloupkova, Radka; Damborsky, Jiri; Nagata, Yuji; Senda, Toshiya

Enzymes are widely used for the synthesis of pharmaceuticals, agrochemicals, and food additives because they can catalyze high enantioselective transformations. In order to construct selective enzymes by protein engineering, it is important to understand the molecular basis of enzyme-substrate interactions that contribute to enantioselectivity. The haloalkane dehalogenase DbjA showed high enantioselectivity for two racemic mixtures: α-bromoesters and β-bromoalkanes. Thermodynamic analysis, protein crystallography, and computer simulations indicated that DbjA carries two bases for the enantiodiscrimination of each racemic mixture. This study helps us understand the molecular basis of the enantioselectivity and opens up new possibilities for constructing enantiospecific biocatalysts through protein engineering.

Application of multiplex PCR, pulsed-field gel electrophoresis (PFGE), and BOX-PCR for molecular analysis of enterococci

USDA-ARS?s Scientific Manuscript database

The objective of the study was to use band-based molecular methods including BOX-PCR (Polymerase Chain Reaction) and Pulsed-Field Gel Electrophoresis (PFGE) to determine if genetically related enterococci were found among different stores, food types, or years. Enterococci were also characterized f...

Discrimination of the rare medicinal plant Dendrobium officinale based on naringenin, bibenzyl, and polysaccharides.

PubMed

Chen, Xiaomei; Wang, Fangfei; Wang, Yunqiang; Li, Xuelan; Wang, Airong; Wang, Chunlan; Guo, Shunxing

2012-12-01

The aim of this study was to establish a method for discriminating Dendrobium officinale from four of its close relatives Dendrobium chrysanthum, Dendrobium crystallinum, Dendrobium aphyllum and Dendrobium devonianum based on chemical composition analysis. We analyzed 62 samples of 24 Dendrobium species. High performance liquid chromatography analysis confirmed that the four low molecular weight compounds 4',5,7-trihydroxyflavanone (naringenin), 3,4-dihydroxy-4',5-dime-thoxybibenzyl (DDB-2), 3',4-dihydroxy-3,5'-dimethoxybibenzyl (gigantol), and 4,4'-dihydroxy-3,3',5-trimethoxybibenzy (moscatilin), were common in the genus. The phenol-sulfuric acid method was used to quantify polysaccharides, and the monosaccharide composition of the polysaccharides was determined by gas chromatography. Stepwise discriminant analysis was used to differentiate among the five closely related species based on the chemical composition analysis. This proved to be a simple and accurate approach for discriminating among these species. The results also showed that the polysaccharide content, the amounts of the four low molecular weight compounds, and the mannose to glucose ratio, were important factors for species discriminant. Therefore, we propose that a chemical analysis based on quantification of naringenin, bibenzyl, and polysaccharides is effective for identifying D. officinale.

Three-dimensional quantitative structure-activity relationship analysis for human pregnane X receptor for the prediction of CYP3A4 induction in human hepatocytes: structure-based comparative molecular field analysis.

PubMed

Handa, Koichi; Nakagome, Izumi; Yamaotsu, Noriyuki; Gouda, Hiroaki; Hirono, Shuichi

2015-01-01

The pregnane X receptor [PXR (NR1I2)] induces the expression of xenobiotic metabolic genes and transporter genes. In this study, we aimed to establish a computational method for quantifying the enzyme-inducing potencies of different compounds via their ability to activate PXR, for the application in drug discovery and development. To achieve this purpose, we developed a three-dimensional quantitative structure-activity relationship (3D-QSAR) model using comparative molecular field analysis (CoMFA) for predicting enzyme-inducing potencies, based on computer-ligand docking to multiple PXR protein structures sampled from the trajectory of a molecular dynamics simulation. Molecular mechanics-generalized born/surface area scores representing the ligand-protein-binding free energies were calculated for each ligand. As a result, the predicted enzyme-inducing potencies for compounds generated by the CoMFA model were in good agreement with the experimental values. Finally, we concluded that this 3D-QSAR model has the potential to predict the enzyme-inducing potencies of novel compounds with high precision and therefore has valuable applications in the early stages of the drug discovery process. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Phylogeny of Salsoleae s.l. (Chenopodiaceae) based on DNA sequence data from ITS, psbB-psbH, and rbcL, with emphasis on taxa of northwestern China

Treesearch

Zhi-Bin Wen; Ming-Li Zhang; Ge-Lin Zhu; Stewart C. Sanderson

2010-01-01

To reconstruct phylogeny and verify the monophyly of major subgroups, a total of 52 species representing almost all species of Salsoleae s.l. in China were sampled, with analysis based on three molecular markers (nrDNA ITS, cpDNA psbB-psbH and rbcL), using maximum parsimony, maximum likelihood, and Bayesian inference methods. Our molecular evidence provides strong...

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

PubMed

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

2013-04-01

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

A ligand-based comparative molecular field analysis (CoMFA) and homology model based molecular docking studies on 3', 4'-dihydroxyflavones as rat 5-lipoxygenase inhibitors: Design of new inhibitors.

PubMed

Ahamed, T K Shameera; Muraleedharan, K

2017-12-01

In this study, ligand based comparative molecular field analysis (CoMFA) with five principal components was performed on class of 3', 4'-dihydroxyflavone derivatives for potent rat 5-LOX inhibitors. The percentage contributions in building of CoMFA model were 91.36% for steric field and 8.6% for electrostatic field. R 2 values for training and test sets were found to be 0.9320 and 0.8259, respectively. In case of LOO, LTO and LMO cross validation test, q 2 values were 0.6587, 0.6479 and 0.5547, respectively. These results indicate that the model has high statistical reliability and good predictive power. The extracted contour maps were used to identify the important regions where the modification was necessary to design a new molecule with improved activity. The study has developed a homology model for rat 5-LOX and recognized the key residues at the binding site. Docking of most active molecule to the binding site of 5-LOX confirmed the stability and rationality of CoMFA model. Based on molecular docking results and CoMFA contour plots, new inhibitors with higher activity with respect to the most active compound in data set were designed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Microfluidic Exosome Analysis toward Liquid Biopsy for Cancer.

PubMed

He, Mei; Zeng, Yong

2016-08-01

Assessment of a tumor's molecular makeup using biofluid samples, known as liquid biopsy, is a prominent research topic in precision medicine for cancer, due to its noninvasive property allowing repeat sampling for monitoring molecular changes of tumors over time. Circulating exosomes recently have been recognized as promising tumor surrogates because they deliver enriched biomarkers, such as proteins, RNAs, and DNA. However, purification and characterization of these exosomes are technically challenging. Microfluidic lab-on-a-chip technology effectively addresses these challenges owing to its inherent advantages in integration and automation of multiple functional modules, enhancing sensing performance, and expediting analysis processes. In this article, we review the state-of-the-art development of microfluidic technologies for exosome isolation and molecular characterization with emphasis on their applications toward liquid biopsy-based analysis of cancer. Finally, we share our perspectives on current challenges and future directions of microfluidic exosome analysis. © 2016 Society for Laboratory Automation and Screening.

Gene expression-based molecular diagnostic system for malignant gliomas is superior to histological diagnosis.

PubMed

Shirahata, Mitsuaki; Iwao-Koizumi, Kyoko; Saito, Sakae; Ueno, Noriko; Oda, Masashi; Hashimoto, Nobuo; Takahashi, Jun A; Kato, Kikuya

2007-12-15

Current morphology-based glioma classification methods do not adequately reflect the complex biology of gliomas, thus limiting their prognostic ability. In this study, we focused on anaplastic oligodendroglioma and glioblastoma, which typically follow distinct clinical courses. Our goal was to construct a clinically useful molecular diagnostic system based on gene expression profiling. The expression of 3,456 genes in 32 patients, 12 and 20 of whom had prognostically distinct anaplastic oligodendroglioma and glioblastoma, respectively, was measured by PCR array. Next to unsupervised methods, we did supervised analysis using a weighted voting algorithm to construct a diagnostic system discriminating anaplastic oligodendroglioma from glioblastoma. The diagnostic accuracy of this system was evaluated by leave-one-out cross-validation. The clinical utility was tested on a microarray-based data set of 50 malignant gliomas from a previous study. Unsupervised analysis showed divergent global gene expression patterns between the two tumor classes. A supervised binary classification model showed 100% (95% confidence interval, 89.4-100%) diagnostic accuracy by leave-one-out cross-validation using 168 diagnostic genes. Applied to a gene expression data set from a previous study, our model correlated better with outcome than histologic diagnosis, and also displayed 96.6% (28 of 29) consistency with the molecular classification scheme used for these histologically controversial gliomas in the original article. Furthermore, we observed that histologically diagnosed glioblastoma samples that shared anaplastic oligodendroglioma molecular characteristics tended to be associated with longer survival. Our molecular diagnostic system showed reproducible clinical utility and prognostic ability superior to traditional histopathologic diagnosis for malignant glioma.

Recent Progress of Microfluidics in Translational Applications.

PubMed

Liu, Zongbin; Han, Xin; Qin, Lidong

2016-04-20

Microfluidics, featuring microfabricated structures, is a technology for manipulating fluids at the micrometer scale. The small dimension and flexibility of microfluidic systems are ideal for mimicking molecular and cellular microenvironment, and show great potential in translational research and development. Here, the recent progress of microfluidics in biological and biomedical applications, including molecular analysis, cellular analysis, and chip-based material delivery and biomimetic design is presented. The potential future developments in the translational microfluidics field are also discussed. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

DTIC Science & Technology

2011-06-17

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

Molecular Analysis of Date Palm Genetic Diversity Using Random Amplified Polymorphic DNA (RAPD) and Inter-Simple Sequence Repeats (ISSRs).

PubMed

El Sharabasy, Sherif F; Soliman, Khaled A

2017-01-01

The date palm is an ancient domesticated plant with great diversity and has been cultivated in the Middle East and North Africa for at last 5000 years. Date palm cultivars are classified based on the fruit moisture content, as dry, semidry, and soft dates. There are a number of biochemical and molecular techniques available for characterization of the date palm variation. This chapter focuses on the DNA-based markers random amplified polymorphic DNA (RAPD) and inter-simple sequence repeats (ISSR) techniques, in addition to biochemical markers based on isozyme analysis. These techniques coupled with appropriate statistical tools proved useful for determining phylogenetic relationships among date palm cultivars and provide information resources for date palm gene banks.

Non-destructive analysis of the conformational differences among feedstock sources and their corresponding co-products from bioethanol production with molecular spectroscopy.

PubMed

Gamage, I H; Jonker, A; Zhang, X; Yu, P

2014-01-24

The objective of this study was to determine the possibility of using molecular spectroscopy with multivariate technique as a fast method to detect the source effects among original feedstock sources of wheat and their corresponding co-products, wheat DDGS, from bioethanol production. Different sources of the bioethanol feedstock and their corresponding bioethanol co-products, three samples per source, were collected from the same newly-built bioethanol plant with current bioethanol processing technology. Multivariate molecular spectral analyses were carried out using agglomerative hierarchical cluster analysis (AHCA) and principal component analysis (PCA). The molecular spectral data of different feedstock sources and their corresponding co-products were compared at four different regions of ca. 1800-1725 cm(-1) (carbonyl CO ester, mainly related to lipid structure conformation), ca. 1725-1482 cm(-1) (amide I and amide II region mainly related to protein structure conformation), ca. 1482-1180 cm(-1) (mainly associated with structural carbohydrate) and ca. 1180-800 cm(-1) (mainly related to carbohydrates) in complex plant-based system. The results showed that the molecular spectroscopy with multivariate technique could reveal the structural differences among the bioethanol feedstock sources and among their corresponding co-products. The AHCA and PCA analyses were able to distinguish the molecular structure differences associated with chemical functional groups among the different sources of the feedstock and their corresponding co-products. The molecular spectral differences indicated the differences in functional, biomolecular and biopolymer groups which were confirmed by wet chemical analysis. These biomolecular and biopolymer structural differences were associated with chemical and nutrient profiles and nutrient utilization and availability. Molecular spectral analyses had the potential to identify molecular structure difference among bioethanol feedstock sources and their corresponding co-products. Copyright © 2013 Elsevier B.V. All rights reserved.

Non-destructive analysis of the conformational differences among feedstock sources and their corresponding co-products from bioethanol production with molecular spectroscopy

NASA Astrophysics Data System (ADS)

Gamage, I. H.; Jonker, A.; Zhang, X.; Yu, P.

2014-01-01

The objective of this study was to determine the possibility of using molecular spectroscopy with multivariate technique as a fast method to detect the source effects among original feedstock sources of wheat and their corresponding co-products, wheat DDGS, from bioethanol production. Different sources of the bioethanol feedstock and their corresponding bioethanol co-products, three samples per source, were collected from the same newly-built bioethanol plant with current bioethanol processing technology. Multivariate molecular spectral analyses were carried out using agglomerative hierarchical cluster analysis (AHCA) and principal component analysis (PCA). The molecular spectral data of different feedstock sources and their corresponding co-products were compared at four different regions of ca. 1800-1725 cm-1 (carbonyl Cdbnd O ester, mainly related to lipid structure conformation), ca. 1725-1482 cm-1 (amide I and amide II region mainly related to protein structure conformation), ca. 1482-1180 cm-1 (mainly associated with structural carbohydrate) and ca. 1180-800 cm-1 (mainly related to carbohydrates) in complex plant-based system. The results showed that the molecular spectroscopy with multivariate technique could reveal the structural differences among the bioethanol feedstock sources and among their corresponding co-products. The AHCA and PCA analyses were able to distinguish the molecular structure differences associated with chemical functional groups among the different sources of the feedstock and their corresponding co-products. The molecular spectral differences indicated the differences in functional, biomolecular and biopolymer groups which were confirmed by wet chemical analysis. These biomolecular and biopolymer structural differences were associated with chemical and nutrient profiles and nutrient utilization and availability. Molecular spectral analyses had the potential to identify molecular structure difference among bioethanol feedstock sources and their corresponding co-products.

Establishment of a Molecular Serotyping Scheme and a Multiplexed Luminex-Based Array for Enterobacter aerogenes

PubMed Central

Guo, Xi; Wang, Min; Wang, Lu; Wang, Yao; Chen, Tingting; Wu, Pan; Chen, Min; Liu, Bin; Feng, Lu

2018-01-01

Serotyping based on surface polysaccharide antigens is important for the clinical detection and epidemiological surveillance of pathogens. Polysaccharide gene clusters (PSgcs) are typically responsible for the diversity of bacterial surface polysaccharides. Through whole-genome sequencing and analysis, eight putative PSgc types were identified in 23 Enterobacter aerogenes strains from several geographic areas, allowing us to present the first molecular serotyping system for E. aerogenes. A conventional antigenic scheme was also established and correlated well with the molecular serotyping system that was based on PSgc genetic variation, indicating that PSgc-based molecular typing and immunological serology provide equally valid results. Further, a multiplex Luminex-based array was developed, and a double-blind test was conducted with 97 clinical specimens from Shanghai, China, to validate our array. The results of these analyses indicated that strains containing PSgc4 and PSgc7 comprised the predominant groups. We then examined 86 publicly available E. aerogenes strain genomes and identified an additional seven novel PSgc types, with PSgc10 being the most abundant type. In total, our study identified 15 PSgc types in E. aerogenes, providing the basis for a molecular serotyping scheme. From these results, differing epidemic patterns were identified between strains that were predominant in different regions. Our study highlights the feasibility and reliability of a serotyping system based on PSgc diversity, and for the first time, presents a molecular serotyping system, as well as an antigenic scheme for E. aerogenes, providing the basis for molecular diagnostics and epidemiological surveillance of this important emerging pathogen. PMID:29616012

Establishment of a Molecular Serotyping Scheme and a Multiplexed Luminex-Based Array for Enterobacter aerogenes.

PubMed

Guo, Xi; Wang, Min; Wang, Lu; Wang, Yao; Chen, Tingting; Wu, Pan; Chen, Min; Liu, Bin; Feng, Lu

2018-01-01

Serotyping based on surface polysaccharide antigens is important for the clinical detection and epidemiological surveillance of pathogens. Polysaccharide gene clusters (PSgcs) are typically responsible for the diversity of bacterial surface polysaccharides. Through whole-genome sequencing and analysis, eight putative PSgc types were identified in 23 Enterobacter aerogenes strains from several geographic areas, allowing us to present the first molecular serotyping system for E. aerogenes . A conventional antigenic scheme was also established and correlated well with the molecular serotyping system that was based on PSgc genetic variation, indicating that PSgc-based molecular typing and immunological serology provide equally valid results. Further, a multiplex Luminex-based array was developed, and a double-blind test was conducted with 97 clinical specimens from Shanghai, China, to validate our array. The results of these analyses indicated that strains containing PSgc4 and PSgc7 comprised the predominant groups. We then examined 86 publicly available E. aerogenes strain genomes and identified an additional seven novel PSgc types, with PSgc10 being the most abundant type. In total, our study identified 15 PSgc types in E. aerogenes , providing the basis for a molecular serotyping scheme. From these results, differing epidemic patterns were identified between strains that were predominant in different regions. Our study highlights the feasibility and reliability of a serotyping system based on PSgc diversity, and for the first time, presents a molecular serotyping system, as well as an antigenic scheme for E. aerogenes , providing the basis for molecular diagnostics and epidemiological surveillance of this important emerging pathogen.

MoleculaRnetworks: an integrated graph theoretic and data mining tool to explore solvent organization in molecular simulation.

PubMed

Mooney, Barbara Logan; Corrales, L René; Clark, Aurora E

2012-03-30

This work discusses scripts for processing molecular simulations data written using the software package R: A Language and Environment for Statistical Computing. These scripts, named moleculaRnetworks, are intended for the geometric and solvent network analysis of aqueous solutes and can be extended to other H-bonded solvents. New algorithms, several of which are based on graph theory, that interrogate the solvent environment about a solute are presented and described. This includes a novel method for identifying the geometric shape adopted by the solvent in the immediate vicinity of the solute and an exploratory approach for describing H-bonding, both based on the PageRank algorithm of Google search fame. The moleculaRnetworks codes include a preprocessor, which distills simulation trajectories into physicochemical data arrays, and an interactive analysis script that enables statistical, trend, and correlation analysis, and other data mining. The goal of these scripts is to increase access to the wealth of structural and dynamical information that can be obtained from molecular simulations. Copyright © 2012 Wiley Periodicals, Inc.

AtomicChargeCalculator: interactive web-based calculation of atomic charges in large biomolecular complexes and drug-like molecules.

PubMed

Ionescu, Crina-Maria; Sehnal, David; Falginella, Francesco L; Pant, Purbaj; Pravda, Lukáš; Bouchal, Tomáš; Svobodová Vařeková, Radka; Geidl, Stanislav; Koča, Jaroslav

2015-01-01

Partial atomic charges are a well-established concept, useful in understanding and modeling the chemical behavior of molecules, from simple compounds, to large biomolecular complexes with many reactive sites. This paper introduces AtomicChargeCalculator (ACC), a web-based application for the calculation and analysis of atomic charges which respond to changes in molecular conformation and chemical environment. ACC relies on an empirical method to rapidly compute atomic charges with accuracy comparable to quantum mechanical approaches. Due to its efficient implementation, ACC can handle any type of molecular system, regardless of size and chemical complexity, from drug-like molecules to biomacromolecular complexes with hundreds of thousands of atoms. ACC writes out atomic charges into common molecular structure files, and offers interactive facilities for statistical analysis and comparison of the results, in both tabular and graphical form. Due to high customizability and speed, easy streamlining and the unified platform for calculation and analysis, ACC caters to all fields of life sciences, from drug design to nanocarriers. ACC is freely available via the Internet at http://ncbr.muni.cz/ACC.

A novel integrated framework and improved methodology of computer-aided drug design.

PubMed

Chen, Calvin Yu-Chian

2013-01-01

Computer-aided drug design (CADD) is a critical initiating step of drug development, but a single model capable of covering all designing aspects remains to be elucidated. Hence, we developed a drug design modeling framework that integrates multiple approaches, including machine learning based quantitative structure-activity relationship (QSAR) analysis, 3D-QSAR, Bayesian network, pharmacophore modeling, and structure-based docking algorithm. Restrictions for each model were defined for improved individual and overall accuracy. An integration method was applied to join the results from each model to minimize bias and errors. In addition, the integrated model adopts both static and dynamic analysis to validate the intermolecular stabilities of the receptor-ligand conformation. The proposed protocol was applied to identifying HER2 inhibitors from traditional Chinese medicine (TCM) as an example for validating our new protocol. Eight potent leads were identified from six TCM sources. A joint validation system comprised of comparative molecular field analysis, comparative molecular similarity indices analysis, and molecular dynamics simulation further characterized the candidates into three potential binding conformations and validated the binding stability of each protein-ligand complex. The ligand pathway was also performed to predict the ligand "in" and "exit" from the binding site. In summary, we propose a novel systematic CADD methodology for the identification, analysis, and characterization of drug-like candidates.

minepath.org: a free interactive pathway analysis web server.

PubMed

Koumakis, Lefteris; Roussos, Panos; Potamias, George

2017-07-03

( www.minepath.org ) is a web-based platform that elaborates on, and radically extends the identification of differentially expressed sub-paths in molecular pathways. Besides the network topology, the underlying MinePath algorithmic processes exploit exact gene-gene molecular relationships (e.g. activation, inhibition) and are able to identify differentially expressed pathway parts. Each pathway is decomposed into all its constituent sub-paths, which in turn are matched with corresponding gene expression profiles. The highly ranked, and phenotype inclined sub-paths are kept. Apart from the pathway analysis algorithm, the fundamental innovation of the MinePath web-server concerns its advanced visualization and interactive capabilities. To our knowledge, this is the first pathway analysis server that introduces and offers visualization of the underlying and active pathway regulatory mechanisms instead of genes. Other features include live interaction, immediate visualization of functional sub-paths per phenotype and dynamic linked annotations for the engaged genes and molecular relations. The user can download not only the results but also the corresponding web viewer framework of the performed analysis. This feature provides the flexibility to immediately publish results without publishing source/expression data, and get all the functionality of a web based pathway analysis viewer. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Evaluation by latent class analysis of a magnetic capture based DNA extraction followed by real-time qPCR as a new diagnostic method for detection of Echinococcus multilocularis in definitive hosts.

PubMed

Maas, Miriam; van Roon, Annika; Dam-Deisz, Cecile; Opsteegh, Marieke; Massolo, Alessandro; Deksne, Gunita; Teunis, Peter; van der Giessen, Joke

2016-10-30

A new method, based on a magnetic capture based DNA extraction followed by qPCR, was developed for the detection of the zoonotic parasite Echinococcus multilocularis in definitive hosts. Latent class analysis was used to compare this new method with the currently used phenol-chloroform DNA extraction followed by single tube nested PCR. In total, 60 red foxes and coyotes from three different locations were tested with both molecular methods and the sedimentation and counting technique (SCT) or intestinal scraping technique (IST). Though based on a limited number of samples, it could be established that the magnetic capture based DNA extraction followed by qPCR showed similar sensitivity and specificity as the currently used phenol-chloroform DNA extraction followed by single tube nested PCR. All methods have a high specificity as shown by Bayesian latent class analysis. Both molecular assays have higher sensitivities than the combined SCT and IST, though the uncertainties in sensitivity estimates were wide for all assays tested. The magnetic capture based DNA extraction followed by qPCR has the advantage of not requiring hazardous chemicals like the phenol-chloroform DNA extraction followed by single tube nested PCR. This supports the replacement of the phenol-chloroform DNA extraction followed by single tube nested PCR by the magnetic capture based DNA extraction followed by qPCR for molecular detection of E. multilocularis in definitive hosts. Copyright © 2016 Elsevier B.V. All rights reserved.

Monte Carlo Analysis of Molecule Absorption Probabilities in Diffusion-Based Nanoscale Communication Systems with Multiple Receivers.

PubMed

Arifler, Dogu; Arifler, Dizem

2017-04-01

For biomedical applications of nanonetworks, employing molecular communication for information transport is advantageous over nano-electromagnetic communication: molecular communication is potentially biocompatible and inherently energy-efficient. Recently, several studies have modeled receivers in diffusion-based molecular communication systems as "perfectly monitoring" or "perfectly absorbing" spheres based on idealized descriptions of chemoreception. In this paper, we focus on perfectly absorbing receivers and present methods to improve the accuracy of simulation procedures that are used to analyze these receivers. We employ schemes available from the chemical physics and biophysics literature and outline a Monte Carlo simulation algorithm that accounts for the possibility of molecule absorption during discrete time steps, leading to a more accurate analysis of absorption probabilities. Unlike most existing studies that consider a single receiver, this paper analyzes absorption probabilities for multiple receivers deterministically or randomly deployed in a region. For random deployments, the ultimate absorption probabilities as a function of transmitter-receiver distance are shown to fit well to power laws; the exponents derived become more negative as the number of receivers increases up to a limit beyond which no additional receivers can be "packed" in the deployment region. This paper is expected to impact the design of molecular nanonetworks with multiple absorbing receivers.

Molecular ecological network analyses.

PubMed

Deng, Ye; Jiang, Yi-Huei; Yang, Yunfeng; He, Zhili; Luo, Feng; Zhou, Jizhong

2012-05-30

Understanding the interaction among different species within a community and their responses to environmental changes is a central goal in ecology. However, defining the network structure in a microbial community is very challenging due to their extremely high diversity and as-yet uncultivated status. Although recent advance of metagenomic technologies, such as high throughout sequencing and functional gene arrays, provide revolutionary tools for analyzing microbial community structure, it is still difficult to examine network interactions in a microbial community based on high-throughput metagenomics data. Here, we describe a novel mathematical and bioinformatics framework to construct ecological association networks named molecular ecological networks (MENs) through Random Matrix Theory (RMT)-based methods. Compared to other network construction methods, this approach is remarkable in that the network is automatically defined and robust to noise, thus providing excellent solutions to several common issues associated with high-throughput metagenomics data. We applied it to determine the network structure of microbial communities subjected to long-term experimental warming based on pyrosequencing data of 16 S rRNA genes. We showed that the constructed MENs under both warming and unwarming conditions exhibited topological features of scale free, small world and modularity, which were consistent with previously described molecular ecological networks. Eigengene analysis indicated that the eigengenes represented the module profiles relatively well. In consistency with many other studies, several major environmental traits including temperature and soil pH were found to be important in determining network interactions in the microbial communities examined. To facilitate its application by the scientific community, all these methods and statistical tools have been integrated into a comprehensive Molecular Ecological Network Analysis Pipeline (MENAP), which is open-accessible now (http://ieg2.ou.edu/MENA). The RMT-based molecular ecological network analysis provides powerful tools to elucidate network interactions in microbial communities and their responses to environmental changes, which are fundamentally important for research in microbial ecology and environmental microbiology.

[Health examination in future at the era of low tuberculosis incidence--from contacts examination toward active epidemiological studies].

PubMed

Maeda, Hideo; Shirai, Chika

2013-03-01

Japan is still "intermediate burden" country as medium-incidence of tuberculosis (TB). But the incidence of TB varies by public health units. The priority for TB control would be lowering in the areas where the incidence of TB is relatively low. In addition, younger age groups get low prevalence of TB infection than elderly persons. As a result, fewer experiences for TB diagnosis and treatment in the hospital and the medical facility would cause the delay in the detection of TB patients which eventually cause outbreaks. Although there are differences in population density and population mobility between urban and rural areas, the socially economic vulnerable patients and foreign patients are the common risks. Any public health units' policies of TB should correspond to the individual situation. At the era of low tuberculosis incidence, the infection risk is to be "From ubiquitous to the uneven distribution". This makes TB detection much more difficult. At this symposium, each speaker presented the case for actually experienced with QFT test and/or VNTR analysis. They mainly focused on the paradigm shift in TB control which is indispensable for resolving the gaps in regional differences and the differences in diagnostic capability. Although the cases in this symposium were not for the low incidence situation, the pioneering approaches presented here would boost the future application of QFT and VNTR analysis nationwide. The discussions also partially covered the technical infrastructure for molecular epidemiology which covers the whole country. By making full use of QFT test and VNTR analysis as a contact screening tool, we can appropriately understand the risk of TB infection in the region from a buildup of bacteria and patient information. Now is the time to prepare for. Active surveillance of TB by this way would clarify the risk of the disease and lead to the advocacy essential for the resolution. 1. Current situation and challenge of contact survey by using QFT test in Tokyo: Hideo MAEDA (Bureau of Social Welfare and Public Health, Tokyo Metropolitan Government). 2. Contact investigation of a tuberculosis outbreak: Kenichi MIYAMOTO (Takaido Community Health Center). We have experienced a TB outbreak in integrated junior and senior high school in Tokyo. Index patient was a student with persistent respiratory symptoms for six months before diagnosis of sputum smear-positive TB. Public health center started contact investigation immediately. QFT-positive rates were high in close contacts, especially in classmates. Additionally, a student outside of contact investigation was diagnosed as TB and considered to be infected from the first patient by VNTR analysis. Therefore, public health center expanded QFT-tests to all students and teachers in this school. Finally, 9 students and 2 teachers in this school were diagnosed as sputum smear-negative TB by contact investigation. 3. Utilization of molecular epidemiological procedure in contact investigation in Kyoto City: Masahiro ITO (Public Health Center of Kyoto City) Molecular epidemiological procedure using VNTR analysis has been used for contact investigation of tuberculosis since January 2011 in Kyoto City. One hundred forty four strains of Mycobacterium tuberculosis from patients with tuberculosis were investigated and 130 strains were fully analyzed. Fourteen clusters were found and the number of strains included in the cluster was ranged from two to 11. Epidemiological relationship between patients in one cluster was found, however, significant relationship in another clusters was not demonstrated. It was suggested that VNTR analysis is useful for molecular epidemiological analysis of tuberculosis. 4. The population based molecular epidemiological studies and QFT test in a contact examination: Riyo FUJIYAMA, Keisuke MATSUBAYASHI, Setsuko MIZUSHIRI, Junko HIGUCHIL Chika SHIRAI, Yuko KATAGAMI, Mieko CHIHARA, Akihiro IJICHI (Kobe City Public Health Center), Kentaro ARIKAWA, Noriko NAKANISHI, Tomotada IWAMOTO (Kobe Institute of Health). The population based molecular epidemiological studies should be made good use of contacts examination. In future, we expect the tuberculosis molecular epdimiological study improve search for the process of tuberculosis infection. The QFT positive rates correlated well with closeness of contact. QFT test is considered useful for diagnosing tuberculosis infection. However, in the judgment of tuberculosis infection, we should consider the total result of contact investigation not only QFT test but also the contact situation. 5. Insights into the TB epidemiology through population based molecular epidemiological studies: Tomotada IWAMOTO (Kobe Institute of Health) The population based molecular epidemiological studies unveiled the transmission dynamics of tuberculosis at bacterial clone level. This provides scientific evidences for achieving better TB control programs. In the advanced stage of the tuberculosis molecular epidemiological study, we expect to change the current geno-typing based molecular epidemiology to whole genome-typing based molecular epidemiology on the basis of the rapid innovation of next-generation sequencing technology.

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

PubMed

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

2015-10-01

Prostate cancer (PCa) molecular subtypes have been defined by essentially mutually exclusive events, including ETS gene fusions (most commonly involving ERG) and SPINK1 overexpression. Clinical assessment may aid in disease stratification, complementing available prognostic tests. To determine the analytical validity and clinicopatholgic associations of microarray-based molecular subtyping. We analyzed Affymetrix GeneChip expression profiles for 1577 patients from eight radical prostatectomy cohorts, including 1351 cases assessed using the Decipher prognostic assay (GenomeDx Biosciences, San Diego, CA, USA) performed in a laboratory with Clinical Laboratory Improvements Amendment certification. A microarray-based (m-) random forest ERG classification model was trained and validated. Outlier expression analysis was used to predict other mutually exclusive non-ERG ETS gene rearrangements (ETS(+)) or SPINK1 overexpression (SPINK1(+)). Associations with clinical features and outcomes by multivariate logistic regression analysis and receiver operating curves. The m-ERG classifier showed 95% accuracy in an independent validation subset (155 samples). Across cohorts, 45% of PCas were classified as m-ERG(+), 9% as m-ETS(+), 8% as m-SPINK1(+), and 38% as triple negative (m-ERG(-)/m-ETS(-)/m-SPINK1(-)). Gene expression profiling supports three underlying molecularly defined groups: m-ERG(+), m-ETS(+), and m-SPINK1(+)/triple negative. On multivariate analysis, m-ERG(+) tumors were associated with lower preoperative serum prostate-specific antigen and Gleason scores, but greater extraprostatic extension (p<0.001). m-ETS(+) tumors were associated with seminal vesicle invasion (p=0.01), while m-SPINK1(+)/triple negative tumors had higher Gleason scores and were more frequent in Black/African American patients (p<0.001). Clinical outcomes were not significantly different among subtypes. A clinically available prognostic test (Decipher) can also assess PCa molecular subtypes, obviating the need for additional testing. Clinicopathologic differences were found among subtypes based on global expression patterns. Molecular subtyping of prostate cancer can be achieved using extra data generated from a clinical-grade, genome-wide expression-profiling prognostic assay (Decipher). Transcriptomic and clinical analysis support three distinct molecular subtypes: (1) m-ERG(+), (2) m-ETS(+), and (3) m-SPINK1(+)/triple negative (m-ERG(-)/m-ETS(-)/m-SPINK1(-)). Incorporation of subtyping into a clinically available assay may facilitate additional applications beyond routine prognosis. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

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.

Detectable states, cycle fluxes, and motility scaling of molecular motor kinesin: An integrative kinetic graph theory analysis

NASA Astrophysics Data System (ADS)

Ren, Jie

2017-12-01

The process by which a kinesin motor couples its ATPase activity with concerted mechanical hand-over-hand steps is a foremost topic of molecular motor physics. Two major routes toward elucidating kinesin mechanisms are the motility performance characterization of velocity and run length, and single-molecular state detection experiments. However, these two sets of experimental approaches are largely uncoupled to date. Here, we introduce an integrative motility state analysis based on a theorized kinetic graph theory for kinesin, which, on one hand, is validated by a wealth of accumulated motility data, and, on the other hand, allows for rigorous quantification of state occurrences and chemomechanical cycling probabilities. An interesting linear scaling for kinesin motility performance across species is discussed as well. An integrative kinetic graph theory analysis provides a powerful tool to bridge motility and state characterization experiments, so as to forge a unified effort for the elucidation of the working mechanisms of molecular motors.

Intracellular applications of fluorescence correlation spectroscopy: prospects for neuroscience.

PubMed

Kim, Sally A; Schwille, Petra

2003-10-01

Based on time-averaging fluctuation analysis of small fluorescent molecular ensembles in equilibrium, fluorescence correlation spectroscopy has recently been applied to investigate processes in the intracellular milieu. The exquisite sensitivity of fluorescence correlation spectroscopy provides access to a multitude of measurement parameters (rates of diffusion, local concentration, states of aggregation and molecular interactions) in real time with fast temporal and high spatial resolution. The introduction of dual-color cross-correlation, imaging, two-photon excitation, and coincidence analysis coupled with fluorescence correlation spectroscopy has expanded the utility of the technique to encompass a wide range of promising applications in living cells that may provide unprecedented insight into understanding the molecular mechanisms of intracellular neurobiological processes.

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

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

Obaid, R.; Applied Chemistry Department, Palestine Polytechnic University, Hebron, Palestine; Leibscher, M., E-mail: monika.leibscher@itp.uni-hannover.de

2015-02-14

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

A phylogenetic analysis of the megadiverse Chalcidoidea (Hymenoptera)

USDA-ARS?s Scientific Manuscript database

Chalcidoidea (Hymenoptera) are extremely diverse with an estimated 500,000 species. We present the first phylogenetic analysis of the superfamily based on a cladistic analysis of both morphological and molecular data. A total of 233 morphological characters were scored for 300 taxa and 265 genera, a...

A methodological investigation of hominoid craniodental morphology and phylogenetics.

PubMed

Bjarnason, Alexander; Chamberlain, Andrew T; Lockwood, Charles A

2011-01-01

The evolutionary relationships of extant great apes and humans have been largely resolved by molecular studies, yet morphology-based phylogenetic analyses continue to provide conflicting results. In order to further investigate this discrepancy we present bootstrap clade support of morphological data based on two quantitative datasets, one dataset consisting of linear measurements of the whole skull from 5 hominoid genera and the second dataset consisting of 3D landmark data from the temporal bone of 5 hominoid genera, including 11 sub-species. Using similar protocols for both datasets, we were able to 1) compare distance-based phylogenetic methods to cladistic parsimony of quantitative data converted into discrete character states, 2) vary outgroup choice to observe its effect on phylogenetic inference, and 3) analyse male and female data separately to observe the effect of sexual dimorphism on phylogenies. Phylogenetic analysis was sensitive to methodological decisions, particularly outgroup selection, where designation of Pongo as an outgroup and removal of Hylobates resulted in greater congruence with the proposed molecular phylogeny. The performance of distance-based methods also justifies their use in phylogenetic analysis of morphological data. It is clear from our analyses that hominoid phylogenetics ought not to be used as an example of conflict between the morphological and molecular, but as an example of how outgroup and methodological choices can affect the outcome of phylogenetic analysis. Copyright © 2010 Elsevier Ltd. All rights reserved.

DSSR-enhanced visualization of nucleic acid structures in Jmol

PubMed Central

Hanson, Robert M.

2017-01-01

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

Detecting transitions in protein dynamics using a recurrence quantification analysis based bootstrap method.

PubMed

Karain, Wael I

2017-11-28

Proteins undergo conformational transitions over different time scales. These transitions are closely intertwined with the protein's function. Numerous standard techniques such as principal component analysis are used to detect these transitions in molecular dynamics simulations. In this work, we add a new method that has the ability to detect transitions in dynamics based on the recurrences in the dynamical system. It combines bootstrapping and recurrence quantification analysis. We start from the assumption that a protein has a "baseline" recurrence structure over a given period of time. Any statistically significant deviation from this recurrence structure, as inferred from complexity measures provided by recurrence quantification analysis, is considered a transition in the dynamics of the protein. We apply this technique to a 132 ns long molecular dynamics simulation of the β-Lactamase Inhibitory Protein BLIP. We are able to detect conformational transitions in the nanosecond range in the recurrence dynamics of the BLIP protein during the simulation. The results compare favorably to those extracted using the principal component analysis technique. The recurrence quantification analysis based bootstrap technique is able to detect transitions between different dynamics states for a protein over different time scales. It is not limited to linear dynamics regimes, and can be generalized to any time scale. It also has the potential to be used to cluster frames in molecular dynamics trajectories according to the nature of their recurrence dynamics. One shortcoming for this method is the need to have large enough time windows to insure good statistical quality for the recurrence complexity measures needed to detect the transitions.

Molecular Diagnostics in Colorectal Carcinoma: Advances and Applications for 2018.

PubMed

Bhalla, Amarpreet; Zulfiqar, Muhammad; Bluth, Martin H

2018-06-01

The molecular pathogenesis and classification of colorectal carcinoma are based on the traditional adenomaecarcinoma sequence, serrated polyp pathway, and microsatellite instability (MSI). The genetic basis for hereditary nonpolyposis colorectal cancer is the detection of mutations in the MLH1, MSH2, MSH6, PMS2, and EPCAM genes. Genetic testing for Lynch syndrome includes MSI testing, methylator phenotype testing, BRAF mutation testing, and molecular testing for germline mutations in MMR genes. Molecular makers with predictive and prognostic implications include quantitative multigene reverse transcriptase polymerase chain reaction assay and KRAS and BRAF mutation analysis. Mismatch repair-deficient tumors have higher rates of programmed death-ligand 1 expression. Cell-free DNA analysis in fluids are proving beneficial for diagnosis and prognosis in these disease states towards effective patient management. Copyright © 2018 Elsevier Inc. All rights reserved.

Molecular characterization of Trichuris serrata.

PubMed

Ketzis, Jennifer K; Verma, Ashutosh; Burgess, Graham

2015-05-01

Trichuris serrata, a whipworm of cats, can cause inflammation in the cecum and upper portion of the large intestine. It is unknown if the virulence and pathology of T. serrata differ from Trichuris campanula, the other species in cats. Distinguishing the species based on egg size is challenging. In addition, Trichuris eggs can be difficult to distinguish from Capillaria spp. This paper presents the first molecular description of T. serrata. The 18S ribosomal RNA (rRNA) gene was sequenced from male adult worms sourced from two unrelated cats on St. Kitts. Based on the analysis of 651 base pairs, T. serrata was found to be different than any other Trichuris species for which published sequencing of the 18S rRNA gene is available. A dendrogram was developed using Molecular Evolutionary Genetics Analysis version 6.0, and evolutionary history was inferred using the minimum evolution method. T. serrata was found to be most closely related to Trichuris vulpis, the Trichuris of dogs. Further development of the methodology could enable distinguishing T. serrata, T. campanula, and Capillaria spp. infections in cats and aid in diagnosis.

Adaptation of Laser Microdissection Technique for the Study of a Spontaneous Metastatic Mammary Carcinoma Mouse Model by NanoString Technologies

PubMed Central

Saylor, Karen L.; Anver, Miriam R.; Salomon, David S.; Golubeva, Yelena G.

2016-01-01

Laser capture microdissection (LCM) of tissue is an established tool in medical research for collection of distinguished cell populations under direct microscopic visualization for molecular analysis. LCM samples have been successfully analyzed in a number of genomic and proteomic downstream molecular applications. However, LCM sample collection and preparation procedure has to be adapted to each downstream analysis platform. In this present manuscript we describe in detail the adaptation of LCM methodology for the collection and preparation of fresh frozen samples for NanoString analysis based on a study of a model of mouse mammary gland carcinoma and its lung metastasis. Our adaptation of LCM sample preparation and workflow to the requirements of the NanoString platform allowed acquiring samples with high RNA quality. The NanoString analysis of such samples provided sensitive detection of genes of interest and their associated molecular pathways. NanoString is a reliable gene expression analysis platform that can be effectively coupled with LCM. PMID:27077656

DNA barcode-based molecular identification system for fish species.

PubMed

Kim, Sungmin; Eo, Hae-Seok; Koo, Hyeyoung; Choi, Jun-Kil; Kim, Won

2010-12-01

In this study, we applied DNA barcoding to identify species using short DNA sequence analysis. We examined the utility of DNA barcoding by identifying 53 Korean freshwater fish species, 233 other freshwater fish species, and 1339 saltwater fish species. We successfully developed a web-based molecular identification system for fish (MISF) using a profile hidden Markov model. MISF facilitates efficient and reliable species identification, overcoming the limitations of conventional taxonomic approaches. MISF is freely accessible at http://bioinfosys.snu.ac.kr:8080/MISF/misf.jsp .

Analyzing ion distributions around DNA: sequence-dependence of potassium ion distributions from microsecond molecular dynamics

PubMed Central

Pasi, Marco; Maddocks, John H.; Lavery, Richard

2015-01-01

Microsecond molecular dynamics simulations of B-DNA oligomers carried out in an aqueous environment with a physiological salt concentration enable us to perform a detailed analysis of how potassium ions interact with the double helix. The oligomers studied contain all 136 distinct tetranucleotides and we are thus able to make a comprehensive analysis of base sequence effects. Using a recently developed curvilinear helicoidal coordinate method we are able to analyze the details of ion populations and densities within the major and minor grooves and in the space surrounding DNA. The results show higher ion populations than have typically been observed in earlier studies and sequence effects that go beyond the nature of individual base pairs or base pair steps. We also show that, in some special cases, ion distributions converge very slowly and, on a microsecond timescale, do not reflect the symmetry of the corresponding base sequence. PMID:25662221

Molecular systematics and Holarctic phylogeography of cestodes of the genus Anoplocephaloides Baer, 1923 s. s. (Cyclophyllidea: Anoplocephalidae) in lemmings (Lemmus, Synaptomys)

USDA-ARS?s Scientific Manuscript database

The present molecular-systematic and phylogeographic analysis is based on sequences of cytochrome c oxidase subunit 1 (cox1) (mtDNA) and 28S ribosomal DNA, and includes 59 isolates of cestodes of the genus Anoplocephaloides Baer, 1923 s. s. (Cyclophyllidea, Anoplocephalidae) from arvicoline rodents ...

Molecular epidemiology of Plum pox virus in Japan.

PubMed

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

2011-05-01

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

Rhizoma Dioscoreae extract protects against alveolar bone loss by regulating the cell cycle: A predictive study based on the protein‑protein interaction network.

PubMed

Zhang, Zhi-Guo; Song, Chang-Heng; Zhang, Fang-Zhen; Chen, Yan-Jing; Xiang, Li-Hua; Xiao, Gary Guishan; Ju, Da-Hong

2016-06-01

Rhizoma Dioscoreae extract (RDE) exhibits a protective effect on alveolar bone loss in ovariectomized (OVX) rats. The aim of this study was to predict the pathways or targets that are regulated by RDE, by re‑assessing our previously reported data and conducting a protein‑protein interaction (PPI) network analysis. In total, 383 differentially expressed genes (≥3‑fold) between alveolar bone samples from the RDE and OVX group rats were identified, and a PPI network was constructed based on these genes. Furthermore, four molecular clusters (A‑D) in the PPI network with the smallest P‑values were detected by molecular complex detection (MCODE) algorithm. Using Database for Annotation, Visualization and Integrated Discovery (DAVID) and Ingenuity Pathway Analysis (IPA) tools, two molecular clusters (A and B) were enriched for biological process in Gene Ontology (GO). Only cluster A was associated with biological pathways in the IPA database. GO and pathway analysis results showed that cluster A, associated with cell cycle regulation, was the most important molecular cluster in the PPI network. In addition, cyclin‑dependent kinase 1 (CDK1) may be a key molecule achieving the cell‑cycle‑regulatory function of cluster A. From the PPI network analysis, it was predicted that delayed cell cycle progression in excessive alveolar bone remodeling via downregulation of CDK1 may be another mechanism underling the anti‑osteopenic effect of RDE on alveolar bone.

Motifs for molecular recognition exploiting hydrophobic enclosure in protein-ligand binding.

PubMed

Young, Tom; Abel, Robert; Kim, Byungchan; Berne, Bruce J; Friesner, Richard A

2007-01-16

The thermodynamic properties and phase behavior of water in confined regions can vary significantly from that observed in the bulk. This is particularly true for systems in which the confinement is on the molecular-length scale. In this study, we use molecular dynamics simulations and a powerful solvent analysis technique based on inhomogenous solvation theory to investigate the properties of water molecules that solvate the confined regions of protein active sites. Our simulations and analysis indicate that the solvation of protein active sites that are characterized by hydrophobic enclosure and correlated hydrogen bonds induce atypical entropic and enthalpic penalties of hydration. These penalties apparently stabilize the protein-ligand complex with respect to the independently solvated ligand and protein, which leads to enhanced binding affinities. Our analysis elucidates several challenging cases, including the super affinity of the streptavidin-biotin system.

Prognostic value of Ki-67 index in adult medulloblastoma after accounting for molecular subgroup: a retrospective clinical and molecular analysis.

PubMed

Zhao, Fu; Zhang, Jing; Li, Peng; Zhou, Qiangyi; Zhang, Shun; Zhao, Chi; Wang, Bo; Yang, Zhijun; Li, Chunde; Liu, Pinan

2018-04-23

Medulloblastoma (MB) is a rare primary brain tumor in adults. We previously evaluated that combining both clinical and molecular classification could improve current risk stratification for adult MB. In this study, we aimed to identify the prognostic value of Ki-67 index in adult MB. Ki-67 index of 51 primary adult MBs was reassessed using a computer-based image analysis (Image-Pro Plus). All patients were followed up ranging from 12 months up to 15 years. Gene expression profiling and immunochemistry were used to establish the molecular subgroups in adult MB. Combined risk stratification models were designed based on clinical characteristics, molecular classification and Ki-67 index, and identified by multivariable Cox proportional hazards analysis. In our cohort, the mean Ki-67 value was 30.0 ± 11.3% (range 6.56-63.55%). The average Ki-67 value was significantly higher in LC/AMB than in CMB and DNMB (P = .001). Among three molecular subgroups, Group 4-tumors had the highest average Ki-67 value compared with WNT- and SHH-tumors (P = .004). Patients with Ki-67 index large than 30% displayed poorer overall survival (OS) and progression free survival (PFS) than those with Ki-67 less than 30% (OS: P = .001; PFS: P = .006). Ki-67 index (i.e. > 30%, < 30%) was identified as an independent significant prognostic factor (OS: P = .017; PFS: P = .024) by using multivariate Cox proportional hazards model. In conclusion, Ki-67 index can be considered as a valuable independent prognostic biomarker for adult patients with MB.

Tuberculosis patients co-infected with Mycobacterium bovis and Mycobacterium tuberculosis in an urban area of Brazil.

PubMed

Silva, Marcio Roberto; Rocha, Adalgiza da Silva; da Costa, Ronaldo Rodrigues; de Alencar, Andrea Padilha; de Oliveira, Vania Maria; Fonseca Júnior, Antônio Augusto; Sales, Mariana Lázaro; Issa, Marina de Azevedo; Filho, Paulo Martins Soares; Pereira, Omara Tereza Vianello; dos Santos, Eduardo Calazans; Mendes, Rejane Silva; Ferreira, Angela Maria de Jesus; Mota, Pedro Moacyr Pinto Coelho; Suffys, Philip Noel; Guimarães, Mark Drew Crosland

2013-05-01

In this cross-sectional study, mycobacteria specimens from 189 tuberculosis (TB) patients living in an urban area in Brazil were characterised from 2008-2010 using phenotypic and molecular speciation methods (pncA gene and oxyR pseudogene analysis). Of these samples, 174 isolates simultaneously grew on Löwenstein-Jensen (LJ) and Stonebrink (SB)-containing media and presented phenotypic and molecular profiles of Mycobacterium tuberculosis, whereas 12 had molecular profiles of M. tuberculosis based on the DNA analysis of formalin-fixed paraffin wax-embedded tissue samples (paraffin blocks). One patient produced two sputum isolates, the first of which simultaneously grew on LJ and SB media and presented phenotypic and molecular profiles of M. tuberculosis, and the second of which only grew on SB media and presented phenotypic profiles of Mycobacterium bovis. One patient provided a bronchial lavage isolate, which simultaneously grew on LJ and SB media and presented phenotypic and molecular profiles of M. tuberculosis, but had molecular profiles of M. bovis from paraffin block DNA analysis, and one sample had molecular profiles of M. tuberculosis and M. bovis identified from two distinct paraffin blocks. Moreover, we found a low prevalence (1.6%) of M. bovis among these isolates, which suggests that local health service procedures likely underestimate its real frequency and that it deserves more attention from public health officials.

SEDFIT-MSTAR: Molecular weight and molecular weight distribution analysis of polymers by sedimentation equilibrium in the ultracentrifuge

PubMed Central

Schuck, Peter; Gillis, Richard B.; Besong, Tabot M.D.; Almutairi, Fahad; Adams, Gary G.; Rowe, Arthur J.; Harding, Stephen E.

2014-01-01

Sedimentation equilibrium (analytical ultracentrifugation) is one of the most inherently suitable methods for the determination of average molecular weights and molecular weight distributions of polymers, because of its absolute basis (no conformation assumptions) and inherent fractionation ability (without the need for columns or membranes and associated assumptions over inertness). With modern instrumentation it is also possible to run up to 21 samples simultaneously in a single run. Its application has been severely hampered because of difficulties in terms of baseline determination (incorporating estimation of the concentration at the air/solution meniscus) and complexity of the analysis procedures. We describe a new method for baseline determination based on a smart-smoothing principle and built into the highly popular platform SEDFIT for the analysis of the sedimentation behavior of natural and synthetic polymer materials. The SEDFIT-MSTAR procedure – which takes only a few minutes to perform - is tested with four synthetic data sets (including a significantly non-ideal system) a naturally occurring protein (human IgG1) and two naturally occurring carbohydrate polymers (pullulan and λ–carrageenan) in terms of (i) weight average molecular weight for the whole distribution of species in the sample (ii) the variation in “point” average molecular weight with local concentration in the ultracentrifuge cell and (iii) molecular weight distribution. PMID:24244936

Dust scattering from the Taurus Molecular Cloud

NASA Astrophysics Data System (ADS)

Narayan, Sathya; Murthy, Jayant; Karuppath, Narayanankutty

2017-04-01

We present an analysis of the diffuse ultraviolet emission near the Taurus Molecular Cloud based on observations made by the Galaxy Evolution Explorer. We used a Monte Carlo dust scattering model to show that about half of the scattered flux originates in the molecular cloud with 25 per cent arising in the foreground and 25 per cent behind the cloud. The best-fitting albedo of the dust grains is 0.3, but the geometry is such that we could not constrain the phase function asymmetry factor (g).

Proceedings of the NATO Advances Research Workshop on Diamond Based Composites, Saint Petersburg, Russia, June 21-22, 1997, Volume 38

DTIC Science & Technology

1997-06-01

composites. The topics ranged from molecular clusters, nanophase materials, growth, processing, and synthesis. Commercial composite materials have been on...example, an analysis of the emission from a GaAs target shows mainly (99.4%) neutral Ga and As atoms. [63] However, the fraction of molecular species...sputtered from ionic crystals can be considerably higher. [64] There is evidence that a large fraction of the molecular species originate from

A novel informatics concept for high-throughput shotgun lipidomics based on the molecular fragmentation query language

PubMed Central

2011-01-01

Shotgun lipidome profiling relies on direct mass spectrometric analysis of total lipid extracts from cells, tissues or organisms and is a powerful tool to elucidate the molecular composition of lipidomes. We present a novel informatics concept of the molecular fragmentation query language implemented within the LipidXplorer open source software kit that supports accurate quantification of individual species of any ionizable lipid class in shotgun spectra acquired on any mass spectrometry platform. PMID:21247462

Synthesis, spectroscopic characterization, DFT studies and antifungal activity of (E)-4-amino-5-[N'-(2-nitro-benzylidene)-hydrazino]-2,4-dihydro-[1,2,4]triazole-3-thione

NASA Astrophysics Data System (ADS)

Joshi, Rachana; Pandey, Nidhi; Yadav, Swatantra Kumar; Tilak, Ragini; Mishra, Hirdyesh; Pokharia, Sandeep

2018-07-01

The hydrazino Schiff base (E)-4-amino-5-[N'-(2-nitro-benzylidene)-hydrazino]-2,4-dihydro-[1,2,4]triazole-3-thione was synthesized and structurally characterized by elemental analysis, FT-IR, Raman, 1H and 13C-NMR and UV-Vis studies. A density functional theory (DFT) based electronic structure calculations were accomplished at B3LYP/6-311++G(d,p) level of theory. A comparative analysis of calculated vibrational frequencies with experimental vibrational frequencies was carried out and significant bands were assigned. The results indicate a good correlation (R2 = 0.9974) between experimental and theoretical IR frequencies. The experimental 1H and 13C-NMR resonance signals were also compared to the calculated values. The theoretical UV-Vis spectral studies were carried out using time dependent-DFT method in gas phase and IEFPCM model in solvent field calculation. The geometrical parameters were calculated in the gas phase. Atomic charges at selected atoms were calculated by Mulliken population analysis (MPA), Hirshfeld population analysis (HPA) and Natural population analysis (NPA) schemes. The molecular electrostatic potential (MEP) map was calculated to assign reactive site on the surface of the molecule. The conceptual-DFT based global and local reactivity descriptors were calculated to obtain an insight into the reactivity behaviour. The frontier molecular orbital analysis was carried out to study the charge transfer within the molecule. The detailed natural bond orbital (NBO) analysis was performed to obtain an insight into the intramolecular conjugative electronic interactions. The titled compound was screened for in vitro antifungal activity against four fungal strains and the results obtained are explained through in silico molecular docking studies.

