Core microbial functional activities in ocean environments revealed by global metagenomic profiling analyses.

KAUST Repository

Ferreira, Ari J S

2014-06-12

Metagenomics-based functional profiling analysis is an effective means of gaining deeper insight into the composition of marine microbial populations and developing a better understanding of the interplay between the functional genome content of microbial communities and abiotic factors. Here we present a comprehensive analysis of 24 datasets covering surface and depth-related environments at 11 sites around the world\\'s oceans. The complete datasets comprises approximately 12 million sequences, totaling 5,358 Mb. Based on profiling patterns of Clusters of Orthologous Groups (COGs) of proteins, a core set of reference photic and aphotic depth-related COGs, and a collection of COGs that are associated with extreme oxygen limitation were defined. Their inferred functions were utilized as indicators to characterize the distribution of light- and oxygen-related biological activities in marine environments. The results reveal that, while light level in the water column is a major determinant of phenotypic adaptation in marine microorganisms, oxygen concentration in the aphotic zone has a significant impact only in extremely hypoxic waters. Phylogenetic profiling of the reference photic/aphotic gene sets revealed a greater variety of source organisms in the aphotic zone, although the majority of individual photic and aphotic depth-related COGs are assigned to the same taxa across the different sites. This increase in phylogenetic and functional diversity of the core aphotic related COGs most probably reflects selection for the utilization of a broad range of alternate energy sources in the absence of light.

Core microbial functional activities in ocean environments revealed by global metagenomic profiling analyses.

KAUST Repository

Ferreira, Ari J S; Siam, Rania; Setubal, Joã o C; Moustafa, Ahmed; Sayed, Ahmed; Chambergo, Felipe S; Dawe, Adam S; Ghazy, Mohamed A; Sharaf, Hazem; Ouf, Amged; Alam, Intikhab; Abdel-Haleem, Alyaa M; Lehvä slaiho, Heikki; Ramadan, Eman; Antunes, André ; Stingl, Ulrich; Archer, John A.C.; Jankovic, Boris R; Sogin, Mitchell; Bajic, Vladimir B.; El-Dorry, Hamza

2014-01-01

Metagenomics-based functional profiling analysis is an effective means of gaining deeper insight into the composition of marine microbial populations and developing a better understanding of the interplay between the functional genome content of microbial communities and abiotic factors. Here we present a comprehensive analysis of 24 datasets covering surface and depth-related environments at 11 sites around the world's oceans. The complete datasets comprises approximately 12 million sequences, totaling 5,358 Mb. Based on profiling patterns of Clusters of Orthologous Groups (COGs) of proteins, a core set of reference photic and aphotic depth-related COGs, and a collection of COGs that are associated with extreme oxygen limitation were defined. Their inferred functions were utilized as indicators to characterize the distribution of light- and oxygen-related biological activities in marine environments. The results reveal that, while light level in the water column is a major determinant of phenotypic adaptation in marine microorganisms, oxygen concentration in the aphotic zone has a significant impact only in extremely hypoxic waters. Phylogenetic profiling of the reference photic/aphotic gene sets revealed a greater variety of source organisms in the aphotic zone, although the majority of individual photic and aphotic depth-related COGs are assigned to the same taxa across the different sites. This increase in phylogenetic and functional diversity of the core aphotic related COGs most probably reflects selection for the utilization of a broad range of alternate energy sources in the absence of light.

Core microbial functional activities in ocean environments revealed by global metagenomic profiling analyses.

Directory of Open Access Journals (Sweden)

Ari J S Ferreira

Full Text Available Metagenomics-based functional profiling analysis is an effective means of gaining deeper insight into the composition of marine microbial populations and developing a better understanding of the interplay between the functional genome content of microbial communities and abiotic factors. Here we present a comprehensive analysis of 24 datasets covering surface and depth-related environments at 11 sites around the world's oceans. The complete datasets comprises approximately 12 million sequences, totaling 5,358 Mb. Based on profiling patterns of Clusters of Orthologous Groups (COGs of proteins, a core set of reference photic and aphotic depth-related COGs, and a collection of COGs that are associated with extreme oxygen limitation were defined. Their inferred functions were utilized as indicators to characterize the distribution of light- and oxygen-related biological activities in marine environments. The results reveal that, while light level in the water column is a major determinant of phenotypic adaptation in marine microorganisms, oxygen concentration in the aphotic zone has a significant impact only in extremely hypoxic waters. Phylogenetic profiling of the reference photic/aphotic gene sets revealed a greater variety of source organisms in the aphotic zone, although the majority of individual photic and aphotic depth-related COGs are assigned to the same taxa across the different sites. This increase in phylogenetic and functional diversity of the core aphotic related COGs most probably reflects selection for the utilization of a broad range of alternate energy sources in the absence of light.

Gene expression profiling reveals new potential players of gonad differentiation in the chicken embryo.

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Gwenn-Aël Carré

Full Text Available BACKGROUND: In birds as in mammals, a genetic switch determines whether the undifferentiated gonad develops into an ovary or a testis. However, understanding of the molecular pathway(s involved in gonad differentiation is still incomplete. METHODOLOGY/PRINCIPAL FINDINGS: With the aim of improving characterization of the molecular pathway(s involved in gonad differentiation in the chicken embryo, we developed a large scale real time reverse transcription polymerase chain reaction approach on 110 selected genes for evaluation of their expression profiles during chicken gonad differentiation between days 5.5 and 19 of incubation. Hierarchical clustering analysis of the resulting datasets discriminated gene clusters expressed preferentially in the ovary or the testis, and/or at early or later periods of embryonic gonad development. Fitting a linear model and testing the comparisons of interest allowed the identification of new potential actors of gonad differentiation, such as Z-linked ADAMTS12, LOC427192 (corresponding to NIM1 protein and CFC1, that are upregulated in the developing testis, and BMP3 and Z-linked ADAMTSL1, that are preferentially expressed in the developing ovary. Interestingly, the expression patterns of several members of the transforming growth factor β family were sexually dimorphic, with inhibin subunits upregulated in the testis, and bone morphogenetic protein subfamily members including BMP2, BMP3, BMP4 and BMP7, upregulated in the ovary. This study also highlighted several genes displaying asymmetric expression profiles such as GREM1 and BMP3 that are potentially involved in different aspects of gonad left-right asymmetry. CONCLUSION/SIGNIFICANCE: This study supports the overall conservation of vertebrate sex differentiation pathways but also reveals some particular feature of gene expression patterns during gonad development in the chicken. In particular, our study revealed new candidate genes which may be potential actors

Gene Expression Profiling Reveals New Potential Players of Gonad Differentiation in the Chicken Embryo

Science.gov (United States)

Carré, Gwenn-Aël; Couty, Isabelle; Hennequet-Antier, Christelle; Govoroun, Marina S.

2011-01-01

Background In birds as in mammals, a genetic switch determines whether the undifferentiated gonad develops into an ovary or a testis. However, understanding of the molecular pathway(s) involved in gonad differentiation is still incomplete. Methodology/Principal Findings With the aim of improving characterization of the molecular pathway(s) involved in gonad differentiation in the chicken embryo, we developed a large scale real time reverse transcription polymerase chain reaction approach on 110 selected genes for evaluation of their expression profiles during chicken gonad differentiation between days 5.5 and 19 of incubation. Hierarchical clustering analysis of the resulting datasets discriminated gene clusters expressed preferentially in the ovary or the testis, and/or at early or later periods of embryonic gonad development. Fitting a linear model and testing the comparisons of interest allowed the identification of new potential actors of gonad differentiation, such as Z-linked ADAMTS12, LOC427192 (corresponding to NIM1 protein) and CFC1, that are upregulated in the developing testis, and BMP3 and Z-linked ADAMTSL1, that are preferentially expressed in the developing ovary. Interestingly, the expression patterns of several members of the transforming growth factor β family were sexually dimorphic, with inhibin subunits upregulated in the testis, and bone morphogenetic protein subfamily members including BMP2, BMP3, BMP4 and BMP7, upregulated in the ovary. This study also highlighted several genes displaying asymmetric expression profiles such as GREM1 and BMP3 that are potentially involved in different aspects of gonad left-right asymmetry. Conclusion/Significance This study supports the overall conservation of vertebrate sex differentiation pathways but also reveals some particular feature of gene expression patterns during gonad development in the chicken. In particular, our study revealed new candidate genes which may be potential actors of chicken gonad

Machine learning and computer vision approaches for phenotypic profiling.

Science.gov (United States)

Grys, Ben T; Lo, Dara S; Sahin, Nil; Kraus, Oren Z; Morris, Quaid; Boone, Charles; Andrews, Brenda J

2017-01-02

With recent advances in high-throughput, automated microscopy, there has been an increased demand for effective computational strategies to analyze large-scale, image-based data. To this end, computer vision approaches have been applied to cell segmentation and feature extraction, whereas machine-learning approaches have been developed to aid in phenotypic classification and clustering of data acquired from biological images. Here, we provide an overview of the commonly used computer vision and machine-learning methods for generating and categorizing phenotypic profiles, highlighting the general biological utility of each approach. © 2017 Grys et al.

Diffusion Profiling via a Histogram Approach Distinguishes Low-grade from High-grade Meningiomas, Can Reflect the Respective Proliferative Potential and Progesterone Receptor Status.

Science.gov (United States)

Gihr, Georg Alexander; Horvath-Rizea, Diana; Garnov, Nikita; Kohlhof-Meinecke, Patricia; Ganslandt, Oliver; Henkes, Hans; Meyer, Hans Jonas; Hoffmann, Karl-Titus; Surov, Alexey; Schob, Stefan

2018-02-01

Presurgical grading, estimation of growth kinetics, and other prognostic factors are becoming increasingly important for selecting the best therapeutic approach for meningioma patients. Diffusion-weighted imaging (DWI) provides microstructural information and reflects tumor biology. A novel DWI approach, histogram profiling of apparent diffusion coefficient (ADC) volumes, provides more distinct information than conventional DWI. Therefore, our study investigated whether ADC histogram profiling distinguishes low-grade from high-grade lesions and reflects Ki-67 expression and progesterone receptor status. Pretreatment ADC volumes of 37 meningioma patients (28 low-grade, 9 high-grade) were used for histogram profiling. WHO grade, Ki-67 expression, and progesterone receptor status were evaluated. Comparative and correlative statistics investigating the association between histogram profiling and neuropathology were performed. The entire ADC profile (p10, p25, p75, p90, mean, median) was significantly lower in high-grade versus low-grade meningiomas. The lower percentiles, mean, and modus showed significant correlations with Ki-67 expression. Skewness and entropy of the ADC volumes were significantly associated with progesterone receptor status and Ki-67 expression. ROC analysis revealed entropy to be the most accurate parameter distinguishing low-grade from high-grade meningiomas. ADC histogram profiling provides a distinct set of parameters, which help differentiate low-grade versus high-grade meningiomas. Also, histogram metrics correlate significantly with histological surrogates of the respective proliferative potential. More specifically, entropy revealed to be the most promising imaging biomarker for presurgical grading. Both, entropy and skewness were significantly associated with progesterone receptor status and Ki-67 expression and therefore should be investigated further as predictors for prognostically relevant tumor biological features. Since absolute ADC

Melodic multi-feature paradigm reveals auditory profiles in music-sound encoding

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Mari eTervaniemi

2014-07-01

Full Text Available Musical expertise modulates preattentive neural sound discrimination. However, this evidence up to great extent originates from paradigms using very simple stimulation. Here we use a novel melody paradigm (revealing the auditory profile for six sound parameters in parallel to compare memory-related MMN and attention-related P3a responses recorded from non-musicians and Finnish Folk musicians. MMN emerged in both groups of participants for all sound changes (except for rhythmic changes in non-musicians. In Folk musicians, the MMN was enlarged for mistuned sounds when compared with non-musicians. This is taken to reflect their familiarity with pitch information which is in key position in Finnish folk music when compared with e.g., rhythmic information. The MMN was followed by P3a after timbre changes, rhythm changes, and melody transposition. The MMN and P3a topographies differentiated the groups for all sound changes. Thus, the melody paradigm offers a fast and cost-effective means for determining the auditory profile for music-sound encoding and also, importantly, for probing the effects of musical expertise on it.

Melodic multi-feature paradigm reveals auditory profiles in music-sound encoding.

Science.gov (United States)

Tervaniemi, Mari; Huotilainen, Minna; Brattico, Elvira

2014-01-01

Musical expertise modulates preattentive neural sound discrimination. However, this evidence up to great extent originates from paradigms using very simple stimulation. Here we use a novel melody paradigm (revealing the auditory profile for six sound parameters in parallel) to compare memory-related mismatch negativity (MMN) and attention-related P3a responses recorded from non-musicians and Finnish Folk musicians. MMN emerged in both groups of participants for all sound changes (except for rhythmic changes in non-musicians). In Folk musicians, the MMN was enlarged for mistuned sounds when compared with non-musicians. This is taken to reflect their familiarity with pitch information which is in key position in Finnish folk music when compared with e.g., rhythmic information. The MMN was followed by P3a after timbre changes, rhythm changes, and melody transposition. The MMN and P3a topographies differentiated the groups for all sound changes. Thus, the melody paradigm offers a fast and cost-effective means for determining the auditory profile for music-sound encoding and also, importantly, for probing the effects of musical expertise on it.

Towards Current Profile Control in ITER: Potential Approaches and Research Needs

Science.gov (United States)

Schuster, E.; Barton, J. E.; Wehner, W. P.

2014-10-01

Many challenging plasma control problems still need to be addressed in order for the ITER Plasma Control System (PCS) to be able to successfully achieve the ITER project goals. For instance, setting up a suitable toroidal current density profile is key for one possible advanced scenario characterized by noninductive sustainment of the plasma current and steady-state operation. The nonlinearity and high dimensionality exhibited by the plasma demand a model-based current-profile control synthesis procedure that can accommodate this complexity through embedding the known physics within the design. The development of a model capturing the dynamics of the plasma relevant for control design enables not only the design of feedback controllers for regulation or tracking but also the design of optimal feedforward controllers for a systematic model-based approach to scenario planning, the design of state estimators for a reliable real-time reconstruction of the plasma internal profiles based on limited and noisy diagnostics, and the development of a fast predictive simulation code for closed-loop performance evaluation before implementation. Progress towards control-oriented modeling of the current profile evolution and associated control design has been reported following both data-driven and first-principles-driven approaches. An overview of these two approaches will be provided, as well as a discussion on research needs associated with each one of the model applications described above. Supported by the US Department of Energy under DE-SC0001334 and DE-SC0010661.

Electron momentum density and Compton profile by a semi-empirical approach

Science.gov (United States)

Aguiar, Julio C.; Mitnik, Darío; Di Rocco, Héctor O.

2015-08-01

Here we propose a semi-empirical approach to describe with good accuracy the electron momentum densities and Compton profiles for a wide range of pure crystalline metals. In the present approach, we use an experimental Compton profile to fit an analytical expression for the momentum densities of the valence electrons. This expression is similar to a Fermi-Dirac distribution function with two parameters, one of which coincides with the ground state kinetic energy of the free-electron gas and the other resembles the electron-electron interaction energy. In the proposed scheme conduction electrons are neither completely free nor completely bound to the atomic nucleus. This procedure allows us to include correlation effects. We tested the approach for all metals with Z=3-50 and showed the results for three representative elements: Li, Be and Al from high-resolution experiments.

What Do Women's Advertised Mate Preferences Reveal? An Analysis of Video Dating Profiles

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Cari D. Goetz

2013-04-01

Full Text Available This study examined women's video dating profiles to determine what their advertised mate preferences revealed about their mate value and relationship interests. Women created a one-minute long video dating profile for a hypothetical dating website. The videos were content analyzed into four categories of stated mate preferences: 1 “good genes” indicators 2 good resource investment potential indicators 3 good parenting indicators and 4 good partner indicators. Long-term mating interest was positively correlated with describing good partner indicators and self-perceived mate value was positively correlated with describing good genes indicators. Short-term mating interest was negatively correlated with describing any mate preferences while attractiveness was positively correlated with doing so. Results suggest that women's advertised mate preferences provide clues to their underlying relationship interests and mate value.

A statistical approach for predicting thermal diffusivity profiles in fusion plasmas as a transport model

International Nuclear Information System (INIS)

Yokoyama, Masayuki

2014-01-01

A statistical approach is proposed to predict thermal diffusivity profiles as a transport “model” in fusion plasmas. It can provide regression expressions for the ion and electron heat diffusivities (χ i and χ e ), separately, to construct their radial profiles. An approach that this letter is proposing outstrips the conventional scaling laws for the global confinement time (τ E ) since it also deals with profiles (temperature, density, heating depositions etc.). This approach has become possible with the analysis database accumulated by the extensive application of the integrated transport analysis suite to experiment data. In this letter, TASK3D-a analysis database for high-ion-temperature (high-T i ) plasmas in the LHD (Large Helical Device) is used as an example to describe an approach. (author)

Profiling Invasiveness in Head and Neck Cancer: Recent Contributions of Genomic and Transcriptomic Approaches

International Nuclear Information System (INIS)

Nisa, Lluís; Aebersold, Daniel Matthias; Giger, Roland; Caversaccio, Marco Domenico; Borner, Urs; Medová, Michaela; Zimmer, Yitzhak

2015-01-01

High-throughput molecular profiling approaches have emerged as precious research tools in the field of head and neck translational oncology. Such approaches have identified and/or confirmed the role of several genes or pathways in the acquisition/maintenance of an invasive phenotype and the execution of cellular programs related to cell invasion. Recently published new-generation sequencing studies in head and neck squamous cell carcinoma (HNSCC) have unveiled prominent roles in carcinogenesis and cell invasion of mutations involving NOTCH1 and PI3K-patwhay components. Gene-expression profiling studies combined with systems biology approaches have allowed identifying and gaining further mechanistic understanding into pathways commonly enriched in invasive HNSCC. These pathways include antigen-presenting and leucocyte adhesion molecules, as well as genes involved in cell-extracellular matrix interactions. Here we review the major insights into invasiveness in head and neck cancer provided by high-throughput molecular profiling approaches

Metabolic profiling of hypoxic cells revealed a catabolic signature required for cell survival.

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Christian Frezza

Full Text Available Hypoxia is one of the features of poorly vascularised areas of solid tumours but cancer cells can survive in these areas despite the low oxygen tension. The adaptation to hypoxia requires both biochemical and genetic responses that culminate in a metabolic rearrangement to counter-balance the decrease in energy supply from mitochondrial respiration. The understanding of metabolic adaptations under hypoxia could reveal novel pathways that, if targeted, would lead to specific death of hypoxic regions. In this study, we developed biochemical and metabolomic analyses to assess the effects of hypoxia on cellular metabolism of HCT116 cancer cell line. We utilized an oxygen fluorescent probe in anaerobic cuvettes to study oxygen consumption rates under hypoxic conditions without the need to re-oxygenate the cells and demonstrated that hypoxic cells can maintain active, though diminished, oxidative phosphorylation even at 1% oxygen. These results were further supported by in situ microscopy analysis of mitochondrial NADH oxidation under hypoxia. We then used metabolomic methodologies, utilizing liquid chromatography-mass spectrometry (LC-MS, to determine the metabolic profile of hypoxic cells. This approach revealed the importance of synchronized and regulated catabolism as a mechanism of adaptation to bioenergetic stress. We then confirmed the presence of autophagy under hypoxic conditions and demonstrated that the inhibition of this catabolic process dramatically reduced the ATP levels in hypoxic cells and stimulated hypoxia-induced cell death. These results suggest that under hypoxia, autophagy is required to support ATP production, in addition to glycolysis, and that the inhibition of autophagy might be used to selectively target hypoxic regions of tumours, the most notoriously resistant areas of solid tumours.

Profiling Invasiveness in Head and Neck Cancer: Recent Contributions of Genomic and Transcriptomic Approaches

Directory of Open Access Journals (Sweden)

Lluís Nisa

2015-03-01

Full Text Available High-throughput molecular profiling approaches have emerged as precious research tools in the field of head and neck translational oncology. Such approaches have identified and/or confirmed the role of several genes or pathways in the acquisition/maintenance of an invasive phenotype and the execution of cellular programs related to cell invasion. Recently published new-generation sequencing studies in head and neck squamous cell carcinoma (HNSCC have unveiled prominent roles in carcinogenesis and cell invasion of mutations involving NOTCH1 and PI3K-patwhay components. Gene-expression profiling studies combined with systems biology approaches have allowed identifying and gaining further mechanistic understanding into pathways commonly enriched in invasive HNSCC. These pathways include antigen-presenting and leucocyte adhesion molecules, as well as genes involved in cell-extracellular matrix interactions. Here we review the major insights into invasiveness in head and neck cancer provided by high-throughput molecular profiling approaches.

Functional gene profiling through metaRNAseq approach reveals diet-dependent variation in rumen microbiota of buffalo (Bubalus bubalis).

Science.gov (United States)

Hinsu, Ankit T; Parmar, Nidhi R; Nathani, Neelam M; Pandit, Ramesh J; Patel, Anand B; Patel, Amrutlal K; Joshi, Chaitanya G

2017-04-01

Recent advances in next generation sequencing technology have enabled analysis of complex microbial community from genome to transcriptome level. In the present study, metatranscriptomic approach was applied to elucidate functionally active bacteria and their biological processes in rumen of buffalo (Bubalus bubalis) adapted to different dietary treatments. Buffaloes were adapted to a diet containing 50:50, 75:25 and 100:0 forage to concentrate ratio, each for 6 weeks, before ruminal content sample collection. Metatranscriptomes from rumen fiber adherent and fiber-free active bacteria were sequenced using Ion Torrent PGM platform followed by annotation using MG-RAST server and CAZYmes (Carbohydrate active enzymes) analysis toolkit. In all the samples Bacteroidetes was the most abundant phylum followed by Firmicutes. Functional analysis using KEGG Orthology database revealed Metabolism as the most abundant category at level 1 within which Carbohydrate metabolism was dominating. Diet treatments also exerted significant differences in proportion of enzymes involved in metabolic pathways for VFA production. Carbohydrate Active Enzyme(CAZy) analysis revealed the abundance of genes encoding glycoside hydrolases with the highest representation of GH13 CAZy family in all the samples. The findings provide an overview of the activities occurring in the rumen as well as active bacterial population and the changes occurring through different dietary treatments. Copyright © 2017 Elsevier Ltd. All rights reserved.

Basis set approach in the constrained interpolation profile method

International Nuclear Information System (INIS)

Utsumi, T.; Koga, J.; Yabe, T.; Ogata, Y.; Matsunaga, E.; Aoki, T.; Sekine, M.

2003-07-01

We propose a simple polynomial basis-set that is easily extendable to any desired higher-order accuracy. This method is based on the Constrained Interpolation Profile (CIP) method and the profile is chosen so that the subgrid scale solution approaches the real solution by the constraints from the spatial derivative of the original equation. Thus the solution even on the subgrid scale becomes consistent with the master equation. By increasing the order of the polynomial, this solution quickly converges. 3rd and 5th order polynomials are tested on the one-dimensional Schroedinger equation and are proved to give solutions a few orders of magnitude higher in accuracy than conventional methods for lower-lying eigenstates. (author)

A security approach based on honeypots: Protecting Online Social network from malicious profiles

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Fatna Elmendili, Nisrine Maqran

2017-04-01

Full Text Available In the recent years, the fast development and the exponential utilization of social networks have prompted an expansion of social Computing. In social networks users are interconnected by edges or links, where Facebook, twitter, LinkedIn are most popular social networks websites. Due to the growing popularity of these sites they serve as a target for cyber criminality and attacks. It is mostly based on how users are using these sites like Twitter and others. Attackers can easily access and gather personal and sensitive user’s information. Users are less aware and least concerned about the security setting. And they easily become victim of identity breach. To detect malicious users or fake profiles different techniques have been proposed like our approach which is based on the use of social honeypots to discover malicious profiles in it. Inspired by security researchers who used honeypots to observe and analyze malicious activity in the networks, this method uses social honeypots to trap malicious users. The two key elements of the approach are: (1 The deployment of social honeypots for harvesting information of malicious profiles. (2 Analysis of the characteristics of these malicious profiles and those of deployed honeypots for creating classifiers that allow to filter the existing profiles and monitor the new profiles.