Evaluation of breast cancer using intravoxel incoherent motion (IVIM) histogram analysis: comparison with malignant status, histological subtype, and molecular prognostic factors.

PubMed

Cho, Gene Young; Moy, Linda; Kim, Sungheon G; Baete, Steven H; Moccaldi, Melanie; Babb, James S; Sodickson, Daniel K; Sigmund, Eric E

2016-08-01

To examine heterogeneous breast cancer through intravoxel incoherent motion (IVIM) histogram analysis. This HIPAA-compliant, IRB-approved retrospective study included 62 patients (age 48.44 ± 11.14 years, 50 malignant lesions and 12 benign) who underwent contrast-enhanced 3 T breast MRI and diffusion-weighted imaging. Apparent diffusion coefficient (ADC) and IVIM biomarkers of tissue diffusivity (Dt), perfusion fraction (fp), and pseudo-diffusivity (Dp) were calculated using voxel-based analysis for the whole lesion volume. Histogram analysis was performed to quantify tumour heterogeneity. Comparisons were made using Mann-Whitney tests between benign/malignant status, histological subtype, and molecular prognostic factor status while Spearman's rank correlation was used to characterize the association between imaging biomarkers and prognostic factor expression. The average values of the ADC and IVIM biomarkers, Dt and fp, showed significant differences between benign and malignant lesions. Additional significant differences were found in the histogram parameters among tumour subtypes and molecular prognostic factor status. IVIM histogram metrics, particularly fp and Dp, showed significant correlation with hormonal factor expression. Advanced diffusion imaging biomarkers show relationships with molecular prognostic factors and breast cancer malignancy. This analysis reveals novel diagnostic metrics that may explain some of the observed variability in treatment response among breast cancer patients. • Novel IVIM biomarkers characterize heterogeneous breast cancer. • Histogram analysis enables quantification of tumour heterogeneity. • IVIM biomarkers show relationships with breast cancer malignancy and molecular prognostic factors.

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

PubMed

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

2015-10-02

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

Molecular dynamics studies of polyurethane nanocomposite hydrogels

NASA Astrophysics Data System (ADS)

Strankowska, J.; Piszczyk, Ł.; Strankowski, M.; Danowska, M.; Szutkowski, K.; Jurga, S.; Kwela, J.

2013-10-01

Polyurethane PEO-based hydrogels have a broad range of biomedical applicability. They are attractive for drug-controlled delivery systems, surgical implants and wound healing dressings. In this study, a PEO based polyurethane hydrogels containing Cloisite® 30B, an organically modified clay mineral, was synthesized. Structure of nanocomposite hydrogels was determined using XRD technique. Its molecular dynamics was studied by means of NMR spectroscopy, DMA and DSC analysis. The mechanical properties and thermal stability of the systems were improved by incorporation of clay and controlled by varying the clay content in polymeric matrix. Molecular dynamics of polymer chains depends on interaction of Cloisite® 30B nanoparticles with soft segments of polyurethanes. The characteristic nanosize effect is observed.

PRO_LIGAND: an approach to de novo molecular design. 2. Design of novel molecules from molecular field analysis (MFA) models and pharmacophores.

PubMed

Waszkowycz, B; Clark, D E; Frenkel, D; Li, J; Murray, C W; Robson, B; Westhead, D R

1994-11-11

A computational approach for molecular design, PRO_LIGAND, has been developed within the PROMETHEUS molecular design and simulation system in order to provide a unified framework for the de novo generation of diverse molecules which are either similar or complementary to a specified target. In this instance, the target is a pharmacophore derived from a series of active structures either by a novel interpretation of molecular field analysis data or by a pharmacophore-mapping procedure based on clique detection. After a brief introduction to PRO_LIGAND, a detailed description is given of the two pharmacophore generation procedures and their abilities are demonstrated by the elucidation of pharmacophores for steroid binding and ACE inhibition, respectively. As a further indication of its efficacy in aiding the rational drug design process, PRO_LIGAND is then employed to build novel organic molecules to satisfy the physicochemical constraints implied by the pharmacophores.

Quantitative analysis of RNA-protein interactions on a massively parallel array for mapping biophysical and evolutionary landscapes

PubMed Central

Buenrostro, Jason D.; Chircus, Lauren M.; Araya, Carlos L.; Layton, Curtis J.; Chang, Howard Y.; Snyder, Michael P.; Greenleaf, William J.

2015-01-01

RNA-protein interactions drive fundamental biological processes and are targets for molecular engineering, yet quantitative and comprehensive understanding of the sequence determinants of affinity remains limited. Here we repurpose a high-throughput sequencing instrument to quantitatively measure binding and dissociation of MS2 coat protein to >107 RNA targets generated on a flow-cell surface by in situ transcription and inter-molecular tethering of RNA to DNA. We decompose the binding energy contributions from primary and secondary RNA structure, finding that differences in affinity are often driven by sequence-specific changes in association rates. By analyzing the biophysical constraints and modeling mutational paths describing the molecular evolution of MS2 from low- to high-affinity hairpins, we quantify widespread molecular epistasis, and a long-hypothesized structure-dependent preference for G:U base pairs over C:A intermediates in evolutionary trajectories. Our results suggest that quantitative analysis of RNA on a massively parallel array (RNAMaP) relationships across molecular variants. PMID:24727714

Molecular Profiling Reveals Biologically Discrete Subsets and Pathways of Progression in Diffuse Glioma.

PubMed

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

2016-01-28

Therapy development for adult diffuse glioma is hindered by incomplete knowledge of somatic glioma driving alterations and suboptimal disease classification. We defined the complete set of genes associated with 1,122 diffuse grade II-III-IV gliomas from The Cancer Genome Atlas and used molecular profiles to improve disease classification, identify molecular correlations, and provide insights into the progression from low- to high-grade disease. Whole-genome sequencing data analysis determined that ATRX but not TERT promoter mutations are associated with increased telomere length. Recent advances in glioma classification based on IDH mutation and 1p/19q co-deletion status were recapitulated through analysis of DNA methylation profiles, which identified clinically relevant molecular subsets. A subtype of IDH mutant glioma was associated with DNA demethylation and poor outcome; a group of IDH-wild-type diffuse glioma showed molecular similarity to pilocytic astrocytoma and relatively favorable survival. Understanding of cohesive disease groups may aid improved clinical outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.

Molecular Modeling Studies of 4,5-Dihydro-1H-pyrazolo[4,3-h] quinazoline Derivatives as Potent CDK2/Cyclin A Inhibitors Using 3D-QSAR and Docking

PubMed Central

Ai, Yong; Wang, Shao-Teng; Sun, Ping-Hua; Song, Fa-Jun

2010-01-01

CDK2/cyclin A has appeared as an attractive drug targets over the years with diverse therapeutic potentials. A computational strategy based on comparative molecular fields analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) followed by molecular docking studies were performed on a series of 4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline derivatives as potent CDK2/cyclin A inhibitors. The CoMFA and CoMSIA models, using 38 molecules in the training set, gave r2cv values of 0.747 and 0.518 and r2 values of 0.970 and 0.934, respectively. 3D contour maps generated by the CoMFA and CoMSIA models were used to identify the key structural requirements responsible for the biological activity. Molecular docking was applied to explore the binding mode between the ligands and the receptor. The information obtained from molecular modeling studies may be helpful to design novel inhibitors of CDK2/cyclin A with desired activity. PMID:21152296

Molecular modeling studies of 4,5-dihydro-1H-pyrazolo[4,3-h] quinazoline derivatives as potent CDK2/Cyclin a inhibitors using 3D-QSAR and docking.

PubMed

Ai, Yong; Wang, Shao-Teng; Sun, Ping-Hua; Song, Fa-Jun

2010-09-28

CDK2/cyclin A has appeared as an attractive drug targets over the years with diverse therapeutic potentials. A computational strategy based on comparative molecular fields analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) followed by molecular docking studies were performed on a series of 4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline derivatives as potent CDK2/cyclin A inhibitors. The CoMFA and CoMSIA models, using 38 molecules in the training set, gave r(2) (cv) values of 0.747 and 0.518 and r(2) values of 0.970 and 0.934, respectively. 3D contour maps generated by the CoMFA and CoMSIA models were used to identify the key structural requirements responsible for the biological activity. Molecular docking was applied to explore the binding mode between the ligands and the receptor. The information obtained from molecular modeling studies may be helpful to design novel inhibitors of CDK2/cyclin A with desired activity.

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.

Double-hairpin molecular-beacon-based amplification detection for gene diagnosis linked to cancer.

PubMed

Xu, Huo; Zhang, Rongbo; Li, Feng; Zhou, Yingying; Peng, Ting; Wang, Xuedong; Shen, Zhifa

2016-09-01

A powerful double-hairpin molecular beacon (DHMB) was developed for cancer-related KRAS gene detection based on the one-to-two stoichiometry. During target DNA detection, DHMB can execute signal transduction even if no any exogenous element is involved. Unlike the conventional molecular beacon based on the one-to-one interaction, one target DNA not only hybridizes with one DHMB and opens its hairpin but also promotes the interaction between two DHMBs, causing the separation of two fluorophores from quenchers. This leads to an enhanced fluorescence signal. As a result, the target KRAS gene is able to be detected within a wide dynamic range from 0.05 to 200 nM with the detection limit of 50 pM, indicating a dramatic improvement compared with traditional molecular beacons. Moreover, the point mutations existing in target DNAs can be easily screened. The potential application for target species in real samples was indicated by the analysis of PCR amplicons of DNAs from the DNA extracted from SW620 cell. Besides becoming a promising candidate probe for molecular biology research and clinical diagnosis of genetic diseases, the DHMB is expected to provide a significant insight into the design of DNA probe-based homogenous sensing systems. Graphical Abstract A powerful double-hairpin molecular beacon (DHMB) was developed for cancer-related gene KRAS detection based on the one-to-two stoichiometry. Without the help of any exogenous probe, the point mutation is easily screened, and the target DNA can be quantified down to 50 pM, indicating a dramatic improvement compared with traditional molecular beacons.

Grid-based International Network for Flu observation (g-INFO).

PubMed

Doan, Trung-Tung; Bernard, Aurélien; Da-Costa, Ana Lucia; Bloch, Vincent; Le, Thanh-Hoa; Legre, Yannick; Maigne, Lydia; Salzemann, Jean; Sarramia, David; Nguyen, Hong-Quang; Breton, Vincent

2010-01-01

The 2009 H1N1 outbreak has demonstrated that continuing vigilance, planning, and strong public health research capability are essential defenses against emerging health threats. Molecular epidemiology of influenza virus strains provides scientists with clues about the temporal and geographic evolution of the virus. In the present paper, researchers from France and Vietnam are proposing a global surveillance network based on grid technology: the goal is to federate influenza data servers and deploy automatically molecular epidemiology studies. A first prototype based on AMGA and the WISDOM Production Environment extracts daily from NCBI influenza H1N1 sequence data which are processed through a phylogenetic analysis pipeline deployed on EGEE and AuverGrid e-infrastructures. The analysis results are displayed on a web portal (http://g-info.healthgrid.org) for epidemiologists to monitor H1N1 pandemics.

Automatized Assessment of Protective Group Reactivity: A Step Toward Big Reaction Data Analysis.

PubMed

Lin, Arkadii I; Madzhidov, Timur I; Klimchuk, Olga; Nugmanov, Ramil I; Antipin, Igor S; Varnek, Alexandre

2016-11-28

We report a new method to assess protective groups (PGs) reactivity as a function of reaction conditions (catalyst, solvent) using raw reaction data. It is based on an intuitive similarity principle for chemical reactions: similar reactions proceed under similar conditions. Technically, reaction similarity can be assessed using the Condensed Graph of Reaction (CGR) approach representing an ensemble of reactants and products as a single molecular graph, i.e., as a pseudomolecule for which molecular descriptors or fingerprints can be calculated. CGR-based in-house tools were used to process data for 142,111 catalytic hydrogenation reactions extracted from the Reaxys database. Our results reveal some contradictions with famous Greene's Reactivity Charts based on manual expert analysis. Models developed in this study show high accuracy (ca. 90%) for predicting optimal experimental conditions of protective group deprotection.

Molecular and pedigree analysis applied to conservation of animal genetic resources: the case of Brazilian Somali hair sheep.

PubMed

Paiva, Samuel R; Facó, Olivardo; Faria, Danielle A; Lacerda, Thaísa; Barretto, Gabriel B; Carneiro, Paulo L S; Lobo, Raimundo N B; McManus, Concepta

2011-10-01

The first registers of Somali sheep in Brazil are from the beginning of the 1900s. This breed, adapted to the dry climate and scarce food supply, is restricted in the northeast region of the country. Molecular marker technologies, especially those based on genotyping microsatellite and mtDNA loci, can be used in conjunction with breeding (pedigree analysis) and consequently the maintenance of genetic variation in herds. Animals from the Brazilian Somali Conservation Nuclei from Embrapa Sheep and Goats in Ceará State were used to validate genetic monitoring by traditional pedigree methods and molecular markers. Nineteen microsatellite markers and 404 base pairs from the control region of mtDNA were used. For total herd diversity, an average 5.32 alleles were found, with expected heterozygosity of 0.5896, observed heterozygosity of 0.6451, 0.4126 for molecular coancestrality, and coefficient of inbreeding (F (IS)) was -0.095. Comparing molecular coancestrality means over the years, there was a consistent increase in this parameter within the herd, increasing from 0.4157 to 0.4769 in 2 years (approx. 12% variation). Sixteen mtDNA haplotypes were identified. Inbreeding and other estimates from genealogical analyses confirm the results from molecular markers. From these results, it is possible to state that microsatellites are useful tools in genetic management of herds, especially when routine herd recording is not carried out, or there were gaps in recent generations. As well as pedigree control, genetic diversity can be optimized. Based on the results, and despite herd recording in the herd of Brazilian Somali of Embrapa Sheep and Goats, additional management measures need to be carried out in this herd to reduce inbreeding and optimize genetic variation.

Multi-color electron microscopy by element-guided identification of cells, organelles and molecules.

PubMed

Scotuzzi, Marijke; Kuipers, Jeroen; Wensveen, Dasha I; de Boer, Pascal; Hagen, Kees C W; Hoogenboom, Jacob P; Giepmans, Ben N G

2017-04-07

Cellular complexity is unraveled at nanometer resolution using electron microscopy (EM), but interpretation of macromolecular functionality is hampered by the difficulty in interpreting grey-scale images and the unidentified molecular content. We perform large-scale EM on mammalian tissue complemented with energy-dispersive X-ray analysis (EDX) to allow EM-data analysis based on elemental composition. Endogenous elements, labels (gold and cadmium-based nanoparticles) as well as stains are analyzed at ultrastructural resolution. This provides a wide palette of colors to paint the traditional grey-scale EM images for composition-based interpretation. Our proof-of-principle application of EM-EDX reveals that endocrine and exocrine vesicles exist in single cells in Islets of Langerhans. This highlights how elemental mapping reveals unbiased biomedical relevant information. Broad application of EM-EDX will further allow experimental analysis on large-scale tissue using endogenous elements, multiple stains, and multiple markers and thus brings nanometer-scale 'color-EM' as a promising tool to unravel molecular (de)regulation in biomedicine.

Multi-color electron microscopy by element-guided identification of cells, organelles and molecules

PubMed Central

Scotuzzi, Marijke; Kuipers, Jeroen; Wensveen, Dasha I.; de Boer, Pascal; Hagen, Kees (C.) W.; Hoogenboom, Jacob P.; Giepmans, Ben N. G.

2017-01-01

Cellular complexity is unraveled at nanometer resolution using electron microscopy (EM), but interpretation of macromolecular functionality is hampered by the difficulty in interpreting grey-scale images and the unidentified molecular content. We perform large-scale EM on mammalian tissue complemented with energy-dispersive X-ray analysis (EDX) to allow EM-data analysis based on elemental composition. Endogenous elements, labels (gold and cadmium-based nanoparticles) as well as stains are analyzed at ultrastructural resolution. This provides a wide palette of colors to paint the traditional grey-scale EM images for composition-based interpretation. Our proof-of-principle application of EM-EDX reveals that endocrine and exocrine vesicles exist in single cells in Islets of Langerhans. This highlights how elemental mapping reveals unbiased biomedical relevant information. Broad application of EM-EDX will further allow experimental analysis on large-scale tissue using endogenous elements, multiple stains, and multiple markers and thus brings nanometer-scale ‘color-EM’ as a promising tool to unravel molecular (de)regulation in biomedicine. PMID:28387351

Molecular evolution inferred from small subunit rRNA sequences: what does it tell us about phylogenetic relationships and taxonomy of the parabasalids?

PubMed

Viscogliosi, E; Edgcomb, V P; Gerbod, D; Noël, C; Delgado-Viscogliosi, P

1999-12-01

The Parabasala are a primitive group of protists divided into two classes: the trichomonads and the hypermastigids. Until recently, phylogeny and taxonomy of parabasalids were mainly based on the comparative analysis of morphological characters primarily linked to the development of their cytoskeleton. Recent use of molecular markers, such as small subunit (SSU) rRNA has led to now insights into the systematics of the Parabasala and other groups of prolists. An updated phylogeny based on SSU rRNA is provided and compared to that inferred from ultrastructural data. The SSU rRNA phylogeny contradicts the dogma equating simple characters with pumitive characters. Hypermastigids, possessing a hyperdeveloped cytoskeleton, exhibit the most basal emergence in the parabasalid lineage. Other observations emerge from the SSU rRNA analysis, such as the secondary loss of some cytoskeleton structures in all representatives of the Monocercomonadidae, the existence of secondarily free living taxa (reversibility of parasitism) and the evidence against the co-evolution of the endobiotic parabasalids and their animal hosts. According to phylogenies based on SSU rRNA, all the trichomonad families are not monophyletic groups, putting into question the validity of current taxonomic assignments. The precise branching order of some taxa remains unclear, but this issue can possibly be addressed by the molecular analysis of additional parabasalids. The goal of such additional analyses would be to propose, in a near future, a revision of the taxonomy of this group of protists that takes into account both molecular and morphological data.

Molecular evolution inferred from small subunit rRNA sequences: what does it tell us about phylogenetic relationships and taxonomy of the parabasalids?

NASA Technical Reports Server (NTRS)

Viscogliosi, E.; Edgcomb, V. P.; Gerbod, D.; Noel, C.; Delgado-Viscogliosi, P.; Sogin, M. L. (Principal Investigator)

1999-01-01

The Parabasala are a primitive group of protists divided into two classes: the trichomonads and the hypermastigids. Until recently, phylogeny and taxonomy of parabasalids were mainly based on the comparative analysis of morphological characters primarily linked to the development of their cytoskeleton. Recent use of molecular markers, such as small subunit (SSU) rRNA has led to now insights into the systematics of the Parabasala and other groups of prolists. An updated phylogeny based on SSU rRNA is provided and compared to that inferred from ultrastructural data. The SSU rRNA phylogeny contradicts the dogma equating simple characters with pumitive characters. Hypermastigids, possessing a hyperdeveloped cytoskeleton, exhibit the most basal emergence in the parabasalid lineage. Other observations emerge from the SSU rRNA analysis, such as the secondary loss of some cytoskeleton structures in all representatives of the Monocercomonadidae, the existence of secondarily free living taxa (reversibility of parasitism) and the evidence against the co-evolution of the endobiotic parabasalids and their animal hosts. According to phylogenies based on SSU rRNA, all the trichomonad families are not monophyletic groups, putting into question the validity of current taxonomic assignments. The precise branching order of some taxa remains unclear, but this issue can possibly be addressed by the molecular analysis of additional parabasalids. The goal of such additional analyses would be to propose, in a near future, a revision of the taxonomy of this group of protists that takes into account both molecular and morphological data.

Tumor invasion unit in gastric cancer revealed by QDs-based in situ molecular imaging and multispectral analysis.

PubMed

Hu, Wen-Qing; Fang, Min; Zhao, Hao-Liang; Yan, Shu-Guang; Yuan, Jing-Ping; Peng, Chun-Wei; Yang, Gui-Fang; Li, Yan; Li, Jian-Ding

2014-04-01

In tumor tissues, cancer cells, tumor infiltrating macrophages and tumor neo-vessels in close spatial vicinity with one another form tumor invasion unit, which is a biologically important tumor microenvironment of metastasis to facilitate cancer invasion and metastasis. Establishing an in situ molecular imaging technology to simultaneously reveal these three components is essential for the in-depth investigation of tumor invasion unit. In this report, we have developed a computer-aided algorithm by quantum dots (QDs)-based multiplexed molecular imaging technique for such purpose. A series of studies on gastric cancer tumor tissues demonstrated that the tumor invasion unit was correlated with major unfavorable pathological features and worse clinical outcomes, which illustrated the significantly negative impacts and predictive power of tumor invasion unit on patient overall survival. This study confirmed the technical advantages of QDs-based in situ and simultaneous molecular imaging of key cancer molecules to gain deeper insights into the biology of cancer invasion. Copyright © 2014 Elsevier Ltd. All rights reserved.

New molecular medicine: Diagnomics and pharmacogenomics

NASA Astrophysics Data System (ADS)

Kauffman, Michael G.

1999-04-01

Millennium Predictive Medicine (MPMx), a subsidiary of Millennium Pharmaceuticals, is focusing on the discovery and clinical validation of Diagnomic and Pharmacogenomic Tests which will replace many of the subjective elements of clinical decision making. Diagnomics are molecular diagnostic markers with prognostic and economic impact. While the majority of currently available diagnostics represent data points, Diagnomics allow patients and physicians to make scientifically based, individualized decisions about their disease and its therapy. Pharmacogenomics are diagnostics that specify the use or avoidance of specific therapeutics based on an individual genotype and/or disease subtype. MPMx uses the broad Millennium genomics, proteomics, and bioinformatics technologies in the analysis of human disease and drug response. These technologies permit global and unbiased approaches towards the elucidation of disease pathways and mechanisms at the molecular level. Germline or somatic mutations, RNA levels, or protein levels comprising these pathways and mechanisms are currently being evaluated as markers for disease predisposition, stage, aggressiveness, and likely drug response or drug toxicity. Diagnomic and Pharmacogenomic Tests are part of the new molecular medicine that is transforming clinical practice forma symptom/pathology-based art into a pre-symptom, mechanism- based science.

Microfluidic approaches to malaria detection

PubMed Central

Gascoyne, Peter; Satayavivad, Jutamaad; Ruchirawat, Mathuros

2009-01-01

Microfluidic systems are under development to address a variety of medical problems. Key advantages of micrototal analysis systems based on microfluidic technology are the promise of small size and the integration of sample handling and measurement functions within a single, automated device having low mass-production costs. Here, we review the spectrum of methods currently used to detect malaria, consider their advantages and disadvantages, and discuss their adaptability towards integration into small, automated micro total analysis systems. Molecular amplification methods emerge as leading candidates for chip-based systems because they offer extremely high sensitivity, the ability to recognize malaria species and strain, and they will be adaptable to the detection of new genotypic signatures that will emerge from current genomic-based research of the disease. Current approaches to the development of chip-based molecular amplification are considered with special emphasis on flow-through PCR, and we present for the first time the method of malaria specimen preparation by dielectrophoretic field-flow-fractionation. Although many challenges must be addressed to realize a micrototal analysis system for malaria diagnosis, it is concluded that the potential benefits of the approach are well worth pursuing. PMID:14744562

A supermatrix analysis of genomic, morphological, and paleontological data from crown Cetacea

PubMed Central

2011-01-01

Background Cetacea (dolphins, porpoises, and whales) is a clade of aquatic species that includes the most massive, deepest diving, and largest brained mammals. Understanding the temporal pattern of diversification in the group as well as the evolution of cetacean anatomy and behavior requires a robust and well-resolved phylogenetic hypothesis. Although a large body of molecular data has accumulated over the past 20 years, DNA sequences of cetaceans have not been directly integrated with the rich, cetacean fossil record to reconcile discrepancies among molecular and morphological characters. Results We combined new nuclear DNA sequences, including segments of six genes (~2800 basepairs) from the functionally extinct Yangtze River dolphin, with an expanded morphological matrix and published genomic data. Diverse analyses of these data resolved the relationships of 74 taxa that represent all extant families and 11 extinct families of Cetacea. The resulting supermatrix (61,155 characters) and its sub-partitions were analyzed using parsimony methods. Bayesian and maximum likelihood (ML) searches were conducted on the molecular partition, and a molecular scaffold obtained from these searches was used to constrain a parsimony search of the morphological partition. Based on analysis of the supermatrix and model-based analyses of the molecular partition, we found overwhelming support for 15 extant clades. When extinct taxa are included, we recovered trees that are significantly correlated with the fossil record. These trees were used to reconstruct the timing of cetacean diversification and the evolution of characters shared by "river dolphins," a non-monophyletic set of species according to all of our phylogenetic analyses. Conclusions The parsimony analysis of the supermatrix and the analysis of morphology constrained to fit the ML/Bayesian molecular tree yielded broadly congruent phylogenetic hypotheses. In trees from both analyses, all Oligocene taxa included in our study fell outside crown Mysticeti and crown Odontoceti, suggesting that these two clades radiated in the late Oligocene or later, contra some recent molecular clock studies. Our trees also imply that many character states shared by river dolphins evolved in their oceanic ancestors, contradicting the hypothesis that these characters are convergent adaptations to fluvial habitats. PMID:21518443

A supermatrix analysis of genomic, morphological, and paleontological data from crown Cetacea.

PubMed

Geisler, Jonathan H; McGowen, Michael R; Yang, Guang; Gatesy, John

2011-04-25

Cetacea (dolphins, porpoises, and whales) is a clade of aquatic species that includes the most massive, deepest diving, and largest brained mammals. Understanding the temporal pattern of diversification in the group as well as the evolution of cetacean anatomy and behavior requires a robust and well-resolved phylogenetic hypothesis. Although a large body of molecular data has accumulated over the past 20 years, DNA sequences of cetaceans have not been directly integrated with the rich, cetacean fossil record to reconcile discrepancies among molecular and morphological characters. We combined new nuclear DNA sequences, including segments of six genes (~2800 basepairs) from the functionally extinct Yangtze River dolphin, with an expanded morphological matrix and published genomic data. Diverse analyses of these data resolved the relationships of 74 taxa that represent all extant families and 11 extinct families of Cetacea. The resulting supermatrix (61,155 characters) and its sub-partitions were analyzed using parsimony methods. Bayesian and maximum likelihood (ML) searches were conducted on the molecular partition, and a molecular scaffold obtained from these searches was used to constrain a parsimony search of the morphological partition. Based on analysis of the supermatrix and model-based analyses of the molecular partition, we found overwhelming support for 15 extant clades. When extinct taxa are included, we recovered trees that are significantly correlated with the fossil record. These trees were used to reconstruct the timing of cetacean diversification and the evolution of characters shared by "river dolphins," a non-monophyletic set of species according to all of our phylogenetic analyses. The parsimony analysis of the supermatrix and the analysis of morphology constrained to fit the ML/Bayesian molecular tree yielded broadly congruent phylogenetic hypotheses. In trees from both analyses, all Oligocene taxa included in our study fell outside crown Mysticeti and crown Odontoceti, suggesting that these two clades radiated in the late Oligocene or later, contra some recent molecular clock studies. Our trees also imply that many character states shared by river dolphins evolved in their oceanic ancestors, contradicting the hypothesis that these characters are convergent adaptations to fluvial habitats.

Accurate Identification of Unknown and Known Metabolic Mixture Components by Combining 3D NMR with Fourier Transform Ion Cyclotron Resonance Tandem Mass Spectrometry.

PubMed

Wang, Cheng; He, Lidong; Li, Da-Wei; Bruschweiler-Li, Lei; Marshall, Alan G; Brüschweiler, Rafael

2017-10-06

Metabolite identification in metabolomics samples is a key step that critically impacts downstream analysis. We recently introduced the SUMMIT NMR/mass spectrometry (MS) hybrid approach for the identification of the molecular structure of unknown metabolites based on the combination of NMR, MS, and combinatorial cheminformatics. Here, we demonstrate the feasibility of the approach for an untargeted analysis of both a model mixture and E. coli cell lysate based on 2D/3D NMR experiments in combination with Fourier transform ion cyclotron resonance MS and MS/MS data. For 19 of the 25 model metabolites, SUMMIT yielded complete structures that matched those in the mixture independent of database information. Of those, seven top-ranked structures matched those in the mixture, and four of those were further validated by positive ion MS/MS. For five metabolites, not part of the 19 metabolites, correct molecular structural motifs could be identified. For E. coli, SUMMIT MS/NMR identified 20 previously known metabolites with three or more 1 H spins independent of database information. Moreover, for 15 unknown metabolites, molecular structural fragments were determined consistent with their spin systems and chemical shifts. By providing structural information for entire metabolites or molecular fragments, SUMMIT MS/NMR greatly assists the targeted or untargeted analysis of complex mixtures of unknown compounds.

Molecular and Morphological Characterizations of Echinococcus granulosus from Human and Animal Isolates in Kashan, Markazi Province, Iran

PubMed Central

ARBABI, Mohsen; PIRESTANI, Majid; DELAVARI, Mahdi; HOOSHYAR, Hossein; ABDOLI, Amir; SARVI, Shahab

2017-01-01

Background: One of the most important zoonotic helminths in the world is known as Echinococcus granulosus. Different strains of the E. granulosus have been described based on morphological and molecular characterizations, however, there is limited information regarding the characteristics of the phenotypes and genotypes of E. granulosus in Iran. Methods: The present study was prepared to evaluate the phenotypic and genotypic diversity of E. granulosus isolates collected from human, goat, sheep, and cattle based on 19 standard morphometric parameters and mitochondrial and nuclear genes (CO1, ND1, and ITS1) in Kashan, Markazi Province, Iran during 2013–2014. Results: The biometric analysis for the 19 characters revealed that the 19 morphometric values of cattle isolates were exceptionally higher than human, goat, and sheep isolates (P<0.05). Molecular analysis confirms the morphological findings. Phylogenic analysis of the CO1, NAD1 and ITS1 genes for all isolates, independent of the host, revealed that the common sheep strain (G1) is traveling among livestock in Kashan and the strains are highly adapted to goats, cattle, sheep, and humans. Conclusion: Both morphological and molecular results of this study indicated that the only genotype G1 of E. granulosus travels between humans and other intermediate hosts of this parasite in the area study. PMID:28761477

Application of subtracted gDNA microarray-assisted Bulked Segregant Analysis for rapid discovery of molecular markers associated with day-neutrality in strawberry (Fragaria x ananassa)

PubMed Central

Gor, Mian Chee; Mantri, Nitin; Pang, Edwin

2016-01-01

A Fragaria Discovery Panel (FDP; strawberry-specific SDA) containing 287 features was constructed by subtracting the pooled gDNA of nine non-angiosperm species from the pooled gDNA of five strawberry genotypes. This FDP was used for Bulk Segregant Analysis (BSA) to enable identification of molecular markers associated with day-neutrality. Analysis of hybridisation patterns of a short day (SD) DNA bulk and three day-neutral (DN) DNA bulks varying in flowering strength allowed identification of a novel feature, FaP2E11, closely linked to CYTOKININ OXIDASE 1 (CKX1) gene possibly involved in promoting flowering under non-inductive condition. The signal intensities of FaP2E11 feature obtained from the strong DN bulk (DN1) is three fold higher than the short day bulk (SD), indicating that the putative marker may linked to a CKX1 variant allele with lower enzyme activity. We propose a model for flowering regulation based on the hypothesis that flowering strength may be regulated by the copy number of FaP2E11-linked CKX1 alleles. This study demonstrates the feasibility of the SDA-based BSA approach for the identification of molecular markers associated with day-neutrality in strawberry. This innovative strategy is an efficient and cost-effective approach for molecular marker discovery. PMID:27586242

Can we trust intraoperative culture results in nonunions?

PubMed

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

2014-07-01

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

Nanostructured solid substrates for efficient laser desorption/ionization mass spectrometry (LDI-MS) of low molecular weight compounds.

PubMed

Silina, Yuliya E; Volmer, Dietrich A

2013-12-07

Analytical applications often require rapid measurement of compounds from complex sample mixtures. High-speed mass spectrometry approaches frequently utilize techniques based on direct ionization of the sample by laser irradiation, mostly by means of matrix-assisted laser desorption/ionization (MALDI). Compounds of low molecular weight are difficult to analyze by MALDI, however, because of severe interferences in the low m/z range from the organic matrix used for desorption/ionization. In recent years, surface-assisted laser desorption/ionization (SALDI) techniques have shown promise for small molecule analysis, due to the unique properties of nanostructured surfaces, in particular, the lack of a chemical background in the low m/z range and enhanced production of analyte ions by SALDI. This short review article presents a summary of the most promising recent developments in SALDI materials for MS analysis of low molecular weight analytes, with emphasis on nanostructured materials based on metals and semiconductors.

System Analysis of LWDH Related Genes Based on Text Mining in Biological Networks

PubMed Central

Miao, Yingbo; Zhang, Liangcai; Wang, Yang; Feng, Rennan; Yang, Lei; Zhang, Shihua; Jiang, Yongshuai; Liu, Guiyou

2014-01-01

Liuwei-dihuang (LWDH) is widely used in traditional Chinese medicine (TCM), but its molecular mechanism about gene interactions is unclear. LWDH genes were extracted from the existing literatures based on text mining technology. To simulate the complex molecular interactions that occur in the whole body, protein-protein interaction networks (PPINs) were constructed and the topological properties of LWDH genes were analyzed. LWDH genes have higher centrality properties and may play important roles in the complex biological network environment. It was also found that the distances within LWDH genes are smaller than expected, which means that the communication of LWDH genes during the biological process is rapid and effectual. At last, a comprehensive network of LWDH genes, including the related drugs and regulatory pathways at both the transcriptional and posttranscriptional levels, was constructed and analyzed. The biological network analysis strategy used in this study may be helpful for the understanding of molecular mechanism of TCM. PMID:25243143

Next generation diagnostic molecular pathology: critical appraisal of quality assurance in Europe.

PubMed

Dubbink, Hendrikus J; Deans, Zandra C; Tops, Bastiaan B J; van Kemenade, Folkert J; Koljenović, S; van Krieken, Han J M; Blokx, Willeke A M; Dinjens, Winand N M; Groenen, Patricia J T A

2014-06-01

Tumor evaluation in pathology is more and more based on a combination of traditional histopathology and molecular analysis. Due to the rapid development of new cancer treatments that specifically target aberrant proteins present in tumor cells, treatment decisions are increasingly based on the molecular features of the tumor. Not only the number of patients eligible for targeted precision medicine, but also the number of molecular targets per patient and tumor type is rising. Diagnostic molecular pathology, the discipline that determines the molecular aberrations present in tumors for diagnostic, prognostic or predictive purposes, is faced with true challenges. The laboratories have to meet the need of comprehensive molecular testing using only limited amount of tumor tissue, mostly fixed in formalin and embedded in paraffin (FFPE), in short turnaround time. Choices must be made for analytical methods that provide accurate, reliable and cost-effective results. Validation of the test procedures and results is essential. In addition, participation and good performance in internal (IQA) and external quality assurance (EQA) schemes is mandatory. In this review, we critically evaluate the validation procedure for comprehensive molecular tests as well as the organization of quality assurance and assessment of competence of diagnostic molecular pathology laboratories within Europe. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

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

PubMed

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

2016-06-20

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

QSAR as a random event: modeling of nanoparticles uptake in PaCa2 cancer cells.

PubMed

Toropov, Andrey A; Toropova, Alla P; Puzyn, Tomasz; Benfenati, Emilio; Gini, Giuseppina; Leszczynska, Danuta; Leszczynski, Jerzy

2013-06-01

Quantitative structure-property/activity relationships (QSPRs/QSARs) are a tool to predict various endpoints for various substances. The "classic" QSPR/QSAR analysis is based on the representation of the molecular structure by the molecular graph. However, simplified molecular input-line entry system (SMILES) gradually becomes most popular representation of the molecular structure in the databases available on the Internet. Under such circumstances, the development of molecular descriptors calculated directly from SMILES becomes attractive alternative to "classic" descriptors. The CORAL software (http://www.insilico.eu/coral) is provider of SMILES-based optimal molecular descriptors which are aimed to correlate with various endpoints. We analyzed data set on nanoparticles uptake in PaCa2 pancreatic cancer cells. The data set includes 109 nanoparticles with the same core but different surface modifiers (small organic molecules). The concept of a QSAR as a random event is suggested in opposition to "classic" QSARs which are based on the only one distribution of available data into the training and the validation sets. In other words, five random splits into the "visible" training set and the "invisible" validation set were examined. The SMILES-based optimal descriptors (obtained by the Monte Carlo technique) for these splits are calculated with the CORAL software. The statistical quality of all these models is good. Copyright © 2013 Elsevier Ltd. All rights reserved.

Ab initio genotype–phenotype association reveals intrinsic modularity in genetic networks

PubMed Central

Slonim, Noam; Elemento, Olivier; Tavazoie, Saeed

2006-01-01

Microbial species express an astonishing diversity of phenotypic traits, behaviors, and metabolic capacities. However, our molecular understanding of these phenotypes is based almost entirely on studies in a handful of model organisms that together represent only a small fraction of this phenotypic diversity. Furthermore, many microbial species are not amenable to traditional laboratory analysis because of their exotic lifestyles and/or lack of suitable molecular genetic techniques. As an adjunct to experimental analysis, we have developed a computational information-theoretic framework that produces high-confidence gene–phenotype predictions using cross-species distributions of genes and phenotypes across 202 fully sequenced archaea and eubacteria. In addition to identifying the genetic basis of complex traits, our approach reveals the organization of these genes into generic preferentially co-inherited modules, many of which correspond directly to known enzymatic pathways, molecular complexes, signaling pathways, and molecular machines. PMID:16732191

Food and forensic molecular identification: update and challenges.

PubMed

Teletchea, Fabrice; Maudet, Celia; Hänni, Catherine

2005-07-01

The need for accurate and reliable methods for animal species identification has steadily increased during past decades, particularly with the recent food scares and the overall crisis of biodiversity primarily resulting from the huge ongoing illegal traffic of endangered species. A relatively new biotechnological field, known as species molecular identification, based on the amplification and analysis of DNA, offers promising solutions. Indeed, despite the fact that retrieval and analysis of DNA in processed products is a real challenge, numerous technically consistent methods are now available and allow the detection of animal species in almost any organic substrate. However, this field is currently facing a turning point and should rely more on knowledge primarily from three fundamental fields--paleogenetics, molecular evolution and systematics.

Comprehensive molecular tumor profiling in radiation oncology: How it could be used for precision medicine.

PubMed

Eke, Iris; Makinde, Adeola Y; Aryankalayil, Molykutty J; Ahmed, Mansoor M; Coleman, C Norman

2016-11-01

New technologies enabling the analysis of various molecules, including DNA, RNA, proteins and small metabolites, can aid in understanding the complex molecular processes in cancer cells. In particular, for the use of novel targeted therapeutics, elucidation of the mechanisms leading to cell death or survival is crucial to eliminate tumor resistance and optimize therapeutic efficacy. While some techniques, such as genomic analysis for identifying specific gene mutations or epigenetic testing of promoter methylation, are already in clinical use, other "omics-based" assays are still evolving. Here, we provide an overview of the current status of molecular profiling methods, including promising research strategies, as well as possible challenges, and their emerging role in radiation oncology. Published by Elsevier Ireland Ltd.

Endemic Scrub Typhus–like Illness, Chile

PubMed Central

Balcells, M. Elvira; Rabagliati, Ricardo; García, Patricia; Poggi, Helena; Oddó, David; Concha, Marcela; Abarca, Katia; Jiang, Ju; Richards, Allen L.; Fuerst, Paul A.

2011-01-01

We report a case of scrub typhus in a 54-year-old man who was bitten by several terrestrial leeches during a trip to Chiloé Island in southern Chile in 2006. A molecular sample, identified as related to Orientia tsutsugamushi based on the sequence of the16S rRNA gene, was obtained from a biopsy specimen of the eschar on the patient’s leg. Serologic analysis showed immunoglobulin G conversion against O. tsutsugamushi whole cell antigen. This case and its associated molecular analyses suggest that an Orientia-like agent is present in the Western Hemisphere that can produce scrub typhus–like illness. The molecular analysis suggests that the infectious agent is closely related, although not identical, to members of the Orientia sp. from Asia. PMID:21888791

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

PubMed

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

2017-12-04

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

Triple-helix molecular switch-based aptasensors and DNA sensors.

PubMed

Bagheri, Elnaz; Abnous, Khalil; Alibolandi, Mona; Ramezani, Mohammad; Taghdisi, Seyed Mohammad

2018-07-15

Utilization of traditional analytical techniques is limited because they are generally time-consuming and require high consumption of reagents, complicated sample preparation and expensive equipment. Therefore, it is of great interest to achieve sensitive, rapid and simple detection methods. It is believed that nucleic acids assays, especially aptamers, are very important in modern life sciences for target detection and biological analysis. Aptamers and DNA-based sensors have been widely used for the design of various sensors owing to their unique features. In recent years, triple-helix molecular switch (THMS)-based aptasensors and DNA sensors have been broadly utilized for the detection and analysis of different targets. The THMS relies on the formation of DNA triplex via Watson-Crick and Hoogsteen base pairings under optimal conditions. This review focuses on recent progresses in the development and applications of electrochemical, colorimetric, fluorescence and SERS aptasensors and DNA sensors, which are based on THMS. Also, the advantages and drawbacks of these methods are discussed. Copyright © 2018 Elsevier B.V. All rights reserved.

Molecular phylogeny of the lionfish genera Dendrochirus and Pterois (Scorpaenidae, Pteroinae) based on mitochondrial DNA sequences.

PubMed

Kochzius, Marc; Söller, Rainer; Khalaf, Maroof A; Blohm, Dietmar

2003-09-01

This study investigates the molecular phylogeny of seven lionfishes of the genera Dendrochirus and Pterois. MP, ML, and NJ phylogenetic analysis based on 964 bp of partial mitochondrial DNA sequences (cytochrome b and 16S rDNA) revealed two main clades: (1) "Pterois" clade (Pterois miles and Pterois volitans), and (2) "Pteropterus-Dendrochirus" clade (remainder of the sampled species). The position of Dendrochirus brachypterus either basal to the main clades or in the "Pteropterus-Dendrochirus" clade cannot be resolved. However, the molecular phylogeny did not support the current separation of the genera Pterois and Dendrochirus. The siblings P. miles and P. volitans are clearly separated and our results support the proposed allopatric or parapatric distribution in the Indian and Pacific Ocean. However, the present analysis cannot reveal if P. miles and P. volitans are separate species or two populations of a single species, because the observed separation in different clades can be either explained by speciation or lineage sorting. Molecular clock estimates for the siblings P. miles and P. volitans suggest a divergence time of 2.4-8.3 mya, which coincide with geological events that created vicariance between populations of the Indian and Pacific Ocean.

Testing the limits of sensitivity in a solid-state structural investigation by combined X-ray powder diffraction, solid-state NMR, and molecular modelling.

PubMed

Filip, Xenia; Borodi, Gheorghe; Filip, Claudiu

2011-10-28

A solid state structural investigation of ethoxzolamide is performed on microcrystalline powder by using a multi-technique approach that combines X-ray powder diffraction (XRPD) data analysis based on direct space methods with information from (13)C((15)N) solid-state Nuclear Magnetic Resonance (SS-NMR) and molecular modeling. Quantum chemical computations of the crystal were employed for geometry optimization and chemical shift calculations based on the Gauge Including Projector Augmented-Wave (GIPAW) method, whereas a systematic search in the conformational space was performed on the isolated molecule using a molecular mechanics (MM) approach. The applied methodology proved useful for: (i) removing ambiguities in the XRPD crystal structure determination process and further refining the derived structure solutions, and (ii) getting important insights into the relationship between the complex network of non-covalent interactions and the induced supra-molecular architectures/crystal packing patterns. It was found that ethoxzolamide provides an ideal case study for testing the accuracy with which this methodology allows to distinguish between various structural features emerging from the analysis of the powder diffraction data. This journal is © the Owner Societies 2011

Phylogeography and population structure of the biologically invasive phytopathogen Erwinia amylovora inferred using minisatellites.

PubMed

Bühlmann, Andreas; Dreo, Tanja; Rezzonico, Fabio; Pothier, Joël F; Smits, Theo H M; Ravnikar, Maja; Frey, Jürg E; Duffy, Brion

2014-07-01

Erwinia amylovora causes a major disease of pome fruit trees worldwide, and is regulated as a quarantine organism in many countries. While some diversity of isolates has been observed, molecular epidemiology of this bacterium is hindered by a lack of simple molecular typing techniques with sufficiently high resolution. We report a molecular typing system of E. amylovora based on variable number of tandem repeats (VNTR) analysis. Repeats in the E. amylovora genome were identified with comparative genomic tools, and VNTR markers were developed and validated. A Multiple-Locus VNTR Analysis (MLVA) was applied to E. amylovora isolates from bacterial collections representing global and regional distribution of the pathogen. Based on six repeats, MLVA allowed the distinction of 227 haplotypes among a collection of 833 isolates of worldwide origin. Three geographically separated groups were recognized among global isolates using Bayesian clustering methods. Analysis of regional outbreaks confirmed presence of diverse haplotypes but also high representation of certain haplotypes during outbreaks. MLVA analysis is a practical method for epidemiological studies of E. amylovora, identifying previously unresolved population structure within outbreaks. Knowledge of such structure can increase our understanding on how plant diseases emerge and spread over a given geographical region. © 2013 Society for Applied Microbiology and John Wiley & Sons Ltd.

Water Vapor Sensitivity Analysis for AVIRIS Radiactive-Transfer-Model-Based Reflectance Inversion

NASA Technical Reports Server (NTRS)

Green, R.

2000-01-01

As with other imaging spectrometers, AVIRIS measures the upwelling specral radiance incident at the sensor. Most research and applications objectives for AVIRIS are based on the molecular absorption and scattering features expressed in the surface reflectance.

The Human Blood Metabolome-Transcriptome Interface

PubMed Central

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

2015-01-01

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

Detection of Fatty Acids from Intact Microorganisms by Molecular Beam Static Secondary Ion Mass Spectrometry

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

Ingram, Jani Cheri; Lehman, Richard Michael; Bauer, William Francis

We report the use of a surface analysis approach, static secondary ion mass spectrometry (SIMS) equipped with a molecular (ReO4-) ion primary beam, to analyze the surface of intact microbial cells. SIMS spectra of 28 microorganisms were compared to fatty acid profiles determined by gas chromatographic analysis of transesterfied fatty acids extracted from the same organisms. The results indicate that surface bombardment using the molecular primary beam cleaved the ester linkage characteristic of bacteria at the glycerophosphate backbone of the phospholipid components of the cell membrane. This cleavage enables direct detection of the fatty acid conjugate base of intact microorganismsmore » by static SIMS. The limit of detection for this approach is approximately 107 bacterial cells/cm2. Multivariate statistical methods were applied in a graded approach to the SIMS microbial data. The results showed that the full data set could initially be statistically grouped based upon major differences in biochemical composition of the cell wall. The gram-positive bacteria were further statistically analyzed, followed by final analysis of a specific bacterial genus that was successfully grouped by species. Additionally, the use of SIMS to detect microbes on mineral surfaces is demonstrated by an analysis of Shewanella oneidensis on crushed hematite. The results of this study provide evidence for the potential of static SIMS to rapidly detect bacterial species based on ion fragments originating from cell membrane lipids directly from sample surfaces.« less

DSSR-enhanced visualization of nucleic acid structures in Jmol.

PubMed

Hanson, Robert M; Lu, Xiang-Jun

2017-07-03

Sophisticated and interactive visualizations are essential for making sense of the intricate 3D structures of macromolecules. For proteins, secondary structural components are routinely featured in molecular graphics visualizations. However, the field of RNA structural bioinformatics is still lagging behind; for example, current molecular graphics tools lack built-in support even for base pairs, double helices, or hairpin loops. DSSR (Dissecting the Spatial Structure of RNA) is an integrated and automated command-line tool for the analysis and annotation of RNA tertiary structures. It calculates a comprehensive and unique set of features for characterizing RNA, as well as DNA structures. Jmol is a widely used, open-source Java viewer for 3D structures, with a powerful scripting language. JSmol, its reincarnation based on native JavaScript, has a predominant position in the post Java-applet era for web-based visualization of molecular structures. The DSSR-Jmol integration presented here makes salient features of DSSR readily accessible, either via the Java-based Jmol application itself, or its HTML5-based equivalent, JSmol. The DSSR web service accepts 3D coordinate files (in mmCIF or PDB format) initiated from a Jmol or JSmol session and returns DSSR-derived structural features in JSON format. This seamless combination of DSSR and Jmol/JSmol brings the molecular graphics of 3D RNA structures to a similar level as that for proteins, and enables a much deeper analysis of structural characteristics. It fills a gap in RNA structural bioinformatics, and is freely accessible (via the Jmol application or the JSmol-based website http://jmol.x3dna.org). © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

GenCLiP 2.0: a web server for functional clustering of genes and construction of molecular networks based on free terms.

PubMed

Wang, Jia-Hong; Zhao, Ling-Feng; Lin, Pei; Su, Xiao-Rong; Chen, Shi-Jun; Huang, Li-Qiang; Wang, Hua-Feng; Zhang, Hai; Hu, Zhen-Fu; Yao, Kai-Tai; Huang, Zhong-Xi

2014-09-01

Identifying biological functions and molecular networks in a gene list and how the genes may relate to various topics is of considerable value to biomedical researchers. Here, we present a web-based text-mining server, GenCLiP 2.0, which can analyze human genes with enriched keywords and molecular interactions. Compared with other similar tools, GenCLiP 2.0 offers two unique features: (i) analysis of gene functions with free terms (i.e. any terms in the literature) generated by literature mining or provided by the user and (ii) accurate identification and integration of comprehensive molecular interactions from Medline abstracts, to construct molecular networks and subnetworks related to the free terms. http://ci.smu.edu.cn. Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Ligand-based 3D QSAR analysis of reactivation potency of mono- and bis-pyridinium aldoximes toward VX-inhibited rat acetylcholinesterase.

PubMed

Dolezal, Rafael; Korabecny, Jan; Malinak, David; Honegr, Jan; Musilek, Kamil; Kuca, Kamil

2015-03-01

To predict unknown reactivation potencies of 12 mono- and bis-pyridinium aldoximes for VX-inhibited rat acetylcholinesterase (rAChE), three-dimensional quantitative structure-activity relationship (3D QSAR) analysis has been carried out. Utilizing molecular interaction fields (MIFs) calculated by molecular mechanical (MMFF94) and quantum chemical (B3LYP/6-31G*) methods, two satisfactory ligand-based CoMFA models have been developed: 1. R(2)=0.9989, Q(LOO)(2)=0.9090, Q(LTO)(2)=0.8921, Q(LMO(20%))(2)=0.8853, R(ext)(2)=0.9259, SDEP(ext)=6.8938; 2. R(2)=0.9962, Q(LOO)(2)=0.9368, Q(LTO)(2)=0.9298, Q(LMO(20%))(2)=0.9248, R(ext)(2)=0.8905, SDEP(ext)=6.6756. High statistical significance of the 3D QSAR models has been achieved through the application of several data noise reduction techniques (i.e. smart region definition SRD, fractional factor design FFD, uninformative/iterative variable elimination UVE/IVE) on the original MIFs. Besides the ligand-based CoMFA models, an alignment molecular set constructed by flexible molecular docking has been also studied. The contour maps as well as the predicted reactivation potencies resulting from 3D QSAR analyses help better understand which structural features are associated with increased reactivation potency of studied compounds. Copyright © 2014 Elsevier Inc. All rights reserved.

Measuring molecular biomarkers in epidemiologic studies: laboratory techniques and biospecimen considerations.

PubMed

Erickson, Heidi S

2012-09-28

The future of personalized medicine depends on the ability to efficiently and rapidly elucidate a reliable set of disease-specific molecular biomarkers. High-throughput molecular biomarker analysis methods have been developed to identify disease risk, diagnostic, prognostic, and therapeutic targets in human clinical samples. Currently, high throughput screening allows us to analyze thousands of markers from one sample or one marker from thousands of samples and will eventually allow us to analyze thousands of markers from thousands of samples. Unfortunately, the inherent nature of current high throughput methodologies, clinical specimens, and cost of analysis is often prohibitive for extensive high throughput biomarker analysis. This review summarizes the current state of high throughput biomarker screening of clinical specimens applicable to genetic epidemiology and longitudinal population-based studies with a focus on considerations related to biospecimens, laboratory techniques, and sample pooling. Copyright © 2012 John Wiley & Sons, Ltd.

MM/PBSA analysis of molecular dynamics simulations of bovine beta-lactoglobulin: free energy gradients in conformational transitions?