Vertical Soil Profiling Using a Galvanic Contact Resistivity Scanning Approach

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Luan Pan

2014-07-01

Full Text Available Proximal sensing of soil electromagnetic properties is widely used to map spatial land heterogeneity. The mapping instruments use galvanic contact, capacitive coupling or electromagnetic induction. Regardless of the type of instrument, the geometrical configuration between signal transmitting and receiving elements typically defines the shape of the depth response function. To assess vertical soil profiles, many modern instruments use multiple transmitter-receiver pairs. Alternatively, vertical electrical sounding can be used to measure changes in apparent soil electrical conductivity with depth at a specific location. This paper examines the possibility for the assessment of soil profiles using a dynamic surface galvanic contact resistivity scanning approach, with transmitting and receiving electrodes configured in an equatorial dipole-dipole array. An automated scanner system was developed and tested in agricultural fields with different soil profiles. While operating in the field, the distance between current injecting and measuring pairs of rolling electrodes was varied continuously from 40 to 190 cm. The preliminary evaluation included a comparison of scan results from 20 locations to shallow (less than 1.2 m deep soil profiles and to a two-layer soil profile model defined using an electromagnetic induction instrument.

Two approaches to the reactor-relevant high-beta plasmas with profile control in the Large Helical Device

International Nuclear Information System (INIS)

Ohdachi, S.; Watanabe, K.Y.; Sakakibara, S.

2008-10-01

From detailed optimization of configuration, volume averaged beta ∼ 5% has been achieved in the Large Helical Device(LHD). While the heating efficiency was the main point to be optimized in this approach, to form a more peaked pressure profile is another promising approach towards the high beta regime. A higher electron density profile with a steeper pressure gradient has been formed by pellet injection. From the MHD stability analysis, this peaked pressure profile is stable against the ideal MHD modes. By both approaches, the central plasma β 0 reaches about 10%. (author)

Embryonic stem cell-like features of testicular carcinoma in situ revealed by genome-wide gene expression profiling

DEFF Research Database (Denmark)

Almstrup, Kristian; Hoei-Hansen, Christina E; Wirkner, Ute

2004-01-01

in their stoichiometry on progression into embryonic carcinoma. We compared the CIS expression profile with patterns reported in embryonic stem cells (ESCs), which revealed a substantial overlap that may be as high as 50%. We also demonstrated an over-representation of expressed genes in regions of 17q and 12, reported......Carcinoma in situ (CIS) is the common precursor of histologically heterogeneous testicular germ cell tumors (TGCTs), which in recent decades have markedly increased and now are the most common malignancy of young men. Using genome-wide gene expression profiling, we identified >200 genes highly...

Liver protein profiles in insulin receptor-knockout mice reveal novel molecules involved in the diabetes pathophysiology.

Science.gov (United States)

Capuani, Barbara; Della-Morte, David; Donadel, Giulia; Caratelli, Sara; Bova, Luca; Pastore, Donatella; De Canio, Michele; D'Aguanno, Simona; Coppola, Andrea; Pacifici, Francesca; Arriga, Roberto; Bellia, Alfonso; Ferrelli, Francesca; Tesauro, Manfredi; Federici, Massimo; Neri, Anna; Bernardini, Sergio; Sbraccia, Paolo; Di Daniele, Nicola; Sconocchia, Giuseppe; Orlandi, Augusto; Urbani, Andrea; Lauro, Davide

2015-05-01

Liver has a principal role in glucose regulation and lipids homeostasis. It is under a complex control by substrates such as hormones, nutrients, and neuronal impulses. Insulin promotes glycogen synthesis, lipogenesis, and lipoprotein synthesis and inhibits gluconeogenesis, glycogenolysis, and VLDL secretion by modifying the expression and enzymatic activity of specific molecules. To understand the pathophysiological mechanisms leading to metabolic liver disease, we analyzed liver protein patterns expressed in a mouse model of diabetes by proteomic approaches. We used insulin receptor-knockout (IR(-/-)) and heterozygous (IR(+/-)) mice as a murine model of liver metabolic dysfunction associated with diabetic ketoacidosis and insulin resistance. We evaluated liver fatty acid levels by microscopic examination and protein expression profiles by orthogonal experimental strategies using protein 2-DE MALDI-TOF/TOF and peptic nLC-MS/MS shotgun profiling. Identified proteins were then loaded into Ingenuity Pathways Analysis to find possible molecular networks. Twenty-eight proteins identified by 2-DE analysis and 24 identified by nLC-MS/MS shotgun were differentially expressed among the three genotypes. Bioinformatic analysis revealed a central role of high-mobility group box 1/2 and huntigtin never reported before in association with metabolic and related liver disease. A different modulation of these proteins in both blood and hepatic tissue further suggests their role in these processes. These results provide new insight into pathophysiology of insulin resistance and hepatic steatosis and could be useful in identifying novel biomarkers to predict risk for diabetes and its complications. Copyright © 2015 the American Physiological Society.

In-Depth Two-Year Study of Phenolic Profile Variability among Olive Oils from Autochthonous and Mediterranean Varieties in Morocco, as Revealed by a LC-MS Chemometric Profiling Approach

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Aadil Bajoub

2016-12-01

Full Text Available Olive oil phenolic fraction considerably contributes to the sensory quality and nutritional value of this foodstuff. Herein, the phenolic fraction of 203 olive oil samples extracted from fruits of four autochthonous Moroccan cultivars (“Picholine Marocaine”, “Dahbia”, “Haouzia” and “Menara”, and nine Mediterranean varieties recently introduced in Morocco (“Arbequina”, “Arbosana”, “Cornicabra”, “Frantoio”, “Hojiblanca”, “Koroneiki”, “Manzanilla”, “Picholine de Languedoc” and “Picual”, were explored over two consecutive crop seasons (2012/2013 and 2013/2014 by using liquid chromatography-mass spectrometry. A total of 32 phenolic compounds (and quinic acid, belonging to five chemical classes (secoiridoids, simple phenols, flavonoids, lignans and phenolic acids were identified and quantified. Phenolic profiling revealed that the determined phenolic compounds showed variety-dependent levels, being, at the same time, significantly affected by the crop season. Moreover, based on the obtained phenolic composition and chemometric linear discriminant analysis, statistical models were obtained allowing a very satisfactory classification and prediction of the varietal origin of the studied oils.

Risk Profile Indicators and Spanish Banks’ Probability of Default from a Regulatory Approach

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Pilar Gómez-Fernández-Aguado

2018-04-01

Full Text Available This paper analyses the relationships between the traditional bank risk profile indicators and a new measure of banks’ probability of default that considers the Basel regulatory framework. First, based on the SYstemic Model of Bank Originated Losses (SYMBOL, we calculated the individual probabilities of default (PD of a representative sample of Spanish credit institutions during the period of 2008–2016. Then, panel data regressions were estimated to explore the influence of the risk indicators on the PD. Our findings on the Spanish banking system could be important to regulatory and supervisory authorities. First, the PD based on the SYMBOL model could be used to analyse bank risk from a regulatory approach. Second, the results might be useful for designing new regulations focused on the key factors that affect the banks’ probability of default. Third, our findings reveal that the emphasis on regulation and supervision should differ by type of entity.

The Genetic Relationship between Leishmania aethiopica and Leishmania tropica Revealed by Comparing Microsatellite Profiles.

Science.gov (United States)

Krayter, Lena; Schnur, Lionel F; Schönian, Gabriele

2015-01-01

Leishmania (Leishmania) aethiopica and L. (L.) tropica cause cutaneous leishmaniases and appear to be related. L. aethiopica is geographically restricted to Ethiopia and Kenya; L. tropica is widely dispersed from the Eastern Mediterranean, through the Middle East into eastern India and in north, east and south Africa. Their phylogenetic inter-relationship is only partially revealed. Some studies indicate a close relationship. Here, eight strains of L. aethiopica were characterized genetically and compared with 156 strains of L. tropica from most of the latter species' geographical range to discern the closeness. Twelve unlinked microsatellite markers previously used to genotype strains of L. tropica were successfully applied to the eight strains of L. aethiopica and their microsatellite profiles were compared to those of 156 strains of L. tropica from various geographical locations that were isolated from human cases of cutaneous and visceral leishmaniasis, hyraxes and sand fly vectors. All the microsatellite profiles were subjected to various analytical algorithms: Bayesian statistics, distance-based and factorial correspondence analysis, revealing: (i) the species L. aethiopica, though geographically restricted, is genetically very heterogeneous; (ii) the strains of L. aethiopica formed a distinct genetic cluster; and (iii) strains of L. aethiopica are closely related to strains of L. tropica and more so to the African ones, although, by factorial correspondence analysis, clearly separate from them. The successful application of the 12 microsatellite markers, originally considered species-specific for the species L. tropica, to strains of L. aethiopica confirmed the close relationship between these two species. The Bayesian and distance-based methods clustered the strains of L. aethiopica among African strains of L. tropica, while the factorial correspondence analysis indicated a clear separation between the two species. There was no correlation between

Impact of measurement approach on the quality of gamma scanning density profile in a tray type lab-scale column

International Nuclear Information System (INIS)

Shahabinejad, H.; Feghhi, S.A.H.; Khorsandi, M.

2014-01-01

This article presents a study for investigating impact of the measurement approach on the quality of gamma scanning density profile in tray type columns using experimental and computational evaluations. Experimental density profiles from the total and the photopeak count measurements, as two approaches in gamma ray column scanning technique, has been compared with the computational density profile from Monte Carlo simulation results. We used a laboratory distillation column of 51 cm diameter as an illustrative example for this investigation. 137 Cs was used as a gamma ray source with the activity of 296 MBq (8 mCi), with a NaI(Tl) detector. MCNP4C Monte Carlo code has been used for simulations. The quality of the density profile in the photopeak count approach is relatively within 155–204% better than that of the total count approach for experimental results. The same comparison for simulation results leads to a relative difference within 100–135% for the density profile. - Highlights: • The quality of density profile in gamma scanning technique has been studied. • Quality of density profile depends on the measurement approach. • A laboratory distillation column has been used as an illustrative example. • MCNP4C Monte Carlo code has been used for simulations

Quantitative proteomics reveals protein profiles underlying major transitions in aspen wood development.

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Obudulu, Ogonna; Bygdell, Joakim; Sundberg, Björn; Moritz, Thomas; Hvidsten, Torgeir R; Trygg, Johan; Wingsle, Gunnar

2016-02-18

Wood development is of outstanding interest both to basic research and industry due to the associated cellulose and lignin biomass production. Efforts to elucidate wood formation (which is essential for numerous aspects of both pure and applied plant science) have been made using transcriptomic analyses and/or low-resolution sampling. However, transcriptomic data do not correlate perfectly with levels of expressed proteins due to effects of post-translational modifications and variations in turnover rates. In addition, high-resolution analysis is needed to characterize key transitions. In order to identify protein profiles across the developmental region of wood formation, an in-depth and tissue specific sampling was performed. We examined protein profiles, using an ultra-performance liquid chromatography/quadrupole time of flight mass spectrometry system, in high-resolution tangential sections spanning all wood development zones in Populus tremula from undifferentiated cambium to mature phloem and xylem, including cell expansion and cell death zones. In total, we analyzed 482 sections, 20-160 μm thick, from four 47-year-old trees growing wild in Sweden. We obtained high quality expression profiles for 3,082 proteins exhibiting consistency across the replicates, considering that the trees were growing in an uncontrolled environment. A combination of Principal Component Analysis (PCA), Orthogonal Projections to Latent Structures (OPLS) modeling and an enhanced stepwise linear modeling approach identified several major transitions in global protein expression profiles, pinpointing (for example) locations of the cambial division leading to phloem and xylem cells, and secondary cell wall formation zones. We also identified key proteins and associated pathways underlying these developmental landmarks. For example, many of the lignocellulosic related proteins were upregulated in the expansion to the early developmental xylem zone, and for laccases with a rapid decrease

Control of plasma profile in microwave discharges via inverse-problem approach

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Yasuyoshi Yasaka

2013-12-01

Full Text Available In the manufacturing process of semiconductors, plasma processing is an essential technology, and the plasma used in the process is required to be of high density, low temperature, large diameter, and high uniformity. This research focuses on the microwave-excited plasma that meets these needs, and the research target is a spatial profile control. Two novel techniques are introduced to control the uniformity; one is a segmented slot antenna that can change radial distribution of the radiated field during operation, and the other is a hyper simulator that can predict microwave power distribution necessary for a desired radial density profile. The control system including these techniques provides a method of controlling radial profiles of the microwave plasma via inverse-problem approach, and is investigated numerically and experimentally.

Mutational Profiling of Malignant Mesothelioma Revealed Potential Therapeutic Targets in EGFR and NRAS

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Jeong Eun Kim

2018-04-01

Full Text Available Pemetrexed and platinum (PP combination chemotherapy is the current standard first-line therapy for treatment of malignant mesothelioma (MM. However, a useful predictive biomarker for PP therapy is yet to be found. Here, we performed targeted exome sequencing to profile somatic mutations and copy number variations in 12 MM patients treated with PP therapy. We identified 187 somatic mutations in 12 patients (65 synonymous, 102 missense, 2 nonsense, 5 splice site, and 13 small coding insertions/deletions. We identified somatic mutations in 23 genes including BAP1, TP53, NRAS, and EGFR. Interestingly, rare NRAS p.Q61K and EGFR exon 19 deletions were observed in 2 patients. We also found somatic chromosomal copy number deletions in CDKN2A and CDKN2B genes. Genetic alteration related to response after PP therapy was not found. Somatic mutation profiling in MM patients receiving PP therapy revealed genetic alterations in potential therapeutic targets such as NRAS and EGFR. No alterations in genes with potential predictive role for PP therapy were found.

Mutational Profiling of Malignant Mesothelioma Revealed Potential Therapeutic Targets in EGFR and NRAS.

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Kim, Jeong Eun; Kim, Deokhoon; Hong, Yong Sang; Kim, Kyu-Pyo; Yoon, Young Kwang; Lee, Dae Ho; Kim, Sang-We; Chun, Sung-Min; Jang, Se Jin; Kim, Tae Won

2018-04-01

Pemetrexed and platinum (PP) combination chemotherapy is the current standard first-line therapy for treatment of malignant mesothelioma (MM). However, a useful predictive biomarker for PP therapy is yet to be found. Here, we performed targeted exome sequencing to profile somatic mutations and copy number variations in 12 MM patients treated with PP therapy. We identified 187 somatic mutations in 12 patients (65 synonymous, 102 missense, 2 nonsense, 5 splice site, and 13 small coding insertions/deletions). We identified somatic mutations in 23 genes including BAP1, TP53, NRAS, and EGFR. Interestingly, rare NRAS p.Q61K and EGFR exon 19 deletions were observed in 2 patients. We also found somatic chromosomal copy number deletions in CDKN2A and CDKN2B genes. Genetic alteration related to response after PP therapy was not found. Somatic mutation profiling in MM patients receiving PP therapy revealed genetic alterations in potential therapeutic targets such as NRAS and EGFR. No alterations in genes with potential predictive role for PP therapy were found. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Proteome Profiling Outperforms Transcriptome Profiling for Coexpression Based Gene Function Prediction

Energy Technology Data Exchange (ETDEWEB)

Wang, Jing; Ma, Zihao; Carr, Steven A.; Mertins, Philipp; Zhang, Hui; Zhang, Zhen; Chan, Daniel W.; Ellis, Matthew J. C.; Townsend, R. Reid; Smith, Richard D.; McDermott, Jason E.; Chen, Xian; Paulovich, Amanda G.; Boja, Emily S.; Mesri, Mehdi; Kinsinger, Christopher R.; Rodriguez, Henry; Rodland, Karin D.; Liebler, Daniel C.; Zhang, Bing

2016-11-11

Coexpression of mRNAs under multiple conditions is commonly used to infer cofunctionality of their gene products despite well-known limitations of this “guilt-by-association” (GBA) approach. Recent advancements in mass spectrometry-based proteomic technologies have enabled global expression profiling at the protein level; however, whether proteome profiling data can outperform transcriptome profiling data for coexpression based gene function prediction has not been systematically investigated. Here, we address this question by constructing and analyzing mRNA and protein coexpression networks for three cancer types with matched mRNA and protein profiling data from The Cancer Genome Atlas (TCGA) and the Clinical Proteomic Tumor Analysis Consortium (CPTAC). Our analyses revealed a marked difference in wiring between the mRNA and protein coexpression networks. Whereas protein coexpression was driven primarily by functional similarity between coexpressed genes, mRNA coexpression was driven by both cofunction and chromosomal colocalization of the genes. Functionally coherent mRNA modules were more likely to have their edges preserved in corresponding protein networks than functionally incoherent mRNA modules. Proteomic data strengthened the link between gene expression and function for at least 75% of Gene Ontology (GO) biological processes and 90% of KEGG pathways. A web application Gene2Net (http://cptac.gene2net.org) developed based on the three protein coexpression networks revealed novel gene-function relationships, such as linking ERBB2 (HER2) to lipid biosynthetic process in breast cancer, identifying PLG as a new gene involved in complement activation, and identifying AEBP1 as a new epithelial-mesenchymal transition (EMT) marker. Our results demonstrate that proteome profiling outperforms transcriptome profiling for coexpression based gene function prediction. Proteomics should be integrated if not preferred in gene function and human disease studies

Creating Rich Portraits: A Mixed-Methods Approach to Understanding Profiles of Intrinsic and Extrinsic Motivations

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Corpus, Jennifer Henderlong; Wormington, Stephanie V.; Haimovitz, Kyla

2016-01-01

A person-centered, mixed-methods approach (self-report surveys, semistructured interviews, school records) was used to characterize and evaluate profiles of intrinsic and extrinsic motivations among 243 third- through eighth-grade students. Cluster analysis suggested four distinct profiles: high quantity (high intrinsic, high extrinsic), primarily…

Multi-Omics Analysis Reveals a Correlation between the Host Phylogeny, Gut Microbiota and Metabolite Profiles in Cyprinid Fishes

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Li, Tongtong; Long, Meng; Li, Huan; Gatesoupe, François-Joël; Zhang, Xujie; Zhang, Qianqian; Feng, Dongyue; Li, Aihua

2017-01-01

Gut microbiota play key roles in host nutrition and metabolism. However, little is known about the relationship between host genetics, gut microbiota and metabolic profiles. Here, we used high-throughput sequencing and gas chromatography/mass spectrometry approaches to characterize the microbiota composition and the metabolite profiles in the gut of five cyprinid fish species with three different feeding habits raised under identical husbandry conditions. Our results showed that host species and feeding habits significantly affect not only gut microbiota composition but also metabolite profiles (ANOSIM, p ≤ 0.05). Mantel test demonstrated that host phylogeny, gut microbiota, and metabolite profiles were significantly related to each other (p ≤ 0.05). Additionally, the carps with the same feeding habits had more similarity in gut microbiota composition and metabolite profiles. Various metabolites were correlated positively with bacterial taxa involved in food degradation. Our results shed new light on the microbiome and metabolite profiles in the gut content of cyprinid fishes, and highlighted the correlations between host genotype, fish gut microbiome and putative functions, and gut metabolite profiles. PMID:28367147

The distinctive gastric fluid proteome in gastric cancer reveals a multi-biomarker diagnostic profile

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Eng Alvin KH

2008-10-01

Full Text Available Abstract Background Overall gastric cancer survival remains poor mainly because there are no reliable methods for identifying highly curable early stage disease. Multi-protein profiling of gastric fluids, obtained from the anatomic site of pathology, could reveal diagnostic proteomic fingerprints. Methods Protein profiles were generated from gastric fluid samples of 19 gastric cancer and 36 benign gastritides patients undergoing elective, clinically-indicated gastroscopy using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry on multiple ProteinChip arrays. Proteomic features were compared by significance analysis of microarray algorithm and two-way hierarchical clustering. A second blinded sample set (24 gastric cancers and 29 clinically benign gastritides was used for validation. Results By significance analysyis of microarray, 60 proteomic features were up-regulated and 46 were down-regulated in gastric cancer samples (p Conclusion This simple and reproducible multimarker proteomic assay could supplement clinical gastroscopic evaluation of symptomatic patients to enhance diagnostic accuracy for gastric cancer and pre-malignant lesions.

Melodic multi-feature paradigm reveals auditory profiles in music-sound encoding

DEFF Research Database (Denmark)

Tervaniemi, Mari; Huotilainen, Minna; Brattico, Elvira

2014-01-01

Musical expertise modulates preattentive neural sound discrimination. However, this evidence up to great extent originates from paradigms using very simple stimulation. Here we use a novel melody paradigm (revealing the auditory profile for six sound parameters in parallel) to compare memory......-related mismatch negativity (MMN) and attention-related P3a responses recorded from non-musicians and Finnish Folk musicians. MMN emerged in both groups of participants for all sound changes (except for rhythmic changes in non-musicians). In Folk musicians, the MMN was enlarged for mistuned sounds when compared...... with non-musicians. This is taken to reflect their familiarity with pitch information which is in key position in Finnish folk music when compared with e.g., rhythmic information. The MMN was followed by P3a after timbre changes, rhythm changes, and melody transposition. The MMN and P3a topographies...

Offset-electrode profile acquisition strategy for electrical resistivity tomography

Science.gov (United States)

Robbins, Austin R.; Plattner, Alain

2018-04-01

We present an electrode layout strategy that allows electrical resistivity profiles to image the third dimension close to the profile plane. This "offset-electrode profile" approach involves laterally displacing electrodes away from the profile line in an alternating fashion and then inverting the resulting data using three-dimensional electrical resistivity tomography software. In our synthetic and field surveys, the offset-electrode method succeeds in revealing three-dimensional structures in the vicinity of the profile plane, which we could not achieve using three-dimensional inversions of linear profiles. We confirm and explain the limits of linear electrode profiles through a discussion of the three-dimensional sensitivity patterns: For a homogeneous starting model together with a linear electrode layout, all sensitivities remain symmetric with respect to the profile plane through each inversion step. This limitation can be overcome with offset-electrode layouts by breaking the symmetry pattern among the sensitivities. Thanks to freely available powerful three-dimensional resistivity tomography software and cheap modern computing power, the requirement for full three-dimensional calculations does not create a significant burden and renders the offset-electrode approach a cost-effective method. By offsetting the electrodes in an alternating pattern, as opposed to laying the profile out in a U-shape, we minimize shortening the profile length.

Differential lysine acetylation profiles of Erwinia amylovora strains revealed by proteomics

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Wu, Xia; Vellaichamy, Adaikkalam; Wang, Dongping; Zamdborg, Leonid; Kelleher, Neil L.; Huber, Steven C.; Zhao, Youfu

2015-01-01

Protein lysine acetylation (LysAc) has recently been demonstrated to be widespread in E. coli and Salmonella, and to broadly regulate bacterial physiology and metabolism. However, LysAc in plant pathogenic bacteria is largely unknown. Here we first report the lysine acetylome of Erwinia amylovora, an enterobacterium causing serious fire blight disease of apples and pears. Immunoblots using generic anti-lysine acetylation antibodies demonstrated that growth conditions strongly affected the LysAc profiles in E. amylovora. Differential LysAc profiles were also observed for two E. amylovora strains, known to have differential virulence in plants, indicating translational modification of proteins may be important in determining virulence of bacterial strains. Proteomic analysis of LysAc in two E. amylovora strains identified 141 LysAc sites in 96 proteins that function in a wide range of biological pathways. Consistent with previous reports, 44% of the proteins are involved in metabolic processes, including central metabolism, lipopolysaccharide, nucleotide and amino acid metabolism. Interestingly, for the first time, several proteins involved in E. amylovora virulence, including exopolysaccharide amylovoran biosynthesis- and type III secretion-associated proteins, were found to be lysine acetylated, suggesting that LysAc may play a major role in bacterial virulence. Comparative analysis of LysAc sites in E. amylovora and E. coli further revealed the sequence and structural commonality for LysAc in the two organisms. Collectively, these results reinforce the notion that LysAc of proteins is widespread in bacterial metabolism and virulence. PMID:23234799

A fast approach to determine a fed batch feeding profile for recombinant Pichia pastoris strains

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Herwig Christoph

2011-10-01

Full Text Available Abstract Background The microorganism Pichia pastoris is a commonly used microbial host for the expression of recombinant proteins in biotechnology and biopharmaceutical industry. To speed up process development, a fast methodology to determine strain characteristic parameters, which are needed to subsequently set up fed batch feeding profiles, is required. Results Here, we show the general applicability of a novel approach to quantify a certain minimal set of bioprocess-relevant parameters, i.e. the adaptation time of the culture to methanol, the specific substrate uptake rate during the adaptation phase and the maximum specific substrate uptake rate, based on fast and easy-to-do batch cultivations with repeated methanol pulses in a batch culture. A detailed analysis of the adaptation of different P. pastoris strains to methanol was conducted and revealed that each strain showed very different characteristics during adaptation, illustrating the need of individual screenings for an optimal parameter definition during this phase. Based on the results obtained in batch cultivations, dynamic feeding profiles based on the specific substrate uptake rate were employed for different P. pastoris strains. In these experiments the maximum specific substrate uptake rate, which had been defined in batch experiments, also represented the upper limit of methanol uptake, underlining the validity of the determined process-relevant parameters and the overall experimental strategy. Conclusion In this study, we show that a fast approach to determine a minimal set of strain characteristic parameters based on easy-to-do batch cultivations with methanol pulses is generally applicable for different P. pastoris strains and that dynamic fed batch strategies can be designed on the specific substrate uptake rate without running the risk of methanol accumulation.

Pre-clinical cognitive phenotypes for Alzheimer disease: a latent profile approach.

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Hayden, Kathleen M; Kuchibhatla, Maragatha; Romero, Heather R; Plassman, Brenda L; Burke, James R; Browndyke, Jeffrey N; Welsh-Bohmer, Kathleen A

2014-11-01

Cognitive profiles for pre-clinical Alzheimer disease (AD) can be used to identify groups of individuals at risk for disease and better characterize pre-clinical disease. Profiles or patterns of performance as pre-clinical phenotypes may be more useful than individual test scores or measures of global decline. To evaluate patterns of cognitive performance in cognitively normal individuals to derive latent profiles associated with later onset of disease using a combination of factor analysis and latent profile analysis. The National Alzheimer Coordinating Centers collect data, including a battery of neuropsychological tests, from participants at 29 National Institute on Aging-funded Alzheimer Disease Centers across the United States. Prior factor analyses of this battery demonstrated a four-factor structure comprising memory, attention, language, and executive function. Factor scores from these analyses were used in a latent profile approach to characterize cognition among a group of cognitively normal participants (N = 3,911). Associations between latent profiles and disease outcomes an average of 3 years later were evaluated with multinomial regression models. Similar analyses were used to determine predictors of profile membership. Four groups were identified; each with distinct characteristics and significantly associated with later disease outcomes. Two groups were significantly associated with development of cognitive impairment. In post hoc analyses, both the Trail Making Test Part B, and a contrast score (Delayed Recall - Trails B), significantly predicted group membership and later cognitive impairment. Latent profile analysis is a useful method to evaluate patterns of cognition in large samples for the identification of preclinical AD phenotypes; comparable results, however, can be achieved with very sensitive tests and contrast scores. Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Training Second-Career Teachers: A Different Student Profile, A Different Training Approach?

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Marlies Baeten

2016-08-01

Full Text Available Second-career teachers are career changers who leave their current jobs to become teachers. This study conducts a narrative literature review which explores the student profiles of these teachers, asking how they differ from school leavers entering teacher education. The literature review also explores the characteristics of training approaches that are most suitable for second-career teachers based on their general student profile. Results show that second-career teachers are older, have strong intrinsic motivation, possess a wide range of knowledge and skills, have a self-directed and application-oriented approach to learning and teaching, and appreciate peer support. They benefit from teacher education programs that are flexible and include a preparatory period, that transfer their expertise into the teaching profession, provide opportunities for self-directed learning and peer support, integrate coursework and field experience, offer a significant amount of field experience and provide intensive mentoring support.

Airline Passenger Profiling Based on Fuzzy Deep Machine Learning.

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Zheng, Yu-Jun; Sheng, Wei-Guo; Sun, Xing-Ming; Chen, Sheng-Yong

2017-12-01

Passenger profiling plays a vital part of commercial aviation security, but classical methods become very inefficient in handling the rapidly increasing amounts of electronic records. This paper proposes a deep learning approach to passenger profiling. The center of our approach is a Pythagorean fuzzy deep Boltzmann machine (PFDBM), whose parameters are expressed by Pythagorean fuzzy numbers such that each neuron can learn how a feature affects the production of the correct output from both the positive and negative sides. We propose a hybrid algorithm combining a gradient-based method and an evolutionary algorithm for training the PFDBM. Based on the novel learning model, we develop a deep neural network (DNN) for classifying normal passengers and potential attackers, and further develop an integrated DNN for identifying group attackers whose individual features are insufficient to reveal the abnormality. Experiments on data sets from Air China show that our approach provides much higher learning ability and classification accuracy than existing profilers. It is expected that the fuzzy deep learning approach can be adapted for a variety of complex pattern analysis tasks.

GC-MS metabolic profiling of Cabernet Sauvignon and Merlot cultivars during grapevine berry development and network analysis reveals a stage- and cultivar-dependent connectivity of primary metabolites.

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Cuadros-Inostroza, Alvaro; Ruíz-Lara, Simón; González, Enrique; Eckardt, Aenne; Willmitzer, Lothar; Peña-Cortés, Hugo

Information about the total chemical composition of primary metabolites during grape berry development is scarce, as are comparative studies trying to understand to what extent metabolite modifications differ between cultivars during ripening. Thus, correlating the metabolic profiles with the changes occurring in berry development and ripening processes is essential to progress in their comprehension as well in the development of new approaches to improve fruit attributes. Here, the developmental metabolic profiling analysis across six stages from flowering to fully mature berries of two cultivars, Cabernet Sauvignon and Merlot, is reported at metabolite level. Based on a gas chromatography-mass spectrometry untargeted approach, 115 metabolites were identified and relative quantified in both cultivars. Sugars and amino acids levels show an opposite behaviour in both cultivars undergoing a highly coordinated shift of metabolite associated to primary metabolism during the stages involved in growth, development and ripening of berries. The changes are characteristic for each stage, the most pronounced ones occuring at fruit setting and pre-Veraison. They are associated to a reduction of the levels of metabolites present in the earlier corresponding stage, revealing a required catabolic activity of primary metabolites for grape berry developmental process. Network analysis revealed that the network connectivity of primary metabolites is stage- and cultivar-dependent, suggesting differences in metabolism regulation between both cultivars as the maturity process progresses. Furthermore, network analysis may represent an appropriate method to display the association between primary metabolites during berry developmental processes among different grapevine cultivars and for identifying potential biologically relevant metabolites.

Evaluation of vertical profiles to design continuous descent approach procedure

Science.gov (United States)

Pradeep, Priyank

The current research focuses on predictability, variability and operational feasibility aspect of Continuous Descent Approach (CDA), which is among the key concepts of the Next Generation Air Transportation System (NextGen). The idle-thrust CDA is a fuel economical, noise and emission abatement procedure, but requires increased separation to accommodate for variability and uncertainties in vertical and speed profiles of arriving aircraft. Although a considerable amount of researches have been devoted to the estimation of potential benefits of the CDA, only few have attempted to explain the predictability, variability and operational feasibility aspect of CDA. The analytical equations derived using flight dynamics and Base of Aircraft and Data (BADA) Total Energy Model (TEM) in this research gives insight into dependency of vertical profile of CDA on various factors like wind speed and gradient, weight, aircraft type and configuration, thrust settings, atmospheric factors (deviation from ISA (DISA), pressure and density of the air) and descent speed profile. Application of the derived equations to idle-thrust CDA gives an insight into sensitivity of its vertical profile to multiple factors. This suggests fixed geometric flight path angle (FPA) CDA has higher degree of predictability and lesser variability at the cost of non-idle and low thrust engine settings. However, with optimized design this impact can be overall minimized. The CDA simulations were performed using Future ATM Concept Evaluation Tool (FACET) based on radar-track and aircraft type data (BADA) of the real air-traffic to some of the busiest airports in the USA (ATL, SFO and New York Metroplex (JFK, EWR and LGA)). The statistical analysis of the vertical profiles of CDA shows 1) mean geometric FPAs derived from various simulated vertical profiles are consistently shallower than 3° glideslope angle and 2) high level of variability in vertical profiles of idle-thrust CDA even in absence of

Metabolite Profiling of Peppers of Various Colors Reveals Relationships Between Tocopherol, Carotenoid, and Phytosterol Content.

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Kim, Tae Jin; Choi, Jaehyuk; Kim, Kil Won; Ahn, Soon Kil; Ha, Sun-Hwa; Choi, Yongsoo; Park, Nam Il; Kim, Jae Kwang

2017-12-01

Peppers are widely consumed in Korea; the varietal development of peppers with increased content of beneficial plant metabolites is, therefore, of considerable interest. This requires a comprehensive understanding of the metabolic profile of pepper plants and the factors affecting this profile. To this end, we determined the content of various metabolites, such as hydrophilic and lipophilic compounds, phenolic acids, carotenoids, and capsaicinoids in peppers of various colors (green, red, pale green, and violet peppers) and in a high-pungency (green) pepper. We also performed principal component analysis (PCA), Pearson's correlation analysis, and hierarchical clustering analysis (HCA) to determine the relationships among these metabolites in peppers. PCA results indicated no significant variances among the 3 sample replicates. The HCA showed correlations between the metabolites resulting from common or closely linked biosynthesis pathways. Our results showed that carotenoids correlated positively with tocopherols and negatively with phytosterols; our findings also indicated a close relationship between the methylerythritol 4-phosphate and mevalonic acid biosynthesis pathways, providing evidence in favor of an earlier hypothesis regarding crosstalk across the chloroplast membrane. We, thus, demonstrate that metabolic profiling combined with multivariate analysis is a useful tool for analyzing metabolic networks. A total of 71 metabolites were measured in 5 peppers of different colors. The metabolic profiling with multivariate analysis revealed that tocopherol content had a positive correlation with the carotenoid content and a negative correlation with the phytosterol content. The results of this study may help in breeding programs to produce new germplasm with enhanced nutritional quality. © 2017 Institute of Food Technologists®.

Kinome-wide transcriptional profiling of uveal melanoma reveals new vulnerabilities to targeted therapeutics.

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Bailey, Fiona P; Clarke, Kim; Kalirai, Helen; Kenyani, Jenna; Shahidipour, Haleh; Falciani, Francesco; Coulson, Judy M; Sacco, Joseph J; Coupland, Sarah E; Eyers, Patrick A

2018-03-01

Metastatic uveal melanoma (UM) is invariably fatal, usually within a year of diagnosis. There are currently no effective therapies, and clinical studies employing kinase inhibitors have so far demonstrated limited success. This is despite common activating mutations in GNAQ/11 genes, which trigger signalling pathways that might predispose tumours to a variety of targeted drugs. In this study, we have profiled kinome expression network dynamics in various human ocular melanomas. We uncovered a shared transcriptional profile in human primary UM samples and across a variety of experimental cell-based models. The poor overall response of UM cells to FDA-approved kinase inhibitors contrasted with much higher sensitivity to the bromodomain inhibitor JQ1, a broad transcriptional repressor. Mechanistically, we identified a repressed FOXM1-dependent kinase subnetwork in JQ1-exposed cells that contained multiple cell cycle-regulated protein kinases. Consistently, we demonstrated vulnerability of UM cells to inhibitors of mitotic protein kinases within this network, including the investigational PLK1 inhibitor BI6727. We conclude that analysis of kinome-wide signalling network dynamics has the potential to reveal actionable drug targets and inhibitors of potential therapeutic benefit for UM patients. © 2017 The Authors. Pigment Cell & Melanoma Research Published by John Wiley & Sons.

MicroRNA profiling reveals dysregulated microRNAs and their target gene regulatory networks in cemento-ossifying fibroma.

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Pereira, Thaís Dos Santos Fontes; Brito, João Artur Ricieri; Guimarães, André Luiz Sena; Gomes, Carolina Cavaliéri; de Lacerda, Júlio Cesar Tanos; de Castro, Wagner Henriques; Coimbra, Roney Santos; Diniz, Marina Gonçalves; Gomez, Ricardo Santiago

2018-01-01

Cemento-ossifying fibroma (COF) is a benign fibro-osseous neoplasm of uncertain pathogenesis, and its treatment results in morbidity. MicroRNAs (miRNA) are small non-coding RNAs that regulate gene expression and may represent therapeutic targets. The purpose of the study was to generate a comprehensive miRNA profile of COF compared to normal bone. Additionally, the most relevant pathways and target genes of differentially expressed miRNA were investigated by in silico analysis. Nine COF and ten normal bone samples were included in the study. miRNA profiling was carried out by using TaqMan® OpenArray® Human microRNA panel containing 754 validated human miRNAs. We identified the most relevant miRNAs target genes through the leader gene approach, using STRING and Cytoscape software. Pathways enrichment analysis was performed using DIANA-miRPath. Eleven miRNAs were downregulated (hsa-miR-95-3p, hsa-miR-141-3p, hsa-miR-205-5p, hsa-miR-223-3p, hsa-miR-31-5p, hsa-miR-944, hsa-miR-200b-3p, hsa-miR-135b-5p, hsa-miR-31-3p, hsa-miR-223-5p and hsa-miR-200c-3p), and five were upregulated (hsa-miR-181a-5p, hsa-miR-181c-5p, hsa-miR-149-5p, hsa-miR-138-5p and hsa-miR-199a-3p) in COF compared to normal bone. Eighteen common target genes were predicted, and the leader genes approach identified the following genes involved in human COF: EZH2, XIAP, MET and TGFBR1. According to the biology of bone and COF, the most relevant KEGG pathways revealed by enrichment analysis were proteoglycans in cancer, miRNAs in cancer, pathways in cancer, p53-, PI3K-Akt-, FoxO- and TGF-beta signalling pathways, which were previously found to be differentially regulated in bone neoplasms, odontogenic tumours and osteogenesis. miRNA dysregulation occurs in COF, and EZH2, XIAP, MET and TGFBR1 are potential targets for functional analysis validation. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

On the analysis of line profile variations: A statistical approach

International Nuclear Information System (INIS)

McCandliss, S.R.

1988-01-01

This study is concerned with the empirical characterization of the line profile variations (LPV), which occur in many of and Wolf-Rayet stars. The goal of the analysis is to gain insight into the physical mechanisms producing the variations. The analytic approach uses a statistical method to quantify the significance of the LPV and to identify those regions in the line profile which are undergoing statistically significant variations. Line positions and flux variations are then measured and subject to temporal and correlative analysis. Previous studies of LPV have for the most part been restricted to observations of a single line. Important information concerning the range and amplitude of the physical mechanisms involved can be obtained by simultaneously observing spectral features formed over a range of depths in the extended mass losing atmospheres of massive, luminous stars. Time series of a Wolf-Rayet and two of stars with nearly complete spectral coverage from 3940 angstrom to 6610 angstrom and with spectral resolution of R = 10,000 are analyzed here. These three stars exhibit a wide range of both spectral and temporal line profile variations. The HeII Pickering lines of HD 191765 show a monotonic increase in the peak rms variation amplitude with lines formed at progressively larger radii in the Wolf-Rayet star wind. Two times scales of variation have been identified in this star: a less than one day variation associated with small scale flickering in the peaks of the line profiles and a greater than one day variation associated with large scale asymmetric changes in the overall line profile shapes. However, no convincing period phenomena are evident at those periods which are well sampled in this time series

New approach to the suction force at the leading edge of a profile with zero thickness

NARCIS (Netherlands)

Sparenberg, JA; de Jager, EM

2004-01-01

This paper considers the suction force at the leading edge of a profile with zero thickness in an incompressible and inviscid fluid flow. The theory is linear, and the approach to the suction force is from the innerside of the profile. It is shown that the suction force can be considered as an

1H NMR-based metabolic profiling reveals inherent biological variation in yeast and nematode model systems

International Nuclear Information System (INIS)

Szeto, Samuel S. W.; Reinke, Stacey N.; Lemire, Bernard D.

2011-01-01

The application of metabolomics to human and animal model systems is poised to provide great insight into our understanding of disease etiology and the metabolic changes that are associated with these conditions. However, metabolomic studies have also revealed that there is significant, inherent biological variation in human samples and even in samples from animal model systems where the animals are housed under carefully controlled conditions. This inherent biological variability is an important consideration for all metabolomics analyses. In this study, we examined the biological variation in 1 H NMR-based metabolic profiling of two model systems, the yeast Saccharomyces cerevisiae and the nematode Caenorhabditis elegans. Using relative standard deviations (RSD) as a measure of variability, our results reveal that both model systems have significant amounts of biological variation. The C. elegans metabolome possesses greater metabolic variance with average RSD values of 29 and 39%, depending on the food source that was used. The S. cerevisiae exometabolome RSD values ranged from 8% to 12% for the four strains examined. We also determined whether biological variation occurs between pairs of phenotypically identical yeast strains. Multivariate statistical analysis allowed us to discriminate between pair members based on their metabolic phenotypes. Our results highlight the variability of the metabolome that exists even for less complex model systems cultured under defined conditions. We also highlight the efficacy of metabolic profiling for defining these subtle metabolic alterations.

Transcriptional profiling at whole population and single cell levels reveals somatosensory neuron molecular diversity

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Chiu, Isaac M; Barrett, Lee B; Williams, Erika K; Strochlic, David E; Lee, Seungkyu; Weyer, Andy D; Lou, Shan; Bryman, Gregory S; Roberson, David P; Ghasemlou, Nader; Piccoli, Cara; Ahat, Ezgi; Wang, Victor; Cobos, Enrique J; Stucky, Cheryl L; Ma, Qiufu; Liberles, Stephen D; Woolf, Clifford J

2014-01-01

The somatosensory nervous system is critical for the organism's ability to respond to mechanical, thermal, and nociceptive stimuli. Somatosensory neurons are functionally and anatomically diverse but their molecular profiles are not well-defined. Here, we used transcriptional profiling to analyze the detailed molecular signatures of dorsal root ganglion (DRG) sensory neurons. We used two mouse reporter lines and surface IB4 labeling to purify three major non-overlapping classes of neurons: 1) IB4+SNS-Cre/TdTomato+, 2) IB4−SNS-Cre/TdTomato+, and 3) Parv-Cre/TdTomato+ cells, encompassing the majority of nociceptive, pruriceptive, and proprioceptive neurons. These neurons displayed distinct expression patterns of ion channels, transcription factors, and GPCRs. Highly parallel qRT-PCR analysis of 334 single neurons selected by membership of the three populations demonstrated further diversity, with unbiased clustering analysis identifying six distinct subgroups. These data significantly increase our knowledge of the molecular identities of known DRG populations and uncover potentially novel subsets, revealing the complexity and diversity of those neurons underlying somatosensation. DOI: http://dx.doi.org/10.7554/eLife.04660.001 PMID:25525749

Embryonic stem cell-like features of testicular carcinoma in situ revealed by genome-wide gene expression profiling.

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Almstrup, Kristian; Hoei-Hansen, Christina E; Wirkner, Ute; Blake, Jonathon; Schwager, Christian; Ansorge, Wilhelm; Nielsen, John E; Skakkebaek, Niels E; Rajpert-De Meyts, Ewa; Leffers, Henrik

2004-07-15

Carcinoma in situ (CIS) is the common precursor of histologically heterogeneous testicular germ cell tumors (TGCTs), which in recent decades have markedly increased and now are the most common malignancy of young men. Using genome-wide gene expression profiling, we identified >200 genes highly expressed in testicular CIS, including many never reported in testicular neoplasms. Expression was further verified by semiquantitative reverse transcription-PCR and in situ hybridization. Among the highest expressed genes were NANOG and POU5F1, and reverse transcription-PCR revealed possible changes in their stoichiometry on progression into embryonic carcinoma. We compared the CIS expression profile with patterns reported in embryonic stem cells (ESCs), which revealed a substantial overlap that may be as high as 50%. We also demonstrated an over-representation of expressed genes in regions of 17q and 12, reported as unstable in cultured ESCs. The close similarity between CIS and ESCs explains the pluripotency of CIS. Moreover, the findings are consistent with an early prenatal origin of TGCTs and thus suggest that etiologic factors operating in utero are of primary importance for the incidence trends of TGCTs. Finally, some of the highly expressed genes identified in this study are promising candidates for new diagnostic markers for CIS and/or TGCTs.

Phenolic profiling of caffeic acid O-methyltransferase-deficient poplar reveals novel benzodioxane oligolignols.

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Morreel, Kris; Ralph, John; Lu, Fachuang; Goeminne, Geert; Busson, Roger; Herdewijn, Piet; Goeman, Jan L; Van der Eycken, Johan; Boerjan, Wout; Messens, Eric

2004-12-01

Caffeic acid O-methyltransferase (COMT) catalyzes preferentially the methylation of 5-hydroxyconiferaldehyde to sinapaldehyde in monolignol biosynthesis. Here, we have compared HPLC profiles of the methanol-soluble phenolics fraction of xylem tissue from COMT-deficient and control poplars (Populus spp.), using statistical analysis of the peak heights. COMT down-regulation results in significant concentration differences for 25 of the 91 analyzed peaks. Eight peaks were exclusively detected in COMT-deficient poplar, of which four could be purified for further identification using mass spectrometry/mass spectrometry, nuclear magnetic resonance, and spiking of synthesized reference compounds. These new compounds were derived from 5-hydroxyconiferyl alcohol or 5-hydroxyconiferaldehyde and were characterized by benzodioxane moieties, a structural type that is also increased in the lignins of COMT-deficient plants. One of these four benzodioxanes amounted to the most abundant oligolignol in the HPLC profile. Furthermore, all of the differentially accumulating oligolignols involving sinapyl units were either reduced in abundance or undetectable. The concentration levels of all identified oligolignols were in agreement with the relative supply of monolignols and with their chemical coupling propensities, which supports the random coupling hypothesis. Chiral HPLC analysis of the most abundant benzodioxane dimer revealed the presence of both enantiomers in equal amounts, indicating that they were formed by radical coupling reactions under simple chemical control rather than guided by dirigent proteins.

A FIRST APPROACH TO THE LEXICAL PROFILE OF TELECOMMUNICATION ENGLISH: FREQUENCY, DISTRIBUTION, RESTRICTION AND KEYNESS

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Camino Rea Rizzo

2009-10-01

Full Text Available This corpus-based study is conducted to gain an insight into the lexis of Telecommunication English, with the aim of characterizing the lexical profile of this specialized language. The applied methodology integrates quantitative techniques and qualitative interpretations to perform an analysis from two different perspectives, and according to two parameters: restriction and keyness. The first approach is focused on the lexical behaviour and the extent that a word is restricted to the constituent areas of a domain, whereas the second approach is directed towards the extent that a word is significant in the domain, regardless of lexical category. The set of empirical and statistical data obtained contribute to map the lexical profile and will serve as a baseline for future studies.

Coping profiles, perceived stress and health-related behaviors: a cluster analysis approach.

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Doron, Julie; Trouillet, Raphael; Maneveau, Anaïs; Ninot, Grégory; Neveu, Dorine

2015-03-01

Using cluster analytical procedure, this study aimed (i) to determine whether people could be differentiated on the basis of coping profiles (or unique combinations of coping strategies); and (ii) to examine the relationships between these profiles and perceived stress and health-related behaviors. A sample of 578 French students (345 females, 233 males; M(age)= 21.78, SD(age)= 2.21) completed the Perceived Stress Scale-14 ( Bruchon-Schweitzer, 2002), the Brief COPE ( Muller and Spitz, 2003) and a series of items measuring health-related behaviors. A two-phased cluster analytic procedure (i.e. hierarchical and non-hierarchical-k-means) was employed to derive clusters of coping strategy profiles. The results yielded four distinctive coping profiles: High Copers, Adaptive Copers, Avoidant Copers and Low Copers. The results showed that clusters differed significantly in perceived stress and health-related behaviors. High Copers and Avoidant Copers displayed higher levels of perceived stress and engaged more in unhealthy behavior, compared with Adaptive Copers and Low Copers who reported lower levels of stress and engaged more in healthy behaviors. These findings suggested that individuals' relative reliance on some strategies and de-emphasis on others may be a more advantageous way of understanding the manner in which individuals cope with stress. Therefore, cluster analysis approach may provide an advantage over more traditional statistical techniques by identifying distinct coping profiles that might best benefit from interventions. Future research should consider coping profiles to provide a deeper understanding of the relationships between coping strategies and health outcomes and to identify risk groups. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Multitaxon activity profiling reveals differential microbial response to reduced seawater pH and oil pollution.