PubMed

Fogolari, Federico; Moroni, Elisabetta; Wojciechowski, Marcin; Baginski, Maciej; Ragona, Laura; Molinari, Henriette

2005-04-01

The pH-driven opening and closure of beta-lactoglobulin EF loop, acting as a lid and closing the internal cavity of the protein, has been studied by molecular dynamics (MD) simulations and free energy calculations based on molecular mechanics/Poisson-Boltzmann (PB) solvent-accessible surface area (MM/PBSA) methodology. The forms above and below the transition pH differ presumably only in the protonation state of residue Glu89. MM/PBSA calculations are able to reproduce qualitatively the thermodynamics of the transition. The analysis of MD simulations using a combination of MM/PBSA methodology and the colony energy approach is able to highlight the driving forces implied in the transition. The analysis suggests that global rearrangements take place before the equilibrium local conformation is reached. This conclusion may bear general relevance to conformational transitions in all lipocalins and proteins in general. (c) 2005 Wiley-Liss, Inc.

Low-molecular-weight heparin for prevention of placenta-mediated pregnancy complications: protocol for a systematic review and individual patient data meta-analysis (AFFIRM)

PubMed Central

2014-01-01

Background Placenta-mediated pregnancy complications include pre-eclampsia, late pregnancy loss, placental abruption, and the small-for-gestational age newborn. They are leading causes of maternal, fetal, and neonatal morbidity and mortality in developed nations. Women who have experienced these complications are at an elevated risk of recurrence in subsequent pregnancies. However, despite decades of research no effective strategies to prevent recurrence have been identified, until recently. We completed a pooled summary-based meta-analysis that strongly suggests that low-molecular-weight heparin reduces the risk of recurrent placenta-mediated complications. The proposed individual patient data meta-analysis builds on this successful collaboration. The project is called AFFIRM, An individual patient data meta-analysis oF low-molecular-weight heparin For prevention of placenta-medIated pRegnancy coMplications. Methods/Design We conducted a systematic review to identify randomized controlled trials with a low-molecular-weight heparin intervention for the prevention of recurrent placenta-mediated pregnancy complications. Investigators and statisticians representing eight trials met to discuss the outcomes and analysis plan for an individual patient data meta-analysis. An additional trial has since been added for a total of nine eligible trials. The primary analyses from the original trials will be replicated for quality assurance prior to recoding the data from each trial and combining it into a common dataset for analysis. Using the anonymized combined data we will conduct logistic regression and subgroup analyses aimed at identifying which women with previous pregnancy complications benefit most from treatment with low-molecular-weight heparin during pregnancy. Discussion The goal of the proposed individual patient data meta-analysis is a thorough estimation of treatment effects in patients with prior individual placenta-mediated pregnancy complications and exploration of which complications are specifically prevented by low-molecular-weight heparin. Systematic review registration PROSPERO (International Prospective Registry of Systematic Reviews) 23 December 2013, CRD42013006249 PMID:24969227

POLYVIEW-MM: web-based platform for animation and analysis of molecular simulations

PubMed Central

Porollo, Aleksey; Meller, Jaroslaw

2010-01-01

Molecular simulations offer important mechanistic and functional clues in studies of proteins and other macromolecules. However, interpreting the results of such simulations increasingly requires tools that can combine information from multiple structural databases and other web resources, and provide highly integrated and versatile analysis tools. Here, we present a new web server that integrates high-quality animation of molecular motion (MM) with structural and functional analysis of macromolecules. The new tool, dubbed POLYVIEW-MM, enables animation of trajectories generated by molecular dynamics and related simulation techniques, as well as visualization of alternative conformers, e.g. obtained as a result of protein structure prediction methods or small molecule docking. To facilitate structural analysis, POLYVIEW-MM combines interactive view and analysis of conformational changes using Jmol and its tailored extensions, publication quality animation using PyMol, and customizable 2D summary plots that provide an overview of MM, e.g. in terms of changes in secondary structure states and relative solvent accessibility of individual residues in proteins. Furthermore, POLYVIEW-MM integrates visualization with various structural annotations, including automated mapping of known inter-action sites from structural homologs, mapping of cavities and ligand binding sites, transmembrane regions and protein domains. URL: http://polyview.cchmc.org/conform.html. PMID:20504857

Differentiation of five body fluids from forensic samples by expression analysis of four microRNAs using quantitative PCR.

PubMed

Sauer, Eva; Reinke, Ann-Kathrin; Courts, Cornelius

2016-05-01

Applying molecular genetic approaches for the identification of forensically relevant body fluids, which often yield crucial information for the reconstruction of a potential crime, is a current topic of forensic research. Due to their body fluid specific expression patterns and stability against degradation, microRNAs (miRNA) emerged as a promising molecular species, with a range of candidate markers published. The analysis of miRNA via quantitative Real-Time PCR, however, should be based on a relevant strategy of normalization of non-biological variances to deliver reliable and biologically meaningful results. The herein presented work is the as yet most comprehensive study of forensic body fluid identification via miRNA expression analysis based on a thoroughly validated qPCR procedure and unbiased statistical decision making to identify single source samples. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A new species of the genus Aulacorthum (Hemiptera: Aphididae) from the Korean Peninsula and its discrimination from a closely-related species using morphological and molecular characters.

PubMed

Lee, Wonhoon; Kim, Hyojoong; Havelka, Jan; Lee, Seunghwan

2011-04-01

Aulacorthum sp. collected on Artemisia princeps and Artemisia stolonifera (Asteraceae) in the Korean Peninsula was compared with the eight Aulacorthum species using molecular and morphological characters. In the sequence analysis, the genetic divergences of two mitochondrial genes, COI and CytB, between Aulacorthum sp. and the congeneric species were higher than those among the congeneric species. In the morphometric analysis, principal components analysis using 13 morphological characters reveals that Aulacorthum sp. is distinguished from the congeneric species, especially Aulacorthum albimagnoliae, which is morphologically most similar to Aulacorthum sp.. Based on these results, we propose a new species, Aulacorthum (Aulacorthum) artemisiphaga Lee, Havelka, and Lee sp. nov., with a description of apterous and alate viviparous females and an identification key to species in the genus Aulacorthum in the Korean Peninsula based on apterous viviparous females.

Molecular Diagnostics in Transfusion Medicine: In Capillary, on a Chip, in Silico, or in Flight?

PubMed Central

Garritsen, Henk S.P.; Xiu-Cheng Fan, Alex; Lenz, Daniela; Hannig, Horst; Yan Zhong, Xiao; Geffers, Robert; Lindenmaier, Werner; Dittmar, Kurt E.J.; Wörmann, Bernhard

2009-01-01

Summary Serology, defined as antibody-based diagnostics, has been regarded as the diagnostic gold standard in transfusion medicine. Nowadays however the impact of molecular diagnostics in transfusion medicine is rapidly growing. Molecular diagnostics can improve tissue typing (HLA typing), increase safety of blood products (NAT testing of infectious diseases), and enable blood group typing in difficult situations (after transfusion of blood products or prenatal non-invasive RhD typing). Most of the molecular testing involves the determination of the presence of single nucleotide polymorphisms (SNPs). Antigens (e.g. blood group antigens) mostly result from single nucleotide differences in critical positions. However, most blood group systems cannot be determined by looking at a single SNP. To identify members of a blood group system a number of critical SNPs have to be taken into account. The platforms which are currently used to perform molecular diagnostics are mostly gel-based, requiring time-consuming multiple manual steps. To implement molecular methods in transfusion medicine in the future the development of higher-throughput SNP genotyping non-gel-based platforms which allow a rapid, cost-effective screening are essential. Because of its potential for automation, high throughput and cost effectiveness the special focus of this paper is a relative new technique: SNP genotyping by MALDI-TOF MS analysis. PMID:21113259

Molecular-based surveillance of campylobacteriosis in New Zealand--from source attribution to genomic epidemiology.

PubMed

Muellner, P; Pleydell, E; Pirie, R; Baker, M G; Campbell, D; Carter, P E; French, N P

2013-01-17

Molecular-based surveillance of campylobacteriosis in New Zealand contributed to the implementation of interventions that led to a 50% reduction in notified and hospitalised cases of the country's most important zoonosis. From a pre-intervention high of 384 per 100,000 population in 2006, incidence dropped by 50% in 2008; a reduction that has been sustained since. This article illustrates many aspects of the successful use of molecular-based surveillance, including the distinction between control-focused and strategy-focused surveillance and advances in source attribution. We discuss how microbial genetic data can enhance the understanding of epidemiological explanatory and response variables and thereby enrich the epidemiological analysis. Sequence data can be fitted to evolutionary and epidemiological models to gain new insights into pathogen evolution, the nature of associations between strains of pathogens and host species, and aspects of between-host transmission. With the advent of newer sequencing technologies and the availability of rapid, high-coverage genome sequence data, such techniques may be extended and refined within the emerging discipline of genomic epidemiology. The aim of this article is to summarise the experience gained in New Zealand with molecular-based surveillance of campylobacteriosis and to discuss how this experience could be used to further advance the use of molecular tools in surveillance.

Direct mass spectrometry approaches to characterize polyphenol composition of complex samples.

PubMed

Fulcrand, Hélène; Mané, Carine; Preys, Sébastien; Mazerolles, Gérard; Bouchut, Claire; Mazauric, Jean-Paul; Souquet, Jean-Marc; Meudec, Emmanuelle; Li, Yan; Cole, Richard B; Cheynier, Véronique

2008-12-01

Lower molecular weight polyphenols including proanthocyanidin oligomers can be analyzed after HPLC separation on either reversed-phase or normal phase columns. However, these techniques are time consuming and can have poor resolution as polymer chain length and structural diversity increase. The detection of higher molecular weight compounds, as well as the determination of molecular weight distributions, remain major challenges in polyphenol analysis. Approaches based on direct mass spectrometry (MS) analysis that are proposed to help overcome these problems are reviewed. Thus, direct flow injection electrospray ionization mass spectrometry analysis can be used to establish polyphenol fingerprints of complex extracts such as in wine. This technique enabled discrimination of samples on the basis of their phenolic (i.e. anthocyanin, phenolic acid and flavan-3-ol) compositions, but larger oligomers and polymers were poorly detectable. Detection of higher molecular weight proanthocyanidins was also restricted with matrix-assisted laser desorption ionization (MALDI) MS, suggesting that they are difficult to desorb as gas-phase ions. The mass distribution of polymeric fractions could, however, be determined by analyzing the mass distributions of bovine serum albumin/proanthocyanidin complexes using MALDI-TOF-MS.

Nanomaterials as Assisted Matrix of Laser Desorption/Ionization Time-of-Flight Mass Spectrometry for the Analysis of Small Molecules.

PubMed

Lu, Minghua; Yang, Xueqing; Yang, Yixin; Qin, Peige; Wu, Xiuru; Cai, Zongwei

2017-04-21

Matrix-assisted laser desorption/ionization (MALDI), a soft ionization method, coupling with time-of-flight mass spectrometry (TOF MS) has become an indispensible tool for analyzing macromolecules, such as peptides, proteins, nucleic acids and polymers. However, the application of MALDI for the analysis of small molecules (<700 Da) has become the great challenge because of the interference from the conventional matrix in low mass region. To overcome this drawback, more attention has been paid to explore interference-free methods in the past decade. The technique of applying nanomaterials as matrix of laser desorption/ionization (LDI), also called nanomaterial-assisted laser desorption/ionization (nanomaterial-assisted LDI), has attracted considerable attention in the analysis of low-molecular weight compounds in TOF MS. This review mainly summarized the applications of different types of nanomaterials including carbon-based, metal-based and metal-organic frameworks as assisted matrices for LDI in the analysis of small biological molecules, environmental pollutants and other low-molecular weight compounds.

Nanomaterials as Assisted Matrix of Laser Desorption/Ionization Time-of-Flight Mass Spectrometry for the Analysis of Small Molecules

PubMed Central

Lu, Minghua; Yang, Xueqing; Yang, Yixin; Qin, Peige; Wu, Xiuru; Cai, Zongwei

2017-01-01

Matrix-assisted laser desorption/ionization (MALDI), a soft ionization method, coupling with time-of-flight mass spectrometry (TOF MS) has become an indispensible tool for analyzing macromolecules, such as peptides, proteins, nucleic acids and polymers. However, the application of MALDI for the analysis of small molecules (<700 Da) has become the great challenge because of the interference from the conventional matrix in low mass region. To overcome this drawback, more attention has been paid to explore interference-free methods in the past decade. The technique of applying nanomaterials as matrix of laser desorption/ionization (LDI), also called nanomaterial-assisted laser desorption/ionization (nanomaterial-assisted LDI), has attracted considerable attention in the analysis of low-molecular weight compounds in TOF MS. This review mainly summarized the applications of different types of nanomaterials including carbon-based, metal-based and metal-organic frameworks as assisted matrices for LDI in the analysis of small biological molecules, environmental pollutants and other low-molecular weight compounds. PMID:28430138

WormQTL—public archive and analysis web portal for natural variation data in Caenorhabditis spp

PubMed Central

Snoek, L. Basten; Van der Velde, K. Joeri; Arends, Danny; Li, Yang; Beyer, Antje; Elvin, Mark; Fisher, Jasmin; Hajnal, Alex; Hengartner, Michael O.; Poulin, Gino B.; Rodriguez, Miriam; Schmid, Tobias; Schrimpf, Sabine; Xue, Feng; Jansen, Ritsert C.; Kammenga, Jan E.; Swertz, Morris A.

2013-01-01

Here, we present WormQTL (http://www.wormqtl.org), an easily accessible database enabling search, comparative analysis and meta-analysis of all data on variation in Caenorhabditis spp. Over the past decade, Caenorhabditis elegans has become instrumental for molecular quantitative genetics and the systems biology of natural variation. These efforts have resulted in a valuable amount of phenotypic, high-throughput molecular and genotypic data across different developmental worm stages and environments in hundreds of C. elegans strains. WormQTL provides a workbench of analysis tools for genotype–phenotype linkage and association mapping based on but not limited to R/qtl (http://www.rqtl.org). All data can be uploaded and downloaded using simple delimited text or Excel formats and are accessible via a public web user interface for biologists and R statistic and web service interfaces for bioinformaticians, based on open source MOLGENIS and xQTL workbench software. WormQTL welcomes data submissions from other worm researchers. PMID:23180786

WormQTL--public archive and analysis web portal for natural variation data in Caenorhabditis spp.

PubMed

Snoek, L Basten; Van der Velde, K Joeri; Arends, Danny; Li, Yang; Beyer, Antje; Elvin, Mark; Fisher, Jasmin; Hajnal, Alex; Hengartner, Michael O; Poulin, Gino B; Rodriguez, Miriam; Schmid, Tobias; Schrimpf, Sabine; Xue, Feng; Jansen, Ritsert C; Kammenga, Jan E; Swertz, Morris A

2013-01-01

Here, we present WormQTL (http://www.wormqtl.org), an easily accessible database enabling search, comparative analysis and meta-analysis of all data on variation in Caenorhabditis spp. Over the past decade, Caenorhabditis elegans has become instrumental for molecular quantitative genetics and the systems biology of natural variation. These efforts have resulted in a valuable amount of phenotypic, high-throughput molecular and genotypic data across different developmental worm stages and environments in hundreds of C. elegans strains. WormQTL provides a workbench of analysis tools for genotype-phenotype linkage and association mapping based on but not limited to R/qtl (http://www.rqtl.org). All data can be uploaded and downloaded using simple delimited text or Excel formats and are accessible via a public web user interface for biologists and R statistic and web service interfaces for bioinformaticians, based on open source MOLGENIS and xQTL workbench software. WormQTL welcomes data submissions from other worm researchers.

An investigation about the structures, thermodynamics and kinetics of the formic acid involved molecular clusters

NASA Astrophysics Data System (ADS)

Zhang, Rui; Jiang, Shuai; Liu, Yi-Rong; Wen, Hui; Feng, Ya-Juan; Huang, Teng; Huang, Wei

2018-05-01

Despite the very important role of atmospheric aerosol nucleation in climate change and air quality, the detailed aerosol nucleation mechanism is still unclear. Here we investigated the formic acid (FA) involved multicomponent nucleation molecular clusters including sulfuric acid (SA), dimethylamine (DMA) and water (W) through a quantum chemical method. The thermodynamics and kinetics analysis was based on the global minima given by Basin-Hopping (BH) algorithm coupled with Density Functional Theory (DFT) and subsequent benchmarked calculations. Then the interaction analysis based on ElectroStatic Potential (ESP), Topological and Atomic Charges analysis was made to characterize the binding features of the clusters. The results show that FA binds weakly with the other molecules in the cluster while W binds more weakly. Further kinetic analysis about the time evolution of the clusters show that even though the formic acid's weak interaction with other nucleation precursors, its effect on sulfuric acid dimer steady state concentration cannot be neglected due to its high concentration in the atmosphere.

High-Performance Computational Analysis of Glioblastoma Pathology Images with Database Support Identifies Molecular and Survival Correlates.

PubMed

Kong, Jun; Wang, Fusheng; Teodoro, George; Cooper, Lee; Moreno, Carlos S; Kurc, Tahsin; Pan, Tony; Saltz, Joel; Brat, Daniel

2013-12-01

In this paper, we present a novel framework for microscopic image analysis of nuclei, data management, and high performance computation to support translational research involving nuclear morphometry features, molecular data, and clinical outcomes. Our image analysis pipeline consists of nuclei segmentation and feature computation facilitated by high performance computing with coordinated execution in multi-core CPUs and Graphical Processor Units (GPUs). All data derived from image analysis are managed in a spatial relational database supporting highly efficient scientific queries. We applied our image analysis workflow to 159 glioblastomas (GBM) from The Cancer Genome Atlas dataset. With integrative studies, we found statistics of four specific nuclear features were significantly associated with patient survival. Additionally, we correlated nuclear features with molecular data and found interesting results that support pathologic domain knowledge. We found that Proneural subtype GBMs had the smallest mean of nuclear Eccentricity and the largest mean of nuclear Extent, and MinorAxisLength. We also found gene expressions of stem cell marker MYC and cell proliferation maker MKI67 were correlated with nuclear features. To complement and inform pathologists of relevant diagnostic features, we queried the most representative nuclear instances from each patient population based on genetic and transcriptional classes. Our results demonstrate that specific nuclear features carry prognostic significance and associations with transcriptional and genetic classes, highlighting the potential of high throughput pathology image analysis as a complementary approach to human-based review and translational research.

Combining molecular docking and QSAR studies for modeling the anti-tyrosinase activity of aromatic heterocycle thiosemicarbazone analogues

NASA Astrophysics Data System (ADS)

Dong, Huanhuan; Liu, Jing; Liu, Xiaoru; Yu, Yanying; Cao, Shuwen

2018-01-01

A collection of thirty-six aromatic heterocycle thiosemicarbazone analogues presented a broad span of anti-tyrosinase activities were designed and obtained. A robust and reliable two-dimensional quantitative structure-activity relationship model, as evidenced by the high q2 and r2 values (0.848 and 0.893, respectively), was gained based on the analogues to predict the quantitative chemical-biological relationship and the new modifier direction. Inhibitory activities of the compounds were found to greatly depend on molecular shape and orbital energy. Substituents brought out large ovality and high highest-occupied molecular orbital energy values helped to improve the activity of these analogues. The molecular docking results provided visual evidence for QSAR analysis and inhibition mechanism. Based on these, two novel tyrosinase inhibitors O04 and O05 with predicted IC50 of 0.5384 and 0.8752 nM were designed and suggested for further research.

Investigation of potent lead for acquired immunodeficiency syndrome from traditional Chinese medicine.

PubMed

Hung, Tzu-Chieh; Lee, Wen-Yuan; Chen, Kuen-Bao; Chan, Yueh-Chiu; Chen, Calvin Yu-Chian

2014-01-01

Acquired immunodeficiency syndrome (AIDS), caused by human immunodeficiency virus (HIV), has become, because of the rapid spread of the disease, a serious global problem and cannot be treated. Recent studies indicate that VIF is a protein of HIV to prevent all of human immunity to attack HIV. Molecular compounds of traditional Chinese medicine (TCM) database filtered through molecular docking and molecular dynamics simulations to inhibit VIF can protect against HIV. Glutamic acid, plantagoguanidinic acid, and Aurantiamide acetate based docking score higher with other TCM compounds selected. Molecular dynamics are useful for analysis and detection ligand interactions. According to the docking position, hydrophobic interactions, hydrogen bonding changes, and structure variation, the study try to select the efficacy of traditional Chinese medicine compound Aurantiamide acetate is better than the other for protein-ligand interactions to maintain the protein composition, based on changes in the structure.

Performance of a docking/molecular dynamics protocol for virtual screening of nutlin-class inhibitors of Mdmx.

PubMed

Bharatham, Nagakumar; Finch, Kristin E; Min, Jaeki; Mayasundari, Anand; Dyer, Michael A; Guy, R Kiplin; Bashford, Donald

2017-06-01

A virtual screening protocol involving docking and molecular dynamics has been tested against the results of fluorescence polarization assays testing the potency of a series of compounds of the nutlin class for inhibition of the interaction between p53 and Mdmx, an interaction identified as a driver of certain cancers. The protocol uses a standard docking method (AutoDock) with a cutoff based on the AutoDock score (ADscore), followed by molecular dynamics simulation with a cutoff based on root-mean-square-deviation (RMSD) from the docked pose. An analysis of the experimental and computational results shows modest performance of ADscore alone, but dramatically improved performance when RMSD is also used. Published by Elsevier Inc.

Univariate and multivariate molecular spectral analyses of lipid related molecular structural components in relation to nutrient profile in feed and food mixtures

NASA Astrophysics Data System (ADS)

Abeysekara, Saman; Damiran, Daalkhaijav; Yu, Peiqiang

2013-02-01

The objectives of this study were (i) to determine lipid related molecular structures components (functional groups) in feed combination of cereal grain (barley, Hordeum vulgare) and wheat (Triticum aestivum) based dried distillers grain solubles (wheat DDGSs) from bioethanol processing at five different combination ratios using univariate and multivariate molecular spectral analyses with infrared Fourier transform molecular spectroscopy, and (ii) to correlate lipid-related molecular-functional structure spectral profile to nutrient profiles. The spectral intensity of (i) CH3 asymmetric, CH2 asymmetric, CH3 symmetric and CH2 symmetric groups, (ii) unsaturation (Cdbnd C) group, and (iii) carbonyl ester (Cdbnd O) group were determined. Spectral differences of functional groups were detected by hierarchical cluster analysis (HCA) and principal components analysis (PCA). The results showed that the combination treatments significantly inflicted modifications (P < 0.05) in nutrient profile and lipid related molecular spectral intensity (CH2 asymmetric stretching peak height, CH2 symmetric stretching peak height, ratio of CH2 to CH3 symmetric stretching peak intensity, and carbonyl peak area). Ratio of CH2 to CH3 symmetric stretching peak intensity, and carbonyl peak significantly correlated with nutrient profiles. Both PCA and HCA differentiated lipid-related spectrum. In conclusion, the changes of lipid molecular structure spectral profiles through feed combination could be detected using molecular spectroscopy. These changes were associated with nutrient profiles and functionality.

Structure-wise discrimination of cytosine, thymine, and uracil by proteins in terms of their nonbonded interactions.

PubMed

Usha, S; Selvaraj, S

2014-01-01

The molecular recognition and discrimination of very similar ligand moieties by proteins are important subjects in protein-ligand interaction studies. Specificity in the recognition of molecules is determined by the arrangement of protein and ligand atoms in space. The three pyrimidine bases, viz. cytosine, thymine, and uracil, are structurally similar, but the proteins that bind to them are able to discriminate them and form interactions. Since nonbonded interactions are responsible for molecular recognition processes in biological systems, our work attempts to understand some of the underlying principles of such recognition of pyrimidine molecular structures by proteins. The preferences of the amino acid residues to contact the pyrimidine bases in terms of nonbonded interactions; amino acid residue-ligand atom preferences; main chain and side chain atom contributions of amino acid residues; and solvent-accessible surface area of ligand atoms when forming complexes are analyzed. Our analysis shows that the amino acid residues, tyrosine and phenyl alanine, are highly involved in the pyrimidine interactions. Arginine prefers contacts with the cytosine base. The similarities and differences that exist between the interactions of the amino acid residues with each of the three pyrimidine base atoms in our analysis provide insights that can be exploited in designing specific inhibitors competitive to the ligands.

A Molecular Dynamics-Quantum Mechanics Theoretical Study of DNA-Mediated Charge Transport in Hydrated Ionic Liquids.

PubMed

Meng, Zhenyu; Kubar, Tomas; Mu, Yuguang; Shao, Fangwei

2018-05-08

Charge transport (CT) through biomolecules is of high significance in the research fields of biology, nanotechnology, and molecular devices. Inspired by our previous work that showed the binding of ionic liquid (IL) facilitated charge transport in duplex DNA, in silico simulation is a useful means to understand the microscopic mechanism of the facilitation phenomenon. Here molecular dynamics simulations (MD) of duplex DNA in water and hydrated ionic liquids were employed to explore the helical parameters. Principal component analysis was further applied to capture the subtle conformational changes of helical DNA upon different environmental impacts. Sequentially, CT rates were calculated by a QM/MM simulation of the flickering resonance model based upon MD trajectories. Herein, MD simulation illustrated that the binding of ionic liquids can restrain dynamic conformation and lower the on-site energy of the DNA base. Confined movement among the adjacent base pairs was highly related to the increase of electronic coupling among base pairs, which may lead DNA to a CT facilitated state. Sequentially combining MD and QM/MM analysis, the rational correlations among the binding modes, the conformational changes, and CT rates illustrated the facilitation effects from hydrated IL on DNA CT and supported a conformational-gating mechanism.

Validation of RNA-based molecular clonotype analysis for virus-specific CD8+ T-cells in formaldehyde-fixed specimens isolated from peripheral blood

PubMed Central

van Bockel, David; Price, David A.; Asher, Tedi E.; Venturi, Vanessa; Suzuki, Kazuo; Warton, Kristina; Davenport, Miles P.; Cooper, David A.; Douek, Daniel C.; Kelleher, Anthony D.

2007-01-01

Recent advances in the field of molecular clonotype analysis have enabled detailed repertoire characterization of viably isolated antigen-specific T cell populations directly ex vivo. However, in the absence of a biologically contained FACS facility, peripheral blood mononuclear cell (PBMC) preparations derived from patients infected with agents such as HIV must be formaldehyde fixed to inactivate the pathogen; this procedure adversely affects nucleic acid template quality. Here, we developed and validated a method to amplify and sequence mRNA species derived from formaldehyde fixed PBMC specimens. Antigen-specific CD8+ cytotoxic T-lymphocyte populations were identified with standard fluorochrome-conjugated peptide-major histocompatibility complex class I tetramers refolded around synthetic peptides representing immunodominant epitopes from HIV p24 Gag (KRWII[M/L]GLNK/HLA B*2705) and CMV pp65 (NLVPMVATV/HLA A*0201 and TPRVTGGGAM/HLA B*0702), and acquired in separate laboratories with or without fixation. In the presence of proteinase K pre-treatment, the observed antigen-specific CD8+ T-cell repertoire determined by molecular clonotype analysis was statistically no different whether derived from fixed or unfixed PBMC. However, oligo-dT recovery methods were not suitable for use with fixed tissue as significant skewing of clonotypic representation was observed. Thus, we have developed a reliable RNA-based method for molecular clonotype analysis that is compatible with formaldehyde fixation and therefore suitable for use with primary human samples isolated by FACS outside the context of a biological safety level 3 containment facility. PMID:17716684

Molecular imaging assessment of periodontitis lesions in an experimental mouse model.

PubMed

Ideguchi, Hidetaka; Yamashiro, Keisuke; Yamamoto, Tadashi; Shimoe, Masayuki; Hongo, Shoichi; Kochi, Shinsuke; Yoshihara-Hirata, Chiaki; Aoyagi, Hiroaki; Kawamura, Mari; Takashiba, Shogo

2018-06-06

We aimed to evaluate molecular imaging as a novel diagnostic tool for mice periodontitis model induced by ligature and Porphyromonas gingivalis (Pg) inoculation. Twelve female mice were assigned to the following groups: no treatment as control group (n = 4); periodontitis group induced by ligature and Pg as Pg group (n = 4); and Pg group treated with glycyrrhizinic acid (GA) as Pg + GA group (n = 4). All mice were administered a myeloperoxidase (MPO) activity-specific luminescent probe and observed using a charge-coupled device camera on day 14. Image analysis on all mice was conducted using software to determine the signal intensity of inflammation. Additionally, histological and radiographic evaluation for periodontal inflammation and bone resorption at the site of periodontitis, and quantitative enzyme-linked immunosorbent assay (ELISA) were conducted on three mice for each group. Each experiment was performed three times. Levels of serum IgG antibody against P. gingivalis were significantly higher in the Pg than in the Pg + GA group. Histological analyses indicated that the number of osteoclasts and neutrophils were significantly lower in the Pg + GA than in the Pg group. Micro-CT image analysis indicated no difference in bone resorption between the Pg and Pg + GA groups. The signal intensity of MPO activity was detected on the complete craniofacial image; moreover, strong signal intensity was localized specifically at the periodontitis site in the ex vivo palate, with group-wise differences. Molecular imaging analysis based on MPO activity showed high sensitivity of detection of periodontal inflammation in mice. Molecular imaging analysis based on MPO activity has potential as a diagnostic tool for periodontitis.

Structural Analysis of Chemokine Receptor–Ligand Interactions

PubMed Central

2017-01-01

This review focuses on the construction and application of structural chemokine receptor models for the elucidation of molecular determinants of chemokine receptor modulation and the structure-based discovery and design of chemokine receptor ligands. A comparative analysis of ligand binding pockets in chemokine receptors is presented, including a detailed description of the CXCR4, CCR2, CCR5, CCR9, and US28 X-ray structures, and their implication for modeling molecular interactions of chemokine receptors with small-molecule ligands, peptide ligands, and large antibodies and chemokines. These studies demonstrate how the integration of new structural information on chemokine receptors with extensive structure–activity relationship and site-directed mutagenesis data facilitates the prediction of the structure of chemokine receptor–ligand complexes that have not been crystallized. Finally, a review of structure-based ligand discovery and design studies based on chemokine receptor crystal structures and homology models illustrates the possibilities and challenges to find novel ligands for chemokine receptors. PMID:28165741

Computational Nanotechnology of Materials, Devices, and Machines: Carbon Nanotubes

NASA Technical Reports Server (NTRS)

Srivastava, Deepak; Kwak, Dolhan (Technical Monitor)

2000-01-01

The mechanics and chemistry of carbon nanotubes have relevance for their numerous electronic applications. Mechanical deformations such as bending and twisting affect the nanotube's conductive properties, and at the same time they possess high strength and elasticity. Two principal techniques were utilized including the analysis of large scale classical molecular dynamics on a shared memory architecture machine and a quantum molecular dynamics methodology. In carbon based electronics, nanotubes are used as molecular wires with topological defects which are mediated through various means. Nanotubes can be connected to form junctions.

Using VMD - An Introductory Tutorial

PubMed Central

Hsin, Jen; Arkhipov, Anton; Yin, Ying; Stone, John E.; Schulten, Klaus

2010-01-01

VMD (Visual Molecular Dynamics) is a molecular visualization and analysis program designed for biological systems such as proteins, nucleic acids, lipid bilayer assemblies, etc. This unit will serve as an introductory VMD tutorial. We will present several step-by-step examples of some of VMD’s most popular features, including visualizing molecules in three dimensions with different drawing and coloring methods, rendering publication-quality figures, animate and analyze the trajectory of a molecular dynamics simulation, scripting in the text-based Tcl/Tk interface, and analyzing both sequence and structure data for proteins. PMID:19085979

mmpdb: An Open-Source Matched Molecular Pair Platform for Large Multiproperty Data Sets.

PubMed

Dalke, Andrew; Hert, Jérôme; Kramer, Christian

2018-05-29

Matched molecular pair analysis (MMPA) enables the automated and systematic compilation of medicinal chemistry rules from compound/property data sets. Here we present mmpdb, an open-source matched molecular pair (MMP) platform to create, compile, store, retrieve, and use MMP rules. mmpdb is suitable for the large data sets typically found in pharmaceutical and agrochemical companies and provides new algorithms for fragment canonicalization and stereochemistry handling. The platform is written in Python and based on the RDKit toolkit. It is freely available from https://github.com/rdkit/mmpdb .

Computer aided drug design

NASA Astrophysics Data System (ADS)

Jain, A.

2017-08-01

Computer based method can help in discovery of leads and can potentially eliminate chemical synthesis and screening of many irrelevant compounds, and in this way, it save time as well as cost. Molecular modeling systems are powerful tools for building, visualizing, analyzing and storing models of complex molecular structure that can help to interpretate structure activity relationship. The use of various techniques of molecular mechanics and dynamics and software in Computer aided drug design along with statistics analysis is powerful tool for the medicinal chemistry to synthesis therapeutic and effective drugs with minimum side effect.

Identification of Potent Chloride Intracellular Channel Protein 1 Inhibitors from Traditional Chinese Medicine through Structure-Based Virtual Screening and Molecular Dynamics Analysis

PubMed Central

Wan, Minghui; Liao, Dongjiang; Peng, Guilin; Xu, Xin; Yin, Weiqiang; Guo, Guixin; Jiang, Funeng; Zhong, Weide

2017-01-01

Chloride intracellular channel 1 (CLIC1) is involved in the development of most aggressive human tumors, including gastric, colon, lung, liver, and glioblastoma cancers. It has become an attractive new therapeutic target for several types of cancer. In this work, we aim to identify natural products as potent CLIC1 inhibitors from Traditional Chinese Medicine (TCM) database using structure-based virtual screening and molecular dynamics (MD) simulation. First, structure-based docking was employed to screen the refined TCM database and the top 500 TCM compounds were obtained and reranked by X-Score. Then, 30 potent hits were achieved from the top 500 TCM compounds using cluster and ligand-protein interaction analysis. Finally, MD simulation was employed to validate the stability of interactions between each hit and CLIC1 protein from docking simulation, and Molecular Mechanics/Generalized Born Surface Area (MM-GBSA) analysis was used to refine the virtual hits. Six TCM compounds with top MM-GBSA scores and ideal-binding models were confirmed as the final hits. Our study provides information about the interaction between TCM compounds and CLIC1 protein, which may be helpful for further experimental investigations. In addition, the top 6 natural products structural scaffolds could serve as building blocks in designing drug-like molecules for CLIC1 inhibition. PMID:29147652

Purification and characterization of a novel high molecular weight exotoxin produced by red tide phytoplankton, Alexandrium tamarense.

PubMed

Yamasaki, Yasuhiro; Katsuo, Daisuke; Nakayasu, Seiichiro; Salati, Cristina; Duan, JingJing; Zou, Yanan; Matsuyama, Yukihiko; Yamaguchi, Kenichi; Oda, Tatsuya

2008-01-01

Our recent studies have demonstrated that the aqueous extract prepared from Alexandrium tamarense, a harmful red tide phytoplankton, showed cytotoxicity on Vero cells. In this study, the toxic substance was purified from the culture supernatant of A. tamarense. Based on the gel-filtration profile, the molecular mass of a purified toxin was estimated to be about 1,000 kDa. On sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis, a main band with molecular mass of 1,000 kDa was detected with periodic acid-Schiff (PAS) staining, but no protein bands were detected by Coomassie brilliant blue (CBB) protein staining. Sugar composition analysis of the toxin suggested that the toxin contains galactose, fucose, mannose, N-acetylglucosamine, xylose, and other minor saccharides, whereas no significant levels of amino acids were detected by amino acid analysis. These results suggest that the toxin is a polysaccharide-based compound. The toxin showed cytotoxic effects on various cell lines in a concentration-dependent manner. Among the cell lines tested, U937 cells were the most susceptible to the toxin. In U937 cells treated with the toxin, a typical apoptotic nuclear morphological change and DNA fragmentation were observed. This is the first report demonstrating that a polysaccharide-based toxin isolated from red tide phytoplankton can induce apoptotic cell death. (c) 2008 Wiley Periodicals, Inc.

Analysis of A Drug Target-based Classification System using Molecular Descriptors.

PubMed

Lu, Jing; Zhang, Pin; Bi, Yi; Luo, Xiaomin

2016-01-01

Drug-target interaction is an important topic in drug discovery and drug repositioning. KEGG database offers a drug annotation and classification using a target-based classification system. In this study, we gave an investigation on five target-based classes: (I) G protein-coupled receptors; (II) Nuclear receptors; (III) Ion channels; (IV) Enzymes; (V) Pathogens, using molecular descriptors to represent each drug compound. Two popular feature selection methods, maximum relevance minimum redundancy and incremental feature selection, were adopted to extract the important descriptors. Meanwhile, an optimal prediction model based on nearest neighbor algorithm was constructed, which got the best result in identifying drug target-based classes. Finally, some key descriptors were discussed to uncover their important roles in the identification of drug-target classes.

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

PubMed Central

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

2015-01-01

Background Prostate cancer (PCa) molecular subtypes have been defined by essentially mutually exclusive events, including ETS gene fusions (most commonly involving ERG) and SPINK1 over-expression. Clinical assessment may aid in disease stratification, complementing available prognostic tests. Objective To determine the analytical validity and clinicopatholgical associations of microarray-based molecular subtyping. Design, Setting and Participants We analyzed Affymetrix GeneChip expression profiles for 1,577 patients from eight radical prostatectomy (RP) cohorts, including 1,351 cases assessed using the Decipher prognostic assay (performed in a CLIA-certified laboratory). A microarray-based (m-) random forest ERG classification model was trained and validated. Outlier expression analysis was used to predict other mutually exclusive non-ERG ETS gene rearrangements (ETS+) or SPINK1 over-expression (SPINK1+). Outcome Measurements Associations with clinical features and outcomes by multivariable logistic regression analysis and receiver operating curves. Results and Limitations The m-ERG classifier showed 95% accuracy in an independent validation subset (n=155 samples). Across cohorts, 45%, 9%, 8% and 38% of PCa were classified as m-ERG+, m-ETS+, m-SPINK1+, and triple negative (m-ERG−/m-ETS−/m-SPINK1−), respectively. Gene expression profiling supports three underlying molecularly defined groups (m-ERG+, m-ETS+ and m-SPINK1+/triple negative). On multivariable analysis, m-ERG+ tumors were associated with lower preoperative serum PSA and Gleason scores, but enriched for extraprostatic extension (p<0.001). m-ETS+ tumors were associated with seminal vesicle invasion (p=0.01), while m-SPINK1+/triple negative tumors had higher Gleason scores and were more frequent in Black/African American patients (p<0.001). Clinical outcomes were not significantly different between subtypes. Conclusions A clinically available prognostic test (Decipher) can also assess PCa molecular subtypes, obviating the need for additional testing. Clinicopathological differences were found among subtypes based on global expression patterns. PMID:25964175

Studies of New Fused Benzazepine as Selective Dopamine D3 Receptor Antagonists Using 3D-QSAR, Molecular Docking and Molecular Dynamics

PubMed Central

Liu, Jing; Li, Yan; Zhang, Shuwei; Xiao, Zhengtao; Ai, Chunzhi

2011-01-01

In recent years, great interest has been paid to the development of compounds with high selectivity for central dopamine (DA) D3 receptors, an interesting therapeutic target in the treatment of different neurological disorders. In the present work, based on a dataset of 110 collected benzazepine (BAZ) DA D3 antagonists with diverse kinds of structures, a variety of in silico modeling approaches, including comparative molecular field analysis (CoMFA), comparative similarity indices analysis (CoMSIA), homology modeling, molecular docking and molecular dynamics (MD) were carried out to reveal the requisite 3D structural features for activity. Our results show that both the receptor-based (Q2 = 0.603, R2ncv = 0.829, R2pre = 0.690, SEE = 0.316, SEP = 0.406) and ligand-based 3D-QSAR models (Q2 = 0.506, R2ncv =0.838, R2pre = 0.794, SEE = 0.316, SEP = 0.296) are reliable with proper predictive capacity. In addition, a combined analysis between the CoMFA, CoMSIA contour maps and MD results with a homology DA receptor model shows that: (1) ring-A, position-2 and R3 substituent in ring-D are crucial in the design of antagonists with higher activity; (2) more bulky R1 substituents (at position-2 of ring-A) of antagonists may well fit in the binding pocket; (3) hydrophobicity represented by MlogP is important for building satisfactory QSAR models; (4) key amino acids of the binding pocket are CYS101, ILE105, LEU106, VAL151, PHE175, PHE184, PRO254 and ALA251. To our best knowledge, this work is the first report on 3D-QSAR modeling of the new fused BAZs as DA D3 antagonists. These results might provide information for a better understanding of the mechanism of antagonism and thus be helpful in designing new potent DA D3 antagonists. PMID:21541053

Studies of new fused benzazepine as selective dopamine D3 receptor antagonists using 3D-QSAR, molecular docking and molecular dynamics.

PubMed

Liu, Jing; Li, Yan; Zhang, Shuwei; Xiao, Zhengtao; Ai, Chunzhi

2011-02-18

In recent years, great interest has been paid to the development of compounds with high selectivity for central dopamine (DA) D3 receptors, an interesting therapeutic target in the treatment of different neurological disorders. In the present work, based on a dataset of 110 collected benzazepine (BAZ) DA D3 antagonists with diverse kinds of structures, a variety of in silico modeling approaches, including comparative molecular field analysis (CoMFA), comparative similarity indices analysis (CoMSIA), homology modeling, molecular docking and molecular dynamics (MD) were carried out to reveal the requisite 3D structural features for activity. Our results show that both the receptor-based (Q(2) = 0.603, R(2) (ncv) = 0.829, R(2) (pre) = 0.690, SEE = 0.316, SEP = 0.406) and ligand-based 3D-QSAR models (Q(2) = 0.506, R(2) (ncv) =0.838, R(2) (pre) = 0.794, SEE = 0.316, SEP = 0.296) are reliable with proper predictive capacity. In addition, a combined analysis between the CoMFA, CoMSIA contour maps and MD results with a homology DA receptor model shows that: (1) ring-A, position-2 and R(3) substituent in ring-D are crucial in the design of antagonists with higher activity; (2) more bulky R(1) substituents (at position-2 of ring-A) of antagonists may well fit in the binding pocket; (3) hydrophobicity represented by MlogP is important for building satisfactory QSAR models; (4) key amino acids of the binding pocket are CYS101, ILE105, LEU106, VAL151, PHE175, PHE184, PRO254 and ALA251. To our best knowledge, this work is the first report on 3D-QSAR modeling of the new fused BAZs as DA D3 antagonists. These results might provide information for a better understanding of the mechanism of antagonism and thus be helpful in designing new potent DA D3 antagonists.

Lab Plays Central Role in Groundbreaking National Clinical Trial in Precision Medicine | Poster

Cancer.gov

The Molecular Characterization Laboratory lies at the heart of an ambitious new approach for testing cancer drugs that will use the newest tools of precision medicine to select the best treatment for individual patients based on the genetic makeup of their tumors. The protocol, called NCI-Molecular Analysis for Therapy Choice (NCI-MATCH), will start with tumor biopsies from as

Bayesian species delimitation in Pleophylla chafers (Coleoptera) - the importance of prior choice and morphology.

PubMed

Eberle, Jonas; Warnock, Rachel C M; Ahrens, Dirk

2016-05-05

Defining species units can be challenging, especially during the earliest stages of speciation, when phylogenetic inference and delimitation methods may be compromised by incomplete lineage sorting (ILS) or secondary gene flow. Integrative approaches to taxonomy, which combine molecular and morphological evidence, have the potential to be valuable in such cases. In this study we investigated the South African scarab beetle genus Pleophylla using data collected from 110 individuals of eight putative morphospecies. The dataset included four molecular markers (cox1, 16S, rrnL, ITS1) and morphometric data based on male genital morphology. We applied a suite of molecular and morphological approaches to species delimitation, and implemented a novel Bayesian approach in the software iBPP, which enables continuous morphological trait and molecular data to be combined. Traditional morphology-based species assignments were supported quantitatively by morphometric analyses of the male genitalia (eigenshape analysis, CVA, LDA). While the ITS1-based delineation was also broadly congruent with the morphospecies, the cox1 data resulted in over-splitting (GMYC modelling, haplotype networks, PTP, ABGD). In the most extreme case morphospecies shared identical haplotypes, which may be attributable to ILS based on statistical tests performed using the software JML. We found the strongest support for putative morphospecies based on phylogenetic evidence using the combined approach implemented in iBPP. However, support for putative species was sensitive to the use of alternative guide trees and alternative combinations of priors on the population size (θ) and rootage (τ 0 ) parameters, especially when the analysis was based on molecular or morphological data alone. We demonstrate that continuous morphological trait data can be extremely valuable in assessing competing hypotheses to species delimitation. In particular, we show that the inclusion of morphological data in an integrative Bayesian framework can improve the resolution of inferred species units. However, we also demonstrate that this approach is extremely sensitive to guide tree and prior parameter choice. These parameters should be chosen with caution - if possible - based on independent empirical evidence, or careful sensitivity analyses should be performed to assess the robustness of results. Young species provide exemplars for investigating the mechanisms of speciation and for assessing the performance of tools used to delimit species on the basis of molecular and/or morphological evidence.

Personalized comprehensive molecular profiling of high risk osteosarcoma: Implications and limitations for precision medicine.

PubMed

Subbiah, Vivek; Wagner, Michael J; McGuire, Mary F; Sarwari, Nawid M; Devarajan, Eswaran; Lewis, Valerae O; Westin, Shanon; Kato, Shumei; Brown, Robert E; Anderson, Pete

2015-12-01

Despite advances in molecular medicine over recent decades, there has been little advancement in the treatment of osteosarcoma. We performed comprehensive molecular profiling in two cases of metastatic and chemotherapy-refractory osteosarcoma to guide molecularly targeted therapy. Hybridization capture of >300 cancer-related genes plus introns from 28 genes often rearranged or altered in cancer was applied to >50 ng of DNA extracted from tumor samples from two patients with recurrent, metastatic osteosarcoma. The DNA from each sample was sequenced to high, uniform coverage. Immunohistochemical probes and morphoproteomics analysis were performed, in addition to fluorescence in situ hybridization. All analyses were performed in CLIA-certified laboratories. Molecularly targeted therapy based on the resulting profiles was offered to the patients. Biomedical analytics were performed using QIAGEN's Ingenuity® Pathway Analysis. In Patient #1, comprehensive next-generation exome sequencing showed MET amplification, PIK3CA mutation, CCNE1 amplification, and PTPRD mutation. Immunohistochemistry-based morphoproteomic analysis revealed c-Met expression [(p)-c-Met (Tyr1234/1235)] and activation of mTOR/AKT pathway [IGF-1R (Tyr1165/1166), p-mTOR [Ser2448], p-Akt (Ser473)] and expression of SPARC and COX2. Targeted therapy was administered to match the P1K3CA, c-MET, and SPARC and COX2 aberrations with sirolimus+ crizotinib and abraxane+ celecoxib. In Patient #2, aberrations included NF2 loss in exons 2-16, PDGFRα amplification, and TP53 mutation. This patient was enrolled on a clinical trial combining targeted agents temsirolimus, sorafenib and bevacizumab, to match NF2, PDGFRα and TP53 aberrations. Both the patients did not benefit from matched therapy. Relapsed osteosarcoma is characterized by complex signaling and drug resistance pathways. Comprehensive molecular profiling holds great promise for tailoring personalized therapies for cancer. Methods for such profiling are evolving and need to be refined to better assist clinicians in making treatment decisions based on the large amount of data that results from this type of testing. Further research in this area is warranted.

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.

Quantum mechanical calculations related to ionization and charge transfer in DNA

NASA Astrophysics Data System (ADS)

Cauët, E.; Valiev, M.; Weare, J. H.; Liévin, J.

2012-07-01

Ionization and charge migration in DNA play crucial roles in mechanisms of DNA damage caused by ionizing radiation, oxidizing agents and photo-irradiation. Therefore, an evaluation of the ionization properties of the DNA bases is central to the full interpretation and understanding of the elementary reactive processes that occur at the molecular level during the initial exposure and afterwards. Ab initio quantum mechanical (QM) methods have been successful in providing highly accurate evaluations of key parameters, such as ionization energies (IE) of DNA bases. Hence, in this study, we performed high-level QM calculations to characterize the molecular energy levels and potential energy surfaces, which shed light on ionization and charge migration between DNA bases. In particular, we examined the IEs of guanine, the most easily oxidized base, isolated and embedded in base clusters, and investigated the mechanism of charge migration over two and three stacked guanines. The IE of guanine in the human telomere sequence has also been evaluated. We report a simple molecular orbital analysis to explain how modifications in the base sequence are expected to change the efficiency of the sequence as a hole trap. Finally, the application of a hybrid approach combining quantum mechanics with molecular mechanics brings an interesting discussion as to how the native aqueous DNA environment affects the IE threshold of nucleobases.

Molecular phylogeography of the Andean alpine plant, Gunnera magellanica

NASA Astrophysics Data System (ADS)

Shimizu, M.; Fujii, N.; Ito, M.; Asakawa, T.; Nishida, H.; Suyama, C.; Ueda, K.

2015-12-01

To clarify the evolutionary history of Gunnera magellanica (Gunneraceae), an alpine plant of the Andes mountains, we performed molecular phylogeographic analyses based on the sequences of an internal transcribed spacer (ITS) of nuclear ribosomal DNA and four non-coding regions (trnH-psbA, trnL-trnF, atpB-rbcL, rpl16 intron) of chloroplast DNA. We investigated 3, 4, 4 and 11 populations in, Ecuador, Bolivia, Argentina, and Chile, respectively, and detected six ITS genotypes (Types A-F) in G. magellanica. Five genotypes (Types A-E) were observed in the northern Andes population (Ecuador and Bolivia); only one ITS genotype (Type F) was observed in the southern Andes population (Chile and Argentina). Phylogenetic analyses showed that the ITS genotypes of the northern and southern Andes populations form different clades with high bootstrap probability. Furthermore, network analysis, analysis of molecular variance, and spatial analysis of molecular variance showed that there were two major clusters (the northern and southern Andes populations) in this species. Furthermore, in chloroplast DNA analysis, three major clades (northern Andes, Chillan, and southern Andes) were inferred from phylogenetic analyses using four non-coding regions, a finding that was supported by the above three types of analysis. The Chillan clade is the northernmost population in the southern Andes populations. With the exception of the Chillan clade (Chillan population), results of nuclear DNA and chloroplast DNA analyses were consistent. Both markers showed that the northern and southern Andes populations of G. magellanica were genetically different from each other. This type of clear phylogeographical structure was supported by PERMUT analysis according to Pons & Petit (1995, 1996). Moreover, based on our preliminary estimation that is based on the ITS sequences, the northern and southern Andes clades diverged ~0.63-3 million years ago, during a period of upheaval in the Andes. This suggests that the populations of G. magellanica that were distributed along the Andes have been divided into the two local populations of the northern and southern Andes during the uplift of the Andes.

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

PubMed

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

2018-01-01

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

Molecular weight determination and correlation analysis of Dalbergia sissoo polysaccharide with constituent oligosaccharides.

PubMed

Kumar, Vineet; Rana, Vikas; Soni, P L

2013-01-01

Mucilaginous polysaccharide extracted from Dalbergia sissoo Roxb. leaves has a number of medicinal applications. Molecular weight studies and correlation analysis of the structure of polysaccharide with oligosaccharides can be helpful for further utilisation, modification and structure-activity relationship for biological applications. To determine molecular weight of medicinally important polysaccharide. To establish an unequivocal correlation of the polysaccharide monosugars with constituting oligosaccharides and glucuronic acid content based on gas-liquid chromatography (GLC) with the spectrophotometric method. Complete and partial hydrolytic studies of pure polysaccharide yielded constituting monosugars and oligosaccharides. The ratio of sugars in polysaccharide and oligosaccharides was studied by preparation of alditol acetates and analysed using GLC. The uronic acid content was studied by GLC analysis and spectrophotometry. Molecular weight of the polysaccharide was determined using the viscometric method. Dalbergia sissoo leaves yielded 14.0% pure polysaccharide, containing 15.7% of glucuronic acid. Complete hydrolysis and GLC analysis of alditol acetate derivatives of reduced and unreduced monosugars indicated the presence of L-rhamnose, D-glucuronic acid, D-galactose and D-glucose in 1.00:1.00:2.00:2.33 molar ratios. Partial hydrolysis followed by monosugar analysis of oligosaccharides established the monosugar ratio in complete agreement with polysaccharide, thereby corroborating the sugar ratio. Similar uronic acid content was obtained by GLC and spectrophotometry. The polysaccharide had an average molecular weight of 1.5 × 10⁵  Da. The study has established an obvious correlation of the structure of polysaccharide with oligosaccharides, leading to unambiguous identification of monosaccharides, which normally is not studied conclusively while reporting the polysaccharide structure. The molecular weight of the polysaccharide was determined. Copyright © 2012 John Wiley & Sons, Ltd.

Stretch or contraction induced inversion of rectification in diblock molecular junctions

NASA Astrophysics Data System (ADS)

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

2013-09-01

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

Molecular Diagnostic Yield of Chromosomal Microarray Analysis and Whole-Exome Sequencing in Children With Autism Spectrum Disorder.

PubMed

Tammimies, Kristiina; Marshall, Christian R; Walker, Susan; Kaur, Gaganjot; Thiruvahindrapuram, Bhooma; Lionel, Anath C; Yuen, Ryan K C; Uddin, Mohammed; Roberts, Wendy; Weksberg, Rosanna; Woodbury-Smith, Marc; Zwaigenbaum, Lonnie; Anagnostou, Evdokia; Wang, Zhuozhi; Wei, John; Howe, Jennifer L; Gazzellone, Matthew J; Lau, Lynette; Sung, Wilson W L; Whitten, Kathy; Vardy, Cathy; Crosbie, Victoria; Tsang, Brian; D'Abate, Lia; Tong, Winnie W L; Luscombe, Sandra; Doyle, Tyna; Carter, Melissa T; Szatmari, Peter; Stuckless, Susan; Merico, Daniele; Stavropoulos, Dimitri J; Scherer, Stephen W; Fernandez, Bridget A

2015-09-01

The use of genome-wide tests to provide molecular diagnosis for individuals with autism spectrum disorder (ASD) requires more study. To perform chromosomal microarray analysis (CMA) and whole-exome sequencing (WES) in a heterogeneous group of children with ASD to determine the molecular diagnostic yield of these tests in a sample typical of a developmental pediatric clinic. The sample consisted of 258 consecutively ascertained unrelated children with ASD who underwent detailed assessments to define morphology scores based on the presence of major congenital abnormalities and minor physical anomalies. The children were recruited between 2008 and 2013 in Newfoundland and Labrador, Canada. The probands were stratified into 3 groups of increasing morphological severity: essential, equivocal, and complex (scores of 0-3, 4-5, and ≥6). All probands underwent CMA, with WES performed for 95 proband-parent trios. The overall molecular diagnostic yield for CMA and WES in a population-based ASD sample stratified in 3 phenotypic groups. Of 258 probands, 24 (9.3%, 95%CI, 6.1%-13.5%) received a molecular diagnosis from CMA and 8 of 95 (8.4%, 95%CI, 3.7%-15.9%) from WES. The yields were statistically different between the morphological groups. Among the children who underwent both CMA and WES testing, the estimated proportion with an identifiable genetic etiology was 15.8% (95%CI, 9.1%-24.7%; 15/95 children). This included 2 children who received molecular diagnoses from both tests. The combined yield was significantly higher in the complex group when compared with the essential group (pairwise comparison, P = .002). [table: see text]. Among a heterogeneous sample of children with ASD, the molecular diagnostic yields of CMA and WES were comparable, and the combined molecular diagnostic yield was higher in children with more complex morphological phenotypes in comparison with the children in the essential category. If replicated in additional populations, these findings may inform appropriate selection of molecular diagnostic testing for children affected by ASD.

Proximity-Based Differential Single-Cell Analysis of the Niche to Identify Stem/Progenitor Cell Regulators.

PubMed

Silberstein, Lev; Goncalves, Kevin A; Kharchenko, Peter V; Turcotte, Raphael; Kfoury, Youmna; Mercier, Francois; Baryawno, Ninib; Severe, Nicolas; Bachand, Jacqueline; Spencer, Joel A; Papazian, Ani; Lee, Dongjun; Chitteti, Brahmananda Reddy; Srour, Edward F; Hoggatt, Jonathan; Tate, Tiffany; Lo Celso, Cristina; Ono, Noriaki; Nutt, Stephen; Heino, Jyrki; Sipilä, Kalle; Shioda, Toshihiro; Osawa, Masatake; Lin, Charles P; Hu, Guo-Fu; Scadden, David T

2016-10-06

Physiological stem cell function is regulated by secreted factors produced by niche cells. In this study, we describe an unbiased approach based on the differential single-cell gene expression analysis of mesenchymal osteolineage cells close to, and further removed from, hematopoietic stem/progenitor cells (HSPCs) to identify candidate niche factors. Mesenchymal cells displayed distinct molecular profiles based on their relative location. We functionally examined, among the genes that were preferentially expressed in proximal cells, three secreted or cell-surface molecules not previously connected to HSPC biology-the secreted RNase angiogenin, the cytokine IL18, and the adhesion molecule Embigin-and discovered that all of these factors are HSPC quiescence regulators. Therefore, our proximity-based differential single-cell approach reveals molecular heterogeneity within niche cells and can be used to identify novel extrinsic stem/progenitor cell regulators. Similar approaches could also be applied to other stem cell/niche pairs to advance the understanding of microenvironmental regulation of stem cell function. Copyright © 2016 Elsevier Inc. All rights reserved.

Spectroscopic analysis and molecular docking of imidazole derivatives and investigation of its reactive properties by DFT and molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Thomas, Renjith; Hossain, Mossaraf; Mary, Y. Sheena; Resmi, K. S.; Armaković, Stevan; Armaković, Sanja J.; Nanda, Ashis Kumar; Ranjan, Vivek Kumar; Vijayakumar, G.; Van Alsenoy, C.

2018-04-01

Solvent-free synthesis pathway for obtaining two imidazole derivatives (2-chloro-1-(4-methoxyphenyl)-4,5-dimethyl-1H-imidazole (CLMPDI) and 1-(4-bromophenyl)-2-chloro-4,5-dimethyl-1H-imidazole (BPCLDI) has been reported in this work, followed by detailed experimental and computational spectroscopic characterization and reactivity study. Spectroscopic methods encompassed IR, FT-Raman and NMR techniques, with the mutual comparison of experimentally and computationally obtained results at DFT/B3LYP level of theory. Reactivity study based on DFT calculations encompassed molecular orbitals analysis, followed by calculations of molecular electrostatic potential (MEP) and average local ionization energy (ALIE) values, Fukui functions and bond dissociation energies (BDE). Additionally, the stability of title molecules in water has been investigated via molecular dynamics (MD) simulations, while interactivity with aspulvinonedimethylallyl transferase protein has been evaluated by molecular docking procedure. CLMPDI compound showed antimicrobial activity against all four bacterial strain in both gram positive and gram negative bacteria while, BPCLDI showed only in gram positive bacteria, Staphylococcus Aureus (MTCC1144). The first order hyperpolarizability of CLMPDI and BPCLDI are 20.15 and 6.10 times that of the standard NLO material urea.

Intelligent Techniques Using Molecular Data Analysis in Leukaemia: An Opportunity for Personalized Medicine Support System

PubMed Central

Adelson, David; Brown, Fred; Chaudhri, Naeem

2017-01-01

The use of intelligent techniques in medicine has brought a ray of hope in terms of treating leukaemia patients. Personalized treatment uses patient's genetic profile to select a mode of treatment. This process makes use of molecular technology and machine learning, to determine the most suitable approach to treating a leukaemia patient. Until now, no reviews have been published from a computational perspective concerning the development of personalized medicine intelligent techniques for leukaemia patients using molecular data analysis. This review studies the published empirical research on personalized medicine in leukaemia and synthesizes findings across studies related to intelligence techniques in leukaemia, with specific attention to particular categories of these studies to help identify opportunities for further research into personalized medicine support systems in chronic myeloid leukaemia. A systematic search was carried out to identify studies using intelligence techniques in leukaemia and to categorize these studies based on leukaemia type and also the task, data source, and purpose of the studies. Most studies used molecular data analysis for personalized medicine, but future advancement for leukaemia patients requires molecular models that use advanced machine-learning methods to automate decision-making in treatment management to deliver supportive medical information to the patient in clinical practice. PMID:28812013

Intelligent Techniques Using Molecular Data Analysis in Leukaemia: An Opportunity for Personalized Medicine Support System.

PubMed

Banjar, Haneen; Adelson, David; Brown, Fred; Chaudhri, Naeem

2017-01-01

The use of intelligent techniques in medicine has brought a ray of hope in terms of treating leukaemia patients. Personalized treatment uses patient's genetic profile to select a mode of treatment. This process makes use of molecular technology and machine learning, to determine the most suitable approach to treating a leukaemia patient. Until now, no reviews have been published from a computational perspective concerning the development of personalized medicine intelligent techniques for leukaemia patients using molecular data analysis. This review studies the published empirical research on personalized medicine in leukaemia and synthesizes findings across studies related to intelligence techniques in leukaemia, with specific attention to particular categories of these studies to help identify opportunities for further research into personalized medicine support systems in chronic myeloid leukaemia. A systematic search was carried out to identify studies using intelligence techniques in leukaemia and to categorize these studies based on leukaemia type and also the task, data source, and purpose of the studies. Most studies used molecular data analysis for personalized medicine, but future advancement for leukaemia patients requires molecular models that use advanced machine-learning methods to automate decision-making in treatment management to deliver supportive medical information to the patient in clinical practice.

Of truth and pathways: chasing bits of information through myriads of articles.

PubMed

Krauthammer, Michael; Kra, Pauline; Iossifov, Ivan; Gomez, Shawn M; Hripcsak, George; Hatzivassiloglou, Vasileios; Friedman, Carol; Rzhetsky, Andrey

2002-01-01

Knowledge on interactions between molecules in living cells is indispensable for theoretical analysis and practical applications in modern genomics and molecular biology. Building such networks relies on the assumption that the correct molecular interactions are known or can be identified by reading a few research articles. However, this assumption does not necessarily hold, as truth is rather an emerging property based on many potentially conflicting facts. This paper explores the processes of knowledge generation and publishing in the molecular biology literature using modelling and analysis of real molecular interaction data. The data analysed in this article were automatically extracted from 50000 research articles in molecular biology using a computer system called GeneWays containing a natural language processing module. The paper indicates that truthfulness of statements is associated in the minds of scientists with the relative importance (connectedness) of substances under study, revealing a potential selection bias in the reporting of research results. Aiming at understanding the statistical properties of the life cycle of biological facts reported in research articles, we formulate a stochastic model describing generation and propagation of knowledge about molecular interactions through scientific publications. We hope that in the future such a model can be useful for automatically producing consensus views of molecular interaction data.

The molecular genetics of insecticide resistance.

PubMed

Ffrench-Constant, Richard H

2013-08-01

The past 60 years have seen a revolution in our understanding of the molecular genetics of insecticide resistance. While at first the field was split by arguments about the relative importance of mono- vs. polygenic resistance and field- vs. laboratory-based selection, the application of molecular cloning to insecticide targets and to the metabolic enzymes that degrade insecticides before they reach those targets has brought out an exponential growth in our understanding of the mutations involved. Molecular analysis has confirmed the relative importance of single major genes in target-site resistance and has also revealed some interesting surprises about the multi-gene families, such as cytochrome P450s, involved in metabolic resistance. Identification of the mutations involved in resistance has also led to parallel advances in our understanding of the enzymes and receptors involved, often with implications for the role of these receptors in humans. This Review seeks to provide an historical perspective on the impact of molecular biology on our understanding of resistance and to begin to look forward to the likely impact of rapid advances in both sequencing and genome-wide association analysis.

Morphological variability in leaves and molecular characterization of novel table grape candidate cultivars (Vitis vinifera L.).

PubMed

Alba, Vittorio; Bergamini, Carlo; Cardone, Maria Francesca; Gasparro, Marica; Perniola, Rocco; Genghi, Rosalinda; Antonacci, Donato

2014-06-01

The present work report the characterization of twenty-one table grapes candidate cultivars plus five registered ones included as reference, by means of 47 ampelographic traits, 23 ampelometric measurements and six microsatellite loci. The final goal of the research was to analyse the possibility of reducing the number of morphological and molecular tools required for a precise and effective description of a grape genotype or cultivar. This would be of great help for future biodiversity description on a larger sample of more than 300 table grapes accessions today grown at the 'Consiglio per la Ricerca e la sperimentazione in Agricoltura (C.R.A.)-Unità di ricerca per l'uva da tavola e la vitivinicoltura in ambiente mediterraneo (Bari-Italy)'. OIV ampelographic traits showed a clear distinction among all twenty-six genotypes analysed, suggesting the relevant morphological variability investigated. Principal component analysis based on ampelometric traits revealed main veins ON(3), ON(4) and O(3)N(4); ratios between main veins; angles between main veins and of petiolar sinus, to be the most effective records in differentiating cultivars, for a total variation of 69.9 % described by the first three components. Molecular analysis based on six microsatellite loci was performed on all genotypes, providing a detailed molecular profile and a dendrogram of genetic similarity, in which all genotypes were clearly distinguishable. Finally, with the goal of using the minimum possible number of markers to differentiate genotypes, microsatellites VVMD5 and VVMD27 were selected to be sufficient to distinguish among all the candidate cultivars included in the analysis, representing a possible 'step by step' approach when a molecular characterization has to be undertaken on a large number of genotypes, by first testing few markers and increasing their number only if necessary.

A molecular approach for the rapid, selective and sensitive detection of Exophiala jeanselmei in environmental samples: development and performance assessment of a real-time PCR assay.

PubMed

Libert, X; Chasseur, C; Packeu, A; Bureau, F; Roosens, N H; De Keersmaecker, S J C

2016-02-01

Exophiala jeanselmei is an opportunistic pathogenic black yeast growing in humid environments such as water reservoirs of air-conditioning systems. Because this fungal contaminant could be vaporized into the air and subsequently cause health problems, its monitoring is recommended. Currently, this monitoring is based on culture and microscopic identification which are complex, sometimes ambiguous and time-demanding, i.e., up to 21 days. Therefore, molecular, culture-independent methods could be more advantageous for the monitoring of E. jeanselmei. In this study, we developed a SYBR®green real-time PCR assay based on the internal transcribed spacer 2 from the 18S ribosomal DNA complex for the specific detection of E. jeanselmei. The selectivity (100 %), PCR efficiency (95.5 %), dynamic range and repeatability of this qPCR assay were subsequently evaluated. The limit of detection for this qPCR assay was determined to be 1 copy of genomic DNA of E. jeanselmei. Finally, water samples collected from cooling reservoirs were analyzed using this qPCR assay to deliver a proof of concept for the molecular detection of E. jeanselmei in environmental samples. The results obtained by molecular analysis were compared with those of classical methods (i.e., culture and microscopic identification) used in routine analysis and were 100 % matching. This comparison demonstrated that this SYBR®green qPCR assay can be used as a molecular alternative for monitoring and routine investigation of samples contaminated by E. jeanselmei, while eliminating the need for culturing and thereby considerably decreasing the required analysis time to 2 days.

Synchrotron IR microspectroscopy for protein structure analysis: Potential and questions

DOE PAGES

Yu, Peiqiang

2006-01-01

Synchrotron radiation-based Fourier transform infrared microspectroscopy (S-FTIR) has been developed as a rapid, direct, non-destructive, bioanalytical technique. This technique takes advantage of synchrotron light brightness and small effective source size and is capable of exploring the molecular chemical make-up within microstructures of a biological tissue without destruction of inherent structures at ultra-spatial resolutions within cellular dimension. To date there has been very little application of this advanced technique to the study of pure protein inherent structure at a cellular level in biological tissues. In this review, a novel approach was introduced to show the potential of the newly developed, advancedmore » synchrotron-based analytical technology, which can be used to localize relatively “pure“ protein in the plant tissues and relatively reveal protein inherent structure and protein molecular chemical make-up within intact tissue at cellular and subcellular levels. Several complex protein IR spectra data analytical techniques (Gaussian and Lorentzian multi-component peak modeling, univariate and multivariate analysis, principal component analysis (PCA), and hierarchical cluster analysis (CLA) are employed to relatively reveal features of protein inherent structure and distinguish protein inherent structure differences between varieties/species and treatments in plant tissues. By using a multi-peak modeling procedure, RELATIVE estimates (but not EXACT determinations) for protein secondary structure analysis can be made for comparison purpose. The issues of pro- and anti-multi-peaking modeling/fitting procedure for relative estimation of protein structure were discussed. By using the PCA and CLA analyses, the plant molecular structure can be qualitatively separate one group from another, statistically, even though the spectral assignments are not known. The synchrotron-based technology provides a new approach for protein structure research in biological tissues at ultraspatial resolutions.« less

The Role of Liquid Based Cytology and Ancillary Techniques in the Peritoneal Washing Analysis: Our Institutional Experience.

PubMed

Rossi, Esther; Bizzarro, Tommaso; Martini, Maurizio; Longatto-Filho, Adhemar; Schmitt, Fernando; Fagotti, Anna; Scambia, Giovanni; Zannoni, Gian Franco

2017-01-01

The cytological analysis of peritoneal effusions serves as a diagnostic and prognostic aid for either primary or metastatic diseases. Among the different cytological preparations, liquid based cytology (LBC) represents a feasible and reliable method ensuring also the application of ancillary techniques (i.e immunocytochemistry-ICC and molecular testing). We recorded 10348 LBC peritoneal effusions between January 2000 and December 2014. They were classified as non-diagnostic (ND), negative for malignancy-NM, atypical-suspicious for malignancy-SM and positive for malignancy-PM. The cytological diagnosis included 218 ND, 9.035 NM, 213 SM and 882 PM. A total of 8048 (7228 NM, 115SM, 705 PM) cases with histological follow-up were included. Our NM included 21 malignant and 7207 benign histological diagnoses. Our 820 SMs+PMs were diagnosed as 107 unknown malignancies (30SM and 77PM), 691 metastatic lesions (81SM and 610PM), 9 lymphomas (2SM and 7PM), 9 mesotheliomas (1SM and 8SM), 4 sarcomas (1SM and 3PM). Primary gynecological cancers contributed with 64% of the cases. We documented 97.4% sensitivity, 99.9% specificity, 98% diagnostic accuracy, 99.7% negative predictive value (NPV) and 99.7% positive predictive value (PPV). Furthermore, the morphological diagnoses were supported by either 173 conclusive ICC results or 50 molecular analyses. Specifically the molecular testing was performed for the EGFR and KRAS mutational analysis based on the previous or contemporary diagnoses of Non Small Cell Lung Cancer (NSCLC) and colon carcinomas. We identified 10 EGFR in NSCCL and 7 KRAS mutations on LBC stored material. Peritoneal cytology is an adjunctive tool in the surgical management of tumors mostly gynecological cancers. LBC maximizes the application of ancillary techniques such as ICC and molecular analysis with feasible diagnostic and predictive yields also in controversial cases.

The Role of Liquid Based Cytology and Ancillary Techniques in the Peritoneal Washing Analysis: Our Institutional Experience

PubMed Central

Rossi, Esther; Bizzarro, Tommaso; Martini, Maurizio; Longatto-Filho, Adhemar; Schmitt, Fernando; Fagotti, Anna; Scambia, Giovanni; Zannoni, Gian Franco

2017-01-01

Background The cytological analysis of peritoneal effusions serves as a diagnostic and prognostic aid for either primary or metastatic diseases. Among the different cytological preparations, liquid based cytology (LBC) represents a feasible and reliable method ensuring also the application of ancillary techniques (i.e immunocytochemistry-ICC and molecular testing). Methods We recorded 10348 LBC peritoneal effusions between January 2000 and December 2014. They were classified as non-diagnostic (ND), negative for malignancy-NM, atypical-suspicious for malignancy-SM and positive for malignancy-PM. Results The cytological diagnosis included 218 ND, 9.035 NM, 213 SM and 882 PM. A total of 8048 (7228 NM, 115SM, 705 PM) cases with histological follow-up were included. Our NM included 21 malignant and 7207 benign histological diagnoses. Our 820 SMs+PMs were diagnosed as 107 unknown malignancies (30SM and 77PM), 691 metastatic lesions (81SM and 610PM), 9 lymphomas (2SM and 7PM), 9 mesotheliomas (1SM and 8SM), 4 sarcomas (1SM and 3PM). Primary gynecological cancers contributed with 64% of the cases. We documented 97.4% sensitivity, 99.9% specificity, 98% diagnostic accuracy, 99.7% negative predictive value (NPV) and 99.7% positive predictive value (PPV). Furthermore, the morphological diagnoses were supported by either 173 conclusive ICC results or 50 molecular analyses. Specifically the molecular testing was performed for the EGFR and KRAS mutational analysis based on the previous or contemporary diagnoses of Non Small Cell Lung Cancer (NSCLC) and colon carcinomas. We identified 10 EGFR in NSCCL and 7 KRAS mutations on LBC stored material. Conclusions Peritoneal cytology is an adjunctive tool in the surgical management of tumors mostly gynecological cancers. LBC maximizes the application of ancillary techniques such as ICC and molecular analysis with feasible diagnostic and predictive yields also in controversial cases. PMID:28099523

Specificity and Catalytic Mechanism in Family 5 Uracil DNA Glycosylase*

PubMed Central

Xia, Bo; Liu, Yinling; Li, Wei; Brice, Allyn R.; Dominy, Brian N.; Cao, Weiguo

2014-01-01

UDGb belongs to family 5 of the uracil DNA glycosylase (UDG) superfamily. Here, we report that family 5 UDGb from Thermus thermophilus HB8 is not only a uracil DNA glycosyase acting on G/U, T/U, C/U, and A/U base pairs, but also a hypoxanthine DNA glycosylase acting on G/I, T/I, and A/I base pairs and a xanthine DNA glycosylase acting on all double-stranded and single-stranded xanthine-containing DNA. Analysis of potentials of mean force indicates that the tendency of hypoxanthine base flipping follows the order of G/I > T/I, A/I > C/I, matching the trend of hypoxanthine DNA glycosylase activity observed in vitro. Genetic analysis indicates that family 5 UDGb can also act as an enzyme to remove uracil incorporated into DNA through the existence of dUTP in the nucleotide pool. Mutational analysis coupled with molecular modeling and molecular dynamics analysis reveals that although hydrogen bonding to O2 of uracil underlies the UDG activity in a dissociative fashion, Tth UDGb relies on multiple catalytic residues to facilitate its excision of hypoxanthine and xanthine. This study underscores the structural and functional diversity in the UDG superfamily. PMID:24838246

A reduced basis method for molecular dynamics simulation

NASA Astrophysics Data System (ADS)

Vincent-Finley, Rachel Elisabeth

In this dissertation, we develop a method for molecular simulation based on principal component analysis (PCA) of a molecular dynamics trajectory and least squares approximation of a potential energy function. Molecular dynamics (MD) simulation is a computational tool used to study molecular systems as they evolve through time. With respect to protein dynamics, local motions, such as bond stretching, occur within femtoseconds, while rigid body and large-scale motions, occur within a range of nanoseconds to seconds. To capture motion at all levels, time steps on the order of a femtosecond are employed when solving the equations of motion and simulations must continue long enough to capture the desired large-scale motion. To date, simulations of solvated proteins on the order of nanoseconds have been reported. It is typically the case that simulations of a few nanoseconds do not provide adequate information for the study of large-scale motions. Thus, the development of techniques that allow longer simulation times can advance the study of protein function and dynamics. In this dissertation we use principal component analysis (PCA) to identify the dominant characteristics of an MD trajectory and to represent the coordinates with respect to these characteristics. We augment PCA with an updating scheme based on a reduced representation of a molecule and consider equations of motion with respect to the reduced representation. We apply our method to butane and BPTI and compare the results to standard MD simulations of these molecules. Our results indicate that the molecular activity with respect to our simulation method is analogous to that observed in the standard MD simulation with simulations on the order of picoseconds.

Molecular Strain Typing of Mycobacterium tuberculosis: a Review of Frequently Used Methods

PubMed Central

2016-01-01

Tuberculosis, caused by the bacterium Mycobacterium tuberculosis, remains one of the most serious global health problems. Molecular typing of M. tuberculosis has been used for various epidemiologic purposes as well as for clinical management. Currently, many techniques are available to type M. tuberculosis. Choosing the most appropriate technique in accordance with the existing laboratory conditions and the specific features of the geographic region is important. Insertion sequence IS6110-based restriction fragment length polymorphism (RFLP) analysis is considered the gold standard for the molecular epidemiologic investigations of tuberculosis. However, other polymerase chain reaction-based methods such as spacer oligonucleotide typing (spoligotyping), which detects 43 spacer sequence-interspersing direct repeats (DRs) in the genomic DR region; mycobacterial interspersed repetitive units–variable number tandem repeats, (MIRU-VNTR), which determines the number and size of tandem repetitive DNA sequences; repetitive-sequence-based PCR (rep-PCR), which provides high-throughput genotypic fingerprinting of multiple Mycobacterium species; and the recently developed genome-based whole genome sequencing methods demonstrate similar discriminatory power and greater convenience. This review focuses on techniques frequently used for the molecular typing of M. tuberculosis and discusses their general aspects and applications. PMID:27709842

Molecular Strain Typing of Mycobacterium tuberculosis: a Review of Frequently Used Methods.

PubMed

Ei, Phyu Win; Aung, Wah Wah; Lee, Jong Seok; Choi, Go Eun; Chang, Chulhun L

2016-11-01

Tuberculosis, caused by the bacterium Mycobacterium tuberculosis, remains one of the most serious global health problems. Molecular typing of M. tuberculosis has been used for various epidemiologic purposes as well as for clinical management. Currently, many techniques are available to type M. tuberculosis. Choosing the most appropriate technique in accordance with the existing laboratory conditions and the specific features of the geographic region is important. Insertion sequence IS6110-based restriction fragment length polymorphism (RFLP) analysis is considered the gold standard for the molecular epidemiologic investigations of tuberculosis. However, other polymerase chain reaction-based methods such as spacer oligonucleotide typing (spoligotyping), which detects 43 spacer sequence-interspersing direct repeats (DRs) in the genomic DR region; mycobacterial interspersed repetitive units-variable number tandem repeats, (MIRU-VNTR), which determines the number and size of tandem repetitive DNA sequences; repetitive-sequence-based PCR (rep-PCR), which provides high-throughput genotypic fingerprinting of multiple Mycobacterium species; and the recently developed genome-based whole genome sequencing methods demonstrate similar discriminatory power and greater convenience. This review focuses on techniques frequently used for the molecular typing of M. tuberculosis and discusses their general aspects and applications.

Prognostic value of DNA repair based stratification of hepatocellular carcinoma

PubMed Central

Lin, Zhuo; Xu, Shi-Hao; Wang, Hai-Qing; Cai, Yi-Jing; Ying, Li; Song, Mei; Wang, Yu-Qun; Du, Shan-Jie; Shi, Ke-Qing; Zhou, Meng-Tao

2016-01-01

Aberrant activation of DNA repair is frequently associated with tumor progression and response to therapy in hepatocellular carcinoma (HCC). Bioinformatics analyses of HCC data in the Cancer Genome Atlas (TCGA) were performed to define DNA repair based molecular classification that could predict the prognosis of patients with HCC. Furthermore, we tested its predictive performance in 120 independent cases. Four molecular subgroups were identified on the basis of coordinate DNA repair cluster (CDRC) comprising 15 genes in TCGA dataset. Increasing expression of CDRC genes were significantly associated with TP53 mutation. High CDRC was significantly correlated with advanced tumor grades, advanced pathological stage and increased vascular invasion rate. Multivariate Cox regression analysis indicated that the molecular subgrouping was an independent prognostic parameter for both overall survival (p = 0.004, hazard ratio (HR): 2.989) and tumor-free survival (p = 0.049, HR: 3.366) in TCGA dataset. Similar results were also obtained by analyzing the independent cohort. These data suggest that distinct dysregulation of DNA repair constituents based molecular classes in HCC would be useful for predicting prognosis and designing clinical trials for targeted therapy. PMID:27174663

Kim Magrini | NREL

Science.gov Websites

Developing char-based soil amendments Soil carbon and char analysis via molecular beam mass spectrometry depth profiling, Fourier transform infrared [FTIR]) Rapid soil carbon analysis using analytical DRIFTS, 13C NMR, and py-MBMS to Characterize the Effects of Soil Science Oxidation Assays on Soil Organic

Association analysis and marker development for grain quality traits using USDA diverse rice germplasm collections

USDA-ARS?s Scientific Manuscript database

New molecular markers are being designed and validated for grain quality improvement based on computationally assisted analysis of genome wide association study (GWAS) findings across multiple panels and multiple grain quality traits. The traits include grain dimensions, apparent amylose content (A...

Agarose and Polyacrylamide Gel Electrophoresis Methods for Molecular Mass Analysis of 5–500 kDa Hyaluronan

PubMed Central

Bhilocha, Shardul; Amin, Ripal; Pandya, Monika; Yuan, Han; Tank, Mihir; LoBello, Jaclyn; Shytuhina, Anastasia; Wang, Wenlan; Wisniewski, Hans-Georg; de la Motte, Carol; Cowman, Mary K.

2011-01-01

Agarose and polyacrylamide gel electrophoresis systems for the molecular mass-dependent separation of hyaluronan (HA) in the size range of approximately 5–500 kDa have been investigated. For agarose-based systems, the suitability of different agarose types, agarose concentrations, and buffers systems were determined. Using chemoenzymatically synthesized HA standards of low polydispersity, the molecular mass range was determined for each gel composition, over which the relationship between HA mobility and logarithm of the molecular mass was linear. Excellent linear calibration was obtained for HA molecular mass as low as approximately 9 kDa in agarose gels. For higher resolution separation, and for extension to molecular masses as low as approximately 5 kDa, gradient polyacrylamide gels were superior. Densitometric scanning of stained gels allowed analysis of the range of molecular masses present in a sample, and calculation of weight-average and number-average values. The methods were validated for polydisperse HA samples with viscosity-average molecular masses of 112, 59, 37, and 22 kDa, at sample loads of 0.5 µg (for polyacrylamide) to 2.5 µg (for agarose). Use of the methods for electrophoretic mobility shift assays was demonstrated for binding of the HA-binding region of aggrecan (recombinant human aggrecan G1-IGD-G2 domains) to a 150 kDa HA standard. PMID:21684248

Forensic molecular genetic diversity analysis of Chinese Hui ethnic group based on a novel STR panel.

PubMed

Fang, Yating; Guo, Yuxin; Xie, Tong; Jin, Xiaoye; Lan, Qiong; Zhou, Yongsong; Zhu, Bofeng

2018-03-26

In present study, the genetic polymorphisms of 22 autosomal short tandem repeat (STR) loci were analyzed in 496 unrelated Chinese Xinjiang Hui individuals. These autosomal STR loci were multiplex amplified and genotyped based on a novel STR panel. There were 246 observed alleles with the allele frequencies ranging from 0.0010 to 0.3609. All polymorphic information content values were higher than 0.7. The combined power of discrimination and the combined probability of exclusion were 0.999999999999999999999999999426766 and 0.999999999860491, respectively. Based on analysis of molecular variance method, genetic differentiation analysis between the Xinjiang Hui and other reported groups were conducted at these 22 loci. The results indicated that there were no significant differences in statistics between Hui group and Northern Han group (including Han groups from Hebei, Henan, Shaanxi provinces), and significant deviations with Southern Han group (including those from Guangdong, Guangxi provinces) at 7 loci, and Uygur group at 10 loci. To sum up, these 22 autosomal STR loci were high genetic polymorphic in Xinjiang Hui group.

Predicting RNA Duplex Dimerization Free-Energy Changes upon Mutations Using Molecular Dynamics Simulations.

PubMed

Sakuraba, Shun; Asai, Kiyoshi; Kameda, Tomoshi

2015-11-05

The dimerization free energies of RNA-RNA duplexes are fundamental values that represent the structural stability of RNA complexes. We report a comparative analysis of RNA-RNA duplex dimerization free-energy changes upon mutations, estimated from a molecular dynamics simulation and experiments. A linear regression for nine pairs of double-stranded RNA sequences, six base pairs each, yielded a mean absolute deviation of 0.55 kcal/mol and an R(2) value of 0.97, indicating quantitative agreement between simulations and experimental data. The observed accuracy indicates that the molecular dynamics simulation with the current molecular force field is capable of estimating the thermodynamic properties of RNA molecules.

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

PubMed

Li, D; Peng, S

2000-04-01

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

Microfluidic-Based Enrichment and Retrieval of Circulating Tumor Cells for RT-PCR Analysis.

PubMed

Gogoi, Priya; Sepehri, Saedeh; Chow, Will; Handique, Kalyan; Wang, Yixin

2017-01-01

Molecular analysis of circulating tumor cells (CTCs) is hindered by low sensitivity and high level of background leukocytes of currently available CTC enrichment technologies. We have developed a novel device to enrich and retrieve CTCs from blood samples by using a microfluidic chip. The Celsee PREP100 device captures CTCs with high sensitivity and allows the captured CTCs to be retrieved for molecular analysis. It uses the microfluidic chip which has approximately 56,320 capture chambers. Based on differences in cell size and deformability, each chamber ensures that small blood escape while larger CTCs of varying sizes are trapped and isolated in the chambers. In this report, we used the Celsee PREP100 to capture cancer cells spiked into normal donor blood samples. We were able to show that the device can capture as low as 10 cells with high reproducibility. The captured CTCs were retrieved from the microfluidic chip. The cell recovery rate of this back-flow procedure is 100% and the level of remaining background leukocytes is very low (about 300-400 cells). RNA from the retrieved cells are extracted and converted to cDNA, and gene expression analysis of selected cancer markers can be carried out by using RT-PCR assays. The sensitive and easy-to-use Celsee PREP100 system represents a promising technology for capturing and molecular characterization of CTCs.

Population Structure, Genetic Diversity and Molecular Marker-Trait Association Analysis for High Temperature Stress Tolerance in Rice

PubMed Central

Barik, Saumya Ranjan; Sahoo, Ambika; Mohapatra, Sudipti; Nayak, Deepak Kumar; Mahender, Anumalla; Meher, Jitandriya; Anandan, Annamalai

2016-01-01

Rice exhibits enormous genetic diversity, population structure and molecular marker-traits associated with abiotic stress tolerance to high temperature stress. A set of breeding lines and landraces representing 240 germplasm lines were studied. Based on spikelet fertility percent under high temperature, tolerant genotypes were broadly classified into four classes. Genetic diversity indicated a moderate level of genetic base of the population for the trait studied. Wright’s F statistic estimates showed a deviation of Hardy-Weinberg expectation in the population. The analysis of molecular variance revealed 25 percent variation between population, 61 percent among individuals and 14 percent within individuals in the set. The STRUCTURE analysis categorized the entire population into three sub-populations and suggested that most of the landraces in each sub-population had a common primary ancestor with few admix individuals. The composition of materials in the panel showed the presence of many QTLs representing the entire genome for the expression of tolerance. The strongly associated marker RM547 tagged with spikelet fertility under stress and the markers like RM228, RM205, RM247, RM242, INDEL3 and RM314 indirectly controlling the high temperature stress tolerance were detected through both mixed linear model and general linear model TASSEL analysis. These markers can be deployed as a resource for marker-assisted breeding program of high temperature stress tolerance. PMID:27494320

Population Structure, Genetic Diversity and Molecular Marker-Trait Association Analysis for High Temperature Stress Tolerance in Rice.

PubMed

Pradhan, Sharat Kumar; Barik, Saumya Ranjan; Sahoo, Ambika; Mohapatra, Sudipti; Nayak, Deepak Kumar; Mahender, Anumalla; Meher, Jitandriya; Anandan, Annamalai; Pandit, Elssa

2016-01-01

Rice exhibits enormous genetic diversity, population structure and molecular marker-traits associated with abiotic stress tolerance to high temperature stress. A set of breeding lines and landraces representing 240 germplasm lines were studied. Based on spikelet fertility percent under high temperature, tolerant genotypes were broadly classified into four classes. Genetic diversity indicated a moderate level of genetic base of the population for the trait studied. Wright's F statistic estimates showed a deviation of Hardy-Weinberg expectation in the population. The analysis of molecular variance revealed 25 percent variation between population, 61 percent among individuals and 14 percent within individuals in the set. The STRUCTURE analysis categorized the entire population into three sub-populations and suggested that most of the landraces in each sub-population had a common primary ancestor with few admix individuals. The composition of materials in the panel showed the presence of many QTLs representing the entire genome for the expression of tolerance. The strongly associated marker RM547 tagged with spikelet fertility under stress and the markers like RM228, RM205, RM247, RM242, INDEL3 and RM314 indirectly controlling the high temperature stress tolerance were detected through both mixed linear model and general linear model TASSEL analysis. These markers can be deployed as a resource for marker-assisted breeding program of high temperature stress tolerance.

A protein and mRNA expression-based classification of gastric cancer.

PubMed

Setia, Namrata; Agoston, Agoston T; Han, Hye S; Mullen, John T; Duda, Dan G; Clark, Jeffrey W; Deshpande, Vikram; Mino-Kenudson, Mari; Srivastava, Amitabh; Lennerz, Jochen K; Hong, Theodore S; Kwak, Eunice L; Lauwers, Gregory Y

2016-07-01

The overall survival of gastric carcinoma patients remains poor despite improved control over known risk factors and surveillance. This highlights the need for new classifications, driven towards identification of potential therapeutic targets. Using sophisticated molecular technologies and analysis, three groups recently provided genetic and epigenetic molecular classifications of gastric cancer (The Cancer Genome Atlas, 'Singapore-Duke' study, and Asian Cancer Research Group). Suggested by these classifications, here, we examined the expression of 14 biomarkers in a cohort of 146 gastric adenocarcinomas and performed unsupervised hierarchical clustering analysis using less expensive and widely available immunohistochemistry and in situ hybridization. Ultimately, we identified five groups of gastric cancers based on Epstein-Barr virus (EBV) positivity, microsatellite instability, aberrant E-cadherin, and p53 expression; the remaining cases constituted a group characterized by normal p53 expression. In addition, the five categories correspond to the reported molecular subgroups by virtue of clinicopathologic features. Furthermore, evaluation between these clusters and survival using the Cox proportional hazards model showed a trend for superior survival in the EBV and microsatellite-instable related adenocarcinomas. In conclusion, we offer as a proposal a simplified algorithm that is able to reproduce the recently proposed molecular subgroups of gastric adenocarcinoma, using immunohistochemical and in situ hybridization techniques.

Racial Variations in Prostate Cancer Molecular Subtypes and Androgen Receptor Signaling Reflect Anatomic Tumor Location.

PubMed

Faisal, Farzana A; Sundi, Debasish; Tosoian, Jeffrey J; Choeurng, Voleak; Alshalalfa, Mohammed; Ross, Ashley E; Klein, Eric; Den, Robert; Dicker, Adam; Erho, Nicholas; Davicioni, Elai; Lotan, Tamara L; Schaeffer, Edward M

2016-07-01

Prostate cancer (PCa) subtypes based on ETS gene expression have been described. Recent studies suggest there are racial differences in tumor location, with PCa located anteriorly more often among African-American (AA) compared to Caucasian-American (CA) men. In this retrospective analysis of a multi-institutional cohort treated by radical prostatectomy (179 CA, 121 AA), we evaluated associations among molecular subtype, race, anatomic tumor location, and androgen receptor (AR) signaling. Subtype (m-ERG(+), m-ETS(+), m-SPINK1(+), or triple-negative) was determined using distribution-based outlier analysis. AR signaling was investigated using gene expression profiling of canonical AR targets. m-ERG(+) was more common in CA than AA men (47% vs 22%, p<0.001). AA men were more likely to be m-SPINK1(+) (13% vs 7%; p=0.069) and triple-negative (50% vs 37%; p=0.043). Racial differences in molecular subtypes did not persist when tumors were analyzed by location, suggesting a biologically important relationship between tumor location and subtype. Accordingly, anterior tumor location was associated with higher Decipher scores and lower global AR signaling. This study demonstrates associations among patient race, prostate cancer molecular subtypes, and tumor location. Location-specific differences in androgen regulation may further underlie these relationships. Copyright © 2015. Published by Elsevier B.V.

Integrating a Numerical Taxonomic Method and Molecular Phylogeny for Species Delimitation of Melampsora Species (Melampsoraceae, Pucciniales) on Willows in China

PubMed Central

Zhao, Peng; Wang, Qing-Hong; Tian, Cheng-Ming; Kakishima, Makoto

2015-01-01

The species in genus Melampsora are the causal agents of leaf rust diseases on willows in natural habitats and plantations. However, the classification and recognition of species diversity are challenging because morphological characteristics are scant and morphological variation in Melampsora on willows has not been thoroughly evaluated. Thus, the taxonomy of Melampsora species on willows remains confused, especially in China where 31 species were reported based on either European or Japanese taxonomic systems. To clarify the species boundaries of Melampsora species on willows in China, we tested two approaches for species delimitation inferred from morphological and molecular variations. Morphological species boundaries were determined based on numerical taxonomic analyses of morphological characteristics in the uredinial and telial stages by cluster analysis and one-way analysis of variance. Phylogenetic species boundaries were delineated based on the generalized mixed Yule-coalescent (GMYC) model analysis of the sequences of the internal transcribed spacer (ITS1 and ITS2) regions including the 5.8S and D1/D2 regions of the large nuclear subunit of the ribosomal RNA gene. Numerical taxonomic analyses of 14 morphological characteristics recognized in the uredinial-telial stages revealed 22 morphological species, whereas the GMYC results recovered 29 phylogenetic species. In total, 17 morphological species were in concordance with the phylogenetic species and 5 morphological species were in concordance with 12 phylogenetic species. Both the morphological and molecular data supported 14 morphological characteristics, including 5 newly recognized characteristics and 9 traditionally emphasized characteristics, as effective for the differentiation of Melampsora species on willows in China. Based on the concordance and discordance of the two species delimitation approaches, we concluded that integrative taxonomy by using both morphological and molecular variations was an effective approach for delimitating Melampsora species on willows in China. PMID:26680416

Integrated software environment based on COMKAT for analyzing tracer pharmacokinetics with molecular imaging.

PubMed

Fang, Yu-Hua Dean; Asthana, Pravesh; Salinas, Cristian; Huang, Hsuan-Ming; Muzic, Raymond F

2010-01-01

An integrated software package, Compartment Model Kinetic Analysis Tool (COMKAT), is presented in this report. COMKAT is an open-source software package with many functions for incorporating pharmacokinetic analysis in molecular imaging research and has both command-line and graphical user interfaces. With COMKAT, users may load and display images, draw regions of interest, load input functions, select kinetic models from a predefined list, or create a novel model and perform parameter estimation, all without having to write any computer code. For image analysis, COMKAT image tool supports multiple image file formats, including the Digital Imaging and Communications in Medicine (DICOM) standard. Image contrast, zoom, reslicing, display color table, and frame summation can be adjusted in COMKAT image tool. It also displays and automatically registers images from 2 modalities. Parametric imaging capability is provided and can be combined with the distributed computing support to enhance computation speeds. For users without MATLAB licenses, a compiled, executable version of COMKAT is available, although it currently has only a subset of the full COMKAT capability. Both the compiled and the noncompiled versions of COMKAT are free for academic research use. Extensive documentation, examples, and COMKAT itself are available on its wiki-based Web site, http://comkat.case.edu. Users are encouraged to contribute, sharing their experience, examples, and extensions of COMKAT. With integrated functionality specifically designed for imaging and kinetic modeling analysis, COMKAT can be used as a software environment for molecular imaging and pharmacokinetic analysis.

DDBJ read annotation pipeline: a cloud computing-based pipeline for high-throughput analysis of next-generation sequencing data.

PubMed

Nagasaki, Hideki; Mochizuki, Takako; Kodama, Yuichi; Saruhashi, Satoshi; Morizaki, Shota; Sugawara, Hideaki; Ohyanagi, Hajime; Kurata, Nori; Okubo, Kousaku; Takagi, Toshihisa; Kaminuma, Eli; Nakamura, Yasukazu

2013-08-01

High-performance next-generation sequencing (NGS) technologies are advancing genomics and molecular biological research. However, the immense amount of sequence data requires computational skills and suitable hardware resources that are a challenge to molecular biologists. The DNA Data Bank of Japan (DDBJ) of the National Institute of Genetics (NIG) has initiated a cloud computing-based analytical pipeline, the DDBJ Read Annotation Pipeline (DDBJ Pipeline), for a high-throughput annotation of NGS reads. The DDBJ Pipeline offers a user-friendly graphical web interface and processes massive NGS datasets using decentralized processing by NIG supercomputers currently free of charge. The proposed pipeline consists of two analysis components: basic analysis for reference genome mapping and de novo assembly and subsequent high-level analysis of structural and functional annotations. Users may smoothly switch between the two components in the pipeline, facilitating web-based operations on a supercomputer for high-throughput data analysis. Moreover, public NGS reads of the DDBJ Sequence Read Archive located on the same supercomputer can be imported into the pipeline through the input of only an accession number. This proposed pipeline will facilitate research by utilizing unified analytical workflows applied to the NGS data. The DDBJ Pipeline is accessible at http://p.ddbj.nig.ac.jp/.

DDBJ Read Annotation Pipeline: A Cloud Computing-Based Pipeline for High-Throughput Analysis of Next-Generation Sequencing Data

PubMed Central

Nagasaki, Hideki; Mochizuki, Takako; Kodama, Yuichi; Saruhashi, Satoshi; Morizaki, Shota; Sugawara, Hideaki; Ohyanagi, Hajime; Kurata, Nori; Okubo, Kousaku; Takagi, Toshihisa; Kaminuma, Eli; Nakamura, Yasukazu

2013-01-01

High-performance next-generation sequencing (NGS) technologies are advancing genomics and molecular biological research. However, the immense amount of sequence data requires computational skills and suitable hardware resources that are a challenge to molecular biologists. The DNA Data Bank of Japan (DDBJ) of the National Institute of Genetics (NIG) has initiated a cloud computing-based analytical pipeline, the DDBJ Read Annotation Pipeline (DDBJ Pipeline), for a high-throughput annotation of NGS reads. The DDBJ Pipeline offers a user-friendly graphical web interface and processes massive NGS datasets using decentralized processing by NIG supercomputers currently free of charge. The proposed pipeline consists of two analysis components: basic analysis for reference genome mapping and de novo assembly and subsequent high-level analysis of structural and functional annotations. Users may smoothly switch between the two components in the pipeline, facilitating web-based operations on a supercomputer for high-throughput data analysis. Moreover, public NGS reads of the DDBJ Sequence Read Archive located on the same supercomputer can be imported into the pipeline through the input of only an accession number. This proposed pipeline will facilitate research by utilizing unified analytical workflows applied to the NGS data. The DDBJ Pipeline is accessible at http://p.ddbj.nig.ac.jp/. PMID:23657089

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

PubMed

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

2017-03-04

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

Formaldehyde substitute fixatives: effects on nucleic acid preservation.

PubMed

Moelans, Cathy B; Oostenrijk, Daphne; Moons, Michiel J; van Diest, Paul J

2011-11-01

In surgical pathology, formalin-fixed paraffin-embedded tissues are increasingly being used as a source of DNA and RNA for molecular assays in addition to histopathological evaluation. However, the commonly used formalin fixative is carcinogenic, and its crosslinking impairs DNA and RNA quality. The suitability of three new presumably less toxic, crosslinking (F-Solv) and non-crosslinking (FineFIX, RCL2) alcohol-based fixatives was tested for routine molecular pathology in comparison with neutral buffered formalin (NBF) as gold standard. Size ladder PCR, epidermal growth factor receptor sequence analysis, microsatellite instability (MSI), chromogenic (CISH), fluorescence in situ hybridisation (FISH) and qPCR were performed. The alcohol-based non-crosslinking fixatives (FineFIX and RCL2) resulted in a higher DNA yield and quality compared with crosslinking fixatives (NBF and F-Solv). Size ladder PCR resulted in a shorter amplicon size (300 bp) for both crosslinking fixatives compared with the non-crosslinking fixatives (400 bp). All four fixatives were directly applicable for MSI and epidermal growth factor receptor sequence analysis. All fixatives except F-Solv showed clear signals in CISH and FISH. RNA yield and quality were superior after non-crosslinking fixation. qPCR resulted in lower Ct values for RCL2 and FineFIX. The alcohol-based non-crosslinking fixatives performed better than crosslinking fixatives with regard to DNA and RNA yield, quality and applicability in molecular diagnostics. Given the higher yield, less starting material may be necessary, thereby increasing the applicability of biopsies for molecular studies.

Molecular Electron Density Theory: A Modern View of Reactivity in Organic Chemistry.

PubMed

Domingo, Luis R

2016-09-30

A new theory for the study of the reactivity in Organic Chemistry, named Molecular Electron Density Theory (MEDT), is proposed herein. MEDT is based on the idea that while the electron density distribution at the ground state is responsible for physical and chemical molecular properties, as proposed by the Density Functional Theory (DFT), the capability for changes in electron density is responsible for molecular reactivity. Within MEDT, the reactivity in Organic Chemistry is studied through a rigorous quantum chemical analysis of the changes of the electron density as well as the energies associated with these changes along the reaction path in order to understand experimental outcomes. Studies performed using MEDT allow establishing a modern rationalisation and to gain insight into molecular mechanisms and reactivity in Organic Chemistry.

Quantitative functional characterization of conserved molecular interactions in the active site of mannitol 2-dehydrogenase

PubMed Central

Lucas, James E; Siegel, Justin B

2015-01-01

Enzyme active site residues are often highly conserved, indicating a significant role in function. In this study we quantitate the functional contribution for all conserved molecular interactions occurring within a Michaelis complex for mannitol 2-dehydrogenase derived from Pseudomonas fluorescens (pfMDH). Through systematic mutagenesis of active site residues, we reveal that the molecular interactions in pfMDH mediated by highly conserved residues not directly involved in reaction chemistry can be as important to catalysis as those directly involved in the reaction chemistry. This quantitative analysis of the molecular interactions within the pfMDH active site provides direct insight into the functional role of each molecular interaction, several of which were unexpected based on canonical sequence conservation and structural analyses. PMID:25752240

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

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

Prates, Luciana Louzada; Yu, Peiqiang

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

Leishmania amazonensis DNA in wild females of Lutzomyia cruzi (Diptera: Psychodidae) in the state of Mato Grosso do Sul, Brazil

PubMed Central

de Oliveira, Everton Falcão; Casaril, Aline Etelvina; Mateus, Nathália Lopes Fontoura; Murat, Paula Guerra; Fernandes, Wagner Souza; Oshiro, Elisa Teruya; de Oliveira, Alessandra Gutierrez; Galati, Eunice Aparecida Bianchi

2015-01-01

Studies on natural infection by Leishmania spp of sandflies collected in endemic and nonendemic areas can provide important information on the distribution and intensity of the transmission of these parasites. This study sought to investigate the natural infection by Leishmaniain wild female sandflies. The specimens were caught in the city of Corumbá, state of Mato Grosso do Sul (Brazil) between October 2012-March 2014, and dissected to investigate flagellates and/or submitted to molecular analysis to detect Leishmania DNA. A total of 1,164 females (77.56% of which were Lutzomyia cruzi) representing 11 species were investigated using molecular analysis; 126 specimens of Lu. cruziwere dissected and also submitted to molecular analysis. The infection rate based on the presence of Leishmania DNA considering all the sandfly species analysed was 0.69%; only Leishmania (Leishmania) amazonensis was identified in Lu. cruzi by the molecular analysis. The dissections were negative for flagellates. This is the first record of the presence of L. (L.) amazonensis DNA in Lu. cruzi, and the first record of this parasite in this area. These findings point to the need for further investigation into the possible role of this sandfly as vector of this parasite. PMID:26602870

Leishmania amazonensis DNA in wild females of Lutzomyia cruzi (Diptera: Psychodidae) in the state of Mato Grosso do Sul, Brazil.

PubMed

Oliveira, Everton Falcão de; Casaril, Aline Etelvina; Mateus, Nathália Lopes Fontoura; Murat, Paula Guerra; Fernandes, Wagner Souza; Oshiro, Elisa Teruya; Oliveira, Alessandra Gutierrez de; Galati, Eunice Aparecida Bianchi

2015-12-01

Studies on natural infection by Leishmania spp of sandflies collected in endemic and nonendemic areas can provide important information on the distribution and intensity of the transmission of these parasites. This study sought to investigate the natural infection by Leishmaniain wild female sandflies. The specimens were caught in the city of Corumbá, state of Mato Grosso do Sul (Brazil) between October 2012-March 2014, and dissected to investigate flagellates and/or submitted to molecular analysis to detect Leishmania DNA. A total of 1,164 females (77.56% of which were Lutzomyia cruzi) representing 11 species were investigated using molecular analysis; 126 specimens of Lu. cruziwere dissected and also submitted to molecular analysis. The infection rate based on the presence of Leishmania DNA considering all the sandfly species analysed was 0.69%; only Leishmania (Leishmania) amazonensis was identified in Lu. cruzi by the molecular analysis. The dissections were negative for flagellates. This is the first record of the presence of L. (L.) amazonensis DNA in Lu. cruzi, and the first record of this parasite in this area. These findings point to the need for further investigation into the possible role of this sandfly as vector of this parasite.

Determination of high-molecular weight polycyclic aromatic hydrocarbons in high performance liquid chromatography fractions of coal tar standard reference material 1597a via solid-phase nanoextraction and laser-excited time-resolved Shpol'skii spectroscopy

PubMed Central

Wilson, Walter B.; Alfarhani, Bassam; Moore, Anthony F. T.; Bisson, Cristina; Wise, Stephen A.; Campiglia, Andres D.

2016-01-01

This article presents an alternative approach for the analysis of high molecular weight – polycyclic aromatic hydrocarbons (HMW-PAHs) with molecular mass 302 Da in complex environmental samples. This is not a trivial task due to the large number of molecular mass 302 Da isomers with very similar chromatographic elution times and similar, possibly even virtually identical, mass fragmentation patterns. The method presented here is based on 4.2 K laser-excited time-resolved Shpol'skii spectroscopy, a high resolution spectroscopic technique with the appropriate selectivity for the unambiguous determination of PAHs with the same molecular mass. The potential of this approach is demonstrated here with the analysis of a coal tar standard reference material (SRM) 1597a. Liquid chromatography fractions were submitted to the spectroscopic analysis of five targeted isomers, namely dibenzo[a,l]pyrene, dibenzo[a,e]pyrene, dibenzo[a,i]pyrene, naphtho[2,3-a]pyrene and dibenzo[a,h]pyrene. Prior to analyte determination, the liquid chromatographic fractions were pre-concentrated with gold nanoparticles. Complete analysis was possible with microliters of chromatographic fractions and organic solvents. The limits of detection varied from 0.05 (dibenzo[a,l]pyrene) to 0.24 μg L−1 (dibenzo[a,e]pyrene). The excellent analytical figures of merit associated to its non-destructive nature, which provides ample opportunity for further analysis with other instrumental methods, makes this approach an attractive alternative for the determination of PAH isomers in complex environmental samples. PMID:26653471

Mathematical analysis of the boundary-integral based electrostatics estimation approximation for molecular solvation: exact results for spherical inclusions.

PubMed

Bardhan, Jaydeep P; Knepley, Matthew G

2011-09-28

We analyze the mathematically rigorous BIBEE (boundary-integral based electrostatics estimation) approximation of the mixed-dielectric continuum model of molecular electrostatics, using the analytically solvable case of a spherical solute containing an arbitrary charge distribution. Our analysis, which builds on Kirkwood's solution using spherical harmonics, clarifies important aspects of the approximation and its relationship to generalized Born models. First, our results suggest a new perspective for analyzing fast electrostatic models: the separation of variables between material properties (the dielectric constants) and geometry (the solute dielectric boundary and charge distribution). Second, we find that the eigenfunctions of the reaction-potential operator are exactly preserved in the BIBEE model for the sphere, which supports the use of this approximation for analyzing charge-charge interactions in molecular binding. Third, a comparison of BIBEE to the recent GBε theory suggests a modified BIBEE model capable of predicting electrostatic solvation free energies to within 4% of a full numerical Poisson calculation. This modified model leads to a projection-framework understanding of BIBEE and suggests opportunities for future improvements. © 2011 American Institute of Physics

Personalizing Chinese medicine by integrating molecular features of diseases and herb ingredient information: application to acute myeloid leukemia

PubMed Central

Xie, Duoli; Shi, Tieliu; Wen, Chengping

2017-01-01

Traditional Chinese Medicine (TCM) has been widely used as a complementary medicine in Acute Myeloid Leukemia (AML) treatment. In this study, we proposed a new classification of Chinese Medicines (CMs) by integrating the latest discoveries in disease molecular mechanisms and traditional medicine theory. We screened out a set of chemical compounds on basis of AML differential expression genes and chemical-protein interactions and then mapped them to Traditional Chinese Medicine Integrated Database. 415 CMs contain those compounds and they were categorized into 8 groups according to the Traditional Chinese Pharmacology. Pathway analysis and synthetic lethality gene pairs were applied to analyze the dissimilarity, generality and intergroup relations of different groups. We defined hub CM pairs and alternative CM groups based on the analysis result and finally proposed a formula to form an effective anti-AML prescription which combined the hub CM pairs with alternative CMs according to patients’ molecular features. Our method of formulating CMs based on patients’ stratification provides novel insights into the new usage of conventional CMs and will promote TCM modernization. PMID:28454110

A molecular phylogeny of the stingless bee genus Melipona (Hymenoptera: Apidae).