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Coelho, Francisco J R C; Cleary, Daniel F R; Costa, Rodrigo; Ferreira, Marina; Polónia, Ana R M; Silva, Artur M S; Simões, Mário M Q; Oliveira, Vanessa; Gomes, Newton C M

2016-09-01

There is growing concern that predicted changes to global ocean chemistry will interact with anthropogenic pollution to significantly alter marine microbial composition and function. However, knowledge of the compounding effects of climate change stressors and anthropogenic pollution is limited. Here, we used 16S and 18S rRNA (cDNA)-based activity profiling to investigate the differential responses of selected microbial taxa to ocean acidification and oil hydrocarbon contamination under controlled laboratory conditions. Our results revealed that a lower relative abundance of sulphate-reducing bacteria (Desulfosarcina/Desulfococcus clade) due to an adverse effect of seawater acidification and oil hydrocarbon contamination (reduced pH-oil treatment) may be coupled to changes in sediment archaeal communities. In particular, we observed a pronounced compositional shift and marked reduction in the prevalence of otherwise abundant operational taxonomic units (OTUs) belonging to the archaeal Marine Benthic Group B and Marine Hydrothermal Vent Group (MHVG) in the reduced pH-oil treatment. Conversely, the abundance of several putative hydrocarbonoclastic fungal OTUs was higher in the reduced pH-oil treatment. Sediment hydrocarbon profiling, furthermore, revealed higher concentrations of several alkanes in the reduced pH-oil treatment, corroborating the functional implications of the structural changes to microbial community composition. Collectively, our results advance the understanding of the response of a complex microbial community to the interaction between reduced pH and anthropogenic pollution. In future acidified marine environments, oil hydrocarbon contamination may alter the typical mixotrophic and k-/r-strategist composition of surface sediment microbiomes towards a more heterotrophic state with lower doubling rates, thereby impairing the ability of the ecosystem to recover from acute oil contamination events. © 2016 John Wiley & Sons Ltd.

MicroRNA Profiling Reveals Marker of Motor Neuron Disease in ALS Models.

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Hoye, Mariah L; Koval, Erica D; Wegener, Amy J; Hyman, Theodore S; Yang, Chengran; O'Brien, David R; Miller, Rebecca L; Cole, Tracy; Schoch, Kathleen M; Shen, Tao; Kunikata, Tomonori; Richard, Jean-Philippe; Gutmann, David H; Maragakis, Nicholas J; Kordasiewicz, Holly B; Dougherty, Joseph D; Miller, Timothy M

2017-05-31

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder marked by the loss of motor neurons (MNs) in the brain and spinal cord, leading to fatally debilitating weakness. Because this disease predominantly affects MNs, we aimed to characterize the distinct expression profile of that cell type to elucidate underlying disease mechanisms and to identify novel targets that inform on MN health during ALS disease time course. microRNAs (miRNAs) are short, noncoding RNAs that can shape the expression profile of a cell and thus often exhibit cell-type-enriched expression. To determine MN-enriched miRNA expression, we used Cre recombinase-dependent miRNA tagging and affinity purification in mice. By defining the in vivo miRNA expression of MNs, all neurons, astrocytes, and microglia, we then focused on MN-enriched miRNAs via a comparative analysis and found that they may functionally distinguish MNs postnatally from other spinal neurons. Characterizing the levels of the MN-enriched miRNAs in CSF harvested from ALS models of MN disease demonstrated that one miRNA (miR-218) tracked with MN loss and was responsive to an ALS therapy in rodent models. Therefore, we have used cellular expression profiling tools to define the distinct miRNA expression of MNs, which is likely to enrich future studies of MN disease. This approach enabled the development of a novel, drug-responsive marker of MN disease in ALS rodents. SIGNIFICANCE STATEMENT Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease in which motor neurons (MNs) in the brain and spinal cord are selectively lost. To develop tools to aid in our understanding of the distinct expression profiles of MNs and, ultimately, to monitor MN disease progression, we identified small regulatory microRNAs (miRNAs) that were highly enriched or exclusive in MNs. The signal for one of these MN-enriched miRNAs is detectable in spinal tap biofluid from an ALS rat model, where its levels change as disease

Transcriptional profiling reveals gland-specific differential expression in the three major salivary glands of the adult mouse.

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Gao, Xin; Oei, Maria S; Ovitt, Catherine E; Sincan, Murat; Melvin, James E

2018-04-01

RNA-Seq was used to better understand the molecular nature of the biological differences among the three major exocrine salivary glands in mammals. Transcriptional profiling found that the adult murine parotid, submandibular, and sublingual salivary glands express greater than 14,300 protein-coding genes, and nearly 2,000 of these genes were differentially expressed. Principle component analysis of the differentially expressed genes revealed three distinct clusters according to gland type. The three salivary gland transcriptomes were dominated by a relatively few number of highly expressed genes (6.3%) that accounted for more than 90% of transcriptional output. Of the 912 transcription factors expressed in the major salivary glands, greater than 90% of them were detected in all three glands, while expression for ~2% of them was enriched in an individual gland. Expression of these unique transcription factors correlated with sublingual and parotid specific subsets of both highly expressed and differentially expressed genes. Gene ontology analyses revealed that the highly expressed genes common to all glands were associated with global functions, while many of the genes expressed in a single gland play a major role in the function of that gland. In summary, transcriptional profiling of the three murine major salivary glands identified a limited number of highly expressed genes, differentially expressed genes, and unique transcription factors that represent the transcriptional signatures underlying gland-specific biological properties.

Serum Steroid Ratio Profiles in Prostate Cancer: A New Diagnostic Tool Toward a Personalized Medicine Approach.

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Albini, Adriana; Bruno, Antonino; Bassani, Barbara; D'Ambrosio, Gioacchino; Pelosi, Giuseppe; Consonni, Paolo; Castellani, Laura; Conti, Matteo; Cristoni, Simone; Noonan, Douglas M

2018-01-01

Serum steroids are crucial molecules altered in prostate cancer (PCa). Mass spectrometry (MS) is currently the elected technology for the analysis of steroids in diverse biological samples. Steroids have complex biological pathways and stoichiometry and it is important to evaluate their quantitative ratio. MS applications to patient hormone profiling could lead to a diagnostic approach. Here, we employed the Surface Activated Chemical Ionization-Electrospray-NIST (SANIST) developed in our laboratories, to obtain quantitative serum steroid ratio relationship profiles with a machine learning Bayesian model to discriminate patients with PCa. The approach is focused on steroid relationship profiles and disease association. A pilot study on patients affected by PCa, benign prostate hypertrophy (BPH), and control subjects [prostate-specific antigen (PSA) lower than 2.5 ng/mL] was done in order to investigate the classification performance of the SANIST platform. The steroid profiles of 71 serum samples (31 controls, 20 patients with PCa and 20 subjects with benign prostate hyperplasia) were evaluated. The levels of 10 steroids were quantitated on the SANIST platform: Aldosterone, Corticosterone, Cortisol, 11-deoxycortisol, Androstenedione, Testosterone, dehydroepiandrosterone, dehydroepiandrosterone sulfate (DHEAS), 17-OH-Progesterone and Progesterone. We performed both traditional and a machine learning analysis. We show that the machine learning approach based on the steroid relationships developed here was much more accurate than the PSA, DHEAS, and direct absolute value match method in separating the PCa, BPH and control subjects, increasing the sensitivity to 90% and specificity to 84%. This technology, if applied in the future to a larger number of samples will be able to detect the individual enzymatic disequilibrium associated with the steroid ratio and correlate it with the disease. This learning machine approach could be valid in a personalized medicine

Proteomic Profiling in the Brain of CLN1 Disease Model Reveals Affected Functional Modules.

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Tikka, Saara; Monogioudi, Evanthia; Gotsopoulos, Athanasios; Soliymani, Rabah; Pezzini, Francesco; Scifo, Enzo; Uusi-Rauva, Kristiina; Tyynelä, Jaana; Baumann, Marc; Jalanko, Anu; Simonati, Alessandro; Lalowski, Maciej

2016-03-01

Neuronal ceroid lipofuscinoses (NCL) are the most commonly inherited progressive encephalopathies of childhood. Pathologically, they are characterized by endolysosomal storage with different ultrastructural features and biochemical compositions. The molecular mechanisms causing progressive neurodegeneration and common molecular pathways linking expression of different NCL genes are largely unknown. We analyzed proteome alterations in the brains of a mouse model of human infantile CLN1 disease-palmitoyl-protein thioesterase 1 (Ppt1) gene knockout and its wild-type age-matched counterpart at different stages: pre-symptomatic, symptomatic and advanced. For this purpose, we utilized a combination of laser capture microdissection-based quantitative liquid chromatography tandem mass spectrometry (MS) and matrix-assisted laser desorption/ionization time-of-flight MS imaging to quantify/visualize the changes in protein expression in disease-affected brain thalamus and cerebral cortex tissue slices, respectively. Proteomic profiling of the pre-symptomatic stage thalamus revealed alterations mostly in metabolic processes and inhibition of various neuronal functions, i.e., neuritogenesis. Down-regulation in dynamics associated with growth of plasma projections and cellular protrusions was further corroborated by findings from RNA sequencing of CLN1 patients' fibroblasts. Changes detected at the symptomatic stage included: mitochondrial functions, synaptic vesicle transport, myelin proteome and signaling cascades, such as RhoA signaling. Considerable dysregulation of processes related to mitochondrial cell death, RhoA/Huntington's disease signaling and myelin sheath breakdown were observed at the advanced stage of the disease. The identified changes in protein levels were further substantiated by bioinformatics and network approaches, immunohistochemistry on brain tissues and literature knowledge, thus identifying various functional modules affected in the CLN1 childhood

Prospective Genomic Profiling of Prostate Cancer Across Disease States Reveals Germline and Somatic Alterations That May Affect Clinical Decision Making.

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Abida, Wassim; Armenia, Joshua; Gopalan, Anuradha; Brennan, Ryan; Walsh, Michael; Barron, David; Danila, Daniel; Rathkopf, Dana; Morris, Michael; Slovin, Susan; McLaughlin, Brigit; Curtis, Kristen; Hyman, David M; Durack, Jeremy C; Solomon, Stephen B; Arcila, Maria E; Zehir, Ahmet; Syed, Aijazuddin; Gao, Jianjiong; Chakravarty, Debyani; Vargas, Hebert Alberto; Robson, Mark E; Joseph, Vijai; Offit, Kenneth; Donoghue, Mark T A; Abeshouse, Adam A; Kundra, Ritika; Heins, Zachary J; Penson, Alexander V; Harris, Christopher; Taylor, Barry S; Ladanyi, Marc; Mandelker, Diana; Zhang, Liying; Reuter, Victor E; Kantoff, Philip W; Solit, David B; Berger, Michael F; Sawyers, Charles L; Schultz, Nikolaus; Scher, Howard I

2017-07-01

A long natural history and a predominant osseous pattern of metastatic spread are impediments to the adoption of precision medicine in patients with prostate cancer. To establish the feasibility of clinical genomic profiling in the disease, we performed targeted deep sequencing of tumor and normal DNA from patients with locoregional, metastatic non-castrate, and metastatic castration-resistant prostate cancer (CRPC). Patients consented to genomic analysis of their tumor and germline DNA. A hybridization capture-based clinical assay was employed to identify single nucleotide variations, small insertions and deletions, copy number alterations and structural rearrangements in over 300 cancer-related genes in tumors and matched normal blood. We successfully sequenced 504 tumors from 451 patients with prostate cancer. Potentially actionable alterations were identified in DNA damage repair (DDR), PI3K, and MAP kinase pathways. 27% of patients harbored a germline or a somatic alteration in a DDR gene that may predict for response to PARP inhibition. Profiling of matched tumors from individual patients revealed that somatic TP53 and BRCA2 alterations arose early in tumors from patients who eventually developed metastatic disease. In contrast, comparative analysis across disease states revealed that APC alterations were enriched in metastatic tumors, while ATM alterations were specifically enriched in CRPC. Through genomic profiling of prostate tumors representing the disease clinical spectrum, we identified a high frequency of potentially actionable alterations and possible drivers of disease initiation, metastasis and castration-resistance. Our findings support the routine use of tumor and germline DNA profiling for patients with advanced prostate cancer, for the purpose of guiding enrollment in targeted clinical trials and counseling families at increased risk of malignancy.

Transcriptional profiling of the dose response: a more powerful approach for characterizing drug activities.

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Rui-Ru Ji

2009-09-01

Full Text Available The dose response curve is the gold standard for measuring the effect of a drug treatment, but is rarely used in genomic scale transcriptional profiling due to perceived obstacles of cost and analysis. One barrier to examining transcriptional dose responses is that existing methods for microarray data analysis can identify patterns, but provide no quantitative pharmacological information. We developed analytical methods that identify transcripts responsive to dose, calculate classical pharmacological parameters such as the EC50, and enable an in-depth analysis of coordinated dose-dependent treatment effects. The approach was applied to a transcriptional profiling study that evaluated four kinase inhibitors (imatinib, nilotinib, dasatinib and PD0325901 across a six-logarithm dose range, using 12 arrays per compound. The transcript responses proved a powerful means to characterize and compare the compounds: the distribution of EC50 values for the transcriptome was linked to specific targets, dose-dependent effects on cellular processes were identified using automated pathway analysis, and a connection was seen between EC50s in standard cellular assays and transcriptional EC50s. Our approach greatly enriches the information that can be obtained from standard transcriptional profiling technology. Moreover, these methods are automated, robust to non-optimized assays, and could be applied to other sources of quantitative data.

Neurodevelopmental profile of Fetal Alcohol Spectrum Disorder: A systematic review.

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Lange, Shannon; Rovet, Joanne; Rehm, Jürgen; Popova, Svetlana

2017-06-23

In an effort to improve the screening and diagnosis of individuals with Fetal Alcohol Spectrum Disorder (FASD), research has focused on the identification of a unique neurodevelopmental profile characteristic of this population. The objective of this review was to identify any existing neurodevelopmental profiles of FASD and review their classification function in order to identify gaps and limitations of the current literature. A systematic search for studies published up to the end of December 2016 reporting an identified neurodevelopmental profile of FASD was conducted using multiple electronic bibliographic databases. The search was not limited geographically or by language of publication. Original research published in a peer-reviewed journal that involved the evaluation of the classification function of an identified neurodevelopmental profile of FASD was included. Two approaches have been taken to determine the pathognomonic neurodevelopmental features of FASD, namely the utilization of i) behavioral observations/ratings by parents/caregivers and ii) subtest scores from standardized test batteries assessing a variety of neurodevelopmental domains. Both approaches show some promise, with the former approach (which is dominated by research on the Neurobehavioral Screening Tool) having good sensitivity (63% to 98%), but varying specificity (42% to 100%), and the latter approach having good specificity (72% to 96%), but varying sensitivity (60% to 88%). The current review revealed that research in this area remains limited and a definitive neurodevelopmental profile of FASD has not been established. However, the identification of a neurodevelopmental profile will aid in the accurate identification of individuals with FASD, by adding to the armamentarium of clinicians. The full review protocol is available in PROSPERO ( http://www.crd.york.ac.uk/PROSPERO/ ); registration number CRD42016039326; registered 20 May 2016.

Proteomic profiling in multiple sclerosis clinical courses reveals potential biomarkers of neurodegeneration.

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Maria Liguori

Full Text Available The aim of our project was to perform an exploratory analysis of the cerebrospinal fluid (CSF proteomic profiles of Multiple Sclerosis (MS patients, collected in different phases of their clinical course, in order to investigate the existence of peculiar profiles characterizing the different MS phenotypes. The study was carried out on 24 Clinically Isolated Syndrome (CIS, 16 Relapsing Remitting (RR MS, 11 Progressive (Pr MS patients. The CSF samples were analysed using the Matrix Assisted Laser Desorption Ionisation Time Of Flight (MALDI-TOF mass spectrometer in linear mode geometry and in delayed extraction mode (m/z range: 1000-25000 Da. Peak lists were imported for normalization and statistical analysis. CSF data were correlated with demographic, clinical and MRI parameters. The evaluation of MALDI-TOF spectra revealed 348 peak signals with relative intensity ≥ 1% in the study range. The peak intensity of the signals corresponding to Secretogranin II and Protein 7B2 were significantly upregulated in RRMS patients compared to PrMS (p<0.05, whereas the signals of Fibrinogen and Fibrinopeptide A were significantly downregulated in CIS compared to PrMS patients (p<0.04. Additionally, the intensity of the Tymosin β4 peak was the only signal to be significantly discriminated between the CIS and RRMS patients (p = 0.013. Although with caution due to the relatively small size of the study populations, and considering that not all the findings remained significant after adjustment for multiple comparisons, in our opinion this mass spectrometry evaluation confirms that this technique may provide useful and important information to improve our understanding of the complex pathogenesis of MS.

Exploring student learning profiles in algebra-based studio physics: A person-centered approach

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Pond, Jarrad W. T.; Chini, Jacquelyn J.

2017-06-01

In this study, we explore the strategic self-regulatory and motivational characteristics of students in studio-mode physics courses at three universities with varying student populations and varying levels of success in their studio-mode courses. We survey students using questions compiled from several existing questionnaires designed to measure students' study strategies, attitudes toward and motivations for learning physics, organization of scientific knowledge, experiences outside the classroom, and demographics. Using a person-centered approach, we utilize cluster analysis methods to group students into learning profiles based on their individual responses to better understand the strategies and motives of algebra-based studio physics students. Previous studies have identified five distinct learning profiles across several student populations using similar methods. We present results from first-semester and second-semester studio-mode introductory physics courses across three universities. We identify these five distinct learning profiles found in previous studies to be present within our population of introductory physics students. In addition, we investigate interactions between these learning profiles and student demographics. We find significant interactions between a student's learning profile and their experience with high school physics, major, gender, grade expectation, and institution. Ultimately, we aim to use this method of analysis to take the characteristics of students into account in the investigation of successful strategies for using studio methods of physics instruction within and across institutions.

Paralytic toxin profile of the marine dinoflagellate Gymnodinium catenatum Graham from the Mexican Pacific as revealed by LC-MS/MS.

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Bustillos-Guzmán, José J; Band-Schmidt, Christine J; Durán-Riveroll, Lorena M; Hernández-Sandoval, Francisco E; López-Cortés, David J; Núñez-Vázquez, Erick J; Cembella, Allan; Krock, Bernd

2015-01-01

The paralytic shellfish toxin (PST) profiles of Gymnodinium catenatum Graham have been reported for several strains from the Pacific coast of Mexico cultured under different laboratory conditions, as well as from natural populations. Up to 15 saxitoxin analogues occurred and the quantity of each toxin depended on the growth phase and culture conditions. Previous analysis of toxin profiles of G. catenatum isolated from Mexico have been based on post-column oxidation liquid chromatography with fluorescence detection (LC-FLD), a method prone to artefacts and non-specificity, leading to misinterpretation of toxin composition. We describe, for the first time, the complete toxin profile for several G. catenatum strains from diverse locations of the Pacific coast of Mexico. The new results confirmed previous reports on the dominance of the less potent sulfocarbamoyl toxins (C1/2); significant differences, however, in the composition (e.g., absence of saxitoxin, gonyautoxin 2/3 and neosaxitoxin) were revealed in our confirmatory analysis. The LC-MS/MS analyses also indicated at least seven putative benzoyl toxin analogues and provided support for their existence. This new toxin profile shows a high similarity (> 80%) to the profiles reported from several regions around the world, suggesting low genetic variability among global populations.

Comparative genomic analysis of Lactobacillus plantarum ZJ316 reveals its genetic adaptation and potential probiotic profiles.

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Li, Ping; Li, Xuan; Gu, Qing; Lou, Xiu-Yu; Zhang, Xiao-Mei; Song, Da-Feng; Zhang, Chen

2016-08-01

In previous studies, Lactobacillus plantarum ZJ316 showed probiotic properties, such as antimicrobial activity against various pathogens and the capacity to significantly improve pig growth and pork quality. The purpose of this study was to reveal the genes potentially related to its genetic adaptation and probiotic profiles based on comparative genomic analysis. The genome sequence of L. plantarum ZJ316 was compared with those of eight L. plantarum strains deposited in GenBank. BLASTN, Mauve, and MUMmer programs were used for genome alignment and comparison. CRISPRFinder was applied for searching the clustered regularly interspaced short palindromic repeats (CRISPRs). We identified genes that encode proteins related to genetic adaptation and probiotic profiles, including carbohydrate transport and metabolism, proteolytic enzyme systems and amino acid biosynthesis, CRISPR adaptive immunity, stress responses, bile salt resistance, ability to adhere to the host intestinal wall, exopolysaccharide (EPS) biosynthesis, and bacteriocin biosynthesis. Comparative characterization of the L. plantarum ZJ316 genome provided the genetic basis for further elucidating the functional mechanisms of its probiotic properties. ZJ316 could be considered a potential probiotic candidate.

Comparative genomic analysis of Lactobacillus plantarum ZJ316 reveals its genetic adaptation and potential probiotic profiles* #

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Li, Ping; Li, Xuan; Gu, Qing; Lou, Xiu-yu; Zhang, Xiao-mei; Song, Da-feng; Zhang, Chen

2016-01-01

Objective: In previous studies, Lactobacillus plantarum ZJ316 showed probiotic properties, such as antimicrobial activity against various pathogens and the capacity to significantly improve pig growth and pork quality. The purpose of this study was to reveal the genes potentially related to its genetic adaptation and probiotic profiles based on comparative genomic analysis. Methods: The genome sequence of L. plantarum ZJ316 was compared with those of eight L. plantarum strains deposited in GenBank. BLASTN, Mauve, and MUMmer programs were used for genome alignment and comparison. CRISPRFinder was applied for searching the clustered regularly interspaced short palindromic repeats (CRISPRs). Results: We identified genes that encode proteins related to genetic adaptation and probiotic profiles, including carbohydrate transport and metabolism, proteolytic enzyme systems and amino acid biosynthesis, CRISPR adaptive immunity, stress responses, bile salt resistance, ability to adhere to the host intestinal wall, exopolysaccharide (EPS) biosynthesis, and bacteriocin biosynthesis. Conclusions: Comparative characterization of the L. plantarum ZJ316 genome provided the genetic basis for further elucidating the functional mechanisms of its probiotic properties. ZJ316 could be considered a potential probiotic candidate. PMID:27487802

Comprehensive examination of conventional and innovative body fluid identification approaches and DNA profiling of laundered blood- and saliva-stained pieces of cloths.

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Kulstein, G; Wiegand, P

2018-01-01

Body fluids like blood and saliva are commonly encountered during investigations of high volume crimes like homicides. The identification of the cellular origin and the composition of the trace can link suspects or victims to a certain crime scene and provide a probative value for criminal investigations. To erase all traces from the crime scene, perpetrators often wash away their traces. Characteristically, items that show exposed stains like blood are commonly cleaned or laundered to free them from potential visible leftovers. Mostly, investigators do not delegate the DNA analysis of laundered items. However, some studies have already revealed that items can still be used for DNA analysis even after they have been laundered. Nonetheless, a systematical evaluation of laundered blood and saliva traces that provides a comparison of different established and newly developed methods for body fluid identification (BFI) is still missing. Herein, we present the results of a comprehensive study of laundered blood- and saliva-stained pieces of cloths that were applied to a broad range of methods for BFI including conventional approaches as well as molecular mRNA profiling. The study included the evaluation of cellular origin as well as DNA profiling of blood- and saliva-stained (synthetic fiber and cotton) pieces of cloths, which have been washed at various washing temperatures for one or multiple times. Our experiments demonstrate that, while STR profiling seems to be sufficiently sensitive for the individualization of laundered items, there is a lack of approaches for BFI with the same sensitivity and specificity allowing to characterize the cellular origin of challenging, particularly laundered, blood and saliva samples.

Analysis of microRNA profile of Anopheles sinensis by deep sequencing and bioinformatic approaches.