PubMed

Ramírez, Santiago R; Nieh, James C; Quental, Tiago B; Roubik, David W; Imperatriz-Fonseca, Vera L; Pierce, Naomi E

2010-08-01

Stingless bees (Meliponini) constitute a diverse group of highly eusocial insects that occur throughout tropical regions around the world. The meliponine genus Melipona is restricted to the New World tropics and has over 50 described species. Melipona, like Apis, possesses the remarkable ability to use representational communication to indicate the location of foraging patches. Although Melipona has been the subject of numerous behavioral, ecological, and genetic studies, the evolutionary history of this genus remains largely unexplored. Here, we implement a multigene phylogenetic approach based on nuclear, mitochondrial, and ribosomal loci, coupled with molecular clock methods, to elucidate the phylogenetic relationships and antiquity of subgenera and species of Melipona. Our phylogenetic analysis resolves the relationship among subgenera and tends to agree with morphology-based classification hypotheses. Our molecular clock analysis indicates that the genus Melipona shared a most recent common ancestor at least approximately 14-17 million years (My) ago. These results provide the groundwork for future comparative analyses aimed at understanding the evolution of complex communication mechanisms in eusocial Apidae. Copyright 2010 Elsevier Inc. All rights reserved.

Personalizing Chinese medicine by integrating molecular features of diseases and herb ingredient information: application to acute myeloid leukemia.

PubMed

Huang, Lin; Li, Haichang; Xie, Duoli; Shi, Tieliu; Wen, Chengping

2017-06-27

Traditional Chinese Medicine (TCM) has been widely used as a complementary medicine in Acute Myeloid Leukemia (AML) treatment. In this study, we proposed a new classification of Chinese Medicines (CMs) by integrating the latest discoveries in disease molecular mechanisms and traditional medicine theory. We screened out a set of chemical compounds on basis of AML differential expression genes and chemical-protein interactions and then mapped them to Traditional Chinese Medicine Integrated Database. 415 CMs contain those compounds and they were categorized into 8 groups according to the Traditional Chinese Pharmacology. Pathway analysis and synthetic lethality gene pairs were applied to analyze the dissimilarity, generality and intergroup relations of different groups. We defined hub CM pairs and alternative CM groups based on the analysis result and finally proposed a formula to form an effective anti-AML prescription which combined the hub CM pairs with alternative CMs according to patients' molecular features. Our method of formulating CMs based on patients' stratification provides novel insights into the new usage of conventional CMs and will promote TCM modernization.

Molecular and phylogenetic characterizations of an Eimeria krijgsmanni Yakimoff & Gouseff, 1938 (Apicomplexa: Eimeriidae) mouse intestinal protozoan parasite by partial 18S ribosomal RNA gene sequence analysis.

PubMed

Takeo, Toshinori; Tanaka, Tetsuya; Matsubayashi, Makoto; Maeda, Hiroki; Kusakisako, Kodai; Matsui, Toshihiro; Mochizuki, Masami; Matsuo, Tomohide

2014-08-01

Previously, we characterized an undocumented strain of Eimeria krijgsmanni by morphological and biological features. Here, we present a detailed molecular phylogenetic analysis of this organism. Namely, 18S ribosomal RNA gene (rDNA) sequences of E. krijgsmanni were analyzed to incorporate this species into a comprehensive Eimeria phylogeny. As a result, partial 18S rDNA sequence from E. krijgsmanni was successfully determined, and two different types, Type A and Type B, that differed by 1 base pair were identified. E. krijgsmanni was originally isolated from a single oocyst, and thus the result show that the two types might have allelic sequence heterogeneity in the 18S rDNA. Based on phylogenetic analyses, the two types of E. krijgsmanni 18S rDNA formed one of two clades among murine Eimeria spp.; these Eimeria clades reflected morphological similarity among the Eimeria spp. This is the third molecular phylogenetic characterization of a murine Eimeria spp. in addition to E. falciformis and E. papillata. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Direct and comprehensive analysis of dyes based on integrated molecular and structural information via laser desorption laser postionization mass spectrometry.

PubMed

Liu, Rong; Yin, Zhibin; Leng, Yixin; Hang, Wei; Huang, Benli

2018-01-01

Laser desorption laser postionization time-of-flight mass spectrometry (LDPI-TOFMS) was employed for direct analysis and determination of typical basic dyes. It was also used for the analysis and comprehensive understanding of complex materials such as blue ballpoint pen inks. Simultaneous emergences of fragmental and molecular information largely simplify and facilitate unambiguous identification of dyes via variable energy of 266nm postionization laser. More specifically, by optimizing postionization laser energy with the same energy of desorption laser, the structurally significant results show definite differences in the fragmentation patterns, which offer opportunities for discrimination of isomeric species with identical molecular weight. Moreover, relatively high spectra resolution can be acquired without the expense of sensitivity. In contrast to laser desorption/ionization mass spectrometry (LDI-MS), LDPI-MS simultaneously offers valuable molecular information about dyes in traces, solvents and additives about inks, thereby offering direct determination and comprehensive understanding of blue ballpoint inks and giving a high level of confidence to discriminate the complicated evidentiary samples. In addition, direct analysis of the inks not only allows the avoidance of the tedious sample preparation processes, significantly shortening the overall analysis time and improving throughput, but allows minimized sample consumption which is important for rare and precious samples. Copyright © 2017 Elsevier B.V. All rights reserved.

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

PubMed

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

2017-06-01

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

Molecular and morphological identification of  pistachio armored scale insects (Hemiptera: Diaspididae), with description of a new species.

PubMed

Hosseininaveh, Fatemeh; Nozari, Jamasb; Kaydan, Mehmet Bora; Hosseininaveh, Vahid

2016-12-01

Members of the family Diaspididae (Hemiptera: Coccomorpha) can be devastating pests that suck parenchyma cell contents from crops and cause severe damage to pistachio trees (Pistacia vera L.). The current research collected and characterized diaspidid species from pistachio orchards in Kerman province, Iran, according to their morphological and molecular features. Lepidosaphes pistaciae Archangelskaya, Suturaspis davatchi (Balachowsky & Kaussari) and Melanaspis inopinata (Leonardi) are redescribed and a new species, Melanaspis pistaciae Hosseininaveh & Kaydan sp. n., is described. Phylogenetic trees based on molecular analysis of COI and 28S rDNA fragments placed all the species in separated clades and confirmed M. pistaciae as a new taxon which is concluded by morphological differences. Molecular analysis suggests non-monophyly of the populations of each species. Melanaspis pistaciae sp. n. has spread to most cultivated pistachio areas in Iran and has probably been misidentified as M. inopinata in the past. Further investigation of the biology of this species may lead to development of more effective approaches for controlling this pest.

Symbiosis between hydra and chlorella: molecular phylogenetic analysis and experimental study provide insight into its origin and evolution.

PubMed

Kawaida, Hitomi; Ohba, Kohki; Koutake, Yuhki; Shimizu, Hiroshi; Tachida, Hidenori; Kobayakawa, Yoshitaka

2013-03-01

Although many physiological studies have been reported on the symbiosis between hydra and green algae, very little information from a molecular phylogenetic aspect of symbiosis is available. In order to understand the origin and evolution of symbiosis between the two organisms, we compared the phylogenetic relationships among symbiotic green algae with the phylogenetic relationships among host hydra strains. To do so, we reconstructed molecular phylogenetic trees of several strains of symbiotic chlorella harbored in the endodermal epithelial cells of viridissima group hydra strains and investigated their congruence with the molecular phylogenetic trees of the host hydra strains. To examine the species specificity between the host and the symbiont with respect to the genetic distance, we also tried to introduce chlorella strains into two aposymbiotic strains of viridissima group hydra in which symbiotic chlorella had been eliminated in advance. We discussed the origin and history of symbiosis between hydra and green algae based on the analysis. Copyright © 2012 Elsevier Inc. All rights reserved.

Univariate and multivariate molecular spectral analyses of lipid related molecular structural components in relation to nutrient profile in feed and food mixtures.

PubMed

Abeysekara, Saman; Damiran, Daalkhaijav; Yu, Peiqiang

2013-02-01

The objectives of this study were (i) to determine lipid related molecular structures components (functional groups) in feed combination of cereal grain (barley, Hordeum vulgare) and wheat (Triticum aestivum) based dried distillers grain solubles (wheat DDGSs) from bioethanol processing at five different combination ratios using univariate and multivariate molecular spectral analyses with infrared Fourier transform molecular spectroscopy, and (ii) to correlate lipid-related molecular-functional structure spectral profile to nutrient profiles. The spectral intensity of (i) CH(3) asymmetric, CH(2) asymmetric, CH(3) symmetric and CH(2) symmetric groups, (ii) unsaturation (CC) group, and (iii) carbonyl ester (CO) group were determined. Spectral differences of functional groups were detected by hierarchical cluster analysis (HCA) and principal components analysis (PCA). The results showed that the combination treatments significantly inflicted modifications (P<0.05) in nutrient profile and lipid related molecular spectral intensity (CH(2) asymmetric stretching peak height, CH(2) symmetric stretching peak height, ratio of CH(2) to CH(3) symmetric stretching peak intensity, and carbonyl peak area). Ratio of CH(2) to CH(3) symmetric stretching peak intensity, and carbonyl peak significantly correlated with nutrient profiles. Both PCA and HCA differentiated lipid-related spectrum. In conclusion, the changes of lipid molecular structure spectral profiles through feed combination could be detected using molecular spectroscopy. These changes were associated with nutrient profiles and functionality. Copyright © 2012 Elsevier B.V. All rights reserved.

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

PubMed

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

2012-09-01

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

Compliance Testing of Eielson Air Force Base Central Heating and Power Plant, Coal Fired Boiler Number 3, Eielson Air Force Base, Alaska

DTIC Science & Technology

1988-12-01

a flue gas grab sample for orsat analysis (measures oxygen, and carbon dioxide for stack gas molecular weight determination and emissions correction... molecular weight, was obtained during particulate sampling. Testing was initially started on boiler 2 at the maximum rated steam output of 120,000 lbs/hr...I, r*~td AN[D l FL B( R\\ ViQ( lPjN L!II(,t 1 (d) Open burning of put.rcible iear- i\\ % ~i~ emisions , ec.dirig c dn jc p. c ,f1 pre- cri :rig pair

[Hepatocellular tumours in noncirrhotic liver tissue].

PubMed

Goltz, D; Fischer, H-P

2015-11-01

In recent years, the spectrum of tissue-based diagnostics of hepatocellular tumours has changed due to novel molecular pathological findings. Innovative radiographics filter out small lesions and ambiguous tumours for bioptical sampling. The spectrum of these tumours includes hepatocellular carcinoma, hepatocellular adenomas, focal nodular hyperplasia and macroregenerative nodules. Primarily, morphological analysis should identify the dignity of a lesion. After exclusion of HCC and reactive liver cell nodules, hepatocellular adenomas should be further subclassified based on immunohistochemical/molecular pathological criteria according to the WHO classification of liver tumours. This procedure provides significant additional information regarding the prognosis and therapeutic implications of hepatocellular adenomas.

Nanoscale tailor-made membranes for precise and rapid molecular sieve separation.

PubMed

Wang, Jing; Zhu, Junyong; Zhang, Yatao; Liu, Jindun; Van der Bruggen, Bart

2017-03-02

The precise and rapid separation of different molecules from aqueous, organic solutions and gas mixtures is critical to many technologies in the context of resource-saving and sustainable development. The strength of membrane-based technologies is well recognized and they are extensively applied as cost-effective, highly efficient separation techniques. Currently, empirical-based approaches, lacking an accurate nanoscale control, are used to prepare the most advanced membranes. In contrast, nanoscale control renders the membrane molecular specificity (sub-2 nm) necessary for efficient and rapid molecular separation. Therefore, as a growing trend in membrane technology, the field of nanoscale tailor-made membranes is highlighted in this review. An in-depth analysis of the latest advances in tailor-made membranes for precise and rapid molecule sieving is given, along with an outlook to future perspectives of such membranes. Special attention is paid to the established processing strategies, as well as the application of molecular dynamics (MD) simulation in nanoporous membrane design. This review will provide useful guidelines for future research in the development of nanoscale tailor-made membranes with a precise and rapid molecular sieve separation property.

Cytological preparations for molecular analysis: A review of technical procedures, advantages and limitations for referring samples for testing.

PubMed

da Cunha Santos, G; Saieg, M A; Troncone, G; Zeppa, P

2018-04-01

Minimally invasive procedures such as endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) must yield not only good quality and quantity of material for morphological assessment, but also an adequate sample for analysis of molecular markers to guide patients to appropriate targeted therapies. In this context, cytopathologists worldwide should be familiar with minimum requirements for refereeing cytological samples for testing. The present manuscript is a review with comprehensive description of the content of the workshop entitled Cytological preparations for molecular analysis: pre-analytical issues for EBUS TBNA, presented at the 40th European Congress of Cytopathology in Liverpool, UK. The present review emphasises the advantages and limitations of different types of cytology substrates used for molecular analysis such as archival smears, liquid-based preparations, archival cytospin preparations and FTA (Flinders Technology Associates) cards, as well as their technical requirements/features. These various types of cytological specimens can be successfully used for an extensive array of molecular studies, but the quality and quantity of extracted nucleic acids rely directly on adequate pre-analytical assessment of those samples. In this setting, cytopathologists must not only be familiar with the different types of specimens and associated technical procedures, but also correctly handle the material provided by minimally invasive procedures, ensuring that there is sufficient amount of material for a precise diagnosis and correct management of the patient through personalised care. © 2018 John Wiley & Sons Ltd.

SNP-based genotyping in lentil: linking sequence information with phenotypes

USDA-ARS?s Scientific Manuscript database

Lentil (Lens culinaris) has been late to enter the world of high throughput molecular analysis due to a general lack of genomic resources. Using a 454 sequencing-based approach, SNPs have been identified in genes across the lentil genome. Several hundred have been turned into single SNP KASP assay...

Molecular evidence of stereo-specific lactoferrin dimers in solution.

PubMed

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

2010-10-01

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

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

PubMed

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

2016-06-16

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

Beyond Molecular Codes: Simple Rules to Wire Complex Brains

PubMed Central

Hassan, Bassem A.; Hiesinger, P. Robin

2015-01-01

Summary Molecular codes, like postal zip codes, are generally considered a robust way to ensure the specificity of neuronal target selection. However, a code capable of unambiguously generating complex neural circuits is difficult to conceive. Here, we re-examine the notion of molecular codes in the light of developmental algorithms. We explore how molecules and mechanisms that have been considered part of a code may alternatively implement simple pattern formation rules sufficient to ensure wiring specificity in neural circuits. This analysis delineates a pattern-based framework for circuit construction that may contribute to our understanding of brain wiring. PMID:26451480

Radiation biodosimetry: Applications for spaceflight

NASA Astrophysics Data System (ADS)

Blakely, W. F.; Miller, A. C.; Grace, M. B.; McLeland, C. B.; Luo, L.; Muderhwa, J. M.; Miner, V. L.; Prasanna, P. G. S.

The multiparametric dosimetry system that we are developing for medical radiological defense applications could be adapted for spaceflight environments. The system complements the internationally accepted personnel dosimeters and cytogenetic analysis of chromosome aberrations, considered the best means of documenting radiation doses for health records. Our system consists of a portable hematology analyzer, molecular biodosimetry using nucleic acid and antigen-based diagnostic equipment, and a dose assessment management software application. A dry-capillary tube reagent-based centrifuge blood cell counter (QBC Autoread Plus, Beckon Dickinson Bioscience) measures peripheral blood lymphocytes and monocytes, which could determine radiation dose based on the kinetics of blood cell depletion. Molecular biomarkers for ionizing radiation exposure (gene expression changes, blood proteins) can be measured in real time using such diagnostic detection technologies as miniaturized nucleic acid sequences and antigen-based biosensors, but they require validation of dose-dependent targets and development of optimized protocols and analysis systems. The Biodosimetry Assessment Tool, a software application, calculates radiation dose based on a patient's physical signs and symptoms and blood cell count analysis. It also annotates location of personnel dosimeters, displays a summary of a patient's dosimetric information to healthcare professionals, and archives the data for further use. These radiation assessment diagnostic technologies can have dual-use applications supporting general medical-related care.

Phylogenetic relationships of Malassezia species based on multilocus sequence analysis.

PubMed

Castellá, Gemma; Coutinho, Selene Dall' Acqua; Cabañes, F Javier

2014-01-01

Members of the genus Malassezia are lipophilic basidiomycetous yeasts, which are part of the normal cutaneous microbiota of humans and other warm-blooded animals. Currently, this genus consists of 14 species that have been characterized by phenetic and molecular methods. Although several molecular methods have been used to identify and/or differentiate Malassezia species, the sequencing of the rRNA genes and the chitin synthase-2 gene (CHS2) are the most widely employed. There is little information about the β-tubulin gene in the genus Malassezia, a gene has been used for the analysis of complex species groups. The aim of the present study was to sequence a fragment of the β-tubulin gene of Malassezia species and analyze their phylogenetic relationship using a multilocus sequence approach based on two rRNA genes (ITS including 5.8S rRNA and D1/D2 region of 26S rRNA) together with two protein encoding genes (CHS2 and β-tubulin). The phylogenetic study of the partial β-tubulin gene sequences indicated that this molecular marker can be used to assess diversity and identify new species. The multilocus sequence analysis of the four loci provides robust support to delineate species at the terminal nodes and could help to estimate divergence times for the origin and diversification of Malassezia species.

Proteome analysis in the assessment of ageing.

PubMed

Nkuipou-Kenfack, Esther; Koeck, Thomas; Mischak, Harald; Pich, Andreas; Schanstra, Joost P; Zürbig, Petra; Schumacher, Björn

2014-11-01

Based on demographic trends, the societies in many developed countries are facing an increasing number and proportion of people over the age of 65. The raise in elderly populations along with improved health-care will be concomitant with an increased prevalence of ageing-associated chronic conditions like cardiovascular, renal, and respiratory diseases, arthritis, dementia, and diabetes mellitus. This is expected to pose unprecedented challenges both for individuals and societies and their health care systems. An ultimate goal of ageing research is therefore the understanding of physiological ageing and the achievement of 'healthy' ageing by decreasing age-related pathologies. However, on a molecular level, ageing is a complex multi-mechanistic process whose contributing factors may vary individually, partly overlap with pathological alterations, and are often poorly understood. Proteome analysis potentially allows modelling of these multifactorial processes. This review summarises recent proteomic research on age-related changes identified in animal models and human studies. We combined this information with pathway analysis to identify molecular mechanisms associated with ageing. We identified some molecular pathways that are affected in most or even all organs and others that are organ-specific. However, appropriately powered studies are needed to confirm these findings based in in silico evaluation. Copyright © 2014 Elsevier B.V. All rights reserved.

Adsorption-induced symmetry reduction of metal-phthalocyanines studied by vibrational spectroscopy

NASA Astrophysics Data System (ADS)

Sforzini, J.; Bocquet, F. C.; Tautz, F. S.

2017-10-01

We investigate the vibrational properties of Pt- and Pd-phthalocyanine (PtPc and PdPc) molecules on Ag(111) with high-resolution electron energy loss spectroscopy (HREELS). In the monolayer regime, both molecules exhibit long-range order. The vibrational spectra prove a flat adsorption geometry. The redshift of specific vibrational modes suggests a moderate interaction of the molecules with the substrate. The presence of asymmetric vibrational peaks indicates an interfacial dynamical charge transfer (IDCT). The molecular orbital that is involved in IDCT is the former Eg lowest unoccupied molecular orbital (LUMO) of the molecules that becomes partially occupied upon adsorption. A group-theoretical analysis of the IDCT modes, based on calculated vibrational frequencies and line shape fits, provides proof for the reduction of the symmetry of the molecule-substrate complex from fourfold D4 h to C2 v(σv) , Cs(σv) , or C2 and the ensuing lifting of the degeneracy of the former LUMO of the molecule. The vibration-based analysis of orbital degeneracies, as carried out here for PtPc/Ag(111) and PdPc/Ag(111), is particularly useful whenever the presence of multiple molecular in-plane orientations at the interface makes the analysis of orbital degeneracies with angle-resolved photoemission spectroscopy difficult.

Closing loop base pairs in RNA loop-loop complexes: structural behavior, interaction energy and solvation analysis through molecular dynamics simulations.

PubMed

Golebiowski, Jérôme; Antonczak, Serge; Fernandez-Carmona, Juan; Condom, Roger; Cabrol-Bass, Daniel

2004-12-01

Nanosecond molecular dynamics using the Ewald summation method have been performed to elucidate the structural and energetic role of the closing base pair in loop-loop RNA duplexes neutralized by Mg2+ counterions in aqueous phases. Mismatches GA, CU and Watson-Crick GC base pairs have been considered for closing the loop of an RNA in complementary interaction with HIV-1 TAR. The simulations reveal that the mismatch GA base, mediated by a water molecule, leads to a complex that presents the best compromise between flexibility and energetic contributions. The mismatch CU base pair, in spite of the presence of an inserted water molecule, is too short to achieve a tight interaction at the closing-loop junction and seems to force TAR to reorganize upon binding. An energetic analysis has allowed us to quantify the strength of the interactions of the closing and the loop-loop pairs throughout the simulations. Although the water-mediated GA closing base pair presents an interaction energy similar to that found on fully geometry-optimized structure, the water-mediated CU closing base pair energy interaction reaches less than half the optimal value.

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.

Histories of molecules: Reconciling the past.

PubMed

O'Malley, Maureen A

2016-02-01

Molecular data and methods have become centrally important to evolutionary analysis, largely because they have enabled global phylogenetic reconstructions of the relationships between organisms in the tree of life. Often, however, molecular stories conflict dramatically with morphology-based histories of lineages. The evolutionary origin of animal groups provides one such case. In other instances, different molecular analyses have so far proved irreconcilable. The ancient and major divergence of eukaryotes from prokaryotic ancestors is an example of this sort of problem. Efforts to overcome these conflicts highlight the role models play in phylogenetic reconstruction. One crucial model is the molecular clock; another is that of 'simple-to-complex' modification. I will examine animal and eukaryote evolution against a backdrop of increasing methodological sophistication in molecular phylogeny, and conclude with some reflections on the nature of historical science in the molecular era of phylogeny. Copyright © 2015 Elsevier Ltd. All rights reserved.

Structural and molecular docking studies of biologically active mercaptopyrimidine Schiff bases

NASA Astrophysics Data System (ADS)

Kirubavathy, S. Jone; Velmurugan, R.; Karvembu, R.; Bhuvanesh, N. S. P.; Enoch, Israel V. M. V.; Selvakumar, P. Mosae; Premnath, D.; Chitra, S.

2017-01-01

Novel Schiff bases derived from the treatment of mercapto-diamino pyrimidine with two different aldehydes are characterized using elemental analysis, single crystal X-ray diffraction and 1H NMR spectroscopy. The pharmacological action of the synthesized compounds viz., antimicrobial, anticancer and antitubercular activities is studied. The Schiff bases show a very good activity against various test pathogens. DNA and β-CD binding interactions of the compounds are studied using UV-Visible absorption and fluorescence spectral measurements. The binding constants of the compounds towards β-CD are in the order of 103 to 104. Molecular docking is done using MOE program on the 3D structure of the enzymes, viz., human thymidylate synthase complexed with dump and raltitrex, candida albicans N-myristoyltransferasepeptidic inhibitor, catalytic domain of protein kinase pKnb from mycobacterium tuberculosis in complex with mitoxantrone, pare, topoisomerase atpase inhibitor, E. coli and lactobacillus casdihydrofolatereductase. The MIC/IC50 values of the Schiff bases are compared with the glide scores from the molecular docking studies. The number of hydrogen bonding interactions between the Schiff bases and amino acid residues are also reported.

Biomedical analysis of formalin-fixed, paraffin-embedded tissue samples: The Holy Grail for molecular diagnostics.

PubMed

Donczo, Boglarka; Guttman, Andras

2018-06-05

More than a century ago in 1893, a revolutionary idea about fixing biological tissue specimens was introduced by Ferdinand Blum, a German physician. Since then, a plethora of fixation methods have been investigated and used. Formalin fixation with paraffin embedment became the most widely used types of fixation and preservation method, due to its proper architectural conservation of tissue structures and cellular shape. The huge collection of formalin-fixed, paraffin-embedded (FFPE) sample archives worldwide holds a large amount of unearthed information about diseases that could be the Holy Grail in contemporary biomarker research utilizing analytical omics based molecular diagnostics. The aim of this review is to critically evaluate the omics options for FFPE tissue sample analysis in the molecular diagnostics field. Copyright © 2018. Published by Elsevier B.V.

Molecular Genetic Analysis of Chlamydia Species.

PubMed

Sixt, Barbara S; Valdivia, Raphael H

2016-09-08

Species of Chlamydia are the etiologic agent of endemic blinding trachoma, the leading cause of bacterial sexually transmitted diseases, significant respiratory pathogens, and a zoonotic threat. Their dependence on an intracellular growth niche and their peculiar developmental cycle are major challenges to elucidating their biology and virulence traits. The last decade has seen tremendous advances in our ability to perform a molecular genetic analysis of Chlamydia species. Major achievements include the generation of large collections of mutant strains, now available for forward- and reverse-genetic applications, and the introduction of a system for plasmid-based transformation enabling complementation of mutations; expression of foreign, modified, or reporter genes; and even targeted gene disruptions. This review summarizes the current status of the molecular genetic toolbox for Chlamydia species and highlights new insights into their biology and new challenges in the nascent field of Chlamydia genetics.

3D-QSAR modeling and molecular docking studies on a series of 2,5 disubstituted 1,3,4-oxadiazoles

NASA Astrophysics Data System (ADS)

Ghaleb, Adib; Aouidate, Adnane; Ghamali, Mounir; Sbai, Abdelouahid; Bouachrine, Mohammed; Lakhlifi, Tahar

2017-10-01

3D-QSAR (comparative molecular field analysis (CoMFA)) and comparative molecular similarity indices analysis (CoMSIA) were performed on novel 2,5 disubstituted 1,3,4-oxadiazoles analogues as anti-fungal agents. The CoMFA and CoMSIA models using 13 compounds in the training set gives Q2 values of 0.52 and 0.51 respectively, while R2 values of 0.92. The adapted alignment method with the suitable parameters resulted in reliable models. The contour maps produced by the CoMFA and CoMSIA models were employed to determine a three-dimensional quantitative structure-activity relationship. Based on this study a set of new molecules with high predicted activities were designed. Surflex-docking confirmed the stability of predicted molecules in the receptor.

Probing Molecular Mechanisms of the Hsp90 Chaperone: Biophysical Modeling Identifies Key Regulators of Functional Dynamics

PubMed Central

Dixit, Anshuman; Verkhivker, Gennady M.

2012-01-01

Deciphering functional mechanisms of the Hsp90 chaperone machinery is an important objective in cancer biology aiming to facilitate discovery of targeted anti-cancer therapies. Despite significant advances in understanding structure and function of molecular chaperones, organizing molecular principles that control the relationship between conformational diversity and functional mechanisms of the Hsp90 activity lack a sufficient quantitative characterization. We combined molecular dynamics simulations, principal component analysis, the energy landscape model and structure-functional analysis of Hsp90 regulatory interactions to systematically investigate functional dynamics of the molecular chaperone. This approach has identified a network of conserved regions common to the Hsp90 chaperones that could play a universal role in coordinating functional dynamics, principal collective motions and allosteric signaling of Hsp90. We have found that these functional motifs may be utilized by the molecular chaperone machinery to act collectively as central regulators of Hsp90 dynamics and activity, including the inter-domain communications, control of ATP hydrolysis, and protein client binding. These findings have provided support to a long-standing assertion that allosteric regulation and catalysis may have emerged via common evolutionary routes. The interaction networks regulating functional motions of Hsp90 may be determined by the inherent structural architecture of the molecular chaperone. At the same time, the thermodynamics-based “conformational selection” of functional states is likely to be activated based on the nature of the binding partner. This mechanistic model of Hsp90 dynamics and function is consistent with the notion that allosteric networks orchestrating cooperative protein motions can be formed by evolutionary conserved and sparsely connected residue clusters. Hence, allosteric signaling through a small network of distantly connected residue clusters may be a rather general functional requirement encoded across molecular chaperones. The obtained insights may be useful in guiding discovery of allosteric Hsp90 inhibitors targeting protein interfaces with co-chaperones and protein binding clients. PMID:22624053

Library of molecular associations: curating the complex molecular basis of liver diseases.

PubMed

Buchkremer, Stefan; Hendel, Jasmin; Krupp, Markus; Weinmann, Arndt; Schlamp, Kai; Maass, Thorsten; Staib, Frank; Galle, Peter R; Teufel, Andreas

2010-03-20

Systems biology approaches offer novel insights into the development of chronic liver diseases. Current genomic databases supporting systems biology analyses are mostly based on microarray data. Although these data often cover genome wide expression, the validity of single microarray experiments remains questionable. However, for systems biology approaches addressing the interactions of molecular networks comprehensive but also highly validated data are necessary. We have therefore generated the first comprehensive database for published molecular associations in human liver diseases. It is based on PubMed published abstracts and aimed to close the gap between genome wide coverage of low validity from microarray data and individual highly validated data from PubMed. After an initial text mining process, the extracted abstracts were all manually validated to confirm content and potential genetic associations and may therefore be highly trusted. All data were stored in a publicly available database, Library of Molecular Associations http://www.medicalgenomics.org/databases/loma/news, currently holding approximately 1260 confirmed molecular associations for chronic liver diseases such as HCC, CCC, liver fibrosis, NASH/fatty liver disease, AIH, PBC, and PSC. We furthermore transformed these data into a powerful resource for molecular liver research by connecting them to multiple biomedical information resources. Together, this database is the first available database providing a comprehensive view and analysis options for published molecular associations on multiple liver diseases.

Cleavable DNA-protein hybrid molecular beacon: A novel efficient signal translator for sensitive fluorescence anisotropy bioassay.

PubMed

Hu, Pan; Yang, Bin

2016-01-15

Due to its unique features such as high sensitivity, homogeneous format, and independence on fluorescent intensity, fluorescence anisotropy (FA) assay has become a hotspot of study in oligonucleotide-based bioassays. However, until now most FA probes require carefully customized structure designs, and thus are neither generalizable for different sensing systems nor effective to obtain sufficient signal response. To address this issue, a cleavable DNA-protein hybrid molecular beacon was successfully engineered for signal amplified FA bioassay, via combining the unique stable structure of molecular beacon and the large molecular mass of streptavidin. Compared with single DNA strand probe or conventional molecular beacon, the DNA-protein hybrid molecular beacon exhibited a much higher FA value, which was potential to obtain high signal-background ratio in sensing process. As proof-of-principle, this novel DNA-protein hybrid molecular beacon was further applied for FA bioassay using DNAzyme-Pb(2+) as a model sensing system. This FA assay approach could selectively detect as low as 0.5nM Pb(2+) in buffer solution, and also be successful for real samples analysis with good recovery values. Compatible with most of oligonucleotide probes' designs and enzyme-based signal amplification strategies, the molecular beacon can serve as a novel signal translator to expand the application prospect of FA technology in various bioassays. Copyright © 2015 Elsevier B.V. All rights reserved.

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

PubMed

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

2010-01-01

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

Geometric and electrostatic modeling using molecular rigidity functions

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

Mu, Lin; Xia, Kelin; Wei, Guowei

Geometric and electrostatic modeling is an essential component in computational biophysics and molecular biology. Commonly used geometric representations admit geometric singularities such as cusps, tips and self-intersecting facets that lead to computational instabilities in the molecular modeling. Our present work explores the use of flexibility and rigidity index (FRI), which has a proved superiority in protein B-factor prediction, for biomolecular geometric representation and associated electrostatic analysis. FRI rigidity surfaces are free of geometric singularities. We propose a rigidity based Poisson–Boltzmann equation for biomolecular electrostatic analysis. These approaches to surface and electrostatic modeling are validated by a set of 21 proteins.more » Our results are compared with those of established methods. Finally, being smooth and analytically differentiable, FRI rigidity functions offer excellent curvature analysis, which characterizes concave and convex regions on protein surfaces. Polarized curvatures constructed by using the product of minimum curvature and electrostatic potential is shown to predict potential protein–ligand binding sites.« less

Geometric and electrostatic modeling using molecular rigidity functions

DOE PAGES

Mu, Lin; Xia, Kelin; Wei, Guowei

2017-03-01

Geometric and electrostatic modeling is an essential component in computational biophysics and molecular biology. Commonly used geometric representations admit geometric singularities such as cusps, tips and self-intersecting facets that lead to computational instabilities in the molecular modeling. Our present work explores the use of flexibility and rigidity index (FRI), which has a proved superiority in protein B-factor prediction, for biomolecular geometric representation and associated electrostatic analysis. FRI rigidity surfaces are free of geometric singularities. We propose a rigidity based Poisson–Boltzmann equation for biomolecular electrostatic analysis. These approaches to surface and electrostatic modeling are validated by a set of 21 proteins.more » Our results are compared with those of established methods. Finally, being smooth and analytically differentiable, FRI rigidity functions offer excellent curvature analysis, which characterizes concave and convex regions on protein surfaces. Polarized curvatures constructed by using the product of minimum curvature and electrostatic potential is shown to predict potential protein–ligand binding sites.« less

Cluster analysis of accelerated molecular dynamics simulations: A case study of the decahedron to icosahedron transition in Pt nanoparticles.

PubMed

Huang, Rao; Lo, Li-Ta; Wen, Yuhua; Voter, Arthur F; Perez, Danny

2017-10-21

Modern molecular-dynamics-based techniques are extremely powerful to investigate the dynamical evolution of materials. With the increase in sophistication of the simulation techniques and the ubiquity of massively parallel computing platforms, atomistic simulations now generate very large amounts of data, which have to be carefully analyzed in order to reveal key features of the underlying trajectories, including the nature and characteristics of the relevant reaction pathways. We show that clustering algorithms, such as the Perron Cluster Cluster Analysis, can provide reduced representations that greatly facilitate the interpretation of complex trajectories. To illustrate this point, clustering tools are used to identify the key kinetic steps in complex accelerated molecular dynamics trajectories exhibiting shape fluctuations in Pt nanoclusters. This analysis provides an easily interpretable coarse representation of the reaction pathways in terms of a handful of clusters, in contrast to the raw trajectory that contains thousands of unique states and tens of thousands of transitions.

Cluster analysis of accelerated molecular dynamics simulations: A case study of the decahedron to icosahedron transition in Pt nanoparticles

NASA Astrophysics Data System (ADS)

Huang, Rao; Lo, Li-Ta; Wen, Yuhua; Voter, Arthur F.; Perez, Danny

2017-10-01

Modern molecular-dynamics-based techniques are extremely powerful to investigate the dynamical evolution of materials. With the increase in sophistication of the simulation techniques and the ubiquity of massively parallel computing platforms, atomistic simulations now generate very large amounts of data, which have to be carefully analyzed in order to reveal key features of the underlying trajectories, including the nature and characteristics of the relevant reaction pathways. We show that clustering algorithms, such as the Perron Cluster Cluster Analysis, can provide reduced representations that greatly facilitate the interpretation of complex trajectories. To illustrate this point, clustering tools are used to identify the key kinetic steps in complex accelerated molecular dynamics trajectories exhibiting shape fluctuations in Pt nanoclusters. This analysis provides an easily interpretable coarse representation of the reaction pathways in terms of a handful of clusters, in contrast to the raw trajectory that contains thousands of unique states and tens of thousands of transitions.

Gene Expression (mRNA) Markers for Differentiating between Malignant and Benign Follicular Thyroid Tumours

PubMed Central

Wojtas, Bartosz; Pfeifer, Aleksandra; Oczko-Wojciechowska, Malgorzata; Krajewska, Jolanta; Czarniecka, Agnieszka; Kukulska, Aleksandra; Eszlinger, Markus; Musholt, Thomas; Stokowy, Tomasz; Swierniak, Michal; Stobiecka, Ewa; Chmielik, Ewa; Rusinek, Dagmara; Tyszkiewicz, Tomasz; Halczok, Monika; Hauptmann, Steffen; Lange, Dariusz; Jarzab, Michal; Paschke, Ralf; Jarzab, Barbara

2017-01-01

Distinguishing between follicular thyroid cancer (FTC) and follicular thyroid adenoma (FTA) constitutes a long-standing diagnostic problem resulting in equivocal histopathological diagnoses. There is therefore a need for additional molecular markers. To identify molecular differences between FTC and FTA, we analyzed the gene expression microarray data of 52 follicular neoplasms. We also performed a meta-analysis involving 14 studies employing high throughput methods (365 follicular neoplasms analyzed). Based on these two analyses, we selected 18 genes differentially expressed between FTA and FTC. We validated them by quantitative real-time polymerase chain reaction (qRT-PCR) in an independent set of 71 follicular neoplasms from formaldehyde-fixed paraffin embedded (FFPE) tissue material. We confirmed differential expression for 7 genes (CPQ, PLVAP, TFF3, ACVRL1, ZFYVE21, FAM189A2, and CLEC3B). Finally, we created a classifier that distinguished between FTC and FTA with an accuracy of 78%, sensitivity of 76%, and specificity of 80%, based on the expression of 4 genes (CPQ, PLVAP, TFF3, ACVRL1). In our study, we have demonstrated that meta-analysis is a valuable method for selecting possible molecular markers. Based on our results, we conclude that there might exist a plausible limit of gene classifier accuracy of approximately 80%, when follicular tumors are discriminated based on formalin-fixed postoperative material. PMID:28574441

Gene Expression (mRNA) Markers for Differentiating between Malignant and Benign Follicular Thyroid Tumours.

PubMed

Wojtas, Bartosz; Pfeifer, Aleksandra; Oczko-Wojciechowska, Malgorzata; Krajewska, Jolanta; Czarniecka, Agnieszka; Kukulska, Aleksandra; Eszlinger, Markus; Musholt, Thomas; Stokowy, Tomasz; Swierniak, Michal; Stobiecka, Ewa; Chmielik, Ewa; Rusinek, Dagmara; Tyszkiewicz, Tomasz; Halczok, Monika; Hauptmann, Steffen; Lange, Dariusz; Jarzab, Michal; Paschke, Ralf; Jarzab, Barbara

2017-06-02

Distinguishing between follicular thyroid cancer (FTC) and follicular thyroid adenoma (FTA) constitutes a long-standing diagnostic problem resulting in equivocal histopathological diagnoses. There is therefore a need for additional molecular markers. To identify molecular differences between FTC and FTA, we analyzed the gene expression microarray data of 52 follicular neoplasms. We also performed a meta-analysis involving 14 studies employing high throughput methods (365 follicular neoplasms analyzed). Based on these two analyses, we selected 18 genes differentially expressed between FTA and FTC. We validated them by quantitative real-time polymerase chain reaction (qRT-PCR) in an independent set of 71 follicular neoplasms from formaldehyde-fixed paraffin embedded (FFPE) tissue material. We confirmed differential expression for 7 genes ( CPQ , PLVAP , TFF3 , ACVRL1 , ZFYVE21 , FAM189A2 , and CLEC3B ). Finally, we created a classifier that distinguished between FTC and FTA with an accuracy of 78%, sensitivity of 76%, and specificity of 80%, based on the expression of 4 genes ( CPQ , PLVAP , TFF3 , ACVRL1 ). In our study, we have demonstrated that meta-analysis is a valuable method for selecting possible molecular markers. Based on our results, we conclude that there might exist a plausible limit of gene classifier accuracy of approximately 80%, when follicular tumors are discriminated based on formalin-fixed postoperative material.

Molecular characterization of Hepatitis A virus causing an outbreak among Thai navy recruits.

PubMed

Theamboonlers, A; Rianthavorn, P; Jiamsiri, S; Kumthong, S; Silaporn, P; Thongmee, C; Poovorawan, Y

2009-12-01

Hepatitis A virus (HAV) infection is a communicable disease, typically transmitted by faecal-oral contamination. HAV outbreaks usually occur in endemic areas. We report an outbreak of HAV from June to July, 2008 among Thai navy recruits who had received training at the Sattahip Navy Base, Chonburi province, Thailand. Upon conclusion of the training, the recruits were deployed to serve at several navy bases across the country. Secondary cases of HAV infection were reported among military personnel from these navy bases. To elucidate origin and distribution of these outbreaks, we characterized the genome and genotype of HAV isolated from the different navy bases. Sera and stool from the subjects were tested for antiHAV IgM, antiHAV IgG and HAV RNA. Subsequently, molecular characterization of HAV was performed by nucleotide sequencing of the VP1-P2A region, BLAST/FASTA and phylogenetic analysis. HAV RNA was detected in specimens obtained from different areas. All isolated strains clustered in the same lineage and belonged to genotype 1A. They shared nearly 100% genome homology indicating a single point source of this outbreak. This study provides essential baseline data as a reference for genetic analysis of HAV strains causing future outbreaks. Early detection of HAV infection and identification of the source by using molecular characterization and prompt preventive measures will hopefully prevent further outbreaks.

Experimental and theoretical spectroscopic studies of anticancer drug rosmarinic acid using HF and density functional theory.

PubMed

Mariappan, G; Sundaraganesan, N; Manoharan, S

2012-11-01

In this work, we reported a combined experimental and theoretical study on molecular structure, vibrational spectra and NBO analysis of anticancer drug of rosmarinic acid. The optimized molecular structure, atomic charges, vibrational frequencies, natural bond orbital analysis and ultraviolet-visible spectral interpretation of rosmarinic acid have been studied by performing HF and DFT/B3LYP/6-31G(d,p) level of theory. The FT-IR (solid and solution phase), FT-Raman (solid phase) spectra were recorded in the region 4000-400 and 3500-50 cm(-1), respectively. The UV-Visible absorption spectra of the compound that dissolved in ethanol were recorded in the range of 200-800 nm. The scaled wavenumbers are compared with the experimental values. The difference between the observed and scaled wavenumber values of most of the fundamentals is very small. The formation of hydrogen bond was investigated in terms of the charge density by the NBO calculations. Based on the UV spectra and TD-DFT calculations, the electronic structure and the assignments of the absorption bands were carried out. Besides, molecular electrostatic potential (MEP), frontier molecular orbitals (FMO) analysis were investigated using theoretical calculations. Copyright © 2012 Elsevier B.V. All rights reserved.

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.

Clinical and Molecular Consequences of NF1 Microdeletion

DTIC Science & Technology

2006-05-01

service based on meta -PCR/sequencing, dosage analysis , and loss of heterozygosity analysis . Genet Test 2004;8(4):368-80. 51. Kluwe L, Mautner VF. Mosaicism...neurofibromin in normal centrosome function and in maintaining genome stability. Our detailed analysis of human and chimpanzee genome sequences were...chromosomes and DNA fibers (1). Tandem duplication of the region would have significant impact on many aspects of NF1 research, e.g., mutational analysis

Systematics of spiny predatory katydids (Tettigoniidae: Listroscelidinae) from the Brazilian Atlantic Forest based on morphology and molecular data.

PubMed

Fialho, Verônica Saraiva; Chamorro-Rengifo, Juliana; Lopes-Andrade, Cristiano; Yotoko, Karla Suemy Clemente

2014-01-01

Listroscelidinae (Orthoptera: Tettigoniidae) are insectivorous Pantropical katydids whose taxonomy presents a long history of controversy, with several genera incertae sedis. This work focused on species occurring in the Brazilian Atlantic Forest, one of the world's most threatened biomes. We examined material deposited in scientific collections and visited 15 conservation units from Rio de Janeiro to southern Bahia between November 2011 and January 2012, catching 104 specimens from 10 conservation units. Based on morphological and molecular data we redefined Listroscelidini, adding a new tribe, new genus and eight new species to the subfamily. Using morphological analysis, we redescribed and added new geographic records for six species, synonymized two species and built a provisional identification key for the Atlantic Forest Listroscelidinae. Molecular results suggest two new species and a new genus to be described, possibly by the fission of the genus Hamayulus. We also proposed a 500 bp region in the final portion of the COI to be used as a molecular barcode. Our data suggest that the Atlantic Forest Listroscelidinae are seriously endangered, because they occur in highly preserved forest remnants, show high rates of endemism and have a narrow geographic distribution. Based on our results, we suggest future collection efforts must take into account the molecular barcode data to accelerate species recognition.

Molecular beacon probes-base multiplex NASBA Real-time for detection of HIV-1 and HCV.

PubMed

Mohammadi-Yeganeh, S; Paryan, M; Mirab Samiee, S; Kia, V; Rezvan, H

2012-06-01

Developed in 1991, nucleic acid sequence-based amplification (NASBA) has been introduced as a rapid molecular diagnostic technique, where it has been shown to give quicker results than PCR, and it can also be more sensitive. This paper describes the development of a molecular beacon-based multiplex NASBA assay for simultaneous detection of HIV-1 and HCV in plasma samples. A well-conserved region in the HIV-1 pol gene and 5'-NCR of HCV genome were used for primers and molecular beacon design. The performance features of HCV/HIV-1 multiplex NASBA assay including analytical sensitivity and specificity, clinical sensitivity and clinical specificity were evaluated. The analysis of scalar concentrations of the samples indicated that the limit of quantification of the assay was <1000 copies/ml for HIV-1 and <500 copies/ml for HCV with 95% confidence interval. Multiplex NASBA assay showed a 98% sensitivity and 100% specificity. The analytical specificity study with BLAST software demonstrated that the primers do not attach to any other sequences except for that of HIV-1 or HCV. The primers and molecular beacon probes detected all HCV genotypes and all major variants of HIV-1. This method may represent a relatively inexpensive isothermal method for detection of HIV-1/HCV co-infection in monitoring of patients.

Recent progress in the analysis of uremic toxins by mass spectrometry.

PubMed

Niwa, Toshimitsu

2009-09-01

Mass spectrometry (MS) has been successfully applied for the identification and quantification of uremic toxins and uremia-associated modified proteins. This review focuses on recent progress in the analysis of uremic toxins by using MS. Uremic toxins include low-molecular-weight compounds (e.g., indoxyl sulfate, p-cresol sulfate, 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid, asymmetric dimethylarginine), middle-molecular-weight peptides, and proteins modified with advanced glycation and oxidation. These uremic toxins are considered to be involved in a variety of symptoms which may appear in patients with stage 5 chronic kidney disease. Based on MS analysis of these uremic toxins, the pathogenesis of the uremic symptoms will be elucidated to prevent and manage the symptoms.

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.

Radiomics biomarkers for accurate tumor progression prediction of oropharyngeal cancer

NASA Astrophysics Data System (ADS)

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

2017-03-01

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

Enhancing undergraduate students' chemistry understanding through project-based learning in an IT environment

NASA Astrophysics Data System (ADS)

Barak, Miri; Dori, Yehudit Judy

2005-01-01

Project-based learning (PBL), which is increasingly supported by information technologies (IT), contributes to fostering student-directed scientific inquiry of problems in a real-world setting. This study investigated the integration of PBL in an IT environment into three undergraduate chemistry courses, each including both experimental and control students. Students in the experimental group volunteered to carry out an individual IT-based project, whereas the control students solved only traditional problems. The project included constructing computerized molecular models, seeking information on scientific phenomena, and inquiring about chemistry theories. The effect of the PBL was examined both quantitatively and qualitatively. The quantitative analysis was based on a pretest, a posttest, and a final examination, which served for comparing the learning gains of the two research groups. For the qualitative analysis, we looked into the experimental students' performance, as reflected by the projects they had submitted. In addition, think alou interviews and observations helped us gain insight into the students' conceptual understanding of molecular structures. Students who participated in the IT-enhanced PBL performed significantly better than their control classmates not only on their posttest but also on their course final examination. Analyzing the qualitative findings, we concluded that the construction of computerized models and Web-based inquiry activities helped promote students' ability of mentally traversing the four levels of chemistry understanding: symbolic, macroscopic, microscopic, and process. More generally, our results indicated that incorporating IT-rich PBL into freshmen courses can enhance students' understanding of chemical concepts, theories, and molecular structures.

[Application of mtDNA polymorphism in species identification of sarcosaphagous insects].

PubMed

Li, Xiang; Cai, Ji-feng

2011-04-01

Species identification of sarcosaphagous insects is one of the important steps in forensic research based on the knowledge of entomology. Recent studies reveal that the application of molecular biology, especially the mtDNA sequences analysis, works well in the species identification of sarcosaphagous insects. The molecular biology characteristics, structures, polymorphism of mtDNA of sarcosaphagous insects, and the recent studies in species identification of sarcosaphagous insects are reviewed in this article.

Analysis of Soil Vapor Extraction Expenses to Estimate Bioventing Expenses

DTIC Science & Technology

1995-11-01

Performance and Cost Summary. Brooks Air Force Base, Texas, July 1994. 2. Atlas , Ronald M, and Richard Bartha . Microbial Ecology : Fundamentals and...and straight-chain alkanes is highly dependent on molecular weight (carbon chain length) and the degree of branching. The book " Microbial Ecology ...must first be the presence of lower- molecular-weight aromatics (Heitkamp and Cerniglia 1988). The " Microbial Ecology " book also points out, on page

Molecular characterization of the Indian poultry nodular tapeworm, Raillietina echinobothrida (Cestoda: Cyclophyllidea: Davaineidae) based on rDNA internal transcribed spacer 2 region.

PubMed

Ramnath; Jyrwa, D B; Dutta, A K; Das, B; Tandon, V

2014-03-01

The nodular tapeworm, Raillietina echinobothrida is a well studied avian gastrointestinal parasite of family Davaineidae (Cestoda: Cyclophyllidea). It is reported to be the largest in size and second most prevalent species infecting chicken in north-east India. In the present study, morphometrical methods coupled with the molecular analysis of the second internal transcribed spacer (ITS2) region of ribosomal DNA were employed for precise identification of the parasite. The annotated ITS2 region was found to be 446 bp long and further utilized to elucidate the phylogenetic relationships and its species-interrelationships at the molecular level. In phylogenetic analysis similar topology was observed among the trees obtained by distance-based neighbor-joining as well as character-based maximum parsimony tree building methods. The query sequence R. echinobothrida is well aligned and placed within the Davaineidae group, with all Raillietina species well separated from the other cyclophyllidean (taeniid and hymenolepid) cestodes, while Diphyllobothrium latum (Pseudophyllidea: Diphyllobothriidae) was rooted as an out-group. Sequence similarities indeed confirmed our hypothesis that Raillietina spp. are neighboring the position with other studied species of order Cyclophyllidea against the out-group order Pseudophyllidea. The present study strengthens the potential of ITS2 as a reliable marker for phylogenetic reconstructions.

Towards Breath Gas Analysis Based on Millimeter-Wave Molecular Spectroscopy

NASA Astrophysics Data System (ADS)

Rothbart, Nick; Hübers, Heinz-Wilhelm; Schmalz, Klaus; Borngräber, Johannes; Kissinger, Dietmar

2018-03-01

Breath gas analysis is a promising non-invasive tool for medical diagnosis as there are thousands of Volatile Organic Compounds (VOCs) in human breath that can be used as health monitoring markers. Millimeter-wave/terahertz molecular spectroscopy is highly suitable for breath gas analysis due to unique fingerprint spectra of many VOCs in that frequency range. We present our recent work on sensor systems for gas spectroscopy based on integrated transmitters (TX) and receivers (RX) fabricated in IHP's 0.13 μm SiGe BiCMOS technology. For a single-band system, spectroscopic measurements and beam profiles are presented. The frequency is tuned by direct voltage-frequency tuning and by a fractional-n PLL, respectively. The spectroscopic system includes a folded gas absorption cell with gas pre-concentration abilities demonstrating the detection of a 50 ppm mixture of ethanol in ambient air corresponding to a minimum detectable concentration of 260 ppb. Finally, the design of a 3-band system covering frequencies from 225 to 273 GHz is introduced.

Karnyothrips flavipes, a previously unreported predatory thrips of the coffee berry borer: DNA-based gut content analysis

USDA-ARS?s Scientific Manuscript database

A new predator of the coffee berry borer, Hypothenemus hampei, was found in the coffee growing area of Kisii in Western Kenya. Field observations, laboratory trials and gut content analysis using molecular tools have confirmed the role of the predatory thrips Karnyothrips flavipes Jones (Phlaeothrip...

Spectroscopic (FTIR, FT-Raman), molecular electrostatic potential, NBO and HOMO-LUMO analysis of P-bromobenzene sulfonyl chloride based on DFT calculations

NASA Astrophysics Data System (ADS)

Jeyavijayan, S.

2015-02-01

The FTIR and FT-Raman spectra of P-bromobenzene sulfonyl chloride (P-BBSC) have been recorded in the regions 4000-400 cm-1 and 3500-50 cm-1, respectively. Utilizing the observed FTIR and FT-Raman data, a complete vibrational assignment and analysis of the fundamental modes of the compound were carried out. The optimum molecular geometry, harmonic vibrational frequencies, infrared intensities and Raman scattering activities, were calculated by density functional theory (DFT/B3LYP) method. A good agreement between experimental and calculated normal modes of vibrations has been observed. A detailed interpretation of the infrared and Raman spectra of P-BBSC is also reported based on total energy distribution (TED). Stability of the molecule arising from hyperconjugative interactions, charge delocalization have been analyzed using natural bond orbital (NBO) analysis. The MEP map shows the negative potential sites are on oxygen atoms as well as the positive potential sites are around the hydrogen atoms. The UV-vis spectral analysis of P-BBSC has also been done which confirms the charge transfer of the molecule.