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Feng, Xinyu; Zhou, Xiaojian; Zhou, Shuisen; Wang, Jingwen; Hu, Wei

2018-03-12

microRNAs (miRNAs) are small non-coding RNAs widely identified in many mosquitoes. They are reported to play important roles in development, differentiation and innate immunity. However, miRNAs in Anopheles sinensis, one of the Chinese malaria mosquitoes, remain largely unknown. We investigated the global miRNA expression profile of An. sinensis using Illumina Hiseq 2000 sequencing. Meanwhile, we applied a bioinformatic approach to identify potential miRNAs in An. sinensis. The identified miRNA profiles were compared and analyzed by two approaches. The selected miRNAs from the sequencing result and the bioinformatic approach were confirmed with qRT-PCR. Moreover, target prediction, GO annotation and pathway analysis were carried out to understand the role of miRNAs in An. sinensis. We identified 49 conserved miRNAs and 12 novel miRNAs by next-generation high-throughput sequencing technology. In contrast, 43 miRNAs were predicted by the bioinformatic approach, of which two were assigned as novel. Comparative analysis of miRNA profiles by two approaches showed that 21 miRNAs were shared between them. Twelve novel miRNAs did not match any known miRNAs of any organism, indicating that they are possibly species-specific. Forty miRNAs were found in many mosquito species, indicating that these miRNAs are evolutionally conserved and may have critical roles in the process of life. Both the selected known and novel miRNAs (asi-miR-281, asi-miR-184, asi-miR-14, asi-miR-nov5, asi-miR-nov4, asi-miR-9383, and asi-miR-2a) could be detected by quantitative real-time PCR (qRT-PCR) in the sequenced sample, and the expression patterns of these miRNAs measured by qRT-PCR were in concordance with the original miRNA sequencing data. The predicted targets for the known and the novel miRNAs covered many important biological roles and pathways indicating the diversity of miRNA functions. We also found 21 conserved miRNAs and eight counterparts of target immune pathway genes in An. sinensis

Glacio-tectonic thrust and deformation structures in the Vejle Fjord, Denmark revealed by high-resolution subbottom-profile data

DEFF Research Database (Denmark)

Andresen, Katrine Juul; Boldreel, Lars Ole; Wahlgreen, Katrine Bak

Surface geomorphological features and partial cliff exposures up till now represent the predominant source of information of glaciation related deformation in Denmark. In this study we apply high-resolution marine reflection seismic data from the Vejle Fjord area, supported by gravity and Rumohr...... coring, to document intense glacio-tectonic deformation in the shallow subsurface of Denmark. The subbottom profiler seismic data have a peak frequency around 13 kHz and a vertical resolution in the order of 10-20 cm. The data reveal several variations of glacio-tectonic deformation structures, primarily...... movements from outcrops and shallow cores. The subbottom profiler data provides larger (longer and deeper) sectional views on for instance deformation and deposition complexes related to ice progressions and retreats and thus represents a very good supplement and valuable input to field mapping and outcrops...

An analytical approach to characterize morbidity profile dissimilarity between distinct cohorts using electronic medical records

OpenAIRE

Schildcrout, Jonathan S.; Basford, Melissa A.; Pulley, Jill M.; Masys, Daniel R.; Roden, Dan M.; Wang, Deede; Chute, Christopher G.; Kullo, Iftikhar J.; Carrell, David; Peissig, Peggy; Kho, Abel; Denny, Joshua C.

2010-01-01

We describe a two-stage analytical approach for characterizing morbidity profile dissimilarity among patient cohorts using electronic medical records. We capture morbidities using the International Statistical Classification of Diseases and Related Health Problems (ICD-9) codes. In the first stage of the approach separate logistic regression analyses for ICD-9 sections (e.g., “hypertensive disease” or “appendicitis”) are conducted, and the odds ratios that describe adjusted differences in pre...

Comparative expression profiling reveals gene functions in female meiosis and gametophyte development in Arabidopsis.

Science.gov (United States)

Zhao, Lihua; He, Jiangman; Cai, Hanyang; Lin, Haiyan; Li, Yanqiang; Liu, Renyi; Yang, Zhenbiao; Qin, Yuan

2014-11-01

Megasporogenesis is essential for female fertility, and requires the accomplishment of meiosis and the formation of functional megaspores. The inaccessibility and low abundance of female meiocytes make it particularly difficult to elucidate the molecular basis underlying megasporogenesis. We used high-throughput tag-sequencing analysis to identify genes expressed in female meiocytes (FMs) by comparing gene expression profiles from wild-type ovules undergoing megasporogenesis with those from the spl mutant ovules, which lack megasporogenesis. A total of 862 genes were identified as FMs, with levels that are consistently reduced in spl ovules in two biological replicates. Fluorescence-assisted cell sorting followed by RNA-seq analysis of DMC1:GFP-labeled female meiocytes confirmed that 90% of the FMs are indeed detected in the female meiocyte protoplast profiling. We performed reverse genetic analysis of 120 candidate genes and identified four FM genes with a function in female meiosis progression in Arabidopsis. We further revealed that KLU, a putative cytochrome P450 monooxygenase, is involved in chromosome pairing during female meiosis, most likely by affecting the normal expression pattern of DMC1 in ovules during female meiosis. Our studies provide valuable information for functional genomic analyses of plant germline development as well as insights into meiosis. © 2014 The Authors The Plant Journal © 2014 John Wiley & Sons Ltd.

Phenolic Profiling of Caffeic Acid O-Methyltransferase-Deficient Poplar Reveals Novel Benzodioxane Oligolignols1

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Morreel, Kris; Ralph, John; Lu, Fachuang; Goeminne, Geert; Busson, Roger; Herdewijn, Piet; Goeman, Jan L.; Van der Eycken, Johan; Boerjan, Wout; Messens, Eric

2004-01-01

Caffeic acid O-methyltransferase (COMT) catalyzes preferentially the methylation of 5-hydroxyconiferaldehyde to sinapaldehyde in monolignol biosynthesis. Here, we have compared HPLC profiles of the methanol-soluble phenolics fraction of xylem tissue from COMT-deficient and control poplars (Populus spp.), using statistical analysis of the peak heights. COMT down-regulation results in significant concentration differences for 25 of the 91 analyzed peaks. Eight peaks were exclusively detected in COMT-deficient poplar, of which four could be purified for further identification using mass spectrometry/mass spectrometry, nuclear magnetic resonance, and spiking of synthesized reference compounds. These new compounds were derived from 5-hydroxyconiferyl alcohol or 5-hydroxyconiferaldehyde and were characterized by benzodioxane moieties, a structural type that is also increased in the lignins of COMT-deficient plants. One of these four benzodioxanes amounted to the most abundant oligolignol in the HPLC profile. Furthermore, all of the differentially accumulating oligolignols involving sinapyl units were either reduced in abundance or undetectable. The concentration levels of all identified oligolignols were in agreement with the relative supply of monolignols and with their chemical coupling propensities, which supports the random coupling hypothesis. Chiral HPLC analysis of the most abundant benzodioxane dimer revealed the presence of both enantiomers in equal amounts, indicating that they were formed by radical coupling reactions under simple chemical control rather than guided by dirigent proteins. PMID:15563622

{sup 1}H NMR-based metabolic profiling reveals inherent biological variation in yeast and nematode model systems

Energy Technology Data Exchange (ETDEWEB)

Szeto, Samuel S. W.; Reinke, Stacey N.; Lemire, Bernard D., E-mail: bernard.lemire@ualberta.ca [University of Alberta, Department of Biochemistry, School of Molecular and Systems Medicine (Canada)

2011-04-15

The application of metabolomics to human and animal model systems is poised to provide great insight into our understanding of disease etiology and the metabolic changes that are associated with these conditions. However, metabolomic studies have also revealed that there is significant, inherent biological variation in human samples and even in samples from animal model systems where the animals are housed under carefully controlled conditions. This inherent biological variability is an important consideration for all metabolomics analyses. In this study, we examined the biological variation in {sup 1}H NMR-based metabolic profiling of two model systems, the yeast Saccharomyces cerevisiae and the nematode Caenorhabditis elegans. Using relative standard deviations (RSD) as a measure of variability, our results reveal that both model systems have significant amounts of biological variation. The C. elegans metabolome possesses greater metabolic variance with average RSD values of 29 and 39%, depending on the food source that was used. The S. cerevisiae exometabolome RSD values ranged from 8% to 12% for the four strains examined. We also determined whether biological variation occurs between pairs of phenotypically identical yeast strains. Multivariate statistical analysis allowed us to discriminate between pair members based on their metabolic phenotypes. Our results highlight the variability of the metabolome that exists even for less complex model systems cultured under defined conditions. We also highlight the efficacy of metabolic profiling for defining these subtle metabolic alterations.

Quantitative microbiome profiling links gut community variation to microbial load.

Science.gov (United States)

Vandeputte, Doris; Kathagen, Gunter; D'hoe, Kevin; Vieira-Silva, Sara; Valles-Colomer, Mireia; Sabino, João; Wang, Jun; Tito, Raul Y; De Commer, Lindsey; Darzi, Youssef; Vermeire, Séverine; Falony, Gwen; Raes, Jeroen

2017-11-23

Current sequencing-based analyses of faecal microbiota quantify microbial taxa and metabolic pathways as fractions of the sample sequence library generated by each analysis. Although these relative approaches permit detection of disease-associated microbiome variation, they are limited in their ability to reveal the interplay between microbiota and host health. Comparative analyses of relative microbiome data cannot provide information about the extent or directionality of changes in taxa abundance or metabolic potential. If microbial load varies substantially between samples, relative profiling will hamper attempts to link microbiome features to quantitative data such as physiological parameters or metabolite concentrations. Saliently, relative approaches ignore the possibility that altered overall microbiota abundance itself could be a key identifier of a disease-associated ecosystem configuration. To enable genuine characterization of host-microbiota interactions, microbiome research must exchange ratios for counts. Here we build a workflow for the quantitative microbiome profiling of faecal material, through parallelization of amplicon sequencing and flow cytometric enumeration of microbial cells. We observe up to tenfold differences in the microbial loads of healthy individuals and relate this variation to enterotype differentiation. We show how microbial abundances underpin both microbiota variation between individuals and covariation with host phenotype. Quantitative profiling bypasses compositionality effects in the reconstruction of gut microbiota interaction networks and reveals that the taxonomic trade-off between Bacteroides and Prevotella is an artefact of relative microbiome analyses. Finally, we identify microbial load as a key driver of observed microbiota alterations in a cohort of patients with Crohn's disease, here associated with a low-cell-count Bacteroides enterotype (as defined through relative profiling).

Endoprotease profiling with double-tagged peptide substrates: a new diagnostic approach in oncology.

Science.gov (United States)

Peccerella, Teresa; Lukan, Nadine; Hofheinz, Ralf; Schadendorf, Dirk; Kostrezewa, Markus; Neumaier, Michael; Findeisen, Peter

2010-02-01

The measurement of disease-related proteolytic activity in complex biological matrices like serum is of emerging interest to improve the diagnosis of malignant diseases. We developed a mass spectrometry (MS)-based functional proteomic profiling approach that tracks degradation of artificial endoprotease substrates in serum specimens. The synthetic reporter peptides that are cleaved by tumor-associated endopeptidases were systematically optimized with regard to flanking affinity tags, linkers, and stabilizing elements. Serum specimens were incubated with reporter peptides under standardized conditions and the peptides subsequently extracted with affinity chromatography before MS. In a pilot study an optimized reporter peptide with the cleavage motif WKPYDAADL was added to serum specimens from colorectal tumor patients (n = 50) and healthy controls (n = 50). This reporter peptide comprised a known cleavage site for the cysteine-endopeptidase "cancer procoagulant." Serial affinity chromatography using biotin- and 6xHis tags was superior to the single affinity enrichment using only 6xHis tags. Furthermore, protease-resistant stop elements ensured signal accumulation after prolonged incubation. In contrast, signals from reporter peptides without stop elements vanished completely after prolonged incubation owing to their total degradation. Reporter-peptide spiking showed good reproducibility, and the difference in proteolytic activity between serum specimens from cancer patients and controls was highly significant (P < 0.001). The introduction of a few structural key elements (affinity tags, linkers, d-amino acids) into synthetic reporter peptides increases the diagnostic sensitivity for MS-based protease profiling of serum specimens. This new approach might lead to functional MS-based protease profiling for improved disease classification.

Three-dimension visualization of transnasal approach for revealing the metasellar organization

Directory of Open Access Journals (Sweden)

Liang XUE

2012-07-01

Full Text Available Objective To elevate the anatomical cognitive level by investigating the metasellar organization viatransnasal approach in a virtual-reality (VR setting. Methods Twenty-eight patients, with spontaneous subarachnoid hemorrhage but without pathological changes of nasal cavity and sella turcica, underwent the lamellar imaging examination and CT angiogram with Discovery Ultra 16. The data were collected and entered in the Dextroscope in DICOM format. Visualization research was carried out viathe transnasal approach in a virtual-reality (VR setting. Results The anatomic structures of transnasal approach were allowed to be observed dynamically and spatially. When exposing the lateral border of cavernous carotid artery, it was important to excise the ethmoid cornu, open posterior ethmoid sinus and sphenopalatine foramen, control sphenopalatine artery, properly drill out pterygoid process and reveal pterygoid canal. Conclusion It is the key point to remove the ethmoid cornu, uncinate process and bone of the anterior region of sphenoidal sinus, and control sphenopalatine artery viatransnasal approach to expose the metasellar structure. The cavernous carotid arteries are the most important anatomic structure, should be adequately exposed and conserved.

Proteomic Characterization of Armillaria mellea Reveals Oxidative Stress Response Mechanisms and Altered Secondary Metabolism Profiles

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Cassandra Collins

2017-09-01

Full Text Available Armillaria mellea is a major plant pathogen. Yet, the strategies the organism uses to infect susceptible species, degrade lignocellulose and other plant material and protect itself against plant defences and its own glycodegradative arsenal are largely unknown. Here, we use a combination of gel and MS-based proteomics to profile A. mellea under conditions of oxidative stress and changes in growth matrix. 2-DE and LC-MS/MS were used to investigate the response of A. mellea to H2O2 and menadione/FeCl3 exposure, respectively. Several proteins were detected with altered abundance in response to H2O2, but not menadione/FeCl3 (i.e., valosin-containing protein, indicating distinct responses to these different forms of oxidative stress. One protein, cobalamin-independent methionine synthase, demonstrated a common response in both conditions, which may be a marker for a more general stress response mechanism. Further changes to the A. mellea proteome were investigated using MS-based proteomics, which identified changes to putative secondary metabolism (SM enzymes upon growth in agar compared to liquid cultures. Metabolomic analyses revealed distinct profiles, highlighting the effect of growth matrix on SM production. This establishes robust methods by which to utilize comparative proteomics to characterize this important phytopathogen.

Skeleton sled velocity profiles: a novel approach to understand critical aspects of the elite athletes' start phases.

Science.gov (United States)

Colyer, Steffi L; Stokes, Keith A; Bilzon, James L J; Salo, Aki I T

2018-06-01

The development of velocity across the skeleton start is critical to performance, yet poorly understood. We aimed to understand which components of the sled velocity profile determine performance and how physical abilities influence these components. Thirteen well-trained skeleton athletes (>85% of athletes in the country) performed dry-land push-starts alongside countermovement jump and sprint tests at multiple time-points. A magnet encoder attached to the sled wheel provided velocity profiles, which were characterised using novel performance descriptors. Stepwise regression revealed four variables (pre-load velocity, pre-load distance, load effectiveness, velocity drop) to explain 99% variance in performance (β weights: 1.70, -0.81, 0.25, -0.07, respectively). Sprint times and jump ability were associated (r ± 90% CI) with pre-load velocity (-0.70 ± 0.27 and 0.88 ± 0.14, respectively) and distance (-0.48 ± 0.39 and 0.67 ± 0.29, respectively), however, unclear relationships between both physical measures and load effectiveness (0.33 ± 0.44 and -0.35 ± 0.48, respectively) were observed. Athletes should develop accelerative ability to attain higher velocity earlier on the track. Additionally, the loading phase should not be overlooked and may be more influenced by technique than physical factors. Future studies should utilise this novel approach when evaluating skeleton starts or interventions to enhance performance.

Diffusion profiling of tumor volumes using a histogram approach can predict proliferation and further microarchitectural features in medulloblastoma.

Science.gov (United States)

Schob, Stefan; Beeskow, Anne; Dieckow, Julia; Meyer, Hans-Jonas; Krause, Matthias; Frydrychowicz, Clara; Hirsch, Franz-Wolfgang; Surov, Alexey

2018-05-31

Medulloblastomas are the most common central nervous system tumors in childhood. Treatment and prognosis strongly depend on histology and transcriptomic profiling. However, the proliferative potential also has prognostical value. Our study aimed to investigate correlations between histogram profiling of diffusion-weighted images and further microarchitectural features. Seven patients (age median 14.6 years, minimum 2 years, maximum 20 years; 5 male, 2 female) were included in this retrospective study. Using a Matlab-based analysis tool, histogram analysis of whole apparent diffusion coefficient (ADC) volumes was performed. ADC entropy revealed a strong inverse correlation with the expression of the proliferation marker Ki67 (r = - 0.962, p = 0.009) and with total nuclear area (r = - 0.888, p = 0.044). Furthermore, ADC percentiles, most of all ADCp90, showed significant correlations with Ki67 expression (r = 0.902, p = 0.036). Diffusion histogram profiling of medulloblastomas provides valuable in vivo information which potentially can be used for risk stratification and prognostication. First of all, entropy revealed to be the most promising imaging biomarker. However, further studies are warranted.

Metabolomics Approach Reveals Integrated Metabolic Network Associated with Serotonin Deficiency

Science.gov (United States)

Weng, Rui; Shen, Sensen; Tian, Yonglu; Burton, Casey; Xu, Xinyuan; Liu, Yi; Chang, Cuilan; Bai, Yu; Liu, Huwei

2015-07-01

Serotonin is an important neurotransmitter that broadly participates in various biological processes. While serotonin deficiency has been associated with multiple pathological conditions such as depression, schizophrenia, Alzheimer’s disease and Parkinson’s disease, the serotonin-dependent mechanisms remain poorly understood. This study therefore aimed to identify novel biomarkers and metabolic pathways perturbed by serotonin deficiency using metabolomics approach in order to gain new metabolic insights into the serotonin deficiency-related molecular mechanisms. Serotonin deficiency was achieved through pharmacological inhibition of tryptophan hydroxylase (Tph) using p-chlorophenylalanine (pCPA) or genetic knockout of the neuronal specific Tph2 isoform. This dual approach improved specificity for the serotonin deficiency-associated biomarkers while minimizing nonspecific effects of pCPA treatment or Tph2 knockout (Tph2-/-). Non-targeted metabolic profiling and a targeted pCPA dose-response study identified 21 biomarkers in the pCPA-treated mice while 17 metabolites in the Tph2-/- mice were found to be significantly altered compared with the control mice. These newly identified biomarkers were associated with amino acid, energy, purine, lipid and gut microflora metabolisms. Oxidative stress was also found to be significantly increased in the serotonin deficient mice. These new biomarkers and the overall metabolic pathways may provide new understanding for the serotonin deficiency-associated mechanisms under multiple pathological states.

A Profile-Based Framework for Factorial Similarity and the Congruence Coefficient.

Science.gov (United States)

Hartley, Anselma G; Furr, R Michael

2017-01-01

We present a novel profile-based framework for understanding factorial similarity in the context of exploratory factor analysis in general, and for understanding the congruence coefficient (a commonly used index of factor similarity) specifically. First, we introduce the profile-based framework articulating factorial similarity in terms of 3 intuitive components: general saturation similarity, differential saturation similarity, and configural similarity. We then articulate the congruence coefficient in terms of these components, along with 2 additional profile-based components, and we explain how these components resolve ambiguities that can be-and are-found when using the congruence coefficient. Finally, we present secondary analyses revealing that profile-based components of factorial are indeed linked to experts' actual evaluations of factorial similarity. Overall, the profile-based approach we present offers new insights into the ways in which researchers can examine factor similarity and holds the potential to enhance researchers' ability to understand the congruence coefficient.

Gut Microbiota Profiling: Metabolomics Based Approach to Unravel Compounds Affecting Human Health.

Science.gov (United States)

Vernocchi, Pamela; Del Chierico, Federica; Putignani, Lorenza

2016-01-01

The gut microbiota is composed of a huge number of different bacteria, that produce a large amount of compounds playing a key role in microbe selection and in the construction of a metabolic signaling network. The microbial activities are affected by environmental stimuli leading to the generation of a wide number of compounds, that influence the host metabolome and human health. Indeed, metabolite profiles related to the gut microbiota can offer deep insights on the impact of lifestyle and dietary factors on chronic and acute diseases. Metagenomics, metaproteomics and metabolomics are some of the meta-omics approaches to study the modulation of the gut microbiota. Metabolomic research applied to biofluids allows to: define the metabolic profile; identify and quantify classes and compounds of interest; characterize small molecules produced by intestinal microbes; and define the biochemical pathways of metabolites. Mass spectrometry and nuclear magnetic resonance spectroscopy are the principal technologies applied to metabolomics in terms of coverage, sensitivity and quantification. Moreover, the use of biostatistics and mathematical approaches coupled with metabolomics play a key role in the extraction of biologically meaningful information from wide datasets. Metabolomic studies in gut microbiota-related research have increased, focusing on the generation of novel biomarkers, which could lead to the development of mechanistic hypotheses potentially applicable to the development of nutritional and personalized therapies.

Parent Prevention Communication Profiles and Adolescent Substance Use: A Latent Profile Analysis and Growth Curve Model

Science.gov (United States)

Choi, Hye Jeong; Miller-Day, Michelle; Shin, YoungJu; Hecht, Michael L.; Pettigrew, Jonathan; Krieger, Janice L.; Lee, JeongKyu; Graham, John W.

2017-01-01

This current study identifies distinct parent prevention communication profiles and examines whether youth with different parental communication profiles have varying substance use trajectories over time. Eleven schools in two rural school districts in the Midwestern United States were selected, and 784 students were surveyed at three time points from the beginning of 7th grade to the end of 8th grade. A series of latent profile analyses were performed to identify discrete profiles/subgroups of substance-specific prevention communication (SSPC). The results revealed a 4-profile model of SSPC: Active-Open, Passive-Open, Active-Silent, and Passive-Silent. A growth curve model revealed different rates of lifetime substance use depending on the youth’s SSPC profile. These findings have implications for parenting interventions and tailoring messages for parents to fit specific SSPC profiles. PMID:29056872

A reliability index for assessment of crack profile reconstructed from ECT signals using a neural-network approach

International Nuclear Information System (INIS)

Yusa, Noritaka; Chen, Zhenmao; Miya, Kenzo; Cheng, Weiying

2002-01-01

This paper proposes a reliability parameter to enhance an version scheme developed by authors. The scheme is based upon an artificial neural network that simulates mapping between eddy current signals and crack profiles. One of the biggest advantages of the scheme is that it can deal with conductive cracks, which is necessary to reconstruct natural cracks. However, it has one significant disadvantage: the reliability of reconstructed profiles was unknown. The parameter provides an index for assessment of the crack profile and overcomes this disadvantage. After the parameter is validated by reconstruction of simulated cracks, it is applied to reconstruction of natural cracks that occurred in steam generator tubes of a pressurized water reactor. It is revealed that the parameter is applicable to not only simulated cracks but also natural ones. (author)

A Remote Sensing Approach to Estimate Vertical Profile Classes of Phytoplankton in a Eutrophic Lake

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Kun Xue

2015-10-01

Full Text Available The extension and frequency of algal blooms in surface waters can be monitored using remote sensing techniques, yet knowledge of their vertical distribution is fundamental to determine total phytoplankton biomass and understanding temporal variability of surface conditions and the underwater light field. However, different vertical distribution classes of phytoplankton may occur in complex inland lakes. Identification of the vertical profile classes of phytoplankton becomes the key and first step to estimate its vertical profile. The vertical distribution profile of phytoplankton is based on a weighted integral of reflected light from all depths and is difficult to determine by reflectance data alone. In this study, four Chla vertical profile classes (vertically uniform, Gaussian, exponential and hyperbolic were found to occur in three in situ vertical surveys (28 May, 19–24 July and 10–12 October in a shallow eutrophic lake, Lake Chaohu. We developed and validated a classification and regression tree (CART to determine vertical phytoplankton biomass profile classes. This was based on an algal bloom index (Normalized Difference algal Bloom Index, NDBI applied to both in situ remote sensing reflectance (Rrs and MODIS Rayleigh-corrected reflectance (Rrc data in combination with data of local wind speed. The results show the potential of retrieving Chla vertical profiles information from integrated information sources following a decision tree approach.