Molecular and clinical profile of von Willebrand disease in Spain (PCM-EVW-ES): comprehensive genetic analysis by next-generation sequencing of 480 patients

PubMed Central

Borràs, Nina; Batlle, Javier; Pérez-Rodríguez, Almudena; López-Fernández, María Fernanda; Rodríguez-Trillo, Ángela; Lourés, Esther; Cid, Ana Rosa; Bonanad, Santiago; Cabrera, Noelia; Moret, Andrés; Parra, Rafael; Mingot-Castellano, María Eva; Balda, Ignacia; Altisent, Carme; Pérez-Montes, Rocío; Fisac, Rosa María; Iruín, Gemma; Herrero, Sonia; Soto, Inmaculada; de Rueda, Beatriz; Jiménez-Yuste, Víctor; Alonso, Nieves; Vilariño, Dolores; Arija, Olga; Campos, Rosa; Paloma, María José; Bermejo, Nuria; Berrueco, Rubén; Mateo, José; Arribalzaga, Karmele; Marco, Pascual; Palomo, Ángeles; Sarmiento, Lizheidy; Iñigo, Belén; Nieto, María del Mar; Vidal, Rosa; Martínez, María Paz; Aguinaco, Reyes; César, Jesús María; Ferreiro, María; García-Frade, Javier; Rodríguez-Huerta, Ana María; Cuesta, Jorge; Rodríguez-González, Ramón; García-Candel, Faustino; Cornudella, Rosa; Aguilar, Carlos; Vidal, Francisco; Corrales, Irene

2017-01-01

Molecular diagnosis of patients with von Willebrand disease is pending in most populations due to the complexity and high cost of conventional molecular analyses. The need for molecular and clinical characterization of von Willebrand disease in Spain prompted the creation of a multicenter project (PCM-EVW-ES) that resulted in the largest prospective cohort study of patients with all types of von Willebrand disease. Molecular analysis of relevant regions of the VWF, including intronic and promoter regions, was achieved in the 556 individuals recruited via the development of a simple, innovative, relatively low-cost protocol based on microfluidic technology and next-generation sequencing. A total of 704 variants (237 different) were identified along VWF, 155 of which had not been previously recorded in the international mutation database. The potential pathogenic effect of these variants was assessed by in silico analysis. Furthermore, four short tandem repeats were analyzed in order to evaluate the ancestral origin of recurrent mutations. The outcome of genetic analysis allowed for the reclassification of 110 patients, identification of 37 asymptomatic carriers (important for genetic counseling) and re-inclusion of 43 patients previously excluded by phenotyping results. In total, 480 patients were definitively diagnosed. Candidate mutations were identified in all patients except 13 type 1 von Willebrand disease, yielding a high genotype-phenotype correlation. Our data reinforce the capital importance and usefulness of genetics in von Willebrand disease diagnostics. The progressive implementation of molecular study as the first-line test for routine diagnosis of this condition will lead to increasingly more personalized and effective care for this patient population. PMID:28971901

Molecular and clinical profile of von Willebrand disease in Spain (PCM-EVW-ES): comprehensive genetic analysis by next-generation sequencing of 480 patients.

PubMed

Borràs, Nina; Batlle, Javier; Pérez-Rodríguez, Almudena; López-Fernández, María Fernanda; Rodríguez-Trillo, Ángela; Lourés, Esther; Cid, Ana Rosa; Bonanad, Santiago; Cabrera, Noelia; Moret, Andrés; Parra, Rafael; Mingot-Castellano, María Eva; Balda, Ignacia; Altisent, Carme; Pérez-Montes, Rocío; Fisac, Rosa María; Iruín, Gemma; Herrero, Sonia; Soto, Inmaculada; de Rueda, Beatriz; Jiménez-Yuste, Víctor; Alonso, Nieves; Vilariño, Dolores; Arija, Olga; Campos, Rosa; Paloma, María José; Bermejo, Nuria; Berrueco, Rubén; Mateo, José; Arribalzaga, Karmele; Marco, Pascual; Palomo, Ángeles; Sarmiento, Lizheidy; Iñigo, Belén; Nieto, María Del Mar; Vidal, Rosa; Martínez, María Paz; Aguinaco, Reyes; César, Jesús María; Ferreiro, María; García-Frade, Javier; Rodríguez-Huerta, Ana María; Cuesta, Jorge; Rodríguez-González, Ramón; García-Candel, Faustino; Cornudella, Rosa; Aguilar, Carlos; Vidal, Francisco; Corrales, Irene

2017-12-01

Molecular diagnosis of patients with von Willebrand disease is pending in most populations due to the complexity and high cost of conventional molecular analyses. The need for molecular and clinical characterization of von Willebrand disease in Spain prompted the creation of a multicenter project (PCM-EVW-ES) that resulted in the largest prospective cohort study of patients with all types of von Willebrand disease. Molecular analysis of relevant regions of the VWF , including intronic and promoter regions, was achieved in the 556 individuals recruited via the development of a simple, innovative, relatively low-cost protocol based on microfluidic technology and next-generation sequencing. A total of 704 variants (237 different) were identified along VWF , 155 of which had not been previously recorded in the international mutation database. The potential pathogenic effect of these variants was assessed by in silico analysis. Furthermore, four short tandem repeats were analyzed in order to evaluate the ancestral origin of recurrent mutations. The outcome of genetic analysis allowed for the reclassification of 110 patients, identification of 37 asymptomatic carriers (important for genetic counseling) and re-inclusion of 43 patients previously excluded by phenotyping results. In total, 480 patients were definitively diagnosed. Candidate mutations were identified in all patients except 13 type 1 von Willebrand disease, yielding a high genotype-phenotype correlation. Our data reinforce the capital importance and usefulness of genetics in von Willebrand disease diagnostics. The progressive implementation of molecular study as the first-line test for routine diagnosis of this condition will lead to increasingly more personalized and effective care for this patient population. Copyright© 2017 Ferrata Storti Foundation.

Respiromics - An integrative analysis linking mitochondrial bioenergetics to molecular signatures.

PubMed

Walheim, Ellen; Wiśniewski, Jacek R; Jastroch, Martin

2018-03-01

Energy metabolism is challenged upon nutrient stress, eventually leading to a variety of metabolic diseases that represent a major global health burden. Here, we combine quantitative mitochondrial respirometry (Seahorse technology) and proteomics (LC-MS/MS-based total protein approach) to understand how molecular changes translate to changes in mitochondrial energy transduction during diet-induced obesity (DIO) in the liver. The integrative analysis reveals that significantly increased palmitoyl-carnitine respiration is supported by an array of proteins enriching lipid metabolism pathways. Upstream of the respiratory chain, the increased capacity for ATP synthesis during DIO associates strongest to mitochondrial uptake of pyruvate, which is routed towards carboxylation. At the respiratory chain, robust increases of complex I are uncovered by cumulative analysis of single subunit concentrations. Specifically, nuclear-encoded accessory subunits, but not mitochondrial-encoded or core units, appear to be permissive for enhanced lipid oxidation. Our integrative analysis, that we dubbed "respiromics", represents an effective tool to link molecular changes to functional mechanisms in liver energy metabolism, and, more generally, can be applied for mitochondrial analysis in a variety of metabolic and mitochondrial disease models. Copyright © 2018 The Authors. Published by Elsevier GmbH.. All rights reserved.

Pharmacophore-based virtual screening, molecular docking, molecular dynamics simulation, and biological evaluation for the discovery of novel BRD4 inhibitors.

PubMed

Yan, Guoyi; Hou, Manzhou; Luo, Jiang; Pu, Chunlan; Hou, Xueyan; Lan, Suke; Li, Rui

2018-02-01

Bromodomain is a recognition module in the signal transduction of acetylated histone. BRD4, one of the bromodomain members, is emerging as an attractive therapeutic target for several types of cancer. Therefore, in this study, an attempt has been made to screen compounds from an integrated database containing 5.5 million compounds for BRD4 inhibitors using pharmacophore-based virtual screening, molecular docking, and molecular dynamics simulations. As a result, two molecules of twelve hits were found to be active in bioactivity tests. Among the molecules, compound 5 exhibited potent anticancer activity, and the IC 50 values against human cancer cell lines MV4-11, A375, and HeLa were 4.2, 7.1, and 11.6 μm, respectively. After that, colony formation assay, cell cycle, apoptosis analysis, wound-healing migration assay, and Western blotting were carried out to learn the bioactivity of compound 5. © 2017 John Wiley & Sons A/S.

Capillary waves' dynamics at the nanoscale

NASA Astrophysics Data System (ADS)

Delgado-Buscalioni, Rafael; Chacón, Enrique; Tarazona, Pedro

2008-12-01

We study the dynamics of thermally excited capillary waves (CW) at molecular scales, using molecular dynamics simulations of simple liquid slabs. The analysis is based on the Fourier modes of the liquid surface, constructed via the intrinsic sampling method (Chacón and Tarazona 2003 Phys. Rev. Lett. 91 166103). We obtain the time autocorrelation of the Fourier modes to get the frequency and damping rate Γd(q) of each mode, with wavenumber q. Continuum hydrodynamics predicts \\Gamma (q) \\propto q\\gamma (q) and thus provides a dynamic measure of the q-dependent surface tension, γd(q). The dynamical estimation is much more robust than the structural prediction based on the amplitude of the Fourier mode, γs(q). Using the optimal estimation of the intrinsic surface, we obtain quantitative agreement between the structural and dynamic pictures. Quite surprisingly, the hydrodynamic prediction for CW remains valid up to wavelengths of about four molecular diameters. Surface tension hydrodynamics break down at shorter scales, whereby a transition to a molecular diffusion regime is observed.

Magnetic dummy molecularly imprinted polymers based on multi-walled carbon nanotubes for rapid selective solid-phase extraction of 4-nonylphenol in aqueous samples.

PubMed

Rao, Wei; Cai, Rong; Yin, Yuli; Long, Fang; Zhang, Zhaohui

2014-10-01

In this paper, a highly selective sample clean-up procedure combining magnetic dummy molecular imprinting with solid-phase extraction was developed for rapid separation and determination of 4-nonylphenol (NP) in the environmental water samples. The magnetic dummy molecularly imprinted polymers (mag-DMIPs) based on multi-walled carbon nanotubes were successfully synthesized with a surface molecular imprinting technique using 4-tert-octylphenol as the dummy template and tetraethylorthosilicate as the cross-linker. The maximum adsorption capacity of the mag-DMIPs for NP was 52.4 mg g(-1) and it took about 20 min to achieve the adsorption equilibrium. The mag-DMIPs exhibited the specific selective adsorption toward NP. Coupled with high performance liquid chromatography analysis, the mag-DMIPs were used to extract solid-phase and detect NP in real water samples successfully with the recoveries of 88.6-98.1%. Copyright © 2014 Elsevier B.V. All rights reserved.

Elucidation of chemosensitization effect of acridones in cancer cell lines: Combined pharmacophore modeling, 3D QSAR, and molecular dynamics studies.

PubMed

Gade, Deepak Reddy; Makkapati, Amareswararao; Yarlagadda, Rajesh Babu; Peters, Godefridus J; Sastry, B S; Rajendra Prasad, V V S

2018-06-01

Overexpression of P-glycoprotein (P-gp) leads to the emergence of multidrug resistance (MDR) in cancer treatment. Acridones have the potential to reverse MDR and sensitize cells. In the present study, we aimed to elucidate the chemosensitization potential of acridones by employing various molecular modelling techniques. Pharmacophore modeling was performed for the dataset of chemosensitizing acridones earlier proved for cytotoxic activity against MCF7 breast cancer cell line. Gaussian-based QSAR studies also performed to predict the favored and disfavored region of the acridone molecules. Molecular dynamics simulations were performed for compound 10 and human P-glycoprotein (obtained from Homology modeling). An efficient pharmacophore containing 2 hydrogen bond acceptors and 3 aromatic rings (AARRR.14) was identified. NCI 2012 chemical database was screened against AARRR.14 CPH and identified 25 best-fit molecules. Potential regions of the compound were identified through Field (Gaussian) based QSAR. Regression analysis of atom-based QSAR resulted in r 2 of 0.95 and q 2 of 0.72, whereas, regression analysis of field-based QSAR resulted in r 2 of 0.92 and q 2 of 0.87 along with r 2 cv as 0.71. The fate of the acridone molecule (compound 10) in the P-glycoprotein environment is analyzed through analyzing the conformational changes occurring during the molecular dynamics simulations. Combined data of different in silico techniques provided basis for deeper understanding of structural and mechanistic insights of interaction phenomenon of acridones with P-glycoprotein and also as strategic basis for designing more potent molecules for anti-cancer and multidrug resistance reversal activities. Copyright © 2018 Elsevier Ltd. All rights reserved.

Comprehensive and quantitative profiling of lipid species in human milk, cow milk and a phospholipid-enriched milk formula by GC and MS/MSALL.

PubMed

Sokol, Elena; Ulven, Trond; Færgeman, Nils J; Ejsing, Christer S

2015-06-01

Here we present a workflow for in-depth analysis of milk lipids that combines gas chromatography (GC) for fatty acid (FA) profiling and a shotgun lipidomics routine termed MS/MS ALL for structural characterization of molecular lipid species. To evaluate the performance of the workflow we performed a comparative lipid analysis of human milk, cow milk, and Lacprodan® PL-20, a phospholipid-enriched milk protein concentrate for infant formula. The GC analysis showed that human milk and Lacprodan have a similar FA profile with higher levels of unsaturated FAs as compared to cow milk. In-depth lipidomic analysis by MS/MS ALL revealed that each type of milk sample comprised distinct composition of molecular lipid species. Lipid class composition showed that the human and cow milk contain a higher proportion of triacylglycerols (TAGs) as compared to Lacprodan. Notably, the MS/MS ALL analysis demonstrated that the similar FA profile of human milk and Lacprodan determined by GC analysis is attributed to the composition of individual TAG species in human milk and glycerophospholipid species in Lacprodan. Moreover, the analysis of TAG molecules in Lacprodan and cow milk showed a high proportion of short-chain FAs that could not be monitored by GC analysis. The results presented here show that complementary GC and MS/MS ALL analysis is a powerful approach for characterization of molecular lipid species in milk and milk products. : Milk lipid analysis is routinely performed using gas chromatography. This method reports the total fatty acid composition of all milk lipids, but provides no structural or quantitative information about individual lipid molecules in milk or milk products. Here we present a workflow that integrates gas chromatography for fatty acid profiling and a shotgun lipidomics routine termed MS/MS ALL for structural analysis and quantification of molecular lipid species. We demonstrate the efficacy of this complementary workflow by a comparative analysis of molecular lipid species in human milk, cow milk, and a milk-based supplement used for infant formula.

Comprehensive and quantitative profiling of lipid species in human milk, cow milk and a phospholipid-enriched milk formula by GC and MS/MSALL

PubMed Central

Sokol, Elena; Ulven, Trond; Færgeman, Nils J; Ejsing, Christer S

2015-01-01

Here we present a workflow for in-depth analysis of milk lipids that combines gas chromatography (GC) for fatty acid (FA) profiling and a shotgun lipidomics routine termed MS/MSALL for structural characterization of molecular lipid species. To evaluate the performance of the workflow we performed a comparative lipid analysis of human milk, cow milk, and Lacprodan® PL-20, a phospholipid-enriched milk protein concentrate for infant formula. The GC analysis showed that human milk and Lacprodan have a similar FA profile with higher levels of unsaturated FAs as compared to cow milk. In-depth lipidomic analysis by MS/MSALL revealed that each type of milk sample comprised distinct composition of molecular lipid species. Lipid class composition showed that the human and cow milk contain a higher proportion of triacylglycerols (TAGs) as compared to Lacprodan. Notably, the MS/MSALL analysis demonstrated that the similar FA profile of human milk and Lacprodan determined by GC analysis is attributed to the composition of individual TAG species in human milk and glycerophospholipid species in Lacprodan. Moreover, the analysis of TAG molecules in Lacprodan and cow milk showed a high proportion of short-chain FAs that could not be monitored by GC analysis. The results presented here show that complementary GC and MS/MSALL analysis is a powerful approach for characterization of molecular lipid species in milk and milk products. Practical applications : Milk lipid analysis is routinely performed using gas chromatography. This method reports the total fatty acid composition of all milk lipids, but provides no structural or quantitative information about individual lipid molecules in milk or milk products. Here we present a workflow that integrates gas chromatography for fatty acid profiling and a shotgun lipidomics routine termed MS/MSALL for structural analysis and quantification of molecular lipid species. We demonstrate the efficacy of this complementary workflow by a comparative analysis of molecular lipid species in human milk, cow milk, and a milk-based supplement used for infant formula. PMID:26089741

Role of the pulmonologist in ordering post-procedure molecular markers in non-small-cell lung cancer: implications for personalized medicine.

PubMed

Murgu, Septimiu; Colt, Henri

2013-11-01

In the growing era of personalized medicine for the treatment of non-small-cell lung cancer (NSCLC), it is becoming increasingly important that sufficient quality and quantity of tumor tissue are available for morphologic diagnosis and molecular analysis. As new treatment options emerge that might require more frequent and possibly higher volume biopsies, the role of the pulmonologist will expand, and it will be important for pulmonologists to work within a multidisciplinary team to provide optimal therapeutic management for patients with NSCLC. In this review, we discuss the rationale for individualized treatment decisions for patients with NSCLC, molecular pathways and specific molecular predictors relevant to personalized NSCLC therapy, assay technologies for molecular marker analysis, and specifics regarding tumor specimen selection, acquisition, and handling. Moreover, we briefly address issues regarding racial and socioeconomic disparities as they relate to molecular testing and treatment decisions, and cost considerations for molecular testing and targeted therapies in NSCLC. We also propose a model for an institution-based multidisciplinary team, including oncologists, pathologists, pulmonologists, interventional radiologists, and thoracic surgeons, to ensure adequate material is available for cytological and histological studies and to standardize methods of tumor specimen handling and processing in an effort to provide beneficial, individualized therapy for patients with NSCLC. Copyright © 2013 Elsevier Inc. All rights reserved.

R-based Tool for a Pairwise Structure-activity Relationship Analysis.

PubMed

Klimenko, Kyrylo

2018-04-01

The Structure-Activity Relationship analysis is a complex process that can be enhanced by computational techniques. This article describes a simple tool for SAR analysis that has a graphic user interface and a flexible approach towards the input of molecular data. The application allows calculating molecular similarity represented by Tanimoto index & Euclid distance, as well as, determining activity cliffs by means of Structure-Activity Landscape Index. The calculation is performed in a pairwise manner either for the reference compound and other compounds or for all possible pairs in the data set. The results of SAR analysis are visualized using two types of plot. The application capability is demonstrated by the analysis of a set of COX2 inhibitors with respect to Isoxicam. This tool is available online: it includes manual and input file examples. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

The market trend analysis and prospects of cancer molecular diagnostics kits.

PubMed

Seo, Ju Hwan; Lee, Joon Woo; Cho, Daemyeong

2018-01-01

The molecular diagnostics market can be broadly divided into PCR (rt-PCR, d-PCR), NGS(Next Generation Sequencing), Microarray, FISH(Fluorescent in situ-hybridization) and other categories, based on the diagnostic technique. Also, depending on the disease being diagnosed, the market can also be divided into cancer, infectious diseases, HIV/STDs (herpes, syphilis), and women's health issues such as breast cancer, cervical cancer, ovarian cancer, HPV(human papillomavirus), and vaginitis.Chromosome analysis (including Fluorescent In-situ Hybridization) is one type of blood cancer diagnostic method, which involves the direct detection of individual cells with chromosomal translocation, but there have been problems of sensitivity when using this method. PCR targeting individual genes or the RT (reverse transcription)-PCR method offers outstanding sensitivity, but one drawback is the risk of false-positive reaction caused by contamination of samples, etc. Blood cancer molecular diagnostics kits allow us to overcome these shortcomings, and related products have been under development, with a focus on improving detection sensitivity, enabling multiple tests, and reducing the cost and diagnostic time. Blood cancer molecular diagnostics is usually performed based on platforms such as PCR. The global market for blood cancer molecular diagnostics kits is $ 335.9 million as of 2016 and is expected to reach $ 6980 million in 2026 with an average annual growth rate of 32.9%. The market in South Korea is anticipated to grow at an average annual rate of 28.9%, from $ 3.75 million as of 2016 to $ 60.89 million in 2026. The Market for blood cancer molecular diagnostics kits is judged to be higher in growth possibility due to the increase in the number of cancer patients.

Conductance in a bis-terpyridine based single molecular breadboard circuit† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c6sc03204d Click here for additional data file.

PubMed Central

Seth, Charu; Suravarapu, Sankarrao; Reber, David; Hong, Wenjing; Wandlowski, Thomas; Lafolet, Frédéric; Broekmann, Peter

2017-01-01

Controlling charge flow in single molecule circuits with multiple electrical contacts and conductance pathways is a much sought after goal in molecular electronics. In this joint experimental and theoretical study, we advance the possibility of creating single molecule breadboard circuits through an analysis of the conductance of a bis-terpyridine based molecule (TP1). The TP1 molecule can adopt multiple conformations through relative rotations of 7 aromatic rings and can attach to electrodes in 61 possible single and multi-terminal configurations through 6 pyridyl groups. Despite this complexity, we show that it is possible to extract well defined conductance features for the TP1 breadboard and assign them rigorously to the underlying constituent circuits. Mechanically controllable break-junction (MCBJ) experiments on the TP1 molecular breadboard show an unprecedented 4 conductance states spanning a range 10 –2 G 0 to 10 –7 G 0. Quantitative theoretical examination of the conductance of TP1 reveals that combinations of 5 types of single terminal 2–5 ring subcircuits are accessed as a function of electrode separation to produce the distinct conductance steps observed in the MCBJ experiments. We estimate the absolute conductance for each single terminal subcircuit and its percentage contribution to the 4 experimentally observed conductance states. We also provide a detailed analysis of the role of quantum interference and thermal fluctuations in modulating conductance within the subcircuits of the TP1 molecular breadboard. Finally, we discuss the possible development of molecular circuit theory and experimental advances necessary for mapping conductance through complex single molecular breadboard circuits in terms of their constituent subcircuits. PMID:28451287

QuBiLS-MAS, open source multi-platform software for atom- and bond-based topological (2D) and chiral (2.5D) algebraic molecular descriptors computations.

PubMed

Valdés-Martiní, José R; Marrero-Ponce, Yovani; García-Jacas, César R; Martinez-Mayorga, Karina; Barigye, Stephen J; Vaz d'Almeida, Yasser Silveira; Pham-The, Hai; Pérez-Giménez, Facundo; Morell, Carlos A

2017-06-07

In previous reports, Marrero-Ponce et al. proposed algebraic formalisms for characterizing topological (2D) and chiral (2.5D) molecular features through atom- and bond-based ToMoCoMD-CARDD (acronym for Topological Molecular Computational Design-Computer Aided Rational Drug Design) molecular descriptors. These MDs codify molecular information based on the bilinear, quadratic and linear algebraic forms and the graph-theoretical electronic-density and edge-adjacency matrices in order to consider atom- and bond-based relations, respectively. These MDs have been successfully applied in the screening of chemical compounds of different therapeutic applications ranging from antimalarials, antibacterials, tyrosinase inhibitors and so on. To compute these MDs, a computational program with the same name was initially developed. However, this in house software barely offered the functionalities required in contemporary molecular modeling tasks, in addition to the inherent limitations that made its usability impractical. Therefore, the present manuscript introduces the QuBiLS-MAS (acronym for Quadratic, Bilinear and N-Linear mapS based on graph-theoretic electronic-density Matrices and Atomic weightingS) software designed to compute topological (0-2.5D) molecular descriptors based on bilinear, quadratic and linear algebraic forms for atom- and bond-based relations. The QuBiLS-MAS module was designed as standalone software, in which extensions and generalizations of the former ToMoCoMD-CARDD 2D-algebraic indices are implemented, considering the following aspects: (a) two new matrix normalization approaches based on double-stochastic and mutual probability formalisms; (b) topological constraints (cut-offs) to take into account particular inter-atomic relations; (c) six additional atomic properties to be used as weighting schemes in the calculation of the molecular vectors; (d) four new local-fragments to consider molecular regions of interest; (e) number of lone-pair electrons in chemical structure defined by diagonal coefficients in matrix representations; and (f) several aggregation operators (invariants) applied over atom/bond-level descriptors in order to compute global indices. This software permits the parallel computation of the indices, contains a batch processing module and data curation functionalities. This program was developed in Java v1.7 using the Chemistry Development Kit library (version 1.4.19). The QuBiLS-MAS software consists of two components: a desktop interface (GUI) and an API library allowing for the easy integration of the latter in chemoinformatics applications. The relevance of the novel extensions and generalizations implemented in this software is demonstrated through three studies. Firstly, a comparative Shannon's entropy based variability study for the proposed QuBiLS-MAS and the DRAGON indices demonstrates superior performance for the former. A principal component analysis reveals that the QuBiLS-MAS approach captures chemical information orthogonal to that codified by the DRAGON descriptors. Lastly, a QSAR study for the binding affinity to the corticosteroid-binding globulin using Cramer's steroid dataset is carried out. From these analyses, it is revealed that the QuBiLS-MAS approach for atom-pair relations yields similar-to-superior performance with regard to other QSAR methodologies reported in the literature. Therefore, the QuBiLS-MAS approach constitutes a useful tool for the diversity analysis of chemical compound datasets and high-throughput screening of structure-activity data.

Quantum-SAR Extension of the Spectral-SAR Algorithm. Application to Polyphenolic Anticancer Bioactivity

PubMed Central

Putz, Mihai V.; Putz, Ana-Maria; Lazea, Marius; Ienciu, Luciana; Chiriac, Adrian

2009-01-01

Aiming to assess the role of individual molecular structures in the molecular mechanism of ligand-receptor interaction correlation analysis, the recent Spectral-SAR approach is employed to introduce the Quantum-SAR (QuaSAR) “wave” and “conversion factor” in terms of difference between inter-endpoint inter-molecular activities for a given set of compounds; this may account for inter-conversion (metabolization) of molecular (concentration) effects while indicating the structural (quantum) based influential/detrimental role on bio-/eco- effect in a causal manner rather than by simple inspection of measured values; the introduced QuaSAR method is then illustrated for a study of the activity of a series of flavonoids on breast cancer resistance protein. PMID:19399244

Molecular Diagnosis and Biomarker Identification on SELDI proteomics data by ADTBoost method.

PubMed

Wang, Lu-Yong; Chakraborty, Amit; Comaniciu, Dorin

2005-01-01

Clinical proteomics is an emerging field that will have great impact on molecular diagnosis, identification of disease biomarkers, drug discovery and clinical trials in the post-genomic era. Protein profiling in tissues and fluids in disease and pathological control and other proteomics techniques will play an important role in molecular diagnosis with therapeutics and personalized healthcare. We introduced a new robust diagnostic method based on ADTboost algorithm, a novel algorithm in proteomics data analysis to improve classification accuracy. It generates classification rules, which are often smaller and easier to interpret. This method often gives most discriminative features, which can be utilized as biomarkers for diagnostic purpose. Also, it has a nice feature of providing a measure of prediction confidence. We carried out this method in amyotrophic lateral sclerosis (ALS) disease data acquired by surface enhanced laser-desorption/ionization-time-of-flight mass spectrometry (SELDI-TOF MS) experiments. Our method is shown to have outstanding prediction capacity through the cross-validation, ROC analysis results and comparative study. Our molecular diagnosis method provides an efficient way to distinguish ALS disease from neurological controls. The results are expressed in a simple and straightforward alternating decision tree format or conditional format. We identified most discriminative peaks in proteomic data, which can be utilized as biomarkers for diagnosis. It will have broad application in molecular diagnosis through proteomics data analysis and personalized medicine in this post-genomic era.

Impact of S100A8 expression on kidney cancer progression and molecular docking studies for kidney cancer therapeutics.

PubMed

Mirza, Zeenat; Schulten, Hans-Juergen; Farsi, Hasan Ma; Al-Maghrabi, Jaudah A; Gari, Mamdooh A; Chaudhary, Adeel Ga; Abuzenadah, Adel M; Al-Qahtani, Mohammed H; Karim, Sajjad

2014-04-01

The proinflammatory protein S100A8, which is expressed in myeloid cells under physiological conditions, is strongly expressed in human cancer tissues. Its role in tumor cell differentiation and tumor progression is largely unclear and virtually unstudied in kidney cancer. In the present study, we investigated whether S100A8 could be a potential anticancer drug target and therapeutic biomarker for kidney cancer, and the underlying molecular mechanisms by exploiting its interaction profile with drugs. Microarray-based transcriptomics experiments using Affymetrix HuGene 1.0 ST arrays were applied to renal cell carcinoma specimens from Saudi patients for identification of significant genes associated with kidney cancer. In addition, we retrieved selected expression data from the National Center for Biotechnology Information Gene Expression Omnibus database for comparative analysis and confirmation of S100A8 expression. Ingenuity Pathway Analysis (IPA) was used to elucidate significant molecular networks and pathways associated with kidney cancer. The probable polar and non-polar interactions of possible S100A8 inhibitors (aspirin, celecoxib, dexamethasone and diclofenac) were examined by performing molecular docking and binding free energy calculations. Detailed analysis of bound structures and their binding free energies was carried out for S100A8, its known partner (S100A9), and S100A8-S100A9 complex (calprotectin). In our microarray experiments, we identified 1,335 significantly differentially expressed genes, including S100A8, in kidney cancer using a cut-off of p<0.05 and fold-change of 2. Functional analysis of kidney cancer-associated genes showed overexpression of genes involved in cell-cycle progression, DNA repair, cell death, tumor morphology and tissue development. Pathway analysis showed significant disruption of pathways of atherosclerosis signaling, liver X receptor/retinoid X receptor (LXR/RXR) activation, notch signaling, and interleukin-12 (IL-12) signaling. We identified S100A8 as a prospective biomarker for kidney cancer and in silico analysis showed that aspirin, celecoxib, dexamethasone and diclofenac binds to S100A8 and may inhibit downstream signaling in kidney cancer. The present study provides an initial overview of differentially expressed genes in kidney cancer of Saudi Arabian patients using whole-transcript, high-density expression arrays. Our analysis suggests distinct transcriptomic signatures, with significantly high levels of S100A8, and underlying molecular mechanisms contributing to kidney cancer progression. Our docking-based findings shed insight into S100A8 protein as an attractive anticancer target for therapeutic intervention in kidney cancer. To our knowledge, this is the first structure-based docking study for the selected protein targets using the chosen ligands.

A RAD-based phylogenetics for Orestias fishes from Lake Titicaca.

PubMed

Takahashi, Tetsumi; Moreno, Edmundo

2015-12-01

The fish genus Orestias is endemic to the Andes highlands, and Lake Titicaca is the centre of the species diversity of the genus. Previous phylogenetic studies based on a single locus of mitochondrial and nuclear DNA strongly support the monophyly of a group composed of many of species endemic to the Lake Titicaca basin (the Lake Titicaca radiation), but the relationships among the species in the radiation remain unclear. Recently, restriction site-associated DNA (RAD) sequencing, which can produce a vast number of short sequences from various loci of nuclear DNA, has emerged as a useful way to resolve complex phylogenetic problems. To propose a new phylogenetic hypothesis of Orestias fishes of the Lake Titicaca radiation, we conducted a cluster analysis based on morphological similarities among fish samples and a molecular phylogenetic analysis based on RAD sequencing. From a morphological cluster analysis, we recognised four species groups in the radiation, and three of the four groups were resolved as monophyletic groups in maximum-likelihood trees based on RAD sequencing data. The other morphology-based group was not resolved as a monophyletic group in molecular phylogenies, and some members of the group were diverged from its sister group close to the root of the Lake Titicaca radiation. The evolution of these fishes is discussed from the phylogenetic relationships. Copyright © 2015 Elsevier Inc. All rights reserved.

The Effect of Molecular Diagnostics on the Treatment of Glioma.

PubMed

Bush, Nancy Ann Oberheim; Butowski, Nicholas

2017-04-01

This review summarizes the use of molecular diagnostics in glioma and its effect on the development of novel therapeutics and management decisions. Genomic and proteomic profiling of brain tumors has provided significant expansion of our understanding of oncogenesis, characterization, and prognostication of brain tumors. Molecular markers such as MGMT, EGFR, IDH, 1p19q, ATRX, TERT, FGFR-TACC, and BRAF are now being used to classify brain tumors as well as influence management decisions. Several of these markers are also being used as therapeutic targets. We review the use of several molecular diagnostics in gliomas and discuss their impact on drug development and clinical trial design. In the future, molecular characterization based on a specific genomic, proteomic as well as transcriptomes for bioformatics analysis will provide clinicians the ability to rationally select drugs with actionable targets for each patient.

Enrichment of low-molecular-weight proteins from biofluids for biomarker discovery.

PubMed

Chertov, Oleg; Simpson, John T; Biragyn, Arya; Conrads, Thomas P; Veenstra, Timothy D; Fisher, Robert J

2005-01-01

The dramatic progress in mass spectrometry-based methods of protein identification has triggered a new quest for disease-associated biomarkers. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and its variant surface-enhanced laser desorption/ionization mass spectrometry, provide effective means to explore the less studied information slice of the human serum proteome -- low-molecular-weight proteins and peptides. These low-molecular-weight proteins and peptides are promising for the detection of important biomarkers. Due to the significant experimental problems imposed by high-abundance and high-molecular-weight proteins, it is important to effectively remove these species prior to mass spectrometry analysis of the low-molecular-weight serum and plasma proteomes. In this review, the advantages afforded by recently introduced methods for prefractionation of serum, as they pertain to the detection and identification of biomarkers, will be discussed.

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

PubMed

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

2012-08-16

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

Fuzzy method of recognition of high molecular substances in evidence-based biology

NASA Astrophysics Data System (ADS)

Olevskyi, V. I.; Smetanin, V. T.; Olevska, Yu. B.

2017-10-01

Nowadays modern requirements to achieving reliable results along with high quality of researches put mathematical analysis methods of results at the forefront. Because of this, evidence-based methods of processing experimental data have become increasingly popular in the biological sciences and medicine. Their basis is meta-analysis, a method of quantitative generalization of a large number of randomized trails contributing to a same special problem, which are often contradictory and performed by different authors. It allows identifying the most important trends and quantitative indicators of the data, verification of advanced hypotheses and discovering new effects in the population genotype. The existing methods of recognizing high molecular substances by gel electrophoresis of proteins under denaturing conditions are based on approximate methods for comparing the contrast of electrophoregrams with a standard solution of known substances. We propose a fuzzy method for modeling experimental data to increase the accuracy and validity of the findings of the detection of new proteins.

Molecular bases of the ABO blood groups of Indians from the Brazilian Amazon region.

PubMed

Franco, R F; Simões, B P; Guerreiro, J F; Santos, S E; Zago, M A

1994-01-01

Phenotype studies of ABO blood groups in most Amerindian populations revealed the exclusive presence of group O. Since group O is the result of the absence of glycosyltransferase activity, its molecular bases may be heterogeneous. We carried out ABO blood group genotyping by analysis of DNA of 30 Indians from 2 Amazonian tribes (Yanomami and Arara), and compared the findings with other populations (Caucasians and Blacks). Two segments of the glycosyltransferase gene were amplified by PCR and digested with KpnI or AluI to detect deletion or base change at positions 258 and 700, respectively. For all subjects, the gene basis of blood group O is the deletion of a single nucleotide at position 258 of the glycosyltransferase A gene, similar to that observed in Caucasoids and Negroids. DNA sequencing of limited regions of the gene supports this conclusion. This finding does not exclude, however, that a heterogeneity of the O allele may be revealed by a more extensive analysis.

Analysis of factors influencing hydration site prediction based on molecular dynamics simulations.

PubMed

Yang, Ying; Hu, Bingjie; Lill, Markus A

2014-10-27

Water contributes significantly to the binding of small molecules to proteins in biochemical systems. Molecular dynamics (MD) simulation based programs such as WaterMap and WATsite have been used to probe the locations and thermodynamic properties of hydration sites at the surface or in the binding site of proteins generating important information for structure-based drug design. However, questions associated with the influence of the simulation protocol on hydration site analysis remain. In this study, we use WATsite to investigate the influence of factors such as simulation length and variations in initial protein conformations on hydration site prediction. We find that 4 ns MD simulation is appropriate to obtain a reliable prediction of the locations and thermodynamic properties of hydration sites. In addition, hydration site prediction can be largely affected by the initial protein conformations used for MD simulations. Here, we provide a first quantification of this effect and further indicate that similar conformations of binding site residues (RMSD < 0.5 Å) are required to obtain consistent hydration site predictions.

Recent Advances in Nanobiotechnology and High-Throughput Molecular Techniques for Systems Biomedicine

PubMed Central

Kim, Eung-Sam; Ahn, Eun Hyun; Chung, Euiheon; Kim, Deok-Ho

2013-01-01

Nanotechnology-based tools are beginning to emerge as promising platforms for quantitative high-throughput analysis of live cells and tissues. Despite unprecedented progress made over the last decade, a challenge still lies in integrating emerging nanotechnology-based tools into macroscopic biomedical apparatuses for practical purposes in biomedical sciences. In this review, we discuss the recent advances and limitations in the analysis and control of mechanical, biochemical, fluidic, and optical interactions in the interface areas of nanotechnology-based materials and living cells in both in vitro and in vivo settings. PMID:24258011

Imaging-based molecular barcoding with pixelated dielectric metasurfaces

NASA Astrophysics Data System (ADS)

Tittl, Andreas; Leitis, Aleksandrs; Liu, Mingkai; Yesilkoy, Filiz; Choi, Duk-Yong; Neshev, Dragomir N.; Kivshar, Yuri S.; Altug, Hatice

2018-06-01

Metasurfaces provide opportunities for wavefront control, flat optics, and subwavelength light focusing. We developed an imaging-based nanophotonic method for detecting mid-infrared molecular fingerprints and implemented it for the chemical identification and compositional analysis of surface-bound analytes. Our technique features a two-dimensional pixelated dielectric metasurface with a range of ultrasharp resonances, each tuned to a discrete frequency; this enables molecular absorption signatures to be read out at multiple spectral points, and the resulting information is then translated into a barcode-like spatial absorption map for imaging. The signatures of biological, polymer, and pesticide molecules can be detected with high sensitivity, covering applications such as biosensing and environmental monitoring. Our chemically specific technique can resolve absorption fingerprints without the need for spectrometry, frequency scanning, or moving mechanical parts, thereby paving the way toward sensitive and versatile miniaturized mid-infrared spectroscopy devices.

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

PubMed

Venkatraman, Vishwesh; Sael, Lee; Kihara, Daisuke

2009-01-01

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

Nanostructure and molecular mechanics of spider dragline silk protein assemblies

PubMed Central

Keten, Sinan; Buehler, Markus J.

2010-01-01

Spider silk is a self-assembling biopolymer that outperforms most known materials in terms of its mechanical performance, despite its underlying weak chemical bonding based on H-bonds. While experimental studies have shown that the molecular structure of silk proteins has a direct influence on the stiffness, toughness and failure strength of silk, no molecular-level analysis of the nanostructure and associated mechanical properties of silk assemblies have been reported. Here, we report atomic-level structures of MaSp1 and MaSp2 proteins from the Nephila clavipes spider dragline silk sequence, obtained using replica exchange molecular dynamics, and subject these structures to mechanical loading for a detailed nanomechanical analysis. The structural analysis reveals that poly-alanine regions in silk predominantly form distinct and orderly beta-sheet crystal domains, while disorderly regions are formed by glycine-rich repeats that consist of 31-helix type structures and beta-turns. Our structural predictions are validated against experimental data based on dihedral angle pair calculations presented in Ramachandran plots, alpha-carbon atomic distances, as well as secondary structure content. Mechanical shearing simulations on selected structures illustrate that the nanoscale behaviour of silk protein assemblies is controlled by the distinctly different secondary structure content and hydrogen bonding in the crystalline and semi-amorphous regions. Both structural and mechanical characterization results show excellent agreement with available experimental evidence. Our findings set the stage for extensive atomistic investigations of silk, which may contribute towards an improved understanding of the source of the strength and toughness of this biological superfibre. PMID:20519206

Nanostructure and molecular mechanics of spider dragline silk protein assemblies.

PubMed

Keten, Sinan; Buehler, Markus J

2010-12-06

Spider silk is a self-assembling biopolymer that outperforms most known materials in terms of its mechanical performance, despite its underlying weak chemical bonding based on H-bonds. While experimental studies have shown that the molecular structure of silk proteins has a direct influence on the stiffness, toughness and failure strength of silk, no molecular-level analysis of the nanostructure and associated mechanical properties of silk assemblies have been reported. Here, we report atomic-level structures of MaSp1 and MaSp2 proteins from the Nephila clavipes spider dragline silk sequence, obtained using replica exchange molecular dynamics, and subject these structures to mechanical loading for a detailed nanomechanical analysis. The structural analysis reveals that poly-alanine regions in silk predominantly form distinct and orderly beta-sheet crystal domains, while disorderly regions are formed by glycine-rich repeats that consist of 3₁-helix type structures and beta-turns. Our structural predictions are validated against experimental data based on dihedral angle pair calculations presented in Ramachandran plots, alpha-carbon atomic distances, as well as secondary structure content. Mechanical shearing simulations on selected structures illustrate that the nanoscale behaviour of silk protein assemblies is controlled by the distinctly different secondary structure content and hydrogen bonding in the crystalline and semi-amorphous regions. Both structural and mechanical characterization results show excellent agreement with available experimental evidence. Our findings set the stage for extensive atomistic investigations of silk, which may contribute towards an improved understanding of the source of the strength and toughness of this biological superfibre.

Measurement and control of detailed electronic properties in a single molecule break junction.

PubMed

Wang, Kun; Hamill, Joseph; Zhou, Jianfeng; Guo, Cunlan; Xu, Bingqian

2014-01-01

The lack of detailed experimental controls has been one of the major obstacles hindering progress in molecular electronics. While large fluctuations have been occurring in the experimental data, specific details, related mechanisms, and data analysis techniques are in high demand to promote our physical understanding at the single-molecule level. A series of modulations we recently developed, based on traditional scanning probe microscopy break junctions (SPMBJs), have helped to discover significant properties in detail which are hidden in the contact interfaces of a single-molecule break junction (SMBJ). For example, in the past we have shown that the correlated force and conductance changes under the saw tooth modulation and stretch-hold mode of PZT movement revealed inherent differences in the contact geometries of a molecular junction. In this paper, using a bias-modulated SPMBJ and utilizing emerging data analysis techniques, we report on the measurement of the altered alignment of the HOMO of benzene molecules with changing the anchoring group which coupled the molecule to metal electrodes. Further calculations based on Landauer fitting and transition voltage spectroscopy (TVS) demonstrated the effects of modulated bias on the location of the frontier molecular orbitals. Understanding the alignment of the molecular orbitals with the Fermi level of the electrodes is essential for understanding the behaviour of SMBJs and for the future design of more complex devices. With these modulations and analysis techniques, fruitful information has been found about the nature of the metal-molecule junction, providing us insightful clues towards the next step for in-depth study.

Improved PCR-Based Detection of Soil Transmitted Helminth Infections Using a Next-Generation Sequencing Approach to Assay Design.

PubMed

Pilotte, Nils; Papaiakovou, Marina; Grant, Jessica R; Bierwert, Lou Ann; Llewellyn, Stacey; McCarthy, James S; Williams, Steven A

2016-03-01

The soil transmitted helminths are a group of parasitic worms responsible for extensive morbidity in many of the world's most economically depressed locations. With growing emphasis on disease mapping and eradication, the availability of accurate and cost-effective diagnostic measures is of paramount importance to global control and elimination efforts. While real-time PCR-based molecular detection assays have shown great promise, to date, these assays have utilized sub-optimal targets. By performing next-generation sequencing-based repeat analyses, we have identified high copy-number, non-coding DNA sequences from a series of soil transmitted pathogens. We have used these repetitive DNA elements as targets in the development of novel, multi-parallel, PCR-based diagnostic assays. Utilizing next-generation sequencing and the Galaxy-based RepeatExplorer web server, we performed repeat DNA analysis on five species of soil transmitted helminths (Necator americanus, Ancylostoma duodenale, Trichuris trichiura, Ascaris lumbricoides, and Strongyloides stercoralis). Employing high copy-number, non-coding repeat DNA sequences as targets, novel real-time PCR assays were designed, and assays were tested against established molecular detection methods. Each assay provided consistent detection of genomic DNA at quantities of 2 fg or less, demonstrated species-specificity, and showed an improved limit of detection over the existing, proven PCR-based assay. The utilization of next-generation sequencing-based repeat DNA analysis methodologies for the identification of molecular diagnostic targets has the ability to improve assay species-specificity and limits of detection. By exploiting such high copy-number repeat sequences, the assays described here will facilitate soil transmitted helminth diagnostic efforts. We recommend similar analyses when designing PCR-based diagnostic tests for the detection of other eukaryotic pathogens.

Synthesis and molecular characterization of chitosan based polyurethane elastomers using aromatic diisocyanate.

PubMed

Zia, Khalid Mahmood; Anjum, Sohail; Zuber, Mohammad; Mujahid, Muhammad; Jamil, Tahir

2014-05-01

The present research work was performed to synthesize a new series of chitosan based polyurethane elastomers (PUEs) using poly(ɛ-caprolactone) (PCL). The chitosan based PUEs were prepared by step-growth polymerization technique using poly(ɛ-caprolactone) (PCL) and 2,4-toluene diisocyanate (TDI). In the second step the PU prepolymer was extended with different mole ratios of chitosan and 1,4-butane diol (BDO). Molecular engineering was carried out during the synthesis. The conventional spectroscopic characterization of the synthesized samples using FT-IR confirms the existence of the proposed chitosan based PUEs structure. Internal morphology of the prepared PUEs was studied using SEM analysis. The SEM images confirmed the incorporation of chitosan molecules into the PU backbone. Copyright © 2014 Elsevier B.V. All rights reserved.

Comparison of semi-automated commercial rep-PCR fingerprinting, spoligotyping, 12-locus MIRU-VNTR typing and single nucleotide polymorphism analysis of the embB gene as molecular typing tools for Mycobacterium bovis.

PubMed

Armas, Federica; Camperio, Cristina; Coltella, Luana; Selvaggini, Serena; Boniotti, Maria Beatrice; Pacciarini, Maria Lodovica; Di Marco Lo Presti, Vincenzo; Marianelli, Cinzia

2017-08-04

Highly discriminatory genotyping strategies are essential in molecular epidemiological studies of tuberculosis. In this study we evaluated, for the first time, the efficacy of the repetitive sequence-based PCR (rep-PCR) DiversiLab Mycobacterium typing kit over spoligotyping, 12-locus mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) typing and embB single nucleotide polymorphism (SNP) analysis for Mycobacterium bovis typing. A total of 49 M. bovis animal isolates were used. DNA was extracted and genomic DNA was amplified using the DiversiLab Mycobacterium typing kit. The amplified fragments were separated and detected using a microfluidics chip with Agilent 2100. The resulting rep-PCR-based DNA fingerprints were uploaded to and analysed using web-based DiversiLab software through Pearson's correlation coefficient. Rep-PCR DiversiLab grouped M. bovis isolates into ten different clusters. Most isolates sharing identical spoligotype, MIRU-VNTR profile or embB gene polymorphism were grouped into different rep-PCR clusters. Rep-PCR DiversiLab displayed greater discriminatory power than spoligotyping and embB SNP analysis but a lower resolution power than the 12-locus MIRU-VNTR analysis. MIRU-VNTR confirmed that it is superior to the other PCR-based methods tested here. In combination with spoligotyping and 12-locus MIRU-VNTR analysis, rep-PCR improved the discriminatory power for M. bovis typing.

N-tuple topological/geometric cutoffs for 3D N-linear algebraic molecular codifications: variability, linear independence and QSAR analysis.

PubMed

García-Jacas, C R; Marrero-Ponce, Y; Barigye, S J; Hernández-Ortega, T; Cabrera-Leyva, L; Fernández-Castillo, A

2016-12-01

Novel N-tuple topological/geometric cutoffs to consider specific inter-atomic relations in the QuBiLS-MIDAS framework are introduced in this manuscript. These molecular cutoffs permit the taking into account of relations between more than two atoms by using (dis-)similarity multi-metrics and the concepts related with topological and Euclidean-geometric distances. To this end, the kth two-, three- and four-tuple topological and geometric neighbourhood quotient (NQ) total (or local-fragment) spatial-(dis)similarity matrices are defined, to represent 3D information corresponding to the relations between two, three and four atoms of the molecular structures that satisfy certain cutoff criteria. First, an analysis of a diverse chemical space for the most common values of topological/Euclidean-geometric distances, bond/dihedral angles, triangle/quadrilateral perimeters, triangle area and volume was performed in order to determine the intervals to take into account in the cutoff procedures. A variability analysis based on Shannon's entropy reveals that better distribution patterns are attained with the descriptors based on the cutoffs proposed (QuBiLS-MIDAS NQ-MDs) with regard to the results obtained when all inter-atomic relations are considered (QuBiLS-MIDAS KA-MDs - 'Keep All'). A principal component analysis shows that the novel molecular cutoffs codify chemical information captured by the respective QuBiLS-MIDAS KA-MDs, as well as information not captured by the latter. Lastly, a QSAR study to obtain deeper knowledge of the contribution of the proposed methods was carried out, using four molecular datasets (steroids (STER), angiotensin converting enzyme (ACE), thermolysin inhibitors (THER) and thrombin inhibitors (THR)) widely used as benchmarks in the evaluation of several methodologies. One to four variable QSAR models based on multiple linear regression were developed for each compound dataset following the original division into training and test sets. The results obtained reveal that the novel cutoff procedures yield superior performances relative to those of the QuBiLS-MIDAS KA-MDs in the prediction of the biological activities considered. From the results achieved, it can be suggested that the proposed N-tuple topological/geometric cutoffs constitute a relevant criteria for generating MDs codifying particular atomic relations, ultimately useful in enhancing the modelling capacity of the QuBiLS-MIDAS 3D-MDs.

Interactive Design Strategy for a Multi-Functional PAMAM Dendrimer-Based Nano-Therapeutic Using Computational Models and Experimental Analysis

PubMed Central

Lee, Inhan; Williams, Christopher R.; Athey, Brian D.; Baker, James R.

2010-01-01

Molecular dynamics simulations of nano-therapeutics as a final product and of all intermediates in the process of generating a multi-functional nano-therapeutic based on a poly(amidoamine) (PAMAM) dendrimer were performed along with chemical analyses of each of them. The actual structures of the dendrimers were predicted, based on potentiometric titration, gel permeation chromatography, and NMR. The chemical analyses determined the numbers of functional molecules, based on the actual structure of the dendrimer. Molecular dynamics simulations calculated the configurations of the intermediates and the radial distributions of functional molecules, based on their numbers. This interactive process between the simulation results and the chemical analyses provided a further strategy to design the next reaction steps and to gain insight into the products at each chemical reaction step. PMID:20700476

Linear Discriminant Analysis for the in Silico Discovery of Mechanism-Based Reversible Covalent Inhibitors of a Serine Protease: Application of Hydration Thermodynamics Analysis and Semi-empirical Molecular Orbital Calculation.

PubMed

Masuda, Yosuke; Yoshida, Tomoki; Yamaotsu, Noriyuki; Hirono, Shuichi

2018-01-01

We recently reported that the Gibbs free energy of hydrolytic water molecules (ΔG wat ) in acyl-trypsin intermediates calculated by hydration thermodynamics analysis could be a useful metric for estimating the catalytic rate constants (k cat ) of mechanism-based reversible covalent inhibitors. For thorough evaluation, the proposed method was tested with an increased number of covalent ligands that have no corresponding crystal structures. After modeling acyl-trypsin intermediate structures using flexible molecular superposition, ΔG wat values were calculated according to the proposed method. The orbital energies of antibonding π* molecular orbitals (MOs) of carbonyl C=O in covalently modified catalytic serine (E orb ) were also calculated by semi-empirical MO calculations. Then, linear discriminant analysis (LDA) was performed to build a model that can discriminate covalent inhibitor candidates from substrate-like ligands using ΔG wat and E orb . The model was built using a training set (10 compounds) and then validated by a test set (4 compounds). As a result, the training set and test set ligands were perfectly discriminated by the model. Hydrolysis was slower when (1) the hydrolytic water molecule has lower ΔG wat ; (2) the covalent ligand presents higher E orb (higher reaction barrier). Results also showed that the entropic term of hydrolytic water molecule (-TΔS wat ) could be used for estimating k cat and for covalent inhibitor optimization; when the rotational freedom of the hydrolytic water molecule is limited, the chance for favorable interaction with the electrophilic acyl group would also be limited. The method proposed in this study would be useful for screening and optimizing the mechanism-based reversible covalent inhibitors.

Comparative Analysis of Disease-Linked Single Nucleotide Polymorphic Markers from Brassica rapa for Their Applicability to Brassica oleracea

PubMed Central

Cho, Young-Il; Ahn, Yul-Kyun; Tripathi, Swati; Kim, Jeong-Ho; Lee, Hye-Eun; Kim, Do-Sun

2015-01-01

Numerous studies using single nucleotide polymorphisms (SNPs) have been conducted in humans, and other animals, and in major crops, including rice, soybean, and Chinese cabbage. However, the number of SNP studies in cabbage is limited. In this present study, we evaluated whether 7,645 SNPs previously identified as molecular markers linked to disease resistance in the Brassica rapa genome could be applied to B. oleracea. In a BLAST analysis using the SNP sequences of B. rapa and B. oleracea genomic sequence data registered in the NCBI database, 256 genes for which SNPs had been identified in B. rapa were found in B. oleracea. These genes were classified into three functional groups: molecular function (64 genes), biological process (96 genes), and cellular component (96 genes). A total of 693 SNP markers, including 145 SNP markers [BRH—developed from the B. rapa genome for high-resolution melt (HRM) analysis], 425 SNP markers (BRP—based on the B. rapa genome that could be applied to B. oleracea), and 123 new SNP markers (BRS—derived from BRP and designed for HRM analysis), were investigated for their ability to amplify sequences from cabbage genomic DNA. In total, 425 of the SNP markers (BRP-based on B. rapa genome), selected from 7,645 SNPs, were successfully applied to B. oleracea. Using PCR, 108 of 145 BRH (74.5%), 415 of 425 BRP (97.6%), and 118 of 123 BRS (95.9%) showed amplification, suggesting that it is possible to apply SNP markers developed based on the B. rapa genome to B. oleracea. These results provide valuable information that can be utilized in cabbage genetics and breeding programs using molecular markers derived from other Brassica species. PMID:25790283

Improving the Molecular Ion Signal Intensity for In Situ Liquid SIMS Analysis.

PubMed

Zhou, Yufan; Yao, Juan; Ding, Yuanzhao; Yu, Jiachao; Hua, Xin; Evans, James E; Yu, Xiaofei; Lao, David B; Heldebrant, David J; Nune, Satish K; Cao, Bin; Bowden, Mark E; Yu, Xiao-Ying; Wang, Xue-Lin; Zhu, Zihua

2016-12-01

In situ liquid secondary ion mass spectrometry (SIMS) enabled by system for analysis at the liquid vacuum interface (SALVI) has proven to be a promising new tool to provide molecular information at solid-liquid and liquid-vacuum interfaces. However, the initial data showed that useful signals in positive ion spectra are too weak to be meaningful in most cases. In addition, it is difficult to obtain strong negative molecular ion signals when m/z>200. These two drawbacks have been the biggest obstacle towards practical use of this new analytical approach. In this study, we report that strong and reliable positive and negative molecular signals are achievable after optimizing the SIMS experimental conditions. Four model systems, including a 1,8-diazabicycloundec-7-ene (DBU)-base switchable ionic liquid, a live Shewanella oneidensis biofilm, a hydrated mammalian epithelia cell, and an electrolyte popularly used in Li ion batteries were studied. A signal enhancement of about two orders of magnitude was obtained in comparison with non-optimized conditions. Therefore, molecular ion signal intensity has become very acceptable for use of in situ liquid SIMS to study solid-liquid and liquid-vacuum interfaces. Graphical Abstract ᅟ.

The discovery of novel histone lysine methyltransferase G9a inhibitors (part 1): molecular design based on a series of substituted 2,4-diamino-7- aminoalkoxyquinazoline by molecular-docking-guided 3D quantitative structure-activity relationship studies.

PubMed

Feng, Taotao; Wang, Hai; Zhang, Xiaojin; Sun, Haopeng; You, Qidong

2014-06-01

Protein lysine methyltransferase G9a, which catalyzes methylation of lysine 9 of histone H3 (H3K9) and lysine 373 (K373) of p53, is overexpressed in human cancers. This suggests that small molecular inhibitors of G9a might be attractive antitumor agents. Herein we report our efforts on the design of novel G9a inhibitor based on the 3D quantitative structure-activity relationship (3D-QSAR) analysis of a series of 2,4-diamino-7-aminoalkoxyquinazolineas G9a inhibitors. The 3D-QSAR model was generated from 47 compounds using docking based molecular alignment. The best predictions were obtained with CoMFA standard model (q2 =0.700, r2 = 0.952) and CoMSIA model combined with steric, electrostatic, hydrophobic, hydrogen bond donor and acceptor fields (q2 = 0.724, r2 =0.960). The structural requirements for substituted 2,4-diamino-7-aminoalkoxyquinazoline for G9a inhibitory activity can be obtained by analysing the COMSIA plots. Based on the information, six novel follow-up analogs were designed.

A Self-Instructional Approach To the Teaching of Enzymology Involving Computer-Based Sequence Analysis and Molecular Modelling.

ERIC Educational Resources Information Center

Attwood, Paul V.

1997-01-01

Describes a self-instructional assignment approach to the teaching of advanced enzymology. Presents an assignment that offers a means of teaching enzymology to students that exposes them to modern computer-based techniques of analyzing protein structure and relates structure to enzyme function. (JRH)

Confirmation of hybrid origin of Cyrtanthus based on the sequence analysis of internal transcribed spacer

USDA-ARS?s Scientific Manuscript database

The objectives of this study were to create interspecific hybrids between Cyrtanthus elatus and C. sanguineus and to confirm the hybrid origin of the progeny based on morphological characters and using molecular markers. The tip of the leaves, the shape and size of cells, and stomata distribution i...

Using Computer-Based "Experiments" in the Analysis of Chemical Reaction Equilibria

ERIC Educational Resources Information Center

Li, Zhao; Corti, David S.

2018-01-01

The application of the Reaction Monte Carlo (RxMC) algorithm to standard textbook problems in chemical reaction equilibria is discussed. The RxMC method is a molecular simulation algorithm for studying the equilibrium properties of reactive systems, and therefore provides the opportunity to develop computer-based "experiments" for the…

Ambient Molecular Analysis of Biological Tissue Using Low-Energy, Femtosecond Laser Vaporization and Nanospray Postionization Mass Spectrometry

NASA Astrophysics Data System (ADS)

Shi, Fengjian; Flanigan, Paul M.; Archer, Jieutonne J.; Levis, Robert J.

2016-03-01

Direct analysis of plant and animal tissue samples by laser electrospray mass spectrometry (LEMS) was investigated using low-energy, femtosecond duration laser vaporization at wavelengths of 800 and 1042 nm followed by nanospray postionization. Low-energy (<50 μJ), fiber-based 1042 nm LEMS (F-LEMS) allowed interrogation of the molecular species in fresh flower petal and leaf samples using 435 fs, 10 Hz bursts of 20 pulses from a Ytterbium-doped fiber laser and revealed comparable results to high energy (75-1120 μJ), 45 fs, 800 nm Ti:Sapphire-based LEMS (Ti:Sapphire-LEMS) measurements. Anthocyanins, sugars, and other metabolites were successfully detected and revealed the anticipated metabolite profile for the petal and leaf samples. Phospholipids, especially phosphatidylcholine, were identified from a fresh mouse brain section sample using Ti:Sapphire-LEMS without the application of matrix. These lipid features were suppressed in both the fiber-based and Ti:Sapphire-based LEMS measurements when the brain sample was prepared using the optimal cutting temperature compounds that are commonly used in animal tissue cryosections.

Ole e 13 is the unique food allergen in olive: Structure-functional, substrates docking, and molecular allergenicity comparative analysis.

PubMed

Jimenez-Lopez, J C; Robles-Bolivar, P; Lopez-Valverde, F J; Lima-Cabello, E; Kotchoni, S O; Alché, J D

2016-05-01

Thaumatin-like proteins (TLPs) are enzymes with important functions in pathogens defense and in the response to biotic and abiotic stresses. Last identified olive allergen (Ole e 13) is a TLP, which may also importantly contribute to food allergy and cross-allergenicity to pollen allergen proteins. The goals of this study are the characterization of the structural-functionality of Ole e 13 with a focus in its catalytic mechanism, and its molecular allergenicity by extensive analysis using different molecular computer-aided approaches covering a) functional-regulatory motifs, b) comparative study of linear sequence, 2-D and 3D structural homology modeling, c) molecular docking with two different β-D-glucans, d) conservational and evolutionary analysis, e) catalytic mechanism modeling, and f) IgE-binding, B- and T-cell epitopes identification and comparison to other allergenic TLPs. Sequence comparison, structure-based features, and phylogenetic analysis identified Ole e 13 as a thaumatin-like protein. 3D structural characterization revealed a conserved overall folding among plants TLPs, with mayor differences in the acidic (catalytic) cleft. Molecular docking analysis using two β-(1,3)-glucans allowed to identify fundamental residues involved in the endo-1,3-β-glucanase activity, and defining E84 as one of the conserved residues of the TLPs responsible of the nucleophilic attack to initiate the enzymatic reaction and D107 as proton donor, thus proposing a catalytic mechanism for Ole e 13. Identification of IgE-binding, B- and T-cell epitopes may help designing strategies to improve diagnosis and immunotherapy to food allergy and cross-allergenic pollen TLPs. Copyright © 2016 Elsevier Inc. All rights reserved.

Spectral analysis, vibrational assignments, NBO analysis, NMR, UV-Vis, hyperpolarizability analysis of 2-aminofluorene by density functional theory.

PubMed

Jone Pradeepa, S; Sundaraganesan, N

2014-05-05

In this present investigation, the collective experimental and theoretical study on molecular structure, vibrational analysis and NBO analysis has been reported for 2-aminofluorene. FT-IR spectrum was recorded in the range 4000-400 cm(-1). FT-Raman spectrum was recorded in the range 4000-50 cm(-1). The molecular geometry, vibrational spectra, and natural bond orbital analysis (NBO) were calculated for 2-aminofluorene using Density Functional Theory (DFT) based on B3LYP/6-31G(d,p) model chemistry. (13)C and (1)H NMR chemical shifts of 2-aminofluorene were calculated using GIAO method. The computed vibrational and NMR spectra were compared with the experimental results. The total energy distribution (TED) was derived to deepen the understanding of different modes of vibrations contributed by respective wavenumber. The experimental UV-Vis spectra was recorded in the region of 400-200 nm and correlated with simulated spectra by suitably solvated B3LYP/6-31G(d,p) model. The HOMO-LUMO energies were measured with time dependent DFT approach. The nonlinearity of the title compound was confirmed by hyperpolarizabilty examination. Using theoretical calculation Molecular Electrostatic Potential (MEP) was investigated. Copyright © 2014 Elsevier B.V. All rights reserved.

NbIT - A New Information Theory-Based Analysis of Allosteric Mechanisms Reveals Residues that Underlie Function in the Leucine Transporter LeuT

PubMed Central

LeVine, Michael V.; Weinstein, Harel

2014-01-01

Complex networks of interacting residues and microdomains in the structures of biomolecular systems underlie the reliable propagation of information from an input signal, such as the concentration of a ligand, to sites that generate the appropriate output signal, such as enzymatic activity. This information transduction often carries the signal across relatively large distances at the molecular scale in a form of allostery that is essential for the physiological functions performed by biomolecules. While allosteric behaviors have been documented from experiments and computation, the mechanism of this form of allostery proved difficult to identify at the molecular level. Here, we introduce a novel analysis framework, called N-body Information Theory (NbIT) analysis, which is based on information theory and uses measures of configurational entropy in a biomolecular system to identify microdomains and individual residues that act as (i)-channels for long-distance information sharing between functional sites, and (ii)-coordinators that organize dynamics within functional sites. Application of the new method to molecular dynamics (MD) trajectories of the occluded state of the bacterial leucine transporter LeuT identifies a channel of allosteric coupling between the functionally important intracellular gate and the substrate binding sites known to modulate it. NbIT analysis is shown also to differentiate residues involved primarily in stabilizing the functional sites, from those that contribute to allosteric couplings between sites. NbIT analysis of MD data thus reveals rigorous mechanistic elements of allostery underlying the dynamics of biomolecular systems. PMID:24785005

Molecular characterization of the vitamin D receptor (VDR) gene in Holstein cows.

PubMed

Ali, Mayar O; El-Adl, Mohamed A; Ibrahim, Hussam M M; Elseedy, Youssef Y; Rizk, Mohamed A; El-Khodery, Sabry A

2018-06-01

Vitamin D plays a vital role in calcium homeostasis, growth, and immunoregulation. Because little is known about the vitamin D receptor (VDR) gene in cattle, the aim of the present investigation was to present the molecular characterization of exons 5 and 6 of the VDR gene in Holstein cows. DNA extraction, genomic sequencing, phylogenetic analysis, synteny mapping and single nucleotide gene polymorphism analysis of the VDR gene were performed to assess blood samples collected from 50 clinically healthy Holstein cows. The results revealed the presence of a 450-base pair (bp) nucleotide sequence that resembled exons 5 and 6 with intron 5 enclosed between these exons. Sequence alignment and phylogenetic analysis revealed a close relationship between the sequenced VDR region and that found in Hereford cattle. A close association between this region and the corresponding region in small ruminants was also documented. Moreover, a single nucleotide polymorphism (SNP) that caused the replacement of a glutamate with an arginine in the deduced amino acid sequence was detected at position 7 of exon 5. In conclusion, Holstein and Hereford cattle differ with respect to exon 5 of the VDR gene. Phylogenetic analysis of the VDR gene based on nucleotide sequence produced different results from prior analyses based on amino acid sequence. Copyright © 2018 Elsevier Ltd. All rights reserved.

Toolbox Approaches Using Molecular Markers and 16S rRNA Gene Amplicon Data Sets for Identification of Fecal Pollution in Surface Water

PubMed Central

Staley, C.; Sadowsky, M. J.; Gyawali, P.; Sidhu, J. P. S.; Palmer, A.; Beale, D. J.; Toze, S.

2015-01-01

In this study, host-associated molecular markers and bacterial 16S rRNA gene community analysis using high-throughput sequencing were used to identify the sources of fecal pollution in environmental waters in Brisbane, Australia. A total of 92 fecal and composite wastewater samples were collected from different host groups (cat, cattle, dog, horse, human, and kangaroo), and 18 water samples were collected from six sites (BR1 to BR6) along the Brisbane River in Queensland, Australia. Bacterial communities in the fecal, wastewater, and river water samples were sequenced. Water samples were also tested for the presence of bird-associated (GFD), cattle-associated (CowM3), horse-associated, and human-associated (HF183) molecular markers, to provide multiple lines of evidence regarding the possible presence of fecal pollution associated with specific hosts. Among the 18 water samples tested, 83%, 33%, 17%, and 17% were real-time PCR positive for the GFD, HF183, CowM3, and horse markers, respectively. Among the potential sources of fecal pollution in water samples from the river, DNA sequencing tended to show relatively small contributions from wastewater treatment plants (up to 13% of sequence reads). Contributions from other animal sources were rarely detected and were very small (<3% of sequence reads). Source contributions determined via sequence analysis versus detection of molecular markers showed variable agreement. A lack of relationships among fecal indicator bacteria, host-associated molecular markers, and 16S rRNA gene community analysis data was also observed. Nonetheless, we show that bacterial community and host-associated molecular marker analyses can be combined to identify potential sources of fecal pollution in an urban river. This study is a proof of concept, and based on the results, we recommend using bacterial community analysis (where possible) along with PCR detection or quantification of host-associated molecular markers to provide information on the sources of fecal pollution in waterways. PMID:26231650

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

PubMed

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

2015-01-01

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

Number and brightness image analysis reveals ATF-induced dimerization kinetics of uPAR in the cell membrane

PubMed Central

Hellriegel, Christian; Caiolfa, Valeria R.; Corti, Valeria; Sidenius, Nicolai; Zamai, Moreno

2011-01-01

We studied the molecular forms of the GPI-anchored urokinase plasminogen activator receptor (uPAR-mEGFP) in the human embryo kidney (HEK293) cell membrane and demonstrated that the binding of the amino-terminal fragment (ATF) of urokinase plasminogen activator is sufficient to induce the dimerization of the receptor. We followed the association kinetics and determined precisely the dimeric stoichiometry of uPAR-mEGFP complexes by applying number and brightness (N&B) image analysis. N&B is a novel fluctuation-based approach for measuring the molecular brightness of fluorophores in an image time sequence in live cells. Because N&B is very sensitive to long-term temporal fluctuations and photobleaching, we have introduced a filtering protocol that corrects for these important sources of error. Critical experimental parameters in N&B analysis are illustrated and analyzed by simulation studies. Control experiments are based on mEGFP-GPI, mEGFP-mEGFP-GPI, and mCherry-GPI, expressed in HEK293. This work provides a first direct demonstration of the dimerization of uPAR in live cells. We also provide the first methodological guide on N&B to discern minor changes in molecular composition such as those due to dimerization events, which are involved in fundamental cell signaling mechanisms.—Hellriegel, C., Caiolfa, V. R., Corti, V., Sidenius, N., Zamai, M. Number and brightness image analysis reveals ATF-induced dimerization kinetics of uPAR in the cell membrane. PMID:21602447

Conformational stability, vibrational spectra, molecular structure, NBO and HOMO-LUMO analysis of 5-nitro-2-furaldehyde oxime based on DFT calculations.

PubMed

Arivazhagan, M; Jeyavijayan, S; Geethapriya, J

2013-03-01

The FTIR and FT-Raman spectra of 5-nitro-2-furaldehyde oxime (NFAO) have been recorded in the regions 4000-400 cm(-1) and 3500-50 cm(-1), respectively. The total energies of different conformations have been obtained from DFT (B3LYP) with 6-311++G(d,p) basis set calculations. The computational results identify the most stable conformer of NFAO as the C1 form. Utilizing the observed FTIR and FT-Raman data, a complete vibrational assignment and analysis of the fundamental modes of the compound were carried out. The optimum molecular geometry, harmonic vibrational frequencies, infrared intensities and Raman scattering activities, were calculated by density functional theory (DFT/B3LYP) method with 6-31+G(d,p) and 6-311++G(d,p) basis sets. The difference between the observed and scaled wavenumber values of most of the fundamentals is very small. A detailed interpretation of the infrared and Raman spectra of NFAO is also reported based on total energy distribution (TED). Stability of the molecule arising from hyperconjugative interactions, charge delocalization have been analyzed using natural bond orbital (NBO) analysis. Besides, molecular electrostatic potential (MEP), HOMO and LUMO analysis, and several thermodynamic properties were performed by the DFT method. Mulliken's net charges have been calculated and compared with the natural atomic charges. Ultraviolet-visible spectrum of the title molecule has also been calculated using TD-DFT method. Copyright © 2012 Elsevier B.V. All rights reserved.

Discovery of novel DAPY-IAS hybrid derivatives as potential HIV-1 inhibitors using molecular hybridization based on crystallographic overlays.

PubMed

Huang, Boshi; Wang, Xueshun; Liu, Xinhao; Chen, Zihui; Li, Wanzhuo; Sun, Songkai; Liu, Huiqing; Daelemans, Dirk; De Clercq, Erik; Pannecouque, Christophe; Zhan, Peng; Liu, Xinyong

2017-08-15

Crystallographic overlap studies and pharmacophoric analysis indicated that diarylpyrimidine (DAPY)-based HIV-1 NNRTIs showed a similar binding mode and pharmacophoric features as indolylarylsulfones (IASs), another class of potent NNRTIs. Thus, a novel series of DAPY-IAS hybrid derivatives were identified as newer NNRTIs using structure-based molecular hybridization. Some target compounds exhibited moderate activities against HIV-1 IIIB strain, among which the two most potent inhibitors possessed EC 50 values of 1.48μM and 1.61μM, respectively. They were much potent than the reference drug ddI (EC 50 =76.0μM) and comparable to 3TC (EC 50 =2.54μM). Compound 7a also exhibited the favorable selectivity index (SI=80). Preliminary structure-activity relationships (SARs), structure-cytotoxicity relationships, molecular modeling studies, and in silico calculation of physicochemical properties of these new inhibitors were also discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

New Aspects in the Differential Diagnosis and Therapy of Bladder Pain Syndrome/Interstitial Cystitis

PubMed Central

Neuhaus, Jochen; Schwalenberg, Thilo; Horn, Lars-Christian; Alexander, Henry; Stolzenburg, Jens-Uwe

2011-01-01

Diagnosis of bladder pain syndrome/interstitial cystitis (BPS/IC) is presently based on mainly clinical symptoms. BPS/IC can be considered as a worst-case scenario of bladder overactivity of unknown origin, including bladder pain. Usually, patients are partially or completely resistant to anticholinergic therapy, and therapeutical options are especially restricted in case of BPS/IC. Therefore, early detection of patients prone to develop BPS/IC symptoms is essential for successful therapy. We propose extended diagnostics including molecular markers. Differential diagnosis should be based on three diagnostical “columns”: (i) clinical diagnostics, (ii) histopathology, and (iii) molecular diagnostics. Analysis of molecular alterations of receptor expression in detrusor smooth muscle cells and urothelial integrity is necessary to develop patient-tailored therapeutical concepts. Although more research is needed to elucidate the pathomechanisms involved, extended BPS/IC diagnostics could already be integrated into routine patient care, allowing evidence-based pharmacotherapy of patients with idiopathic bladder overactivity and BPS/IC. PMID:22028706

New aspects in the differential diagnosis and therapy of bladder pain syndrome/interstitial cystitis.

PubMed

Neuhaus, Jochen; Schwalenberg, Thilo; Horn, Lars-Christian; Alexander, Henry; Stolzenburg, Jens-Uwe

2011-01-01

Diagnosis of bladder pain syndrome/interstitial cystitis (BPS/IC) is presently based on mainly clinical symptoms. BPS/IC can be considered as a worst-case scenario of bladder overactivity of unknown origin, including bladder pain. Usually, patients are partially or completely resistant to anticholinergic therapy, and therapeutical options are especially restricted in case of BPS/IC. Therefore, early detection of patients prone to develop BPS/IC symptoms is essential for successful therapy. We propose extended diagnostics including molecular markers. Differential diagnosis should be based on three diagnostical "columns": (i) clinical diagnostics, (ii) histopathology, and (iii) molecular diagnostics. Analysis of molecular alterations of receptor expression in detrusor smooth muscle cells and urothelial integrity is necessary to develop patient-tailored therapeutical concepts. Although more research is needed to elucidate the pathomechanisms involved, extended BPS/IC diagnostics could already be integrated into routine patient care, allowing evidence-based pharmacotherapy of patients with idiopathic bladder overactivity and BPS/IC.

Ultrasonic promoted synthesis of novel s-triazine-Schiff base derivatives; molecular structure, spectroscopic studies and their preliminary anti-proliferative activities

NASA Astrophysics Data System (ADS)

El-Faham, Ayman; Soliman, Saied M.; Ghabbour, Hazem A.; Elnakady, Yasser A.; Mohaya, Talal A.; Siddiqui, Mohammed R. H.; Albericio, Fernando

2016-12-01

Novel series of s-triazine-Schiff base derivatives were synthesized employing ultrasonic irradiation and characterized by NMR (1H and 13C), FT-IR, and elemental analysis. The use of ultrasonic irradiation has allowed the preparation of the target products with better yields in shorter reaction time and excellent purities compared to the conventional heating. X-ray single crystal diffraction experiments verified the molecular structure of four from the new prepared s-triaizne-Schiff base derivatives. The molecular structures of the studied compounds are computerized using DFT/B3LYP method. The effects of substituent at the triazine and phenyl ring on the electronic and spectroscopic properties of the studied compounds were also investigated. The natural atomic charges showed that pipridino-s-triazine derivatives are richer in electrons than those having morpholino derivatives. The anti-proliferative effects for the prepared compounds were tested against three different cancer cell lines.

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

NASA Astrophysics Data System (ADS)

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

2016-11-01

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

Mathematical Justification of Expression-Based Pathway Activation Scoring (PAS).

PubMed

Aliper, Alexander M; Korzinkin, Michael B; Kuzmina, Natalia B; Zenin, Alexander A; Venkova, Larisa S; Smirnov, Philip Yu; Zhavoronkov, Alex A; Buzdin, Anton A; Borisov, Nikolay M

2017-01-01

Although modeling of activation kinetics for various cell signaling pathways has reached a high grade of sophistication and thoroughness, most such kinetic models still remain of rather limited practical value for biomedicine. Nevertheless, recent advancements have been made in application of signaling pathway science for real needs of prescription of the most effective drugs for individual patients. The methods for such prescription evaluate the degree of pathological changes in the signaling machinery based on two types of data: first, on the results of high-throughput gene expression profiling, and second, on the molecular pathway graphs that reflect interactions between the pathway members. For example, our algorithm OncoFinder evaluates the activation of molecular pathways on the basis of gene/protein expression data in the objects of the interest.Yet, the question of assessment of the relative importance for each gene product in a molecular pathway remains unclear unless one call for the methods of parameter sensitivity /stiffness analysis in the interactomic kinetic models of signaling pathway activation in terms of total concentrations of each gene product.Here we show two principal points: 1. First, the importance coefficients for each gene in pathways that were obtained using the extremely time- and labor-consuming stiffness analysis of full-scaled kinetic models generally differ from much easier-to-calculate expression-based pathway activation score (PAS) not more than by 30%, so the concept of PAS is kinetically justified. 2. Second, the use of pathway-based approach instead of distinct gene analysis, due to the law of large numbers, allows restoring the correlation between the similar samples that were examined using different transcriptome investigation techniques.

Cation solvation with quantum chemical effects modeled by a size-consistent multi-partitioning quantum mechanics/molecular mechanics method.

PubMed

Watanabe, Hiroshi C; Kubillus, Maximilian; Kubař, Tomáš; Stach, Robert; Mizaikoff, Boris; Ishikita, Hiroshi

2017-07-21

In the condensed phase, quantum chemical properties such as many-body effects and intermolecular charge fluctuations are critical determinants of the solvation structure and dynamics. Thus, a quantum mechanical (QM) molecular description is required for both solute and solvent to incorporate these properties. However, it is challenging to conduct molecular dynamics (MD) simulations for condensed systems of sufficient scale when adapting QM potentials. To overcome this problem, we recently developed the size-consistent multi-partitioning (SCMP) quantum mechanics/molecular mechanics (QM/MM) method and realized stable and accurate MD simulations, using the QM potential to a benchmark system. In the present study, as the first application of the SCMP method, we have investigated the structures and dynamics of Na + , K + , and Ca 2+ solutions based on nanosecond-scale sampling, a sampling 100-times longer than that of conventional QM-based samplings. Furthermore, we have evaluated two dynamic properties, the diffusion coefficient and difference spectra, with high statistical certainty. Furthermore the calculation of these properties has not previously been possible within the conventional QM/MM framework. Based on our analysis, we have quantitatively evaluated the quantum chemical solvation effects, which show distinct differences between the cations.

Geological dates and molecular rates: rapid divergence of rivers and their biotas.

PubMed

Waters, Jonathan M; Rowe, Diane L; Apte, Smita; King, Tania M; Wallis, Graham P; Anderson, Leigh; Norris, Richard J; Craw, Dave; Burridge, Christopher P

2007-04-01

We highlight a novel molecular clock calibration system based on geologically dated river reversal and river capture events. Changes in drainage pattern may effect vicariant isolation of freshwater taxa, and thus provide a predictive framework for associated phylogeographic study. As a case in point, New Zealand's Pelorus and Kaituna rivers became geologically isolated from the larger Wairau River system 70 to 130 kyr BP. We conducted mitochondrial DNA phylogeographic analyses of two unrelated freshwater-limited fish taxa native to these river systems (Gobiomorphus breviceps, n = 63; Galaxias divergens, n = 95). Phylogenetic analysis of combined control region and cytochrome b sequences yielded reciprocally monophyletic clades of Pelorus-Kaituna and Wairau haplotypes for each species. Calibrated rates of molecular change based on this freshwater vicariant event are substantially faster than traditionally accepted rates for fishes but consistent with other recent inferences based on geologically young calibration points. A survey of freshwater phylogeographic literature reveals numerous examples in which the ages of recent evolutionary events may have been substantially overestimated through the use of "accepted" calibrations. We recommend that--wherever possible--biologists should start to reassess the conclusions of such studies by using more appropriate molecular calibrations derived from recent geological events.

Smartphone-Based Mobile Detection Platform for Molecular Diagnostics and Spatiotemporal Disease Mapping.

PubMed

Song, Jinzhao; Pandian, Vikram; Mauk, Michael G; Bau, Haim H; Cherry, Sara; Tisi, Laurence C; Liu, Changchun

2018-04-03

Rapid and quantitative molecular diagnostics in the field, at home, and at remote clinics is essential for evidence-based disease management, control, and prevention. Conventional molecular diagnostics requires extensive sample preparation, relatively sophisticated instruments, and trained personnel, restricting its use to centralized laboratories. To overcome these limitations, we designed a simple, inexpensive, hand-held, smartphone-based mobile detection platform, dubbed "smart-connected cup" (SCC), for rapid, connected, and quantitative molecular diagnostics. Our platform combines bioluminescent assay in real-time and loop-mediated isothermal amplification (BART-LAMP) technology with smartphone-based detection, eliminating the need for an excitation source and optical filters that are essential in fluorescent-based detection. The incubation heating for the isothermal amplification is provided, electricity-free, with an exothermic chemical reaction, and incubation temperature is regulated with a phase change material. A custom Android App was developed for bioluminescent signal monitoring and analysis, target quantification, data sharing, and spatiotemporal mapping of disease. SCC's utility is demonstrated by quantitative detection of Zika virus (ZIKV) in urine and saliva and HIV in blood within 45 min. We demonstrate SCC's connectivity for disease spatiotemporal mapping with a custom-designed website. Such a smart- and connected-diagnostic system does not require any lab facilities and is suitable for use at home, in the field, in the clinic, and particularly in resource-limited settings in the context of Internet of Medical Things (IoMT).

Targeted DNA sequencing and in situ mutation analysis using mobile phone microscopy

NASA Astrophysics Data System (ADS)

Kühnemund, Malte; Wei, Qingshan; Darai, Evangelia; Wang, Yingjie; Hernández-Neuta, Iván; Yang, Zhao; Tseng, Derek; Ahlford, Annika; Mathot, Lucy; Sjöblom, Tobias; Ozcan, Aydogan; Nilsson, Mats

2017-01-01

Molecular diagnostics is typically outsourced to well-equipped centralized laboratories, often far from the patient. We developed molecular assays and portable optical imaging designs that permit on-site diagnostics with a cost-effective mobile-phone-based multimodal microscope. We demonstrate that targeted next-generation DNA sequencing reactions and in situ point mutation detection assays in preserved tumour samples can be imaged and analysed using mobile phone microscopy, achieving a new milestone for tele-medicine technologies.

Observing interactions between DNA bases using ion dip spectroscopy.

NASA Astrophysics Data System (ADS)

Vries Mattanjah, De

2002-03-01

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

Morphology and Molecular Phylogeny of Raillietina spp. (Cestoda: Cyclophyllidea: Davaineidae) from Domestic Chickens in Thailand.

PubMed

Butboonchoo, Preeyaporn; Wongsawad, Chalobol; Rojanapaibul, Amnat; Chai, Jong-Yil

2016-12-01

Raillietina species are prevalent in domestic chickens ( Gallus gallus domesticus ) in Phayao province, northern Thailand. Their infection may cause disease and death, which affects the public health and economic situation in chicken farms. The identification of Raillietina has been based on morphology and molecular analysis. In this study, morphological observations using light (LM) and scanning electron microscopies (SEM) coupled with molecular analysis of the internal transcribed spacer 2 (ITS2) region and the nicotinamide adenine dinucleotide dehydrogenase subunit 1 (ND1) gene were employed for precise identification and phylogenetic relationship studies of Raillietina spp. Four Raillietina species, including R. echinobothrida, R. tetragona, R. cesticillus , and Raillietina sp., were recovered in domestic chickens from 4 districts in Phayao province, Thailand. LM and SEM observations revealed differences in the morphology of the scolex, position of the genital pore, number of eggs per egg capsule, and rostellar opening surface structures in all 4 species. Phylogenetic relationships were found among the phylogenetic trees obtained by the maximum likelihood and distance-based neighbor-joining methods. ITS2 and ND1 sequence data recorded from Raillietina sp. appeared to be monophyletic. The query sequences of R. echinobothrida, R. tetragona, R. cesticillus , and Raillietina sp. were separated according to the different morphological characters. This study confirmed that morphological studies combined with molecular analyses can differentiate related species within the genus Raillietina in Thailand.

Molecular docking, spectroscopic studies and quantum calculations on nootropic drug.

PubMed

Uma Maheswari, J; Muthu, S; Sundius, Tom

2014-04-05

A systematic vibrational spectroscopic assignment and analysis of piracetam [(2-oxo-1-pyrrolidineacetamide)] have been carried out using FT-IR and FT-Raman spectral data. The vibrational analysis was aided by an electronic structure calculation based on the hybrid density functional method B3LYP using a 6-311G++(d,p) basis set. Molecular equilibrium geometries, electronic energies, IR and Raman intensities, and harmonic vibrational frequencies have been computed. The assignments are based on the experimental IR and Raman spectra, and a complete assignment of the observed spectra has been proposed. The UV-visible spectrum of the compound was recorded and the electronic properties, such as HOMO and LUMO energies and the maximum absorption wavelengths λmax were determined by the time-dependent DFT (TD-DFT) method. The geometrical parameters, vibrational frequencies and absorption wavelengths were compared with the experimental data. The complete vibrational assignments are performed on the basis of the potential energy distributions (PED) of the vibrational modes in terms of natural internal coordinates. The simulated FT-IR, FT-Raman, and UV spectra of the title compound have been constructed. Molecular docking studies have been carried out in the active site of piracetam by using Argus Lab. In addition, the potential energy surface, HOMO and LUMO energies, first-order hyperpolarizability and the molecular electrostatic potential have been computed. Copyright © 2014 Elsevier B.V. All rights reserved.

Morphology and Molecular Phylogeny of Raillietina spp. (Cestoda: Cyclophyllidea: Davaineidae) from Domestic Chickens in Thailand

PubMed Central

Butboonchoo, Preeyaporn; Wongsawad, Chalobol; Rojanapaibul, Amnat; Chai, Jong-Yil

2016-01-01

Raillietina species are prevalent in domestic chickens (Gallus gallus domesticus) in Phayao province, northern Thailand. Their infection may cause disease and death, which affects the public health and economic situation in chicken farms. The identification of Raillietina has been based on morphology and molecular analysis. In this study, morphological observations using light (LM) and scanning electron microscopies (SEM) coupled with molecular analysis of the internal transcribed spacer 2 (ITS2) region and the nicotinamide adenine dinucleotide dehydrogenase subunit 1 (ND1) gene were employed for precise identification and phylogenetic relationship studies of Raillietina spp. Four Raillietina species, including R. echinobothrida, R. tetragona, R. cesticillus, and Raillietina sp., were recovered in domestic chickens from 4 districts in Phayao province, Thailand. LM and SEM observations revealed differences in the morphology of the scolex, position of the genital pore, number of eggs per egg capsule, and rostellar opening surface structures in all 4 species. Phylogenetic relationships were found among the phylogenetic trees obtained by the maximum likelihood and distance-based neighbor-joining methods. ITS2 and ND1 sequence data recorded from Raillietina sp. appeared to be monophyletic. The query sequences of R. echinobothrida, R. tetragona, R. cesticillus, and Raillietina sp. were separated according to the different morphological characters. This study confirmed that morphological studies combined with molecular analyses can differentiate related species within the genus Raillietina in Thailand. PMID:28095663

CL-20/DNB co-crystal based PBX with PEG: molecular dynamics simulation

NASA Astrophysics Data System (ADS)

Zhang, Jiang; Gao, Pei; Xiao, Ji Jun; Zhao, Feng; Xiao, He Ming

2016-12-01

Molecular dynamics simulation was carried out for CL-20/DNB co-crystal based PBX (polymer-bonded explosive) blended with polymer PEG (polyethylene glycol). In this paper, the miscibility of the PBX models is investigated through the calculated binding energy. Pair correlation function (PCF) analysis is applied to study the interaction of the interface structures in the PBX models. The mechanical properties of PBXs are also discussed to understand the change of the mechanical properties after adding the polymer. Moreover, the calculated diffusion coefficients of the interfacial explosive molecules are used to discuss the dispersal ability of CL-20 and DNB molecules in the interface layer.

Lab Plays Central Role in Groundbreaking National Clinical Trial in Precision Medicine | Poster

Cancer.gov

The Molecular Characterization Laboratory lies at the heart of an ambitious new approach for testing cancer drugs that will use the newest tools of precision medicine to select the best treatment for individual patients based on the genetic makeup of their tumors. The protocol, called NCI-Molecular Analysis for Therapy Choice (NCI-MATCH), will start with tumor biopsies from as many as 3,000 patients to see if they have genetic defects for which a targeted cancer drug is available. Cancers will be treated based on their genetic profiles rather than by their location in the body, which is the conventional approach.

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

Rizzi, Silvio; Hereld, Mark; Insley, Joseph

In this work we perform in-situ visualization of molecular dynamics simulations, which can help scientists to visualize simulation output on-the-fly, without incurring storage overheads. We present a case study to couple LAMMPS, the large-scale molecular dynamics simulation code with vl3, our parallel framework for large-scale visualization and analysis. Our motivation is to identify effective approaches for covisualization and exploration of large-scale atomistic simulations at interactive frame rates.We propose a system of coupled libraries and describe its architecture, with an implementation that runs on GPU-based clusters. We present the results of strong and weak scalability experiments, as well as future researchmore » avenues based on our results.« less

Integration of next-generation sequencing in clinical diagnostic molecular pathology laboratories for analysis of solid tumours; an expert opinion on behalf of IQN Path ASBL.

PubMed

Deans, Zandra C; Costa, Jose Luis; Cree, Ian; Dequeker, Els; Edsjö, Anders; Henderson, Shirley; Hummel, Michael; Ligtenberg, Marjolijn Jl; Loddo, Marco; Machado, Jose Carlos; Marchetti, Antonio; Marquis, Katherine; Mason, Joanne; Normanno, Nicola; Rouleau, Etienne; Schuuring, Ed; Snelson, Keeda-Marie; Thunnissen, Erik; Tops, Bastiaan; Williams, Gareth; van Krieken, Han; Hall, Jacqueline A

2017-01-01

The clinical demand for mutation detection within multiple genes from a single tumour sample requires molecular diagnostic laboratories to develop rapid, high-throughput, highly sensitive, accurate and parallel testing within tight budget constraints. To meet this demand, many laboratories employ next-generation sequencing (NGS) based on small amplicons. Building on existing publications and general guidance for the clinical use of NGS and learnings from germline testing, the following guidelines establish consensus standards for somatic diagnostic testing, specifically for identifying and reporting mutations in solid tumours. These guidelines cover the testing strategy, implementation of testing within clinical service, sample requirements, data analysis and reporting of results. In conjunction with appropriate staff training and international standards for laboratory testing, these consensus standards for the use of NGS in molecular pathology of solid tumours will assist laboratories in implementing NGS in clinical services.

Molecular systematics and global phylogeography of angel sharks (genus Squatina).

PubMed

Stelbrink, Björn; von Rintelen, Thomas; Cliff, Geremy; Kriwet, Jürgen

2010-02-01

Angel sharks of the genus Squatina represent a group comprising 22 extant benthic species inhabiting continental shelves and upper slopes. In the present study, a comprehensive phylogenetic reconstruction of 17 Squatina species based on two mitochondrial markers (COI and 16S rRNA) is provided. The phylogenetic reconstructions are used to test biogeographic patterns. In addition, a molecular clock analysis is conducted to estimate divergence times of the emerged clades. All analyses show Squatina to be monophyletic. Four geographic clades are recognized, of which the Europe-North Africa-Asia clade is probably a result of the Tethys Sea closure. A second sister group relationship emerged in the analyses, including S. californica (eastern North Pacific) and S. dumeril (western North Atlantic), probably related to the rise of the Panamanian isthmus. The molecular clock analysis show that both lineage divergences coincide with the estimated time of these two geological events. Copyright (c) 2009. Published by Elsevier Inc.

Molecular pathology and genetics of gastrointestinal neuroendocrine tumours.

PubMed

Lewis, Mark A; Yao, James C

2014-02-01

Neuroendocrine tumours (NETs) of the luminal gastrointestinal tract and pancreas are increasing in incidence and prevalence. Prior assumptions about the benign nature of 'carcinoids' and the clinical importance of distinguishing functional vs. nonfunctional tumours are being overturned through greater understanding of disease behaviour and heterogeneity. This review highlights the most contemporary genetic and molecular insights into gastroenteropancreatic NETs. Biomarkers such as neuron-specific enolase or chromogranin A could be supplemented or supplanted by PCR-based analysis of NET genes detectable in the blood transcriptome. Conventional pathology, including Ki67 testing, could be enhanced with immunohistochemistry and exome analysis. Prognostic markers and/or putative therapeutic targets uncovered through recent studies include heparanase, Id, ATM, SRC, EGFR, hsp90 and PDGFR. After a long-standing paucity of options for conventional cytotoxic therapy, the comprehension and treatment of gastroenteropancreatic NETs has been enriched by advancements in taxonomy, molecular pathology and genetic/epigenetic testing.

Quantitative profiling of immune repertoires for minor lymphocyte counts using unique molecular identifiers.

PubMed

Egorov, Evgeny S; Merzlyak, Ekaterina M; Shelenkov, Andrew A; Britanova, Olga V; Sharonov, George V; Staroverov, Dmitriy B; Bolotin, Dmitriy A; Davydov, Alexey N; Barsova, Ekaterina; Lebedev, Yuriy B; Shugay, Mikhail; Chudakov, Dmitriy M

2015-06-15

Emerging high-throughput sequencing methods for the analyses of complex structure of TCR and BCR repertoires give a powerful impulse to adaptive immunity studies. However, there are still essential technical obstacles for performing a truly quantitative analysis. Specifically, it remains challenging to obtain comprehensive information on the clonal composition of small lymphocyte populations, such as Ag-specific, functional, or tissue-resident cell subsets isolated by sorting, microdissection, or fine needle aspirates. In this study, we report a robust approach based on unique molecular identifiers that allows profiling Ag receptors for several hundred to thousand lymphocytes while preserving qualitative and quantitative information on clonal composition of the sample. We also describe several general features regarding the data analysis with unique molecular identifiers that are critical for accurate counting of starting molecules in high-throughput sequencing applications. Copyright © 2015 by The American Association of Immunologists, Inc.

Molecular characterization of natural orchid in South slopes of Mount Merapi, Sleman regency, Yogyakarta

NASA Astrophysics Data System (ADS)

Ferdiani, Defika I.; Devi, Fera L.; Koentjana, Johan P.; Milasari, Asri F.; Nur'aini, Indah; Semiarti, Endang

2015-09-01

Natural orchid is one of the most important tropical biodiversity. In Indonesia there are ± 6000 species out of 30000 orchids species in the world, of which there are ± 60 species at Mount Merapi. Repetitive eruption of Merapi have wiped out the biodiversity of orchids, therefore the efforts to conserve the orchids and to establish the database of natural orchids in Mount Merapi are needed. The orchid's database can be created based on DNA analysis, and establish barcoding DNA. DNA-barcodes can be used as molecular markers. The different character of morphology usually shows different pattern in DNA fragments. This research aims to characterize the phenotype and genotype of natural orchids of Mt. Merapi based on morphology and the structure of DNA in trnL-F intergenic region of chloroplasts DNA of orchid. Amplified Fragment Length Polymorphism (AFLP) technique was used to characterize the molecular types of orchids in silico of intergenic space area of orchid chloroplast. In this study, 11 species of orchids were characterized based on morphological and molecular characters. The molecular characters were obtained from trnL-F intergenic region of leaves chloroplasts. The data indicates that there is a conserve DNA pattern in all orchids and the distinctive characters of some orchids. In this study, based on trnL-F intergenic region of chloroplast genome, the phylogenetic tree revealed that 11 species of orchids at Mt. Merapi can be grouped into 2 clades, that matched with morphological characters.

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

Mass Spectrometry-based Approaches to Understand the Molecular Basis of Memory

NASA Astrophysics Data System (ADS)

Pontes, Arthur; de Sousa, Marcelo

2016-10-01

The central nervous system is responsible for an array of cognitive functions such as memory, learning, language and attention. These processes tend to take place in distinct brain regions; yet, they need to be integrated to give rise to adaptive or meaningful behavior. Since cognitive processes result from underlying cellular and molecular changes, genomics and transcriptomics assays have been applied to human and animal models to understand such events. Nevertheless, genes and RNAs are not the end products of most biological functions. In order to gain further insights toward the understanding of brain processes, the field of proteomics has been of increasing importance in the past years. Advancements in liquid chromatography-tandem mass spectrometry (LC-MS/MS) have enable the identification and quantification of thousand of proteins with high accuracy and sensitivity, fostering a revolution in the neurosciences. Herein, we review the molecular bases of explicit memory in the hippocampus. We outline the principles of mass spectrometry (MS)-based proteomics, highlighting the use of this analytical tool to study memory formation. In addition, we discuss MS-based targeted approaches as the future of protein analysis.

Molecularly imprinted polymeric stir bar: Preparation and application for the determination of naftopidil in plasma and urine samples.

PubMed

Peng, Jun; Xiao, Deli; He, Hua; Zhao, Hongyan; Wang, Cuixia; Shi, Tian; Shi, Kexin

2016-01-01

In this study, molecularly imprinting technology and stir bar absorption technology were combined to develop a microextraction approach based on a molecularly imprinted polymeric stir bar. The molecularly imprinted polymer stir bar has a high performance, is specific, economical, and simple to prepare. The obtained naftopidil-imprinted polymer-coated bars could simultaneously agitate and adsorb naftopidil in the sample solution. The ratio of template/monomer/cross-linker and conditions of template removal were optimized to prepare a stir bar with highly efficient adsorption. Fourier transform infrared spectroscopy, scanning electron microscopy, selectivity, and extraction capacity experiments showed that the molecularly imprinted polymer stir bar was prepared successfully. To utilize the molecularly imprinted polymer stir bar for the determination of naftopidil in complex body fluid matrices, the extraction time, stirring speed, eluent, and elution time were optimized. The limits of detection of naftopidil in plasma and urine sample were 7.5 and 4.0 ng/mL, respectively, and the recoveries were in the range of 90-112%. The within-run precision and between-run precision were acceptable (relative standard deviation <7%). These data demonstrated that the molecularly imprinted polymeric stir bar based microextraction with high-performance liquid chromatography was a convenient, rapid, efficient, and specific method for the precise determination of trace naftopidil in clinical analysis. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

New Insights for Diagnosis of Pineapple Fusariosis by MALDI-TOF MS Technique.

PubMed

Santos, Cledir; Ventura, José Aires; Lima, Nelson

2016-08-01

Fusarium is one of the most economically important fungal genus, since it includes many pathogenic species which cause a wide range of plant diseases. Morphological or molecular biology identification of Fusarium species is a limiting step in the fast diagnosis and treatment of plant disease caused by these fungi. Mass spectrometry by matrix-assisted laser/desorption ionisation-time-of-flight (MALDI-TOF)-based fingerprinting approach was applied to the fungal growth monitoring and direct detection of strain Fusarium guttiforme E-480 inoculated in both pineapple cultivars Pérola and Imperial side shoots, that are susceptible and resistant, respectively, to this fungal strain. MALDI-TOF MS technique was capable to detect fungal molecular mass peaks in the susceptible pineapple stem side shoot tissue. It is assumed that these molecular masses are mainly constituted by ribosomal proteins. MALDI-TOF-based fingerprinting approach has herein been demonstrated to be sensitive and accurate for the direct detection of F. guttiforme E-480 molecular masses on both susceptible and resistant pineapple side stem free of any pre-treatment. According to the results obtained, the changing on molecular mass peaks of infected susceptible pineapple tissue together with the possibility of fungal molecular masses analysis into this pineapple tissue can be a good indication for an early diagnosis by MALDI-TOF MS of pineapple fusariosis.

Potential human cholesterol esterase inhibitor design: benefits from the molecular dynamics simulations and pharmacophore modeling studies.

PubMed

John, Shalini; Thangapandian, Sundarapandian; Lee, Keun Woo

2012-01-01

Human pancreatic cholesterol esterase (hCEase) is one of the lipases found to involve in the digestion of large and broad spectrum of substrates including triglycerides, phospholipids, cholesteryl esters, etc. The presence of bile salts is found to be very important for the activation of hCEase. Molecular dynamic simulations were performed for the apoform and bile salt complexed form of hCEase using the co-ordinates of two bile salts from bovine CEase. The stability of the systems throughout the simulation time was checked and two representative structures from the highly populated regions were selected using cluster analysis. These two representative structures were used in pharmacophore model generation. The generated pharmacophore models were validated and used in database screening. The screened hits were refined for their drug-like properties based on Lipinski's rule of five and ADMET properties. The drug-like compounds were further refined by molecular docking simulation using GOLD program based on the GOLD fitness score, mode of binding, and molecular interactions with the active site amino acids. Finally, three hits of novel scaffolds were selected as potential leads to be used in novel and potent hCEase inhibitor design. The stability of binding modes and molecular interactions of these final hits were re-assured by molecular dynamics simulations.

Biomimetic Molecular Signaling using DNA Walkers on Microparticles.

PubMed

Damase, Tulsi Ram; Spencer, Adam; Samuel, Bamidele; Allen, Peter B

2017-06-22

We report the release of catalytic DNA walkers from hydrogel microparticles and the detection of those walkers by substrate-coated microparticles. This might be considered a synthetic biology analog of molecular signal release and reception. One type of particles was coated with components of a DNA one-step strand displacement (OSD) reaction to release the walker. A second type of particle was coated with substrate (or "track") for the molecular walker. We distinguish these particle types using fluorescence barcoding: we synthesized and distinguished multiple particle types with multicolor fluorescence microscopy and automated image analysis software. This represents a step toward amplified, multiplex, and microscopically localized detection based on DNA nanotechnology.

Energy Storage Analysis of a Mixed R161/MOF-5 Nanoparticle Nanofluid Based on Molecular Simulations

PubMed Central

Wang, Qiang; Tang, Shengli; Li, Leilei

2018-01-01

The thermal properties of refrigerants can be modified by adding porous nanoparticles into them. Here, molecular simulations, including molecular dynamics and grand canonical Monte Carlo, were employed to study the thermal energy storage properties of an R161/MOF-5 nanofluid. The results show that the thermodynamic energy change of MOF-5 nanoparticles is linear to the temperature. The adsorption heat calculated by grand canonical Monte Carlo is close to that calculated by the Clausius–Clapeyron equation. Additionally, a negative enhancement of the thermal energy storage capacity of the R161/MOF-5 nanofluid is found near the phase transition area. PMID:29783773

Energy Storage Analysis of a Mixed R161/MOF-5 Nanoparticle Nanofluid Based on Molecular Simulations.

PubMed

Wang, Qiang; Tang, Shengli; Li, Leilei

2018-05-20

The thermal properties of refrigerants can be modified by adding porous nanoparticles into them. Here, molecular simulations, including molecular dynamics and grand canonical Monte Carlo, were employed to study the thermal energy storage properties of an R161/MOF-5 nanofluid. The results show that the thermodynamic energy change of MOF-5 nanoparticles is linear to the temperature. The adsorption heat calculated by grand canonical Monte Carlo is close to that calculated by the Clausius⁻Clapeyron equation. Additionally, a negative enhancement of the thermal energy storage capacity of the R161/MOF-5 nanofluid is found near the phase transition area.

Molecular dynamics simulation of siderite-hematite-quartz flotation with sodium oleate

NASA Astrophysics Data System (ADS)

Li, Lixia; Hao, Haiqing; Yuan, Zhitao; Liu, Jiongtian

2017-10-01

Models of sodium oleate adsorption on siderite, hematite and quartz were investigated by molecular dynamic simulation, respectively. Surface energy was calculated to confirm the cleavage plan of hematite and quartz. Both natural cleavage plane of siderite and calculated plane were used to investigate the flotation of the three minerals. Based on the molecular simulation in solution with water as medium, adsorption quantity and interaction capability of oleate ions on the three minerals indicated that siderite could be collected efficiently by sodium oleate at neutral pH. Results of flotation experiments were further demonstrated by analysis of relative concentration of carbon atoms and oxygen atoms.

Laser spectroscopic visualization of hydrogen bond motions in liquid water

NASA Astrophysics Data System (ADS)

Bratos, S.; Leicknam, J.-Cl.; Pommeret, S.; Gallot, G.

2004-12-01

Ultrafast pump-probe experiments are described permitting a visualization of molecular motions in diluted HDO/D 2O solutions. The experiments were realized in the mid-infrared spectral region with a time resolution of 150 fs. They were interpreted by a careful theoretical analysis, based on the correlation function approach of statistical mechanics. Combining experiment and theory, stretching motions of the OH⋯O bonds as well as HDO rotations were 'filmed' in real time. It was found that molecular rotations are the principal agent of hydrogen bond breaking and making in water. Recent literatures covering the subject, including molecular dynamics simulations, are reviewed in detail.

Density Functional Theory (DFT) Study of Molecularly Imprinted Polymer (MIP) Methacrylic Acid (MAA) with D-Glucose

NASA Astrophysics Data System (ADS)

Wungu, T. D. K.; Marsha, S. E.; Widayani; Suprijadi

2017-07-01

In order to find an alternative biosensor material which enables to detect the glucose level, therefore in this study, the interaction between Methacrylic Acid (MAA) based Molecularly Imprinted Polymer (MIP) with D-Glucose is investigated using the Density Functional Theory (DFT). The aim of this study is to determine whether a molecule of the MAA can be functioned as a bio-sensing of glucose. In this calculation, the Gaussian 09 with B3LYP and 631+G(d) basis sets is used to calculate all electronic properties. It is found that the interaction between a molecule of MAA and a molecule of D-Glucose was observed through the shortened distance between the two molecules. The binding energy of MAA/D-glucose and the Mulliken population analysis are investigated for checking possible interaction. From analysis, the MAA based MIP can be used as a bio-sensing material.

[Precision Oncology and "Molecular Tumor Boards" - Concepts, Chances and Challenges].

PubMed

Holch, Julian Walter; Westphalen, Christoph Benedikt; Hiddemann, Wolfgang; Heinemann, Volker; Jung, Andreas; Metzeler, Klaus Hans

2017-11-01

Recent developments in genomics allow a more and more comprehensive genetic analysis of human malignancies, and have sparked hopes that this will contribute to the development of novel targeted, effective and well-tolerated therapies.While targeted therapies have improved the prognosis of many cancer patients with certain tumor types, "precision oncology" also brings along new challenges. Highly personalized treatment strategies require new strategies for clinical trials and translation into routine clinical practice. We review the current technical approaches for "universal genetic testing" in cancer, and potential pitfalls in the interpretation of such data. We then provide an overview of the available evidence supporting treatment strategies based on extended genetic analysis. Based on the available data, we conclude that "precision oncology" approaches that go beyond the current standard of care should be pursued within the framework of an interdisciplinary "molecular tumor board", and preferably within clinical trials. © Georg Thieme Verlag KG Stuttgart · New York.