Asymmetric Velocity Distributions from Halo Density Profiles in the Eddington Approach

International Nuclear Information System (INIS)

Vergados, J. D.

2015-01-01

We show how to obtain the energy distribution f(E) in our vicinity starting from WIMP density profiles in a self-consistent way by employing the Eddington approach and adding reasonable angular momentum dependent terms in the expression of the energy. We then show how we can obtain the velocity dispersions and the asymmetry parameter β in terms of the parameters describing the angular momentum dependence. From this expression, for f(E), we proceed to construct an axially symmetric WIMP a velocity distribution, which, for a gravitationally bound system, automatically has a velocity upper bound and is characterized by the same asymmetriy β. This approach is tested and clarified by constructing analytic expressions in a simple model, with adequate structure. We then show how such velocity distributions can be used in determining the event rates, including modulation, in both the standard and the directional WIMP searches.

Data analytics approach to create waste generation profiles for waste management and collection.

Science.gov (United States)

Niska, Harri; Serkkola, Ari

2018-04-30

Extensive monitoring data on waste generation is increasingly collected in order to implement cost-efficient and sustainable waste management operations. In addition, geospatial data from different registries of the society are opening for free usage. Novel data analytics approaches can be built on the top of the data to produce more detailed, and in-time waste generation information for the basis of waste management and collection. In this paper, a data-based approach based on the self-organizing map (SOM) and the k-means algorithm is developed for creating a set of waste generation type profiles. The approach is demonstrated using the extensive container-level waste weighting data collected in the metropolitan area of Helsinki, Finland. The results obtained highlight the potential of advanced data analytic approaches in producing more detailed waste generation information e.g. for the basis of tailored feedback services for waste producers and the planning and optimization of waste collection and recycling. Copyright © 2018 Elsevier Ltd. All rights reserved.

Metabolomics reveals variation and correlation among different tissues of olive (Olea europaea L.

Directory of Open Access Journals (Sweden)

Rao Guodong

2017-09-01

Full Text Available Metabolites in olives are associated with nutritional value and physiological properties. However, comprehensive information regarding the olive metabolome is limited. In this study, we identified 226 metabolites from three different tissues of olive using a non-targeted metabolomic profiling approach, of which 76 named metabolites were confirmed. Further statistical analysis revealed that these 76 metabolites covered different types of primary metabolism and some of the secondary metabolism pathways. One-way analysis of variance (ANOVA statistical assay was performed to calculate the variations within the detected metabolites, and levels of 65 metabolites were differentially expressed in different samples. Hierarchical cluster analysis (HCA dendrograms showed variations among different tissues that were similar to the metabolite profiles observed in new leaves and fruit. Additionally, 5776 metabolite-metabolite correlations were detected by a Pearson correlation coefficient approach. Screening of the calculated correlations revealed 3136, 3025, and 5184 were determined to metabolites and had significant correlations in three different combinations, respectively. This work provides the first comprehensive metabolomic of olive, which will provide new insights into understanding the olive metabolism, and potentially help advance studies in olive metabolic engineering.

Whole blood transcriptional profiling reveals significant down-regulation of human leukocyte antigen class I and II genes in essential thrombocythemia, polycythemia vera and myelofibrosis

DEFF Research Database (Denmark)

Skov, Vibe; Riley, Caroline Hasselbalch; Thomassen, Mads

2013-01-01

Gene expression profiling studies in the Philadelphia-negative chronic myeloproliferative neoplasms have revealed significant deregulation of several immune and inflammation genes that might be of importance for clonal evolution due to defective tumor immune surveillance. Other mechanisms might b...

Diagnose Test-Taker's Profile in Terms of Core Profile Patterns: Principal Component (PC) vs. Profile Analysis via MDS (PAMS) Approaches.

Science.gov (United States)

Kim, Se-Kang; Davison, Mark L.

A study was conducted to examine how principal components analysis (PCA) and Profile Analysis via Multidimensional Scaling (PAMS) can be used to diagnose individuals observed score profiles in terms of core profile patterns identified by each method. The standardization sample from the Wechsler Intelligence Scale for Children, Third Edition…

Global transcription profiling reveals comprehensive insights into hypoxic response in Arabidopsis.

Science.gov (United States)

Liu, Fenglong; Vantoai, Tara; Moy, Linda P; Bock, Geoffrey; Linford, Lara D; Quackenbush, John

2005-03-01

Plants have evolved adaptation mechanisms to sense oxygen deficiency in their environments and make coordinated physiological and structural adjustments to enhance their hypoxic tolerance. To gain insight into how plants respond to low-oxygen stress, gene expression profiling using whole-genome DNA amplicon microarrays was carried out at seven time points over 24 h, in wild-type and transgenic P(SAG12):ipt Arabidopsis (Arabidopsis thaliana) plants under normoxic and hypoxic conditions. Transcript levels of genes involved in glycolysis and fermentation pathways, ethylene synthesis and perception, calcium signaling, nitrogen utilization, trehalose metabolism, and alkaloid synthesis were significantly altered in response to oxygen limitation. Analysis based on gene ontology assignments suggested a significant down-regulation of genes whose functions are associated with cell walls, nucleosome structures, water channels, and ion transporters and a significant up-regulation of genes involved in transcriptional regulation, protein kinase activity, and auxin responses under conditions of oxygen shortage. Promoter analysis on a cluster of up-regulated genes revealed a significant overrepresentation of the AtMYB2-binding motif (GT motif), a sugar response element-like motif, and a G-box-related sequence, and also identified several putative anaerobic response elements. Finally, quantitative real-time polymerase chain reactions using 29 selected genes independently verified the microarray results. This study represents one of the most comprehensive analyses conducted to date investigating hypoxia-responsive transcriptional networks in plants.

Patterns of trading profiles at the Nordic Stock Exchange. A correlation-based approach

International Nuclear Information System (INIS)

Musciotto, Federico; Marotta, Luca; Miccichè, Salvatore; Piilo, Jyrki; Mantegna, Rosario N.

2016-01-01

We investigate the trading behavior of Finnish individual investors trading the stocks selected to compute the OMXH25 index in 2003 by tracking the individual daily investment decisions. We verify that the set of investors is a highly heterogeneous system under many aspects. We introduce a correlation based method that is able to detect a hierarchical structure of the trading profiles of heterogeneous individual investors. We verify that the detected hierarchical structure is highly overlapping with the cluster structure obtained with the approach of statistically validated networks when an appropriate threshold of the hierarchical trees is used. We also show that the combination of the correlation based method and of the statistically validated method provides a way to expand the information about the clusters of investors with similar trading profiles in a robust and reliable way.

A Context-Aware Mobile User Behavior-Based Neighbor Finding Approach for Preference Profile Construction †

Science.gov (United States)

Gao, Qian; Fu, Deqian; Dong, Xiangjun

2016-01-01

In this paper, a new approach is adopted to update the user preference profile by seeking users with similar interests based on the context obtainable for a mobile network instead of from desktop networks. The trust degree between mobile users is calculated by analyzing their behavior based on the context, and then the approximate neighbors are chosen by combining the similarity of the mobile user preference and the trust degree. The approach first considers the communication behaviors between mobile users, the mobile network services they use as well as the corresponding context information. Then a similarity degree of the preference between users is calculated with the evaluation score of a certain mobile web service provided by a mobile user. Finally, based on the time attenuation function, the users with similar preference are found, through which we can dynamically update the target user’s preference profile. Experiments are then conducted to test the effect of the context on the credibility among mobile users, the effect of time decay factors and trust degree thresholds. Simulation shows that the proposed approach outperforms two other methods in terms of Recall Ratio, Precision Ratio and Mean Absolute Error, because neither of them consider the context mobile information. PMID:26805852

A Click Chemistry-Based Proteomic Approach Reveals that 1,2,4-Trioxolane and Artemisinin Antimalarials Share a Common Protein Alkylation Profile.

Science.gov (United States)

Ismail, Hanafy M; Barton, Victoria E; Panchana, Matthew; Charoensutthivarakul, Sitthivut; Biagini, Giancarlo A; Ward, Stephen A; O'Neill, Paul M

2016-05-23

In spite of the recent increase in endoperoxide antimalarials under development, it remains unclear if all these chemotypes share a common mechanism of action. This is important since it will influence cross-resistance risks between the different classes. Here we investigate this proposition using novel clickable 1,2,4-trioxolane activity based protein-profiling probes (ABPPs). ABPPs with potent antimalarial activity were able to alkylate protein target(s) within the asexual erythrocytic stage of Plasmodium falciparum (3D7). Importantly, comparison of the alkylation fingerprint with that generated from an artemisinin ABPP equivalent confirms a highly conserved alkylation profile, with both endoperoxide classes targeting proteins in the glycolytic, hemoglobin degradation, antioxidant defence, protein synthesis and protein stress pathways, essential biological processes for plasmodial survival. The alkylation signatures of the two chemotypes show significant overlap (ca. 90 %) both qualitatively and semi-quantitatively, suggesting a common mechanism of action that raises concerns about potential cross-resistance liabilities.

Metabolic profiling reveals potential metabolic markers associated with Hypoxia Inducible Factor-mediated signalling in hypoxic cancer cells.

Science.gov (United States)

Armitage, Emily G; Kotze, Helen L; Allwood, J William; Dunn, Warwick B; Goodacre, Royston; Williams, Kaye J

2015-10-28

Hypoxia inducible factors (HIFs) plays an important role in oxygen compromised environments and therefore in tumour survival. In this research, metabolomics has been applied to study HIFs metabolic function in two cell models: mouse hepatocellular carcinoma and human colon carcinoma, whereby the metabolism has been profiled for a range of oxygen potentials. Wild type cells have been compared to cells deficient in HIF signalling to reveal its effect on cellular metabolism under normal oxygen conditions as well as low oxygen, hypoxic and anoxic environments. Characteristic responses to hypoxia that were conserved across both cell models involved the anti-correlation between 2-hydroxyglutarate, 2-oxoglutarate, fructose, hexadecanoic acid, hypotaurine, pyruvate and octadecenoic acid with 4-hydroxyproline, aspartate, cysteine, glutamine, lysine, malate and pyroglutamate. Further to this, network-based correlation analysis revealed HIF specific pathway responses to each oxygen condition that were also conserved between cell models. From this, 4-hydroxyproline was revealed as a regulating hub in low oxygen survival of WT cells while fructose appeared to be in HIF deficient cells. Pathways surrounding these hubs were built from the direct connections of correlated metabolites that look beyond traditional pathways in order to understand the mechanism of HIF response to low oxygen environments.

Recent aquatic ecosystem response to environmental events revealed from 210Pb sediment profiles

International Nuclear Information System (INIS)

Mulsow, S.; Piovano, E.; Cordoba, F.

2009-01-01

The 210 Pb dating method was first introduced by , and since then has been applied to study sediment from lakes, estuaries and coastal marine environments. Hundreds of studies around the world have used 210 Pb as a geochronological tool in aquatic ecosystems. However little attention has been paid to the potential of this naturally occurring isotope as an environmental tracer of ecological events. Here we report three instances in which 210 Pb profiles measured on undisturbed sediment cores from lakes, rivers and fjords show us the potential of 210 Pb profile as a tracer of natural and anthropogenic processes. The methodology used here is a suite of techniques combining biogeochemistry (micro-electrodes), paleomagnetism (susceptibility), sediment characteristics (LOI) and visualization (SPI and X-ray) applied to the interpretation of 210 Pb profiles. We measured 210 Pb profiles on sediments from a river, Cruces River (Chile), which recorded a clear shift in the water chemistry caused by a pulp mill effluent to the river. Here metal mobilization and remobilization of the tracer may be the cause of the observed profile. We also measured 210 Pb profiles in sediment from two fjords of Southern Chile (Pillan and Renihue), the sudden deposition change of fresh 210 Pb with depth observed could very well be the result of bioturbation but it occurred in a seafloor area deprived of bioturbators. In this case, 210 Pb recorded the onset of aquaculture activities (fish farming) that took place two decades ago. Finally, 210 Pb profiles measured in two lakes in the 'pampa Argentina': Epecuen and Venado showed a particular shape with depth. These profiles apparently registered a sudden depositional event with recent 210 Pb material, probably related to strong shifts in precipitation and drought cycles in that part of the world. These three examples show that 210 Pb profiles provide valuable information not only on geochronology, but also related to natural and anthropogenic short

A New profiling and pipelining approach for HEVC Decoder on ZedBoard Platform

Directory of Open Access Journals (Sweden)

Habib Smei

2017-10-01

Full Text Available New multimedia applications such as mobile video, high-quality Internet video or digital television requires high-performance encoding of video signals to meet technical constraints such as runtime, bandwidth or latency. Video coding standard h.265 HEVC (High Efficiency Video Coding was developed by JCT-VC to replace the MPEG-2, MPEG-4 and h.264 codecs and to respond to these new functional constraints. Currently, there are several implementations of this standard. Some implementations are based on software acceleration techniques; Others, on techniques of purely hardware acceleration and some others combine the two techniques. In software implementations, several techniques are used in order to decrease the video coding and decoding time. We quote data parallelism, tasks parallelism and combined solutions. In the other hand, In order to fulfill the computational demands of the new standard, HEVC includes several coding tools that allow dividing each picture into several partitions that can be processed in parallel, without degrading neither the quality nor the bitrate. In this paper, we adapt one of these approaches, the Tile coding tool to propose a pipeline execution approach of the HEVC / h265 decoder application in its version HM Test model. This approach is based on a fine profiling by using code injection techniques supported by standard profiling tools such as Gprof and Valgrind. Profiling allowed us to divide functions into four groups according to three criteria: the first criterion is based on the minimization of communication between the different functions groups in order to have minimal intergroup communication and maximum intragroup communication. The second criterion is the load balancing between processors. The third criterion is the parallelism between functions. Experiments carried out in this paper are based on the Zedboard platform, which integrates a chip Zynq xilinx with a dual core ARM A9. We start with a purely

The Use of New Technologies in Basic Education: An Approach to Profile of Indigenous Ecuadorians

Science.gov (United States)

Stefos, Efstathios; Castellano, José Manuel; Marchán, Andrés Bonilla; Biloon, Julia Raina Sevy

2017-01-01

This article aims to define the profile of Ecuadorian indigenous students who study at different levels of basic education in Ecuador in the context of the application and use of emerging technologies in the last five years. This approach focuses on a comparative analysis between indigenous and non-indigenous students, based on the national data…

Lipidomics profiling reveals the role of glycerophospholipid metabolism in psoriasis.

Science.gov (United States)

Zeng, Chunwei; Wen, Bo; Hou, Guixue; Lei, Li; Mei, Zhanlong; Jia, Xuekun; Chen, Xiaomin; Zhu, Wu; Li, Jie; Kuang, Yehong; Zeng, Weiqi; Su, Juan; Liu, Siqi; Peng, Cong; Chen, Xiang

2017-10-01

Psoriasis is a common and chronic inflammatory skin disease that is complicated by gene-environment interactions. Although genomic, transcriptomic, and proteomic analyses have been performed to investigate the pathogenesis of psoriasis, the role of metabolites in psoriasis, particularly of lipids, remains unclear. Lipids not only comprise the bulk of the cellular membrane bilayers but also regulate a variety of biological processes such as cell proliferation, apoptosis, immunity, angiogenesis, and inflammation. In this study, an untargeted lipidomics approach was used to study the lipid profiles in psoriasis and to identify lipid metabolite signatures for psoriasis through ultra-performance liquid chromatography-tandem quadrupole mass spectrometry. Plasma samples from 90 participants (45 healthy and 45 psoriasis patients) were collected and analyzed. Statistical analysis was applied to find different metabolites between the disease and healthy groups. In addition, enzyme-linked immunosorbent assay was performed to validate differentially expressed lipids in psoriatic patient plasma. Finally, we identified differential expression of several lipids including lysophosphatidic acid (LPA), lysophosphatidylcholine (LysoPC), phosphatidylinositol (PI), phosphatidylcholine (PC), and phosphatidic acid (PA); among these metabolites, LPA, LysoPC, and PA were significantly increased, while PC and PI were down-regulated in psoriasis patients. We found that elements of glycerophospholipid metabolism such as LPA, LysoPC, PA, PI, and PC were significantly altered in the plasma of psoriatic patients; this study characterizes the circulating lipids in psoriatic patients and provides novel insight into the role of lipids in psoriasis. © The Author 2017. Published by Oxford University Press.

Shotgun microbial profiling of fossil remains

DEFF Research Database (Denmark)

Der Sarkissian, Clio; Ermini, Luca; Jónsson, Hákon

2014-01-01

the specimen of interest, but instead reflect environmental organisms that colonized the specimen after death. Here, we characterize the microbial diversity recovered from seven c. 200- to 13 000-year-old horse bones collected from northern Siberia. We use a robust, taxonomy-based assignment approach...... to identify the microorganisms present in ancient DNA extracts and quantify their relative abundance. Our results suggest that molecular preservation niches exist within ancient samples that can potentially be used to characterize the environments from which the remains are recovered. In addition, microbial...... community profiling of the seven specimens revealed site-specific environmental signatures. These microbial communities appear to comprise mainly organisms that colonized the fossils recently. Our approach significantly extends the amount of useful data that can be recovered from ancient specimens using...

Classification of breast cancer patients using somatic mutation profiles and machine learning approaches.

Science.gov (United States)

Vural, Suleyman; Wang, Xiaosheng; Guda, Chittibabu

2016-08-26

The high degree of heterogeneity observed in breast cancers makes it very difficult to classify the cancer patients into distinct clinical subgroups and consequently limits the ability to devise effective therapeutic strategies. Several classification strategies based on ER/PR/HER2 expression or the expression profiles of a panel of genes have helped, but such methods often produce misleading results due to their dynamic nature. In contrast, somatic DNA mutations are relatively stable and lead to initiation and progression of many sporadic cancers. Hence in this study, we explore the use of gene mutation profiles to classify, characterize and predict the subgroups of breast cancers. We analyzed the whole exome sequencing data from 358 ethnically similar breast cancer patients in The Cancer Genome Atlas (TCGA) project. Somatic and non-synonymous single nucleotide variants identified from each patient were assigned a quantitative score (C-score) that represents the extent of negative impact on the gene function. Using these scores with non-negative matrix factorization method, we clustered the patients into three subgroups. By comparing the clinical stage of patients, we identified an early-stage-enriched and a late-stage-enriched subgroup. Comparison of the mutation scores of early and late-stage-enriched subgroups identified 358 genes that carry significantly higher mutations rates in the late stage subgroup. Functional characterization of these genes revealed important functional gene families that carry a heavy mutational load in the late state rich subgroup of patients. Finally, using the identified subgroups, we also developed a supervised classification model to predict the stage of the patients. This study demonstrates that gene mutation profiles can be effectively used with unsupervised machine-learning methods to identify clinically distinguishable breast cancer subgroups. The classification model developed in this method could provide a reasonable

Metabolic profiling of presymptomatic Huntington’s disease sheep reveals novel biomarkers

Science.gov (United States)

Skene, Debra J.; Middleton, Benita; Fraser, Cara K.; Pennings, Jeroen L. A.; Kuchel, Timothy R.; Rudiger, Skye R.; Bawden, C. Simon; Morton, A. Jennifer

2017-01-01

The pronounced cachexia (unexplained wasting) seen in Huntington’s disease (HD) patients suggests that metabolic dysregulation plays a role in HD pathogenesis, although evidence of metabolic abnormalities in HD patients is inconsistent. We performed metabolic profiling of plasma from presymptomatic HD transgenic and control sheep. Metabolites were quantified in sequential plasma samples taken over a 25 h period using a targeted LC/MS metabolomics approach. Significant changes with respect to genotype were observed in 89/130 identified metabolites, including sphingolipids, biogenic amines, amino acids and urea. Citrulline and arginine increased significantly in HD compared to control sheep. Ten other amino acids decreased in presymptomatic HD sheep, including branched chain amino acids (isoleucine, leucine and valine) that have been identified previously as potential biomarkers of HD. Significant increases in urea, arginine, citrulline, asymmetric and symmetric dimethylarginine, alongside decreases in sphingolipids, indicate that both the urea cycle and nitric oxide pathways are dysregulated at early stages in HD. Logistic prediction modelling identified a set of 8 biomarkers that can identify 80% of the presymptomatic HD sheep as transgenic, with 90% confidence. This level of sensitivity, using minimally invasive methods, offers novel opportunities for monitoring disease progression in HD patients. PMID:28223686

Profiling mRNAs of two Cuscuta species reveals possible candidate transcripts shared by parasitic plants.

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Linjian Jiang

Full Text Available Dodders are among the most important parasitic plants that cause serious yield losses in crop plants. In this report, we sought to unveil the genetic basis of dodder parasitism by profiling the trancriptomes of Cuscuta pentagona and C. suaveolens, two of the most common dodder species using a next-generation RNA sequencing platform. De novo assembly of the sequence reads resulted in more than 46,000 isotigs and contigs (collectively referred to as expressed sequence tags or ESTs for each species, with more than half of them predicted to encode proteins that share significant sequence similarities with known proteins of non-parasitic plants. Comparing our datasets with transcriptomes of 12 other fully sequenced plant species confirmed a close evolutionary relationship between dodder and tomato. Using a rigorous set of filtering parameters, we were able to identify seven pairs of ESTs that appear to be shared exclusively by parasitic plants, thus providing targets for tailored management approaches. In addition, we also discovered ESTs with sequences similarities to known plant viruses, including cryptic viruses, in the dodder sequence assemblies. Together this study represents the first comprehensive transcriptome profiling of parasitic plants in the Cuscuta genus, and is expected to contribute to our understanding of the molecular mechanisms of parasitic plant-host plant interactions.

Profiling mRNAs of two Cuscuta species reveals possible candidate transcripts shared by parasitic plants.

Science.gov (United States)

Jiang, Linjian; Wijeratne, Asela J; Wijeratne, Saranga; Fraga, Martina; Meulia, Tea; Doohan, Doug; Li, Zhaohu; Qu, Feng

2013-01-01

Dodders are among the most important parasitic plants that cause serious yield losses in crop plants. In this report, we sought to unveil the genetic basis of dodder parasitism by profiling the trancriptomes of Cuscuta pentagona and C. suaveolens, two of the most common dodder species using a next-generation RNA sequencing platform. De novo assembly of the sequence reads resulted in more than 46,000 isotigs and contigs (collectively referred to as expressed sequence tags or ESTs) for each species, with more than half of them predicted to encode proteins that share significant sequence similarities with known proteins of non-parasitic plants. Comparing our datasets with transcriptomes of 12 other fully sequenced plant species confirmed a close evolutionary relationship between dodder and tomato. Using a rigorous set of filtering parameters, we were able to identify seven pairs of ESTs that appear to be shared exclusively by parasitic plants, thus providing targets for tailored management approaches. In addition, we also discovered ESTs with sequences similarities to known plant viruses, including cryptic viruses, in the dodder sequence assemblies. Together this study represents the first comprehensive transcriptome profiling of parasitic plants in the Cuscuta genus, and is expected to contribute to our understanding of the molecular mechanisms of parasitic plant-host plant interactions.

Diverse Brain Myeloid Expression Profiles Reveal Distinct Microglial Activation States and Aspects of Alzheimer’s Disease Not Evident in Mouse Models

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Brad A. Friedman

2018-01-01

Full Text Available Microglia, the CNS-resident immune cells, play important roles in disease, but the spectrum of their possible activation states is not well understood. We derived co-regulated gene modules from transcriptional profiles of CNS myeloid cells of diverse mouse models, including new tauopathy model datasets. Using these modules to interpret single-cell data from an Alzheimer’s disease (AD model, we identified microglial subsets—distinct from previously reported “disease-associated microglia”—expressing interferon-related or proliferation modules. We then analyzed whole-tissue RNA profiles from human neurodegenerative diseases, including a new AD dataset. Correcting for altered cellular composition of AD tissue, we observed elevated expression of the neurodegeneration-related modules, but also modules not implicated using expression profiles from mouse models alone. We provide a searchable, interactive database for exploring gene expression in all these datasets (http://research-pub.gene.com/BrainMyeloidLandscape. Understanding the dimensions of CNS myeloid cell activation in human disease may reveal opportunities for therapeutic intervention.