Exploring Wound-Healing Genomic Machinery with a Network-Based Approach

PubMed Central

Vitali, Francesca; Marini, Simone; Balli, Martina; Grosemans, Hanne; Sampaolesi, Maurilio; Lussier, Yves A.; Cusella De Angelis, Maria Gabriella; Bellazzi, Riccardo

2017-01-01

The molecular mechanisms underlying tissue regeneration and wound healing are still poorly understood despite their importance. In this paper we develop a bioinformatics approach, combining biology and network theory to drive experiments for better understanding the genetic underpinnings of wound healing mechanisms and for selecting potential drug targets. We start by selecting literature-relevant genes in murine wound healing, and inferring from them a Protein-Protein Interaction (PPI) network. Then, we analyze the network to rank wound healing-related genes according to their topological properties. Lastly, we perform a procedure for in-silico simulation of a treatment action in a biological pathway. The findings obtained by applying the developed pipeline, including gene expression analysis, confirms how a network-based bioinformatics method is able to prioritize candidate genes for in vitro analysis, thus speeding up the understanding of molecular mechanisms and supporting the discovery of potential drug targets. PMID:28635674

Expression microdissection adapted to commercial laser dissection instruments

PubMed Central

Hanson, Jeffrey C; Tangrea, Michael A; Kim, Skye; Armani, Michael D; Pohida, Thomas J; Bonner, Robert F; Rodriguez-Canales, Jaime; Emmert-Buck, Michael R

2016-01-01

Laser-based microdissection facilitates the isolation of specific cell populations from clinical or animal model tissue specimens for molecular analysis. Expression microdissection (xMD) is a second-generation technology that offers considerable advantages in dissection capabilities; however, until recently the method has not been accessible to investigators. This protocol describes the adaptation of xMD to commonly used laser microdissection instruments and to a commercially available handheld laser device in order to make the technique widely available to the biomedical research community. The method improves dissection speed for many applications by using a targeting probe for cell procurement in place of an operator-based, cell-by-cell selection process. Moreover, xMD can provide improved dissection precision because of the unique characteristics of film activation. The time to complete the protocol is highly dependent on the target cell population and the number of cells needed for subsequent molecular analysis. PMID:21412274

Chemical and protein structural basis for biological crosstalk between PPAR α and COX enzymes

NASA Astrophysics Data System (ADS)

Cleves, Ann E.; Jain, Ajay N.

2015-02-01

We have previously validated a probabilistic framework that combined computational approaches for predicting the biological activities of small molecule drugs. Molecule comparison methods included molecular structural similarity metrics and similarity computed from lexical analysis of text in drug package inserts. Here we present an analysis of novel drug/target predictions, focusing on those that were not obvious based on known pharmacological crosstalk. Considering those cases where the predicted target was an enzyme with known 3D structure allowed incorporation of information from molecular docking and protein binding pocket similarity in addition to ligand-based comparisons. Taken together, the combination of orthogonal information sources led to investigation of a surprising predicted relationship between a transcription factor and an enzyme, specifically, PPAR α and the cyclooxygenase enzymes. These predictions were confirmed by direct biochemical experiments which validate the approach and show for the first time that PPAR α agonists are cyclooxygenase inhibitors.

Use of SSR markers for DNA fingerprinting and diversity analysis of Pakistani sugarcane (Saccharum spp. hybrids) cultivars

USDA-ARS?s Scientific Manuscript database

In recent years SSR markers have been used widely for genetic analysis. The objective of this study was to use an SSR-based marker system to develop the molecular fingerprints and analyze the genetic relationship of sugarcane cultivars grown in Pakistan. Twenty-one highly polymorphic SSR markers wer...

Simulating an Investigative Study of Clinical Cancer Samples: Use of Tissue Slides and PCR-based Promoter-Hypermethylation Analysis

ERIC Educational Resources Information Center

Chew, Yuan Yuan; Chin, Cheen Fei; Yeong, Foong May

2015-01-01

Topics on the molecular basis underlying cancer are quite popular among students. Also, excellent textbooks abound that provide interesting materials for discussion during lectures and tutorials about major events leading to cancer formation and progression. However, much less is available for students to conduct experiments for the analysis of…

Real-world cost analysis of chemotherapy for colorectal cancer in Japan: detailed costs of various regimens during the entire course of chemotherapy.

PubMed

Yajima, Shuichi; Shimizu, Hisanori; Sakamaki, Hiroyuki; Ikeda, Shunya; Ikegami, Naoki; Murayama, Jun-Ichiro

2016-01-04

Various chemotherapy regimens for advanced colorectal cancer have been introduced to clinical practice in Japan over the past decade. The cost profiles of these regimens, however, remain unclear in Japan. To explore the detailed costs of different regimens used to treat advanced colorectal cancer during the entire course of chemotherapy in patients treated in a practical setting, we conducted a so-called "real-world" cost analysis. A detailed cost analysis was performed retrospectively. Patients with advanced colorectal cancer who had received chemotherapy in a practical healthcare setting from July 2004 through October 2010 were extracted from the ordering system database of Showa University Hospital. Direct medical costs of chemotherapy regimens were calculated from the hospital billing data of the patients. The analysis was conducted from a payer's perspective. A total of 30 patients with advanced colorectal cancer were identified. Twenty patients received up to second-line treatment, and 8 received up to third-line treatment. The regimens identified from among all courses of treatment in all patients were 13 oxaliplatin-based regimens, 31 irinotecan-based regimens, and 11 regimens including molecular targeted agents. The average (95% confidence interval [95% CI]) monthly cost during the overall period from the beginning of treatment to the end of treatment was 308,363 (258,792 to 357,933) Japanese yen (JPY). According to the type of regimen, the average monthly cost was 418,463 (357,413 to 479,513) JPY for oxaliplatin-based regimens, 215,499 (188,359 to 242,639) JPY for irinotecan-based regimens, and 705,460 (586,733 to 824,187) JPY for regimens including molecular targeted agents. Anticancer drug costs and hospital fees accounted for 50 to 77% and 11 to 25% of the overall costs of chemotherapy, respectively. The costs of irinotecan-based regimens were lower than those of oxaliplatin-based regimens and regimens including molecular targeted agents in Japan. Using a lower cost regimen for first-line treatment can potentially reduce the overall cost of chemotherapy. The main cost drivers were the anticancer drug costs and hospitalization costs.

Novel Molecular Method for Identification of Streptococcus pneumoniae Applicable to Clinical Microbiology and 16S rRNA Sequence-Based Microbiome Studies

PubMed Central

Scholz, Christian F. P.; Poulsen, Knud

2012-01-01

The close phylogenetic relationship of the important pathogen Streptococcus pneumoniae and several species of commensal streptococci, particularly Streptococcus mitis and Streptococcus pseudopneumoniae, and the recently demonstrated sharing of genes and phenotypic traits previously considered specific for S. pneumoniae hamper the exact identification of S. pneumoniae. Based on sequence analysis of 16S rRNA genes of a collection of 634 streptococcal strains, identified by multilocus sequence analysis, we detected a cytosine at position 203 present in all 440 strains of S. pneumoniae but replaced by an adenosine residue in all strains representing other species of mitis group streptococci. The S. pneumoniae-specific sequence signature could be demonstrated by sequence analysis or indirectly by restriction endonuclease digestion of a PCR amplicon covering the site. The S. pneumoniae-specific signature offers an inexpensive means for validation of the identity of clinical isolates and should be used as an integrated marker in the annotation procedure employed in 16S rRNA-based molecular studies of complex human microbiotas. This may avoid frequent misidentifications such as those we demonstrate to have occurred in previous reports and in reference sequence databases. PMID:22442329

Implementation of Cloud based next generation sequencing data analysis in a clinical laboratory.

PubMed

Onsongo, Getiria; Erdmann, Jesse; Spears, Michael D; Chilton, John; Beckman, Kenneth B; Hauge, Adam; Yohe, Sophia; Schomaker, Matthew; Bower, Matthew; Silverstein, Kevin A T; Thyagarajan, Bharat

2014-05-23

The introduction of next generation sequencing (NGS) has revolutionized molecular diagnostics, though several challenges remain limiting the widespread adoption of NGS testing into clinical practice. One such difficulty includes the development of a robust bioinformatics pipeline that can handle the volume of data generated by high-throughput sequencing in a cost-effective manner. Analysis of sequencing data typically requires a substantial level of computing power that is often cost-prohibitive to most clinical diagnostics laboratories. To address this challenge, our institution has developed a Galaxy-based data analysis pipeline which relies on a web-based, cloud-computing infrastructure to process NGS data and identify genetic variants. It provides additional flexibility, needed to control storage costs, resulting in a pipeline that is cost-effective on a per-sample basis. It does not require the usage of EBS disk to run a sample. We demonstrate the validation and feasibility of implementing this bioinformatics pipeline in a molecular diagnostics laboratory. Four samples were analyzed in duplicate pairs and showed 100% concordance in mutations identified. This pipeline is currently being used in the clinic and all identified pathogenic variants confirmed using Sanger sequencing further validating the software.

Synthesis, characterization, crystal structure and HSA binding of two new N,O,O-donor Schiff-base ligands derived from dihydroxybenzaldehyde and tert-butylamine

NASA Astrophysics Data System (ADS)

Khosravi, Iman; Hosseini, Farnaz; Khorshidifard, Mahsa; Sahihi, Mehdi; Rudbari, Hadi Amiri

2016-09-01

Two new o-hydroxy Schiff-bases compounds, L1 and L2, were derived from the 1:1 M condensation of 2,3-dihydroxybenzaldehyde and 2,4-dihydroxybenzaldehyde with tert-butylamine and were characterized by elemental analysis, FT-IR, 1H and 13C NMR spectroscopies. The crystal structure of L2 was also determined by single crystal X-ray analysis. The crystal structure of L2 showed that the compound exists as a zwitterionic form in the solid state, with the H atom of the phenol group being transferred to the imine N atom. It adopts an E configuration about the central Cdbnd N double bond. Furthermore, binding of these Schiff base ligands to Human Serum Albumin (HSA) was investigated by fluorescence quenching, absorption spectroscopy, molecular docking and molecular dynamics (MD) simulation methods. The fluorescence emission of HSA was quenched by ligands. Also, suitable models were used to analyze the UV-vis absorption spectroscopy data for titration of HSA solution by various amounts of Schiff bases. The spectroscopic studies revealed that these Schiff bases formed 1:1 complex with HSA. Energy transfer mechanism of quenching was discussed and the values of 3.35 and 1.57 nm as the mean distances between the bound ligands and the HSA were calculated for L1 and L2, respectively. Molecular docking results indicated that the main active binding site for these Schiff bases ligands is in subdomain IB. Moreover, MD simulation results suggested that this Schiff base complex can interact with HSA, with a slight modification of its tertiary structure.

Combined 3D-QSAR, molecular docking and molecular dynamics study on thyroid hormone activity of hydroxylated polybrominated diphenyl ethers to thyroid receptors β

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

Li, Xiaolin; Ye, Li; Wang, Xiaoxiang

2012-12-15

Several recent reports suggested that hydroxylated polybrominated diphenyl ethers (HO-PBDEs) may disturb thyroid hormone homeostasis. To illuminate the structural features for thyroid hormone activity of HO-PBDEs and the binding mode between HO-PBDEs and thyroid hormone receptor (TR), the hormone activity of a series of HO-PBDEs to thyroid receptors β was studied based on the combination of 3D-QSAR, molecular docking, and molecular dynamics (MD) methods. The ligand- and receptor-based 3D-QSAR models were obtained using Comparative Molecular Similarity Index Analysis (CoMSIA) method. The optimum CoMSIA model with region focusing yielded satisfactory statistical results: leave-one-out cross-validation correlation coefficient (q{sup 2}) was 0.571 andmore » non-cross-validation correlation coefficient (r{sup 2}) was 0.951. Furthermore, the results of internal validation such as bootstrapping, leave-many-out cross-validation, and progressive scrambling as well as external validation indicated the rationality and good predictive ability of the best model. In addition, molecular docking elucidated the conformations of compounds and key amino acid residues at the docking pocket, MD simulation further determined the binding process and validated the rationality of docking results. -- Highlights: ► The thyroid hormone activities of HO-PBDEs were studied by 3D-QSAR. ► The binding modes between HO-PBDEs and TRβ were explored. ► 3D-QSAR, molecular docking, and molecular dynamics (MD) methods were performed.« less

Molecular markers in disease detection and follow-up of patients with non-muscle invasive bladder cancer.

PubMed

Maas, Moritz; Walz, Simon; Stühler, Viktoria; Aufderklamm, Stefan; Rausch, Steffen; Bedke, Jens; Stenzl, Arnulf; Todenhöfer, Tilman

2018-05-01

Diagnosis and surveillance of non-muscle invasive bladder cancer (NMIBC) is mainly based on endoscopic bladder evaluation and urine cytology. Several assays for determining additional molecular markers (urine-, tissue- or blood-based) have been developed in recent years but have not been included in clinical guidelines so far. Areas covered: This review gives an update on different molecular markers in the urine and evaluates their role in patients with NMIBC in disease detection and surveillance. Moreover, the potential of recent approaches such as DNA methylation assays, multi-panel RNA gene expression assays and cell-free DNA analysis is assessed. Expert commentary: Most studies on various molecular urine markers have mainly focused on a potential replacement of cystoscopy. New developments in high throughput technologies and urine markers may offer further advantages as they may represent a non-invasive approach for molecular characterization of the disease. This opens new options for individualized surveillance strategies and may help to choose the best therapeutic option. The implementation of these technologies in well-designed clinical trials is essential to further promote the use of urine diagnostics in the management of patients with NMIBC.

Preparation of ellagic acid molecularly imprinted polymeric microspheres based on distillation-precipitation polymerization for the efficient purification of a crude extract.

PubMed

Zhang, Hua; Zhao, Shangge; Zhang, Lu; Han, Bo; Yao, Xincheng; Chen, Wen; Hu, Yanli

2016-08-01

Molecularly imprinted polymeric microspheres with a high recognition ability toward the template molecule, ellagic acid, were synthesized based on distillation-precipitation polymerization. The as-obtained polymers were characterized by scanning electron microscopy, infrared spectroscopy, and thermogravimetric analysis. Static, dynamic, and selective binding tests were adopted to study the binding properties and the molecular recognition ability of the prepared polymers for ellagic acid. The results indicated that the maximum static adsorption capacity of the prepared polymers toward ellagic acid was 37.07 mg/g and the adsorption equilibrium time was about 100 min when the concentration of ellagic acid was 40 mg/mL. Molecularly imprinted polymeric microspheres were also highly selective toward ellagic acid compared with its analogue quercetin. It was found that the content of ellagic acid in the pomegranate peel extract was enhanced from 23 to 86% after such molecularly imprinted solid-phase extraction process. This work provides an efficient way for effective separation and enrichment of ellagic acid from complex matrix, which is especially valuable in industrial production. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

First Molecular Characterization of Hypoderma actaeon in Cattle and Red Deer (Cervus elaphus) in Portugal.

PubMed

Ahmed, Haroon; Sousa, Sérgio Ramalho; Simsek, Sami; Anastácio, Sofia; Kilinc, Seyma Gunyakti

2017-12-01

Hypoderma spp. larvae cause subcutaneous myiasis in several animal species. The objective of the present investigation was to identify and characterize morphologically and molecularly the larvae of Hypoderma spp. collected from cattle (Bos taurus taurus) and red deer (Cervus elaphus) in the district of Castelo Branco, Portugal. For this purpose, a total of 8 larvae were collected from cattle (n=2) and red deer (n=6). After morphological identification of Hypoderma spp. larvae, molecular characterization was based on PCR-RFLP and mitochondrial CO1 gene sequence analysis. All larvae were morphologically characterized as the third instar larvae (L3) of H. actaeon. Two restriction enzymes were used for molecular identification of the larvae. TaqI restriction enzyme was not able to cut H. actaeon. However, MboII restriction enzyme differentiated Hypoderma species showing 210 and 450 bp bands in H. actaeon. Furthermore, according to the alignment of the mt-CO1 gene sequences of Hypoderma species and to PCR-RFLP findings, all the identified Hypoderma larvae were confirmed as H. actaeon. This is the first report of identification of Hypoderma spp. (Diptera; Oestridae) from cattle and red deer in Portugal, based on morphological and molecular analyses.

Analog synthetic biology.

PubMed

Sarpeshkar, R

2014-03-28

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

Analog synthetic biology

PubMed Central

Sarpeshkar, R.

2014-01-01

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

A Combined Pharmacophore Modeling, 3D QSAR and Virtual Screening Studies on Imidazopyridines as B-Raf Inhibitors

PubMed Central

Xie, Huiding; Chen, Lijun; Zhang, Jianqiang; Xie, Xiaoguang; Qiu, Kaixiong; Fu, Jijun

2015-01-01

B-Raf kinase is an important target in treatment of cancers. In order to design and find potent B-Raf inhibitors (BRIs), 3D pharmacophore models were created using the Genetic Algorithm with Linear Assignment of Hypermolecular Alignment of Database (GALAHAD). The best pharmacophore model obtained which was used in effective alignment of the data set contains two acceptor atoms, three donor atoms and three hydrophobes. In succession, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were performed on 39 imidazopyridine BRIs to build three dimensional quantitative structure-activity relationship (3D QSAR) models based on both pharmacophore and docking alignments. The CoMSIA model based on the pharmacophore alignment shows the best result (q2 = 0.621, r2pred = 0.885). This 3D QSAR approach provides significant insights that are useful for designing potent BRIs. In addition, the obtained best pharmacophore model was used for virtual screening against the NCI2000 database. The hit compounds were further filtered with molecular docking, and their biological activities were predicted using the CoMSIA model, and three potential BRIs with new skeletons were obtained. PMID:26035757

A Combined Pharmacophore Modeling, 3D QSAR and Virtual Screening Studies on Imidazopyridines as B-Raf Inhibitors.

PubMed

Xie, Huiding; Chen, Lijun; Zhang, Jianqiang; Xie, Xiaoguang; Qiu, Kaixiong; Fu, Jijun

2015-05-29

B-Raf kinase is an important target in treatment of cancers. In order to design and find potent B-Raf inhibitors (BRIs), 3D pharmacophore models were created using the Genetic Algorithm with Linear Assignment of Hypermolecular Alignment of Database (GALAHAD). The best pharmacophore model obtained which was used in effective alignment of the data set contains two acceptor atoms, three donor atoms and three hydrophobes. In succession, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were performed on 39 imidazopyridine BRIs to build three dimensional quantitative structure-activity relationship (3D QSAR) models based on both pharmacophore and docking alignments. The CoMSIA model based on the pharmacophore alignment shows the best result (q(2) = 0.621, r(2)(pred) = 0.885). This 3D QSAR approach provides significant insights that are useful for designing potent BRIs. In addition, the obtained best pharmacophore model was used for virtual screening against the NCI2000 database. The hit compounds were further filtered with molecular docking, and their biological activities were predicted using the CoMSIA model, and three potential BRIs with new skeletons were obtained.

[Construction and application of bioinformatic analysis platform for aquatic pathogen based on the MilkyWay-2 supercomputer].

PubMed

Fang, Xiang; Li, Ning-qiu; Fu, Xiao-zhe; Li, Kai-bin; Lin, Qiang; Liu, Li-hui; Shi, Cun-bin; Wu, Shu-qin

2015-07-01

As a key component of life science, bioinformatics has been widely applied in genomics, transcriptomics, and proteomics. However, the requirement of high-performance computers rather than common personal computers for constructing a bioinformatics platform significantly limited the application of bioinformatics in aquatic science. In this study, we constructed a bioinformatic analysis platform for aquatic pathogen based on the MilkyWay-2 supercomputer. The platform consisted of three functional modules, including genomic and transcriptomic sequencing data analysis, protein structure prediction, and molecular dynamics simulations. To validate the practicability of the platform, we performed bioinformatic analysis on aquatic pathogenic organisms. For example, genes of Flavobacterium johnsoniae M168 were identified and annotated via Blast searches, GO and InterPro annotations. Protein structural models for five small segments of grass carp reovirus HZ-08 were constructed by homology modeling. Molecular dynamics simulations were performed on out membrane protein A of Aeromonas hydrophila, and the changes of system temperature, total energy, root mean square deviation and conformation of the loops during equilibration were also observed. These results showed that the bioinformatic analysis platform for aquatic pathogen has been successfully built on the MilkyWay-2 supercomputer. This study will provide insights into the construction of bioinformatic analysis platform for other subjects.

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.

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

PubMed Central

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

2017-01-01

To understand the molecular mechanism underlying salt stress response in radish, iTRAQ-based proteomic analysis was conducted to investigate the differences in protein species abundance under different salt treatments. In total, 851, 706, and 685 differential abundance protein species (DAPS) were identified between CK vs. Na100, CK vs. Na200, and Na100 vs. Na200, respectively. Functional annotation analysis revealed that salt stress elicited complex proteomic alterations in radish roots involved in carbohydrate and energy metabolism, protein metabolism, signal transduction, transcription regulation, stress and defense and transport. Additionally, the expression levels of nine genes encoding DAPS were further verified using RT-qPCR. The integrative analysis of transcriptomic and proteomic data in conjunction with miRNAs was further performed to strengthen the understanding of radish response to salinity. The genes responsible for signal transduction, ROS scavenging and transport activities as well as several key miRNAs including miR171, miR395, and miR398 played crucial roles in salt stress response in radish. Based on these findings, a schematic genetic regulatory network of salt stress response was proposed. This study provided valuable insights into the molecular mechanism underlying salt stress response in radish roots and would facilitate developing effective strategies toward genetically engineered salt-tolerant radish and other root vegetable crops. PMID:28769938

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

PubMed

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

2015-01-01

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

Controlled Folding, Motional, and Constitutional Dynamic Processes of Polyheterocyclic Molecular Strands.

PubMed

Barboiu, Mihail; Stadler, Adrian-Mihail; Lehn, Jean-Marie

2016-03-18

General design principles have been developed for the control of the structural features of polyheterocyclic strands and their effector-modulated shape changes. Induced defined molecular motions permit designed enforcement of helical as well as linear molecular shapes. The ability of such molecular strands to bind metal cations allows the generation of coiling/uncoiling processes between helically folded and extended linear states. Large molecular motions are produced on coordination of metal ions, which may be made reversible by competition with an ancillary complexing agent and fueled by sequential acid/base neutralization energy. The introduction of hydrazone units into the strands confers upon them constitutional dynamics, whereby interconversion between different strand compositions is achieved through component exchange. These features have relevance for nanomechanical devices. We present a morphological and functional analysis of such systems developed in our laboratories. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Systematics of Spiny Predatory Katydids (Tettigoniidae: Listroscelidinae) from the Brazilian Atlantic Forest Based on Morphology and Molecular Data

PubMed Central

Fialho, Verônica Saraiva; Chamorro-Rengifo, Juliana; Lopes-Andrade, Cristiano; Yotoko, Karla Suemy Clemente

2014-01-01

Listroscelidinae (Orthoptera: Tettigoniidae) are insectivorous Pantropical katydids whose taxonomy presents a long history of controversy, with several genera incertae sedis. This work focused on species occurring in the Brazilian Atlantic Forest, one of the world's most threatened biomes. We examined material deposited in scientific collections and visited 15 conservation units from Rio de Janeiro to southern Bahia between November 2011 and January 2012, catching 104 specimens from 10 conservation units. Based on morphological and molecular data we redefined Listroscelidini, adding a new tribe, new genus and eight new species to the subfamily. Using morphological analysis, we redescribed and added new geographic records for six species, synonymized two species and built a provisional identification key for the Atlantic Forest Listroscelidinae. Molecular results suggest two new species and a new genus to be described, possibly by the fission of the genus Hamayulus. We also proposed a 500 bp region in the final portion of the COI to be used as a molecular barcode. Our data suggest that the Atlantic Forest Listroscelidinae are seriously endangered, because they occur in highly preserved forest remnants, show high rates of endemism and have a narrow geographic distribution. Based on our results, we suggest future collection efforts must take into account the molecular barcode data to accelerate species recognition. PMID:25118712

Nanoscale molecular communication networks: a game-theoretic perspective

NASA Astrophysics Data System (ADS)

Jiang, Chunxiao; Chen, Yan; Ray Liu, K. J.

2015-12-01

Currently, communication between nanomachines is an important topic for the development of novel devices. To implement a nanocommunication system, diffusion-based molecular communication is considered as a promising bio-inspired approach. Various technical issues about molecular communications, including channel capacity, noise and interference, and modulation and coding, have been studied in the literature, while the resource allocation problem among multiple nanomachines has not been well investigated, which is a very important issue since all the nanomachines share the same propagation medium. Considering the limited computation capability of nanomachines and the expensive information exchange cost among them, in this paper, we propose a game-theoretic framework for distributed resource allocation in nanoscale molecular communication systems. We first analyze the inter-symbol and inter-user interference, as well as bit error rate performance, in the molecular communication system. Based on the interference analysis, we formulate the resource allocation problem as a non-cooperative molecule emission control game, where the Nash equilibrium is found and proved to be unique. In order to improve the system efficiency while guaranteeing fairness, we further model the resource allocation problem using a cooperative game based on the Nash bargaining solution, which is proved to be proportionally fair. Simulation results show that the Nash bargaining solution can effectively ensure fairness among multiple nanomachines while achieving comparable social welfare performance with the centralized scheme.

Development of New Candidate Gene and EST-Based Molecular Markers for Gossypium Species

PubMed Central

Buyyarapu, Ramesh; Kantety, Ramesh V.; Yu, John Z.; Saha, Sukumar; Sharma, Govind C.

2011-01-01

New source of molecular markers accelerate the efforts in improving cotton fiber traits and aid in developing high-density integrated genetic maps. We developed new markers based on candidate genes and G. arboreum EST sequences that were used for polymorphism detection followed by genetic and physical mapping. Nineteen gene-based markers were surveyed for polymorphism detection in 26 Gossypium species. Cluster analysis generated a phylogenetic tree with four major sub-clusters for 23 species while three species branched out individually. CAP method enhanced the rate of polymorphism of candidate gene-based markers between G. hirsutum and G. barbadense. Two hundred A-genome based SSR markers were designed after datamining of G. arboreum EST sequences (Mississippi Gossypium arboreum   EST-SSR: MGAES). Over 70% of MGAES markers successfully produced amplicons while 65 of them demonstrated polymorphism between the parents of G. hirsutum and G. barbadense RIL population and formed 14 linkage groups. Chromosomal localization of both candidate gene-based and MGAES markers was assisted by euploid and hypoaneuploid CS-B analysis. Gene-based and MGAES markers were highly informative as they were designed from candidate genes and fiber transcriptome with a potential to be integrated into the existing cotton genetic and physical maps. PMID:22315588

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.

QSAR, molecular docking studies of thiophene and imidazopyridine derivatives as polo-like kinase 1 inhibitors

NASA Astrophysics Data System (ADS)

Cao, Shandong

2012-08-01

The purpose of the present study was to develop in silico models allowing for a reliable prediction of polo-like kinase inhibitors based on a large diverse dataset of 136 compounds. As an effective method, quantitative structure activity relationship (QSAR) was applied using the comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). The proposed QSAR models showed reasonable predictivity of thiophene analogs (Rcv2=0.533, Rpred2=0.845) and included four molecular descriptors, namely IC3, RDF075m, Mor02m and R4e+. The optimal model for imidazopyridine derivatives (Rcv2=0.776, Rpred2=0.876) was shown to perform good in prediction accuracy, using GATS2m and BEHe1 descriptors. Analysis of the contour maps helped to identify structural requirements for the inhibitors and served as a basis for the design of the next generation of the inhibitor analogues. Docking studies were also employed to position the inhibitors into the polo-like kinase active site to determine the most probable binding mode. These studies may help to understand the factors influencing the binding affinity of chemicals and to develop alternative methods for prescreening and designing of polo-like kinase inhibitors.

[Analysis of hot spots and trend of molecular pharmacognosy research based on project supported by National Natural Science Foundation of 1995-2014].

PubMed

Wang, Jun-Wen; Liu, Yang; Tong, Yuan-Yuan; Yang, Ce; Li, Hai-Yan

2016-05-01

This study collected 1995-2014 molecular pharmacognosy study, a total of 595 items, funded by Natural Science Foundation of China (NSFC). TDA and Excel software were used to analyze the data of the projects about general situation, hot spots of research with rank analytic and correlation analytic methods. Supported by NSFC molecular pharmacognosy projects and funding a gradual increase in the number of, the proportion of funds for pharmaceutical research funding tends to be stable; mainly supported by molecular biology methods of genuine medicinal materials, secondary metabolism and Germplasm Resources Research; hot drugs including Radix Salviae Miltiorrhizae, Radix Rehmanniae, Cordyceps sinensis, hot contents including tanshinone biosynthesis, Rehmannia glutinosa continuous cropping obstacle. Copyright© by the Chinese Pharmaceutical Association.

Computer-aided design of polymers and composites

NASA Technical Reports Server (NTRS)

Kaelble, D. H.

1985-01-01

This book on computer-aided design of polymers and composites introduces and discusses the subject from the viewpoint of atomic and molecular models. Thus, the origins of stiffness, strength, extensibility, and fracture toughness in composite materials can be analyzed directly in terms of chemical composition and molecular structure. Aspects of polymer composite reliability are considered along with characterization techniques for composite reliability, relations between atomic and molecular properties, computer aided design and manufacture, polymer CAD/CAM models, and composite CAD/CAM models. Attention is given to multiphase structural adhesives, fibrous composite reliability, metal joint reliability, polymer physical states and transitions, chemical quality assurance, processability testing, cure monitoring and management, nondestructive evaluation (NDE), surface NDE, elementary properties, ionic-covalent bonding, molecular analysis, acid-base interactions, the manufacturing science, and peel mechanics.

Applicability of SCAR markers to food genomics: olive oil traceability.

PubMed

Pafundo, Simona; Agrimonti, Caterina; Maestri, Elena; Marmiroli, Nelson

2007-07-25

DNA analysis with molecular markers has opened a shortcut toward a genomic comprehension of complex organisms. The availability of micro-DNA extraction methods, coupled with selective amplification of the smallest extracted fragments with molecular markers, could equally bring a breakthrough in food genomics: the identification of original components in food. Amplified fragment length polymorphisms (AFLPs) have been instrumental in plant genomics because they may allow rapid and reliable analysis of multiple and potentially polymorphic sites. Nevertheless, their direct application to the analysis of DNA extracted from food matrixes is complicated by the low quality of DNA extracted: its high degradation and the presence of inhibitors of enzymatic reactions. The conversion of an AFLP fragment to a robust and specific single-locus PCR-based marker, therefore, could extend the use of molecular markers to large-scale analysis of complex agro-food matrixes. In the present study is reported the development of sequence characterized amplified regions (SCARs) starting from AFLP profiles of monovarietal olive oils analyzed on agarose gel; one of these was used to identify differences among 56 olive cultivars. All the developed markers were purposefully amplified in olive oils to apply them to olive oil traceability.

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.

Fungal burden exposure assessment in podiatry clinics from Ireland.

PubMed

Viegas, Carla; Coggins, Ann Marie; Faria, Tiago; Caetano, Liliana Aranha; Gomes, Anita Quintal; Sabino, Raquel; Verissimo, Cristina; Roberts, Nigel; Watterson, David; MacGilchrist, Claire; Fleming, Gerard T A

2018-03-26

Fungi are amongst the bioaerosols of most importance, as indicated by the growing interest in this field of research. The aim was to characterize the exposure to fungal burden in podiatry clinics using culture-based and molecular methods. Airborne fungi were collected using an impaction air sampler and surface samples were also performed. Fourteen air samples were collected for direct detection of fungal DNA from filamentous fungi and dermatophytes. Overall, 63.6 % of the evening samples and 46 % of the morning samples surpassed the threshold values (150 CFU/m 3 ). Molecular detection, by real time PCR, of the target fungal species/strains (Aspergillus and Stachybotrys species) was negative for all samples collected. Trichophyton rubrum was detected by PCR analysis in one DNA sample collected on day six. Results suggest the use of both culture-based and molecular methodologies are desirable for a complete evaluation of fungal burden in this particular health care setting.

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

Phylogeny of Collembola based on cuticular compounds:inherent usefulness and limitation of a character type

NASA Astrophysics Data System (ADS)

Porco, David; Deharveng, Louis

2009-08-01

The phylogeny of Collembola, originally discussed from a morphological point of view, has more recently benefited from novel insights brought by molecular analyses. Both morphological and molecular characters produced a well-resolved phylogenetic hypothesis including all orders, most families, and a large number of genera. However, several conflicting points exist between molecular and morphological data, and new characters are clearly needed to resolve these inconsistencies. In this study the usefulness of a new character type not previously used in the phylogenetic study of Collembola was tested: the epicuticular chemical compounds. Our phylogenetic analysis was based on 380 compounds from 26 Collembola species. The results show good resolution for terminal branches but not for internal nodes. This is probably due to the partial involvement of epicuticular lipids in ecological functions such as water conservation and sexual attraction. Thus, this character type is appropriate for reconstructing phylogenetic relationships among recently diversified groups.

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.

A novel approach of dynamic cross correlation analysis on molecular dynamics simulations and its application to Ets1 dimer-DNA complex.

PubMed

Kasahara, Kota; Fukuda, Ikuo; Nakamura, Haruki

2014-01-01

The dynamic cross correlation (DCC) analysis is a popular method for analyzing the trajectories of molecular dynamics (MD) simulations. However, it is difficult to detect correlative motions that appear transiently in only a part of the trajectory, such as atomic contacts between the side-chains of amino acids, which may rapidly flip. In order to capture these multi-modal behaviors of atoms, which often play essential roles, particularly at the interfaces of macromolecules, we have developed the "multi-modal DCC (mDCC)" analysis. The mDCC is an extension of the DCC and it takes advantage of a Bayesian-based pattern recognition technique. We performed MD simulations for molecular systems modeled from the (Ets1)2-DNA complex and analyzed their results with the mDCC method. Ets1 is an essential transcription factor for a variety of physiological processes, such as immunity and cancer development. Although many structural and biochemical studies have so far been performed, its DNA binding properties are still not well characterized. In particular, it is not straightforward to understand the molecular mechanisms how the cooperative binding of two Ets1 molecules facilitates their recognition of Stromelysin-1 gene regulatory elements. A correlation network was constructed among the essential atomic contacts, and the two major pathways by which the two Ets1 molecules communicate were identified. One is a pathway via direct protein-protein interactions and the other is that via the bound DNA intervening two recognition helices. These two pathways intersected at the particular cytosine bases (C110/C11), interacting with the H1, H2, and H3 helices. Furthermore, the mDCC analysis showed that both pathways included the transient interactions at their intermolecular interfaces of Tyr396-C11 and Ala327-Asn380 in multi-modal motions of the amino acid side chains and the nucleotide backbone. Thus, the current mDCC approach is a powerful tool to reveal these complicated behaviors and scrutinize intermolecular communications in a molecular system.

Molecular basis of protein structure in proanthocyanidin and anthocyanin-enhanced Lc-transgenic alfalfa in relation to nutritive value using synchrotron-radiation FTIR microspectroscopy: A novel approach

NASA Astrophysics Data System (ADS)

Yu, Peiqiang; Jonker, Arjan; Gruber, Margaret

2009-09-01

To date there has been very little application of synchrotron radiation-based Fourier transform infrared microspectroscopy (SRFTIRM) to the study of molecular structures in plant forage in relation to livestock digestive behavior and nutrient availability. Protein inherent structure, among other factors such as protein matrix, affects nutritive quality, fermentation and degradation behavior in both humans and animals. The relative percentage of protein secondary structure influences protein value. A high percentage of β-sheets usually reduce the access of gastrointestinal digestive enzymes to the protein. Reduced accessibility results in poor digestibility and as a result, low protein value. The objective of this study was to use SRFTIRM to compare protein molecular structure of alfalfa plant tissues transformed with the maize Lc regulatory gene with non-transgenic alfalfa protein within cellular and subcellular dimensions and to quantify protein inherent structure profiles using Gaussian and Lorentzian methods of multi-component peak modeling. Protein molecular structure revealed by this method included α-helices, β-sheets and other structures such as β-turns and random coils. Hierarchical cluster analysis and principal component analysis of the synchrotron data, as well as accurate spectral analysis based on curve fitting, showed that transgenic alfalfa contained a relatively lower ( P < 0.05) percentage of the model-fitted α-helices (29 vs. 34) and model-fitted β-sheets (22 vs. 27) and a higher ( P < 0.05) percentage of other model-fitted structures (49 vs. 39). Transgenic alfalfa protein displayed no difference ( P > 0.05) in the ratio of α-helices to β-sheets (average: 1.4) and higher ( P < 0.05) ratios of α-helices to others (0.7 vs. 0.9) and β-sheets to others (0.5 vs. 0.8) than the non-transgenic alfalfa protein. The transgenic protein structures also exhibited no difference ( P > 0.05) in the vibrational intensity of protein amide I (average of 24) and amide II areas (average of 10) and their ratio (average of 2.4) compared with non-transgenic alfalfa. Cluster analysis and principal component analysis showed no significant differences between the two genotypes in the broad molecular fingerprint region, amides I and II regions, and the carbohydrate molecular region, indicating they are highly related to each other. The results suggest that transgenic Lc-alfalfa leaves contain similar proteins to non-transgenic alfalfa (because amide I and II intensities were identical), but a subtle difference in protein molecular structure after freeze drying. Further study is needed to understand the relationship between these structural profiles and biological features such as protein nutrient availability, protein bypass and digestive behavior of livestock fed with this type of forage.

Molecular Basis of Protein Structure in Proanthocyanidin and Anthocyanin-Enhanced Lc-transgenic Alfalfa in Relation to Nutritive Value Using Synchrotron-Radiation FTIR Microspectroscopy: A Novel Approach

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

Yu, P.; Jonker, A; Gruber, M

2009-01-01

To date there has been very little application of synchrotron radiation-based Fourier transform infrared microspectroscopy (SRFTIRM) to the study of molecular structures in plant forage in relation to livestock digestive behavior and nutrient availability. Protein inherent structure, among other factors such as protein matrix, affects nutritive quality, fermentation and degradation behavior in both humans and animals. The relative percentage of protein secondary structure influences protein value. A high percentage of e-sheets usually reduce the access of gastrointestinal digestive enzymes to the protein. Reduced accessibility results in poor digestibility and as a result, low protein value. The objective of this studymore » was to use SRFTIRM to compare protein molecular structure of alfalfa plant tissues transformed with the maize Lc regulatory gene with non-transgenic alfalfa protein within cellular and subcellular dimensions and to quantify protein inherent structure profiles using Gaussian and Lorentzian methods of multi-component peak modeling. Protein molecular structure revealed by this method included a-helices, e-sheets and other structures such as e-turns and random coils. Hierarchical cluster analysis and principal component analysis of the synchrotron data, as well as accurate spectral analysis based on curve fitting, showed that transgenic alfalfa contained a relatively lower (P < 0.05) percentage of the model-fitted a-helices (29 vs. 34) and model-fitted e-sheets (22 vs. 27) and a higher (P < 0.05) percentage of other model-fitted structures (49 vs. 39). Transgenic alfalfa protein displayed no difference (P > 0.05) in the ratio of a-helices to e-sheets (average: 1.4) and higher (P < 0.05) ratios of a-helices to others (0.7 vs. 0.9) and e-sheets to others (0.5 vs. 0.8) than the non-transgenic alfalfa protein. The transgenic protein structures also exhibited no difference (P > 0.05) in the vibrational intensity of protein amide I (average of 24) and amide II areas (average of 10) and their ratio (average of 2.4) compared with non-transgenic alfalfa. Cluster analysis and principal component analysis showed no significant differences between the two genotypes in the broad molecular fingerprint region, amides I and II regions, and the carbohydrate molecular region, indicating they are highly related to each other. The results suggest that transgenic Lc-alfalfa leaves contain similar proteins to non-transgenic alfalfa (because amide I and II intensities were identical), but a subtle difference in protein molecular structure after freeze drying. Further study is needed to understand the relationship between these structural profiles and biological features such as protein nutrient availability, protein bypass and digestive behavior of livestock fed with this type of forage.« less

Molecular analysis of Aspergillus section Flavi isolated from Brazil nuts.

PubMed

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

2012-04-01

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

Interface-Engineered Charge-Transport Properties in Benzenedithiol Molecular Electronic Junctions via Chemically p-Doped Graphene Electrodes.

PubMed

Jang, Yeonsik; Kwon, Sung-Joo; Shin, Jaeho; Jeong, Hyunhak; Hwang, Wang-Taek; Kim, Junwoo; Koo, Jeongmin; Ko, Taeg Yeoung; Ryu, Sunmin; Wang, Gunuk; Lee, Tae-Woo; Lee, Takhee

2017-12-06

In this study, we fabricated and characterized vertical molecular junctions consisting of self-assembled monolayers of benzenedithiol (BDT) with a p-doped multilayer graphene electrode. The p-type doping of a graphene film was performed by treating pristine graphene (work function of ∼4.40 eV) with trifluoromethanesulfonic (TFMS) acid, producing a significantly increased work function (∼5.23 eV). The p-doped graphene-electrode molecular junctions statistically showed an order of magnitude higher current density and a lower charge injection barrier height than those of the pristine graphene-electrode molecular junctions, as a result of interface engineering. This enhancement is due to the increased work function of the TFMS-treated p-doped graphene electrode in the highest occupied molecular orbital-mediated tunneling molecular junctions. The validity of these results was proven by a theoretical analysis based on a coherent transport model that considers asymmetric couplings at the electrode-molecule interfaces.

Disseminated histoplasmosis in a domestic cat imported from the USA to Austria

PubMed Central

Klang, Andrea; Loncaric, Igor; Spergser, Joachim; Eigelsreiter, Sabine; Weissenböck, Herbert

2013-01-01

We present a case of disseminated histoplasmosis in a domestic cat imported from the USA to Austria. Histopathological examination revealed a systemic mycosis with most severe involvement of the lungs suggestive of Histoplasma (H.) capsulatum-infection. Molecular confirmation was based on polymerase chain reaction (PCR) and sequence analysis of a fungal culture from liver samples. This is the first case of feline histoplasmosis proven by molecular diagnostic technique in Europe and reported in Austria, etc. PMID:24432230

Targeted DNA sequencing and in situ mutation analysis using mobile phone microscopy

PubMed Central

Kühnemund, Malte; Wei, Qingshan; Darai, Evangelia; Wang, Yingjie; Hernández-Neuta, Iván; Yang, Zhao; Tseng, Derek; Ahlford, Annika; Mathot, Lucy; Sjöblom, Tobias; Ozcan, Aydogan; Nilsson, Mats

2017-01-01

Molecular diagnostics is typically outsourced to well-equipped centralized laboratories, often far from the patient. We developed molecular assays and portable optical imaging designs that permit on-site diagnostics with a cost-effective mobile-phone-based multimodal microscope. We demonstrate that targeted next-generation DNA sequencing reactions and in situ point mutation detection assays in preserved tumour samples can be imaged and analysed using mobile phone microscopy, achieving a new milestone for tele-medicine technologies. PMID:28094784

(D)- and (L)-cyclohexenyl-G, a new class of antiviral agents: synthesis, conformational analysis, molecular modeling, and biological activity.

PubMed

Wang, J; Froeyen, M; Hendrix, C; Andrei, C; Snoeck, R; Lescrinier, E; De Clercq, E; Herdewijn, P

2001-01-01

(D)- and (L)-cyclohexeneyl-G were synthesized enantioselectively starting from (R)-carvone. Both show potent and selective anti-herpesvirus activity (HSV-1, HSV-2, VZV, CMV). Molecular modeling demonstrates that both isomers are bound in the active site of HSV-1 thymidine kinase in a high-energy conformation with the base moiety orienting in an equatorial position. It is believed that the flexibility of the cyclohexene ring is essential for their antiviral activity.

One-Dimensional Analysis of a Liquid Jet in a Regenerative Liquid Propellant Gun

DTIC Science & Technology

1990-04-01

1.400 MOLECULAR WEIGHT(GM/GMOL) 28.960 PROPERTIES OF PROJECTILE 42 MASS(GM) 97.300 LOCATION OF BASE WITH RESPECT TO TUBE ENTRANCE(CM) 0.000 TRAVEL...MPA) 1206.500 DERIVATIVE OF MODULUS W.R.T PRESSURE(-) 2.500 CHEMICAL ENERGY(J/GM) 3240.807 RATIO OF SPECIFIC HEATS OF PRODUCTS(-) 1.267 MOLECULAR ...0.147100 EMISIVITY FACTOR (-) 1.00000 HEAT LOSS MULTIPLIER FACTOR (-) 1.00000 TOTAL PROPELLANT WEIGHT (GM) 117.2470 TOTAL CHEMICAL ENERGY (KJ) 379.9750

Relaxation Estimation of RMSD in Molecular Dynamics Immunosimulations

PubMed Central

Schreiner, Wolfgang; Karch, Rudolf; Knapp, Bernhard; Ilieva, Nevena

2012-01-01

Molecular dynamics simulations have to be sufficiently long to draw reliable conclusions. However, no method exists to prove that a simulation has converged. We suggest the method of “lagged RMSD-analysis” as a tool to judge if an MD simulation has not yet run long enough. The analysis is based on RMSD values between pairs of configurations separated by variable time intervals Δt. Unless RMSD(Δt) has reached a stationary shape, the simulation has not yet converged. PMID:23019425

[A study of culture-based easy identification system for Malassezia].

PubMed

Kaneko, Takamasa

2011-01-01

Most species of this genus are lipid-dependent yeasts, which colonize the seborrheic part of the skin, and they have been reported to be associated with pityriasis versicolor, Malassezia folliculitis, seborrheic dermatitis, and atopic dermatitis. Malassezia have been re-classified into 7 species based on molecular biological analysis of nuclear ribosomal DNA/RNA and new Malassezia species were reported. As members of the genus Malassezia share similar morphological and biochemical characteristics, it was thought to be difficult to differentiate between them based on phenotypic features. While molecular biological techniques are the most reliable methods for identification of Malassezia, they are not available in most clinical laboratories. We studied ( i ) development of an efficient isolation media and culture based easy identification system, ( ii ) the incidence of atypical biochemical features in Malassezia species and propose a culture-based easy identification system for clinically important Malassezia species, M. globosa, M. restricta, and M. furfur.

Optimizing of MALDI-ToF-based low-molecular-weight serum proteome pattern analysis in detection of breast cancer patients; the effect of albumin removal on classification performance.

PubMed

Pietrowska, M; Marczak, L; Polanska, J; Nowicka, E; Behrent, K; Tarnawski, R; Stobiecki, M; Polanski, A; Widlak, P

2010-01-01

Mass spectrometry-based analysis of the serum proteome allows identifying multi-peptide patterns/signatures specific for blood of cancer patients, thus having high potential value for cancer diagnostics. However, because of problems with optimization and standardization of experimental and computational design, none of identified proteome patterns/signatures was approved for diagnostics in clinical practice as yet. Here we compared two methods of serum sample preparation for mass spectrometry-based proteome pattern analysis aimed to identify biomarkers that could be used in early detection of breast cancer patients. Blood samples were collected in a group of 92 patients diagnosed at early (I and II) stages of the disease before the start of therapy, and in a group of age-matched healthy controls (104 women). Serum specimens were purified and analyzed using MALDI-ToF spectrometry, either directly or after membrane filtration (50 kDa cut-off) to remove albumin and other large serum proteins. Mass spectra of the low-molecular-weight fraction (2-10 kDa) of the serum proteome were resolved using the Gaussian mixture decomposition, and identified spectral components were used to build classifiers that differentiated samples from breast cancer patients and healthy persons. Mass spectra of complete serum and membrane-filtered albumin-depleted samples have apparently different structure and peaks specific for both types of samples could be identified. The optimal classifier built for the complete serum specimens consisted of 8 spectral components, and had 81% specificity and 72% sensitivity, while that built for the membrane-filtered samples consisted of 4 components, and had 80% specificity and 81% sensitivity. We concluded that pre-processing of samples to remove albumin might be recommended before MALDI-ToF mass spectrometric analysis of the low-molecular-weight components of human serum Keywords: albumin removal; breast cancer; clinical proteomics; mass spectrometry; pattern analysis; serum proteome.

Pitfalls in lung cancer molecular pathology: how to limit them in routine practice?

PubMed

Ilie, M; Hofman, P

2012-01-01

New treatment options in advanced non-small cell lung carcinoma (NSCLC) targeting activating epidermal growth factor receptor (EGFR) gene mutations and other genetic alterations demonstrated the clinical significance of the molecular features of specific subsets of tumors. Therefore, the development of personalized medicine has stimulated the routine integration into pathology departments of somatic mutation testing. However, clinical mutation testing must be optimized and standardized with regard to histological profile, type of samples, pre-analytical steps, methodology and result reporting. Routine molecular testing in NSCLC is currently moving beyond EGFR mutational analysis. Recent progress of targeted therapies will require molecular testing for a wide panel of mutations for a personalized molecular diagnosis. As a consequence, efficient testing of multiple molecular abnormalities is an urgent requirement in thoracic oncology. Moreover, increasingly limited tumor sample becomes a major challenge for molecular pathology. Continuous efforts should be made for safe, effective and specific molecular analyses. This must be based on close collaboration between the departments involved in the management of lung cancer. In this review we explored the practical issues and pitfalls surrounding the routine implementation of molecular testing in NSCLC in a pathology laboratory.

Nottingham Prognostic Index Plus (NPI+): a modern clinical decision making tool in breast cancer.

PubMed

Rakha, E A; Soria, D; Green, A R; Lemetre, C; Powe, D G; Nolan, C C; Garibaldi, J M; Ball, G; Ellis, I O

2014-04-02

Current management of breast cancer (BC) relies on risk stratification based on well-defined clinicopathologic factors. Global gene expression profiling studies have demonstrated that BC comprises distinct molecular classes with clinical relevance. In this study, we hypothesised that molecular features of BC are a key driver of tumour behaviour and when coupled with a novel and bespoke application of established clinicopathologic prognostic variables can predict both clinical outcome and relevant therapeutic options more accurately than existing methods. In the current study, a comprehensive panel of biomarkers with relevance to BC was applied to a large and well-characterised series of BC, using immunohistochemistry and different multivariate clustering techniques, to identify the key molecular classes. Subsequently, each class was further stratified using a set of well-defined prognostic clinicopathologic variables. These variables were combined in formulae to prognostically stratify different molecular classes, collectively known as the Nottingham Prognostic Index Plus (NPI+). The NPI+ was then used to predict outcome in the different molecular classes. Seven core molecular classes were identified using a selective panel of 10 biomarkers. Incorporation of clinicopathologic variables in a second-stage analysis resulted in identification of distinct prognostic groups within each molecular class (NPI+). Outcome analysis showed that using the bespoke NPI formulae for each biological BC class provides improved patient outcome stratification superior to the traditional NPI. This study provides proof-of-principle evidence for the use of NPI+ in supporting improved individualised clinical decision making.

Non-Invasive Early Detection and Molecular Analysis of Low X-ray Dose Effects in the Lens

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

Goldstein, Lee

This is the Final Progress Report for DOE-funded research project DE-PS02-08ER08-01 titled “Non-Invasive Early Detection and Molecular Analysis of Low X-ray Dose Effects in the Lens”. The project focuses on the effects of low-linear energy transfer (LET) radiation on the ocular lens. The lens is an exquisitely radiosensitive tissue with a highly-ordered molecular structure that is amenable to non-invasive optical study from the periphery. These merits point to the lens as an ideal target for laser-based molecular biodosimetry (MBD). Following exposure to different types of ionizing radiations, the lens demonstrates molecular changes (e.g., oxidation, racemization, crosslinkage, truncation, aggregation, etc.) thatmore » impact the structure and function of the long-lived proteins in the cytosol of lens fiber cells. The vast majority of proteins in the lens comprise the highly-ordered crystallins. These highly conserved lens proteins are amongst the most concentrated and stable in the body. Once synthesized, the crystallins are retained in the fiber cell cytoplasm for life. Taken together, these properties point to the lens as an ideal system for quantitative in vivo MBD assessment using quasi-elastic light scattering (QLS) analysis. In this project, we deploy a purpose-designed non-invasive infrared laser QLS instrument as a quantitative tool for longitudinal assessment of pre-cataractous molecular changes in the lenses of living mice exposed to low-dose low-LET radiation compared to non-irradiated sham controls. We hypothesize that radiation exposure will induce dose-dependent changes in the molecular structure of matrix proteins in the lens. Mechanistic assays to ascertain radiation-induced molecular changes in the lens focus on protein aggregation and gene/protein expression patterns. We anticipate that this study will contribute to our understanding of early molecular changes associated with radiation-induced tissue pathology. This study also affords potential for translational development of molecular biodosimetry instrumentation to assess human exposure to mixed radiation fields.« less

Determination of molecular weight distributions in native and pretreated wood.

PubMed

Leskinen, Timo; Kelley, Stephen S; Argyropoulos, Dimitris S

2015-03-30

The analysis of native wood components by size-exclusion chromatography (SEC) is challenging. Isolation, derivatization and solubilization of wood polymers is required prior to the analysis. The present approach allowed the determination of molecular weight distributions of the carbohydrates and of lignin in native and processed woods, without preparative component isolation steps. For the first time a component selective SEC analysis of sawdust preparations was made possible by the combination of two selective derivatization methods, namely; ionic liquid assisted benzoylation of the carbohydrate fraction and acetobromination of the lignin in acetic acid media. These were optimized for wood samples. The developed method was thus used to examine changes in softwood samples after degradative mechanical and/or chemical treatments, such as ball milling, steam explosion, green liquor pulping, and chemical oxidation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). The methodology can also be applied to examine changes in molecular weight and lignin-carbohydrate linkages that occur during wood-based biorefinery operations, such as pretreatments, and enzymatic saccharification. Copyright © 2014 Elsevier Ltd. All rights reserved.

Molecular characterization and phylogenetic analysis of the causative agent of hemoplasma infection in small Indian Mongoose (Herpestes Javanicus).

PubMed

Sharifiyazdi, Hassan; Nazifi, Saeed; Shirzad Aski, Hesamaddin; Shayegh, Hossein

2014-09-01

Hemoplasmas are the trivial name for a group of erythrocyte-parasitizing bacteria of the genus Mycoplasma. This study is the first report of hemoplasma infection in Small Indian Mongoose (Herpestes Javanicus) based on molecular analysis of 16S rDNA. Whole blood samples were collected by sterile methods, from 14 live captured mongooses, in the south of Iran. Candidatus Mycoplasma turicensis (CMt)-like hemoplasma was detected in blood samples from one animal tested. BLAST search and phylogenetic analysis of partial 16S rDNA sequence (933bp) of the hemoplasma from Small Indian mongoose (KJ530704) revealed only 96-97% identity to the previously described CMt followed by 95% and 91% similarity with Mycoplasma coccoides and Mycoplasma haemomuris, respectively. Accordingly, the Iranian mongoose CMt isolate showed a high intra-specific genetic variation compared to all previously reported CMt strains in GenBank. Further molecular studies using multiple phylogenetic markers are required to characterize the exact species of Mongoose-derived hemoplasma. Copyright © 2014 Elsevier Ltd. All rights reserved.