Motivational profiles of slovenian high school students and their academic performance outcomes.

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Vrtačnik, Margareta; Juriševič, Mojca; Savec, Vesna Ferk

2010-09-01

Self-determination theory defines motivation as a multidimensional concept, with autonomous and controlled motivation as central factors of broader distinctions. Previous research has proven that academic achievements are positively correlated with autonomous motivation. Students from 10 Slovenian grammar schools were involved in empirical study, in which a cluster analysis revealed two motivational profiles: a low quantity motivation group (low controlled and autonomous motivation) and a good quality motivation group (high autonomous and low or average controlled motivation). Statistically significant differences between the two identified motivational profiles were found for students' general as well as chemistry performance in three grades of schooling. Furthermore, a good quality motivation group is also more in favour of autonomy-supportive teaching methods used in chemistry classes. Examination of students' opinions about important chemistry topics, and on the other hand, unimportant ones, and not connected with life, reveals that the basic reason for distinction might lie in the chemistry teacher's approach used while presenting these topics. Some chemistry teachers are not using an autonomy-supportive way of teaching which would contribute to better teaching outcomes; therefore a need for further research on Slovenian chemistry teachers' motivation and their teaching approaches was recognized.

Gene expression profiling in equine polysaccharide storage myopathy revealed inflammation, glycogenesis inhibition, hypoxia and mitochondrial dysfunctions

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Benech Philippe

2009-08-01

Full Text Available Abstract Background Several cases of myopathies have been observed in the horse Norman Cob breed. Muscle histology examinations revealed that some families suffer from a polysaccharide storage myopathy (PSSM. It is assumed that a gene expression signature related to PSSM should be observed at the transcriptional level because the glycogen storage disease could also be linked to other dysfunctions in gene regulation. Thus, the functional genomic approach could be conducted in order to provide new knowledge about the metabolic disorders related to PSSM. We propose exploring the PSSM muscle fiber metabolic disorders by measuring gene expression in relationship with the histological phenotype. Results Genotypying analysis of GYS1 mutation revealed 2 homozygous (AA and 5 heterozygous (GA PSSM horses. In the PSSM muscles, histological data revealed PAS positive amylase resistant abnormal polysaccharides, inflammation, necrosis, and lipomatosis and active regeneration of fibers. Ultrastructural evaluation revealed a decrease of mitochondrial number and structural disorders. Extensive accumulation of an abnormal polysaccharide displaced and partially replaced mitochondria and myofibrils. The severity of the disease was higher in the two homozygous PSSM horses. Gene expression analysis revealed 129 genes significantly modulated (p Conclusion The main disorders observed in PSSM muscles could be related to mitochondrial dysfunctions, glycogenesis inhibition and the chronic hypoxia of the PSSM muscles.

Different Statistical Approaches to Investigate Porcine Muscle Metabolome Profiles to Highlight New Biomarkers for Pork Quality Assessment

Science.gov (United States)

Welzenbach, Julia; Neuhoff, Christiane; Looft, Christian; Schellander, Karl; Tholen, Ernst; Große-Brinkhaus, Christine

2016-01-01

The aim of this study was to elucidate the underlying biochemical processes to identify potential key molecules of meat quality traits drip loss, pH of meat 1 h post-mortem (pH1), pH in meat 24 h post-mortem (pH24) and meat color. An untargeted metabolomics approach detected the profiles of 393 annotated and 1,600 unknown metabolites in 97 Duroc × Pietrain pigs. Despite obvious differences regarding the statistical approaches, the four applied methods, namely correlation analysis, principal component analysis, weighted network analysis (WNA) and random forest regression (RFR), revealed mainly concordant results. Our findings lead to the conclusion that meat quality traits pH1, pH24 and color are strongly influenced by processes of post-mortem energy metabolism like glycolysis and pentose phosphate pathway, whereas drip loss is significantly associated with metabolites of lipid metabolism. In case of drip loss, RFR was the most suitable method to identify reliable biomarkers and to predict the phenotype based on metabolites. On the other hand, WNA provides the best parameters to investigate the metabolite interactions and to clarify the complex molecular background of meat quality traits. In summary, it was possible to attain findings on the interaction of meat quality traits and their underlying biochemical processes. The detected key metabolites might be better indicators of meat quality especially of drip loss than the measured phenotype itself and potentially might be used as bio indicators. PMID:26919205

Deep sequencing-based transcriptome profiling analysis of bacteria-challenged Lateolabrax japonicus reveals insight into the immune-relevant genes in marine fish

Directory of Open Access Journals (Sweden)

Xiang Li-xin

2010-08-01

Full Text Available Abstract Background Systematic research on fish immunogenetics is indispensable in understanding the origin and evolution of immune systems. This has long been a challenging task because of the limited number of deep sequencing technologies and genome backgrounds of non-model fish available. The newly developed Solexa/Illumina RNA-seq and Digital gene expression (DGE are high-throughput sequencing approaches and are powerful tools for genomic studies at the transcriptome level. This study reports the transcriptome profiling analysis of bacteria-challenged Lateolabrax japonicus using RNA-seq and DGE in an attempt to gain insights into the immunogenetics of marine fish. Results RNA-seq analysis generated 169,950 non-redundant consensus sequences, among which 48,987 functional transcripts with complete or various length encoding regions were identified. More than 52% of these transcripts are possibly involved in approximately 219 known metabolic or signalling pathways, while 2,673 transcripts were associated with immune-relevant genes. In addition, approximately 8% of the transcripts appeared to be fish-specific genes that have never been described before. DGE analysis revealed that the host transcriptome profile of Vibrio harveyi-challenged L. japonicus is considerably altered, as indicated by the significant up- or down-regulation of 1,224 strong infection-responsive transcripts. Results indicated an overall conservation of the components and transcriptome alterations underlying innate and adaptive immunity in fish and other vertebrate models. Analysis suggested the acquisition of numerous fish-specific immune system components during early vertebrate evolution. Conclusion This study provided a global survey of host defence gene activities against bacterial challenge in a non-model marine fish. Results can contribute to the in-depth study of candidate genes in marine fish immunity, and help improve current understanding of host

Association between litterers' profile and littering behavior: A chi-square approach

Science.gov (United States)

Asmui, Mas'udah; Zaki, Suhanom Mohd; Wahid, Sharifah Norhuda Syed; Mokhtar, Noorsuraya Mohd; Harith, Siti Suhaila

2017-05-01

Littering is not a novelty, yet a prolonged issue. The solutions have been discussed for a long time; however this issue still remains unresolved. Littering is commonly associated with littering behavior and awareness. The littering behavior is normally influenced by the litter profile such as gender, family income, education level and age. Jengka Street market, which is located in Pahang, is popularly known as a trade market. It offers diversities of wet and dry goods and is awaited by local residents and tourists. This study analyzes association between litterers' profile and littering behavior. Littering behavior is measured based on factors of trash bin facilities, awareness campaign and public littering behavior. 114 respondents were involved in this study with 62 (54.39%) are female aged more than 18 years old and majority of these female respondents are diploma holders. In addition, 78.95% of the respondents have family income below than RM3,000.00 per month. Based on the data analysis, it was found that first-time visitors littered higher than frequent visitors, lack of providing trash bin facilities contributes to positive littering behavior and there is a significant association between litterers' age and littering behavior by using chi-square approach.

Ground-based remote sensing of HDO/H2O ratio profiles: introduction and validation of an innovative retrieval approach

Science.gov (United States)

Schneider, M.; Hase, F.; Blumenstock, T.

2006-10-01

We propose an innovative approach for analysing ground-based FTIR spectra which allows us to detect variabilities of lower and middle/upper tropospheric HDO/H2O ratios. We show that the proposed method is superior to common approaches. We estimate that lower tropospheric HDO/H2O ratios can be detected with a noise to signal ratio of 15% and middle/upper tropospheric ratios with a noise to signal ratio of 50%. The method requires the inversion to be performed on a logarithmic scale and to introduce an inter-species constraint. While common methods calculate the isotope ratio posterior to an independent, optimal estimation of the HDO and H2O profile, the proposed approach is an optimal estimator for the ratio itself. We apply the innovative approach to spectra measured continuously during 15 months and present, for the first time, an annual cycle of tropospheric HDO/H2O ratio profiles as detected by ground-based measurements. Outliers in the detected middle/upper tropospheric ratios are interpreted by backward trajectories.

Targeted metabolite profile of food bioactive compounds by Orbitrap high resolution mass spectrometry: The 'FancyTiles' approach

NARCIS (Netherlands)

Troise, A.D.; Ferracane, R.; Palermo, M.; Fogliano, V.

2014-01-01

In this paper a new targeted metabolic profile approach using Orbitrap high resolution mass spectrometry was described. For each foodmatrix various classes of bioactive compounds and some specificmetabolites of interest were selected on the basis of the existing knowledge creating an easy-to-read

Strain profiles in ion implanted ceramic polycrystals: An approach based on reciprocal-space crystal selection

Energy Technology Data Exchange (ETDEWEB)

Palancher, H., E-mail: herve.palancher@cea.fr; Martin, G.; Fouet, J. [CEA, DEN, DEC, F-13108 Saint Paul lez Durance (France); Goudeau, P. [Institut Pprime, CNRS-Université de Poitiers–ENSMA, SP2MI, F-86360 Chasseneuil (France); Boulle, A. [Science des Procédés Céramiques et Traitements de Surface (SPCTS), CNRS UMR 7315, Centre Européen de la Céramique, 12 rue Atlantis, 87068 Limoges (France); Rieutord, F. [CEA, DSM, INAC, F-38054 Grenoble Cedex 9 (France); Favre-Nicolin, V. [Université Grenoble-Alpes, F-38041 Grenoble, France, Institut Universitaire de France, F-75005 Paris (France); Blanc, N. [Institut NEEL, CNRS-Univ Grenoble Alpes, F-38042 Grenoble (France); Onofri, C. [CEA, DEN, DEC, F-13108 Saint Paul lez Durance (France); CEMES, CNRS UPR 8011, 29 rue Jeanne Marvig, BP 94347, 31055 Toulouse Cedex 4 (France)

2016-01-18

The determination of the state of strain in implanted materials is a key issue in the study of their mechanical stability. Whereas this question is nowadays relatively easily solved in the case of single crystals, it remains a challenging task in the case of polycrystalline materials. In this paper, we take benefit of the intense and parallel beams provided by third generation synchrotron sources combined with a two-dimensional detection system to analyze individual grains in polycrystals, hence obtaining “single crystal-like” data. The feasibility of the approach is demonstrated with implanted UO{sub 2} polycrystals where the in-depth strain profile is extracted for individual grains using numerical simulations of the diffracted signal. The influence of the implantation dose is precisely analyzed for several diffracting planes and grains. This work suggests that, at low fluences, the development of strain is mainly due to ballistic effects with little effect from He ions, independently from the crystallographic orientation. At higher fluences, the evolution of the strain profiles suggests a partial and anisotropic plastic relaxation. With the present approach, robust and reliable structural information can be obtained, even from complex polycrystalline ceramic materials.

Ayurvedic Profiling of Alzheimer's Disease.

Science.gov (United States)

Bredesen, Dale E; Rao, Rammohan V

2017-05-01

Alzheimer's disease (AD) is an age-associated, progressive neurodegenerative disease that is characterized by severe memory loss, personality changes, and an overall decline in cognitive function. The cause of AD is not yet completely defined and efforts to find a cure for it have so far been disappointing. AD is one of the most significant health care problems nationally and globally. Recently, we described a personalized therapeutic approach called metabolic enhancement for neurodegeneration (MEND) that successfully reversed the cognitive decline in patients with early AD. The magnitude of the improvement was exceptional, providing testimony to the fact that a personalized and programmatic approach to cognitive decline is highly effective. Ayurveda is a personalized system of traditional medicine native to India and the Indian subcontinent. Although a direct reference to AD in the ancient Ayurvedic literature is missing, concepts including forgetfulness, memory loss, and brain cell loss have been described. Using the clinical information and the metabolic profiling of AD individuals we recently reported using the MEND program, we now describe in this commentary, 3 subtypes of AD based on the Ayurvedic interpretation. Ayurvedic profiling of patients with AD reveals 3 readily distinguishable subtypes, namely Vata, Pitta, and Krimi, which will prove useful in patients with cognitive decline and those at risk for such decline from the standpoint of specific subtype-based Ayurvedic intervention.

Computational dissection of human episodic memory reveals mental process-specific genetic profiles.

Science.gov (United States)

Luksys, Gediminas; Fastenrath, Matthias; Coynel, David; Freytag, Virginie; Gschwind, Leo; Heck, Angela; Jessen, Frank; Maier, Wolfgang; Milnik, Annette; Riedel-Heller, Steffi G; Scherer, Martin; Spalek, Klara; Vogler, Christian; Wagner, Michael; Wolfsgruber, Steffen; Papassotiropoulos, Andreas; de Quervain, Dominique J-F

2015-09-01

Episodic memory performance is the result of distinct mental processes, such as learning, memory maintenance, and emotional modulation of memory strength. Such processes can be effectively dissociated using computational models. Here we performed gene set enrichment analyses of model parameters estimated from the episodic memory performance of 1,765 healthy young adults. We report robust and replicated associations of the amine compound SLC (solute-carrier) transporters gene set with the learning rate, of the collagen formation and transmembrane receptor protein tyrosine kinase activity gene sets with the modulation of memory strength by negative emotional arousal, and of the L1 cell adhesion molecule (L1CAM) interactions gene set with the repetition-based memory improvement. Furthermore, in a large functional MRI sample of 795 subjects we found that the association between L1CAM interactions and memory maintenance revealed large clusters of differences in brain activity in frontal cortical areas. Our findings provide converging evidence that distinct genetic profiles underlie specific mental processes of human episodic memory. They also provide empirical support to previous theoretical and neurobiological studies linking specific neuromodulators to the learning rate and linking neural cell adhesion molecules to memory maintenance. Furthermore, our study suggests additional memory-related genetic pathways, which may contribute to a better understanding of the neurobiology of human memory.

Computational dissection of human episodic memory reveals mental process-specific genetic profiles

Science.gov (United States)

Luksys, Gediminas; Fastenrath, Matthias; Coynel, David; Freytag, Virginie; Gschwind, Leo; Heck, Angela; Jessen, Frank; Maier, Wolfgang; Milnik, Annette; Riedel-Heller, Steffi G.; Scherer, Martin; Spalek, Klara; Vogler, Christian; Wagner, Michael; Wolfsgruber, Steffen; Papassotiropoulos, Andreas; de Quervain, Dominique J.-F.

2015-01-01

Episodic memory performance is the result of distinct mental processes, such as learning, memory maintenance, and emotional modulation of memory strength. Such processes can be effectively dissociated using computational models. Here we performed gene set enrichment analyses of model parameters estimated from the episodic memory performance of 1,765 healthy young adults. We report robust and replicated associations of the amine compound SLC (solute-carrier) transporters gene set with the learning rate, of the collagen formation and transmembrane receptor protein tyrosine kinase activity gene sets with the modulation of memory strength by negative emotional arousal, and of the L1 cell adhesion molecule (L1CAM) interactions gene set with the repetition-based memory improvement. Furthermore, in a large functional MRI sample of 795 subjects we found that the association between L1CAM interactions and memory maintenance revealed large clusters of differences in brain activity in frontal cortical areas. Our findings provide converging evidence that distinct genetic profiles underlie specific mental processes of human episodic memory. They also provide empirical support to previous theoretical and neurobiological studies linking specific neuromodulators to the learning rate and linking neural cell adhesion molecules to memory maintenance. Furthermore, our study suggests additional memory-related genetic pathways, which may contribute to a better understanding of the neurobiology of human memory. PMID:26261317

Plasma Exosome Profiling of Cancer Patients by a Next Generation Systems Biology Approach.

Science.gov (United States)

Domenyuk, Valeriy; Zhong, Zhenyu; Stark, Adam; Xiao, Nianqing; O'Neill, Heather A; Wei, Xixi; Wang, Jie; Tinder, Teresa T; Tonapi, Sonal; Duncan, Janet; Hornung, Tassilo; Hunter, Andrew; Miglarese, Mark R; Schorr, Joachim; Halbert, David D; Quackenbush, John; Poste, George; Berry, Donald A; Mayer, Günter; Famulok, Michael; Spetzler, David

2017-02-20

Technologies capable of characterizing the full breadth of cellular systems need to be able to measure millions of proteins, isoforms, and complexes simultaneously. We describe an approach that fulfils this criterion: Adaptive Dynamic Artificial Poly-ligand Targeting (ADAPT). ADAPT employs an enriched library of single-stranded oligodeoxynucleotides (ssODNs) to profile complex biological samples, thus achieving an unprecedented coverage of system-wide, native biomolecules. We used ADAPT as a highly specific profiling tool that distinguishes women with or without breast cancer based on circulating exosomes in their blood. To develop ADAPT, we enriched a library of ~10 11 ssODNs for those associating with exosomes from breast cancer patients or controls. The resulting 10 6 enriched ssODNs were then profiled against plasma from independent groups of healthy and breast cancer-positive women. ssODN-mediated affinity purification and mass spectrometry identified low-abundance exosome-associated proteins and protein complexes, some with known significance in both normal homeostasis and disease. Sequencing of the recovered ssODNs provided quantitative measures that were used to build highly accurate multi-analyte signatures for patient classification. Probing plasma from 500 subjects with a smaller subset of 2000 resynthesized ssODNs stratified healthy, breast biopsy-negative, and -positive women. An AUC of 0.73 was obtained when comparing healthy donors with biopsy-positive patients.

In situ profiling of eastern Arabian Sea coastal waters using a new autonomous vertical profiler

Digital Repository Service at National Institute of Oceanography (India)

Desa, E.S.; Madhan, R.; Dabholkar, N.A.; Prabhudesai, S.P.; Navelkar, G.S.; Mascarenhas, A.A.M.Q.; Afzulpurkar, S.; Phaldesai, M.; Maurya, P.

The autonomous vertical profiler (AVP) presented here offers a fast, cost-effective, optimized approach to profiling in coastal waters. It consists of a hands-free, slightly buoyant, motor-driven in situ robot profiler that requires no operator...

Accelerating Information Retrieval from Profile Hidden Markov Model Databases.

Science.gov (United States)

Tamimi, Ahmad; Ashhab, Yaqoub; Tamimi, Hashem

2016-01-01

Profile Hidden Markov Model (Profile-HMM) is an efficient statistical approach to represent protein families. Currently, several databases maintain valuable protein sequence information as profile-HMMs. There is an increasing interest to improve the efficiency of searching Profile-HMM databases to detect sequence-profile or profile-profile homology. However, most efforts to enhance searching efficiency have been focusing on improving the alignment algorithms. Although the performance of these algorithms is fairly acceptable, the growing size of these databases, as well as the increasing demand for using batch query searching approach, are strong motivations that call for further enhancement of information retrieval from profile-HMM databases. This work presents a heuristic method to accelerate the current profile-HMM homology searching approaches. The method works by cluster-based remodeling of the database to reduce the search space, rather than focusing on the alignment algorithms. Using different clustering techniques, 4284 TIGRFAMs profiles were clustered based on their similarities. A representative for each cluster was assigned. To enhance sensitivity, we proposed an extended step that allows overlapping among clusters. A validation benchmark of 6000 randomly selected protein sequences was used to query the clustered profiles. To evaluate the efficiency of our approach, speed and recall values were measured and compared with the sequential search approach. Using hierarchical, k-means, and connected component clustering techniques followed by the extended overlapping step, we obtained an average reduction in time of 41%, and an average recall of 96%. Our results demonstrate that representation of profile-HMMs using a clustering-based approach can significantly accelerate data retrieval from profile-HMM databases.

Double-Track Electrochemical Green Approach for Simultaneous Dissolution Profiling of Naproxen Sodium and Diphenhydramine Hydrochloride.

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Shehata, Mostafa A; Fawaz, Esraa M; El-Rahman, Mohamed K Abd; Abdel-Moety, Ezzat M

2017-11-30

Acquisition of the dissolution profiles of more than single active ingredient in a multi-analyte pharmaceutical formulation is a mandatory manufacturing practice that is dominated by utilization of the off-line separation-based chromatographic methods. This contribution adopts a new "Double-Track" approach with the ultimate goal of advancing the in-line potentiometric sensors to their most effective applicability for simultaneous acquisition of the dissolution profiles of two active ingredients in a binary pharmaceutical formulation. The unique abilities of these sensors for real-time measurements is the key driver for adoption of "green analytical chemistry" (GAC) principles aiming to expand the application of eco-friendly analytical methods With the aim of performing a side-by-side comparison, this work investigates the degree of adherence of ISEs to the 12 principles of GAC in multicomponent dissolution profiling with respect to the HPLC. For the proof of concept, a binary mixture of naproxen sodium (NAPR) and diphenhydramine hydrochloride (DIPH) marketed as Aleve pm ® tablets was selected as a model for which dissolution profiles were attained by two techniques. The first "Double-Track" in-line strategy depends on dipping two highly integrated membrane sensors for continuous monitoring of the dissolution of each active pharmaceutical ingredient (API) by tracing the e.m.f change over the time scale. For the determination of NAPR, sensor I was developed using tridodecyl methyl ammonium chloride as an anion exchanger, while sensor II was developed for the determination of DIPH using potassium tetrakis (4-chlorophenyl) borate as a cation exchanger. The second off-line strategy utilizes a separation-based HPLC method via off-line tracking the increase of peak area by UV detection at 220nm over time using a mobile phase of acetonitrile: water (90:10) pH 3. The advantages of the newly introduced "Double-Track" approach regarding GAC principles are highlighted, and

Glycoprotein profiles of macrophages at different stages of activation as revealed by lectin binding after electrophoretic separation.

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Irimura, T; North, S M; Nicolson, G L

1987-01-01

Glycoprotein profiles of rat macrophages (M phi) at different stages of activation were studied by examining the reactivity of various lectins to the glycoproteins separated by polyacrylamide gel electrophoresis. Ricinus communis agglutinin 1 (RCA1) revealed several components including glycoproteins of Mr 160 kDa and 65 kDa prominent in resident M phi. A pokeweed mitogen (PWM) isolectin, Pa-4, recognizes branched poly(N-acetyllactosamine)-type carbohydrate chains, and revealed a significant increase in glycoproteins of Mr ranging from 70 kDa to 150 kDa on thioglycolate-elicited M phi. Increased reactivity of PWM to thioglycolate-elicited M phi was observed by direct binding of 125I-labeled Pa-4 to intact or glutaraldehyde-fixed M phi. Histochemical staining of formaldehyde-fixed M phi in vitro with biotinylated Pa-4 was consistent with the gel analysis, that is, resident M phi had no reactivity while thioglycolate-elicited M phi showed slight reactivity. Alveolar and intratumoral M phi bound more Pa-4 than resident or thioglycolate-elicited M phi. The PWM isolectin may therefore serve as a marker for an early stage of M phi activation.

Comprehensive Lipidome-Wide Profiling Reveals Dynamic Changes of Tea Lipids during Manufacturing Process of Black Tea.

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Li, Jia; Hua, Jinjie; Zhou, Qinghua; Dong, Chunwang; Wang, Jinjin; Deng, Yuliang; Yuan, Haibo; Jiang, Yongwen

2017-11-22

As important biomolecules in Camellia sinensis L., lipids undergo substantial changes during black tea manufacture, which is considered to contribute to tea sensory quality. However, limited by analytical capacity, detailed lipid composition and its dynamic changes during black tea manufacture remain unclear. Herein, we performed tea lipidome profiling using high resolution liquid chromatography coupled to mass spectrometry (LC-MS), which allows simultaneous and robust analysis of 192 individual lipid species in black tea, covering 17 (sub)classes. Furthermore, dynamic changes of tea lipids during black tea manufacture were investigated. Significant alterations of lipid pattern were revealed, involved with chlorophyll degradation, metabolic pathways of glycoglycerolipids, and other extraplastidial membrane lipids. To our knowledge, this report presented most comprehensive coverage of lipid species in black tea. This study provides a global and in-depth metabolic map of tea lipidome during black tea manufacture.

Yeast Interspecies Comparative Proteomics Reveals Divergence in Expression Profiles and Provides Insights into Proteome Resource Allocation and Evolutionary Roles of Gene Duplication*

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Kito, Keiji; Ito, Haruka; Nohara, Takehiro; Ohnishi, Mihoko; Ishibashi, Yuko; Takeda, Daisuke

2016-01-01

Omics analysis is a versatile approach for understanding the conservation and diversity of molecular systems across multiple taxa. In this study, we compared the proteome expression profiles of four yeast species (Saccharomyces cerevisiae, Saccharomyces mikatae, Kluyveromyces waltii, and Kluyveromyces lactis) grown on glucose- or glycerol-containing media. Conserved expression changes across all species were observed only for a small proportion of all proteins differentially expressed between the two growth conditions. Two Kluyveromyces species, both of which exhibited a high growth rate on glycerol, a nonfermentative carbon source, showed distinct species-specific expression profiles. In K. waltii grown on glycerol, proteins involved in the glyoxylate cycle and gluconeogenesis were expressed in high abundance. In K. lactis grown on glycerol, the expression of glycolytic and ethanol metabolic enzymes was unexpectedly low, whereas proteins involved in cytoplasmic translation, including ribosomal proteins and elongation factors, were highly expressed. These marked differences in the types of predominantly expressed proteins suggest that K. lactis optimizes the balance of proteome resource allocation between metabolism and protein synthesis giving priority to cellular growth. In S. cerevisiae, about 450 duplicate gene pairs were retained after whole-genome duplication. Intriguingly, we found that in the case of duplicates with conserved sequences, the total abundance of proteins encoded by a duplicate pair in S. cerevisiae was similar to that of protein encoded by nonduplicated ortholog in Kluyveromyces yeast. Given the frequency of haploinsufficiency, this observation suggests that conserved duplicate genes, even though minor cases of retained duplicates, do not exhibit a dosage effect in yeast, except for ribosomal proteins. Thus, comparative proteomic analyses across multiple species may reveal not only species-specific characteristics of metabolic processes under

Elderly fall risk prediction based on a physiological profile approach using artificial neural networks.

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Razmara, Jafar; Zaboli, Mohammad Hassan; Hassankhani, Hadi

2016-11-01

Falls play a critical role in older people's life as it is an important source of morbidity and mortality in elders. In this article, elders fall risk is predicted based on a physiological profile approach using a multilayer neural network with back-propagation learning algorithm. The personal physiological profile of 200 elders was collected through a questionnaire and used as the experimental data for learning and testing the neural network. The profile contains a series of simple factors putting elders at risk for falls such as vision abilities, muscle forces, and some other daily activities and grouped into two sets: psychological factors and public factors. The experimental data were investigated to select factors with high impact using principal component analysis. The experimental results show an accuracy of ≈90 percent and ≈87.5 percent for fall prediction among the psychological and public factors, respectively. Furthermore, combining these two datasets yield an accuracy of ≈91 percent that is better than the accuracy of single datasets. The proposed method suggests a set of valid and reliable measurements that can be employed in a range of health care systems and physical therapy to distinguish people who are at risk for falls.

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

International Nuclear Information System (INIS)

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

2010-01-01

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

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

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Vaithilingam Aparna

2010-05-01

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

Driving profile modeling and recognition based on soft computing approach.

Science.gov (United States)

Wahab, Abdul; Quek, Chai; Tan, Chin Keong; Takeda, Kazuya

2009-04-01

Advancements in biometrics-based authentication have led to its increasing prominence and are being incorporated into everyday tasks. Existing vehicle security systems rely only on alarms or smart card as forms of protection. A biometric driver recognition system utilizing driving behaviors is a highly novel and personalized approach and could be incorporated into existing vehicle security system to form a multimodal identification system and offer a greater degree of multilevel protection. In this paper, detailed studies have been conducted to model individual driving behavior in order to identify features that may be efficiently and effectively used to profile each driver. Feature extraction techniques based on Gaussian mixture models (GMMs) are proposed and implemented. Features extracted from the accelerator and brake pedal pressure were then used as inputs to a fuzzy neural network (FNN) system to ascertain the identity of the driver. Two fuzzy neural networks, namely, the evolving fuzzy neural network (EFuNN) and the adaptive network-based fuzzy inference system (ANFIS), are used to demonstrate the viability of the two proposed feature extraction techniques. The performances were compared against an artificial neural network (NN) implementation using the multilayer perceptron (MLP) network and a statistical method based on the GMM. Extensive testing was conducted and the results show great potential in the use of the FNN for real-time driver identification and verification. In addition, the profiling of driver behaviors has numerous other potential applications for use by law enforcement and companies dealing with buses and truck drivers.

Accelerating Information Retrieval from Profile Hidden Markov Model Databases.

Directory of Open Access Journals (Sweden)

Ahmad Tamimi

Full Text Available Profile Hidden Markov Model (Profile-HMM is an efficient statistical approach to represent protein families. Currently, several databases maintain valuable protein sequence information as profile-HMMs. There is an increasing interest to improve the efficiency of searching Profile-HMM databases to detect sequence-profile or profile-profile homology. However, most efforts to enhance searching efficiency have been focusing on improving the alignment algorithms. Although the performance of these algorithms is fairly acceptable, the growing size of these databases, as well as the increasing demand for using batch query searching approach, are strong motivations that call for further enhancement of information retrieval from profile-HMM databases. This work presents a heuristic method to accelerate the current profile-HMM homology searching approaches. The method works by cluster-based remodeling of the database to reduce the search space, rather than focusing on the alignment algorithms. Using different clustering techniques, 4284 TIGRFAMs profiles were clustered based on their similarities. A representative for each cluster was assigned. To enhance sensitivity, we proposed an extended step that allows overlapping among clusters. A validation benchmark of 6000 randomly selected protein sequences was used to query the clustered profiles. To evaluate the efficiency of our approach, speed and recall values were measured and compared with the sequential search approach. Using hierarchical, k-means, and connected component clustering techniques followed by the extended overlapping step, we obtained an average reduction in time of 41%, and an average recall of 96%. Our results demonstrate that representation of profile-HMMs using a clustering-based approach can significantly accelerate data retrieval from profile-HMM databases.

Development of a GC/C/IRMS method--confirmation of a novel steroid profiling approach in doping control.

Science.gov (United States)

Van Renterghem, Pieter; Polet, Michael; Brooker, Lance; Van Gansbeke, Wim; Van Eenoo, Peter

2012-09-01

In doping control, an athlete can only be convicted with the misuse with endogenous steroids like testosterone (T), if abnormal values of steroid metabolites and steroid ratios are observed and if the subsequent analysis with isotope ratios mass spectrometry (IRMS) confirms the presence of exogenously administered androgens. In this work, we compare the results of a novel steroid profiling approach with the performance an in-house developed IRMS method. The developed IRMS has the advantage over other methods to be relatively short in time and with target compounds androsterone, etiocholanolone, 5β-androstane 3α,17β-diol and 5α-androstane 3α,17β-diol. Pregnanediol was used as an endogenous reference compound (ERC). Reference limits for the IRMS values were established and applied as decision limits for the evaluation of excretion urine from administration with oral T, T-gel, dihydrotestosterone (DHT) - gel and dehydroepiandrosterone (DHEA). Results indicated the importance of both androstanediols as important IRMS markers where relative values compared to an ERC (Δδ(13)C) yielded better detection accuracy than absolute δ(13)C-values. The detection times of all administered endogenous steroids were evaluated using the proposed thresholds. The results of traditional steroid profiling and a new approach based upon minor steroid metabolites monitoring introduced in a longitudinal framework were evaluated with IRMS. With traditional steroid profiling methods, 95% of the atypical samples could be confirmed whereas an additional 74% of IRMS confirmed was provided by a new biomarkers strategy. These results prove that the other steroid profiling strategies can improve the efficiency in detection of misuse with endogenous steroids. Copyright © 2012 Elsevier Inc. All rights reserved.

MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias

Science.gov (United States)

Calin, George Adrian; Liu, Chang-Gong; Sevignani, Cinzia; Ferracin, Manuela; Felli, Nadia; Dumitru, Calin Dan; Shimizu, Masayoshi; Cimmino, Amelia; Zupo, Simona; Dono, Mariella; Dell'Aquila, Marie L.; Alder, Hansjuerg; Rassenti, Laura; Kipps, Thomas J.; Bullrich, Florencia; Negrini, Massimo; Croce, Carlo M.

2004-01-01

Little is known about the expression levels or function of micro-RNAs (miRNAs) in normal and neoplastic cells, although it is becoming clear that miRNAs play important roles in the regulation of gene expression during development [Ambros, V. (2003) Cell 113, 673–676; McManus, M. T. (2003) Semin. Cancer Biol. 13, 253–258]. We now report the genomewide expression profiling of miRNAs in human B cell chronic lymphocytic leukemia (CLL) by using a microarray containing hundreds of human precursor and mature miRNA oligonucleotide probes. This approach allowed us to identify significant differences in miRNome expression between CLL samples and normal CD5+ B cells; data were confirmed by Northern blot analyses and real-time RT-PCR. At least two distinct clusters of CLL samples can be identified that were associated with the presence or absence of Zap-70 expression, a predictor of early disease progression. Two miRNA signatures were associated with the presence or absence of mutations in the expressed Ig variableregion genes or with deletions at 13q14, respectively. These data suggest that miRNA expression patterns have relevance to the biological and clinical behavior of this leukemia. PMID:15284443

Gene expression profiling of canine osteosarcoma reveals genes associated with short and long survival times

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Rao Nagesha AS

2009-09-01

Full Text Available Abstract Background Gene expression profiling of spontaneous tumors in the dog offers a unique translational opportunity to identify prognostic biomarkers and signaling pathways that are common to both canine and human. Osteosarcoma (OS accounts for approximately 80% of all malignant bone tumors in the dog. Canine OS are highly comparable with their human counterpart with respect to histology, high metastatic rate and poor long-term survival. This study investigates the prognostic gene profile among thirty-two primary canine OS using canine specific cDNA microarrays representing 20,313 genes to identify genes and cellular signaling pathways associated with survival. This, the first report of its kind in dogs with OS, also demonstrates the advantages of cross-species comparison with human OS. Results The 32 tumors were classified into two prognostic groups based on survival time (ST. They were defined as short survivors (dogs with poor prognosis: surviving fewer than 6 months and long survivors (dogs with better prognosis: surviving 6 months or longer. Fifty-one transcripts were found to be differentially expressed, with common upregulation of these genes in the short survivors. The overexpressed genes in short survivors are associated with possible roles in proliferation, drug resistance or metastasis. Several deregulated pathways identified in the present study, including Wnt signaling, Integrin signaling and Chemokine/cytokine signaling are comparable to the pathway analysis conducted on human OS gene profiles, emphasizing the value of the dog as an excellent model for humans. Conclusion A molecular-based method for discrimination of outcome for short and long survivors is useful for future prognostic stratification at initial diagnosis, where genes and pathways associated with cell cycle/proliferation, drug resistance and metastasis could be potential targets for diagnosis and therapy. The similarities between human and canine OS makes the

Protein profiling in serum after traumatic brain injury in rats reveals potential injury markers.

Science.gov (United States)

Thelin, Eric Peter; Just, David; Frostell, Arvid; Häggmark-Månberg, Anna; Risling, Mårten; Svensson, Mikael; Nilsson, Peter; Bellander, Bo-Michael

2018-03-15

The serum proteome following traumatic brain injury (TBI) could provide information for outcome prediction and injury monitoring. The aim with this affinity proteomic study was to identify serum proteins over time and between normoxic and hypoxic conditions in focal TBI. Sprague Dawley rats (n=73) received a 3mm deep controlled cortical impact ("severe injury"). Following injury, the rats inhaled either a normoxic (22% O 2 ) or hypoxic (11% O 2 ) air mixture for 30min before resuscitation. The rats were sacrificed at day 1, 3, 7, 14 and 28 after trauma. A total of 204 antibodies targeting 143 unique proteins of interest in TBI research, were selected. The sample proteome was analyzed in a suspension bead array set-up. Comparative statistics and factor analysis were used to detect differences as well as variance in the data. We found that complement factor 9 (C9), complement factor B (CFB) and aldolase c (ALDOC) were detected at higher levels the first days after trauma. In contrast, hypoxia inducing factor (HIF)1α, amyloid precursor protein (APP) and WBSCR17 increased over the subsequent weeks. S100A9 levels were higher in hypoxic-compared to normoxic rats, together with a majority of the analyzed proteins, albeit few reached statistical significance. The principal component analysis revealed a variance in the data, highlighting clusters of proteins. Protein profiling of serum following TBI using an antibody based microarray revealed temporal changes of several proteins over an extended period of up to four weeks. Further studies are warranted to confirm our findings. Copyright © 2016 The Author(s). Published by Elsevier B.V. All rights reserved.

Metabolic profiling reveals ethylene mediated metabolic changes and a coordinated adaptive mechanism of 'Jonagold' apple to low oxygen stress.

Science.gov (United States)

Bekele, Elias A; Beshir, Wasiye F; Hertog, Maarten L A T M; Nicolai, Bart M; Geeraerd, Annemie H

2015-11-01

Apples are predominantly stored in controlled atmosphere (CA) storage to delay ripening and prolong their storage life. Profiling the dynamics of metabolic changes during ripening and CA storage is vital for understanding the governing molecular mechanism. In this study, the dynamics of the primary metabolism of 'Jonagold' apples during ripening in regular air (RA) storage and initiation of CA storage was profiled. 1-Methylcyclopropene (1-MCP) was exploited to block ethylene receptors and to get insight into ethylene mediated metabolic changes during ripening of the fruit and in response to hypoxic stress. Metabolic changes were quantified in glycolysis, the tricarboxylic acid (TCA) cycle, the Yang cycle and synthesis of the main amino acids branching from these metabolic pathways. Partial least square discriminant analysis of the metabolic profiles of 1-MCP treated and control apples revealed a metabolic divergence in ethylene, organic acid, sugar and amino acid metabolism. During RA storage at 18°C, most amino acids were higher in 1-MCP treated apples, whereas 1-aminocyclopropane-1-carboxylic acid (ACC) was higher in the control apples. The initial response of the fruit to CA initiation was accompanied by an increase of alanine, succinate and glutamate, but a decline in aspartate. Furthermore, alanine and succinate accumulated to higher levels in control apples than 1-MCP treated apples. The observed metabolic changes in these interlinked metabolites may indicate a coordinated adaptive strategy to maximize energy production. © 2015 Scandinavian Plant Physiology Society.

Network analysis of genomic alteration profiles reveals co-altered functional modules and driver genes for glioblastoma.

Science.gov (United States)

Gu, Yunyan; Wang, Hongwei; Qin, Yao; Zhang, Yujing; Zhao, Wenyuan; Qi, Lishuang; Zhang, Yuannv; Wang, Chenguang; Guo, Zheng

2013-03-01

The heterogeneity of genetic alterations in human cancer genomes presents a major challenge to advancing our understanding of cancer mechanisms and identifying cancer driver genes. To tackle this heterogeneity problem, many approaches have been proposed to investigate genetic alterations and predict driver genes at the individual pathway level. However, most of these approaches ignore the correlation of alteration events between pathways and miss many genes with rare alterations collectively contributing to carcinogenesis. Here, we devise a network-based approach to capture the cooperative functional modules hidden in genome-wide somatic mutation and copy number alteration profiles of glioblastoma (GBM) from The Cancer Genome Atlas (TCGA), where a module is a set of altered genes with dense interactions in the protein interaction network. We identify 7 pairs of significantly co-altered modules that involve the main pathways known to be altered in GBM (TP53, RB and RTK signaling pathways) and highlight the striking co-occurring alterations among these GBM pathways. By taking into account the non-random correlation of gene alterations, the property of co-alteration could distinguish oncogenic modules that contain driver genes involved in the progression of GBM. The collaboration among cancer pathways suggests that the redundant models and aggravating models could shed new light on the potential mechanisms during carcinogenesis and provide new indications for the design of cancer therapeutic strategies.

Metabolic Profiling of Alpine and Ecuadorian Lichens

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Verena K. Mittermeier

2015-10-01

Full Text Available Non-targeted 1H-NMR methods were used to determine metabolite profiles from crude extracts of Alpine and Ecuadorian lichens collected from their natural habitats. In control experiments, the robustness of metabolite detection and quantification was estimated using replicate measurements of Stereocaulon alpinum extracts. The deviations in the overall metabolite fingerprints were low when analyzing S. alpinum collections from different locations or during different annual and seasonal periods. In contrast, metabolite profiles observed from extracts of different Alpine and Ecuadorian lichens clearly revealed genus- and species-specific profiles. The discriminating functions determining cluster formation in principle component analysis (PCA were due to differences in the amounts of genus-specific compounds such as sticticin from the Sticta species, but also in the amounts of ubiquitous metabolites, such as sugar alcohols or trehalose. However, varying concentrations of these metabolites from the same lichen species e.g., due to different environmental conditions appeared of minor relevance for the overall cluster formation in PCA. The metabolic clusters matched phylogenetic analyses using nuclear ribosomal DNA (nrDNA internal transcribed spacer (ITS sequences of lichen mycobionts, as exemplified for the genus Sticta. It can be concluded that NMR-based non-targeted metabolic profiling is a useful tool in the chemo-taxonomy of lichens. The same approach could also facilitate the discovery of novel lichen metabolites on a rapid and systematical basis.

Profiling Oman education data using data mining approach

Science.gov (United States)

Alawi, Sultan Juma Sultan; Shaharanee, Izwan Nizal Mohd; Jamil, Jastini Mohd

2017-10-01

Nowadays, with a large amount of data generated by many application services in different learning fields has led to the new challenges in education field. Education portal is an important system that leads to a better development of education field. This research paper presents an innovative data mining techniques to understand and summarizes the information of Oman's education data generated from the Ministry of Education Oman "Educational Portal". This research embarks into performing student profiling of the Oman student database. This study utilized the k-means clustering technique to determine the students' profiles. An amount of 42484-student records from Sultanate of Oman has been extracted for this study. The findings of this study show the practicality of clustering technique to investigating student's profiles. Allowing for a better understanding of student's behavior and their academic performance. Oman Education Portal contain a large amounts of user activity and interaction data. Analyses of this large data can be meaningful for educator to improve the student performance level and recognize students who needed additional attention.

Proteomic profiling reveals candidate markers for arsenic-induced skin keratosis.

Science.gov (United States)

Guo, Zhiling; Hu, Qin; Tian, Jijing; Yan, Li; Jing, Chuanyong; Xie, Heidi Qunhui; Bao, Wenjun; Rice, Robert H; Zhao, Bin; Jiang, Guibin

2016-11-01

Proteomics technology is an attractive biomarker candidate discovery tool that can be applied to study large sets of biological molecules. To identify novel biomarkers and molecular targets in arsenic-induced skin lesions, we have determined the protein profile of arsenic-affected human epidermal stratum corneum by shotgun proteomics. Samples of palm and foot sole from healthy subjects were analyzed, demonstrating similar protein patterns in palm and sole. Samples were collected from the palms of subjects with arsenic keratosis (lesional and adjacent non-lesional samples) and arsenic-exposed subjects without lesions (normal). Samples from non-exposed healthy individuals served as controls. We found that three proteins in arsenic-exposed lesional epidermis were consistently distinguishably expressed from the unaffected epidermis. One of these proteins, the cadherin-like transmembrane glycoprotein, desmoglein 1 (DSG1) was suppressed. Down-regulation of DSG1 may lead to reduced cell-cell adhesion, resulting in abnormal epidermal differentiation. The expression of keratin 6c (KRT6C) and fatty acid binding protein 5 (FABP5) were significantly increased. FABP5 is an intracellular lipid chaperone that plays an essential role in fatty acid metabolism in human skin. This raises a possibility that overexpression of FABP5 may affect the proliferation or differentiation of keratinocytes by altering lipid metabolism. KRT6C is a constituent of the cytoskeleton that maintains epidermal integrity and cohesion. Abnormal expression of KRT6C may affect its structural role in the epidermis. Our findings suggest an important approach for future studies of arsenic-mediated toxicity and skin cancer, where certain proteins may represent useful biomarkers of early diagnoses in high-risk populations and hopefully new treatment targets. Further studies are required to understand the biological role of these markers in skin pathogenesis from arsenic exposure. Copyright © 2016 Elsevier Ltd

Optimization of rootkit revealing system resources – A game theoretic approach

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K. Muthumanickam

2015-10-01

Full Text Available Malicious rootkit is a collection of programs designed with the intent of infecting and monitoring the victim computer without the user’s permission. After the victim has been compromised, the remote attacker can easily cause further damage. In order to infect, compromise and monitor, rootkits adopt Native Application Programming Interface (API hooking technique. To reveal the hidden rootkits, current rootkit detection techniques check different data structures which hold reference to Native APIs. To verify these data structures, a large amount of system resources are required. This is because of the number of APIs in these data structures being quite large. Game theoretic approach is a useful mathematical tool to simulate network attacks. In this paper, a mathematical model is framed to optimize resource consumption using game-theory. To the best of our knowledge, this is the first work to be proposed for optimizing resource consumption while revealing rootkit presence using game theory. Non-cooperative game model is taken to discuss the problem. Analysis and simulation results show that our game theoretic model can effectively reduce the resource consumption by selectively monitoring the number of APIs in windows platform.

On the Anonymity Risk of Time-Varying User Profiles

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Silvia Puglisi

2017-04-01

Full Text Available Websites and applications use personalisation services to profile their users, collect their patterns and activities and eventually use this data to provide tailored suggestions. User preferences and social interactions are therefore aggregated and analysed. Every time a user publishes a new post or creates a link with another entity, either another user, or some online resource, new information is added to the user profile. Exposing private data does not only reveal information about single users’ preferences, increasing their privacy risk, but can expose more about their network that single actors intended. This mechanism is self-evident in social networks where users receive suggestions based on their friends’ activities. We propose an information-theoretic approach to measure the differential update of the anonymity risk of time-varying user profiles. This expresses how privacy is affected when new content is posted and how much third-party services get to know about the users when a new activity is shared. We use actual Facebook data to show how our model can be applied to a real-world scenario.

Analysis of biostimulated microbial communities from two field experiments reveals temporal and spatial differences in proteome profiles

Energy Technology Data Exchange (ETDEWEB)

Callister, S.J.; Wilkins, M.J.; Nicora, C.D.; Williams, K.H.; Banfield, J.F.; VerBerkmoes, N.C.; Hettich, R.L.; NGuessan, A.L.; Mouser, P.J.; Elifantz, H.; Smith, R.D.; Lovley, D.R.; Lipton, M.S.; Long, P.E.

2010-07-15

Stimulated by an acetate-amendment field experiment conducted in 2007, anaerobic microbial populations in the aquifer at the Rifle Integrated Field Research Challenge site in Colorado reduced mobile U(VI) to insoluble U(IV). During this experiment, planktonic biomass was sampled at various time points to quantitatively evaluate proteomes. In 2008, an acetate-amended field experiment was again conducted in a similar manner to the 2007 experiment. As there was no comprehensive metagenome sequence available for use in proteomics analysis, we systematically evaluated 12 different organism genome sequences to generate sets of aggregate genomes, or “pseudo-metagenomes”, for supplying relative quantitative peptide and protein identifications. Proteomics results support previous observations of the dominance of Geobacteraceae during biostimulation using acetate as sole electron donor, and revealed a shift from an early stage of iron reduction to a late stage of iron reduction. Additionally, a shift from iron reduction to sulfate reduction was indicated by changes in the contribution of proteome information contributed by different organism genome sequences within the aggregate set. In addition, the comparison of proteome measurements made between the 2007 field experiment and 2008 field experiment revealed differences in proteome profiles. These differences may be the result of alterations in abundance and population structure within the planktonic biomass samples collected for analysis.

A probabilistic approach for the interpretation of RNA profiles as cell type evidence.

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de Zoete, Jacob; Curran, James; Sjerps, Marjan

2016-01-01

DNA profiles can be used as evidence to distinguish between possible donors of a crime stain. In some cases, both the prosecution and the defence claim that the cell material was left by the suspect but they dispute which cell type was left behind. For example, in sexual offense cases the prosecution could claim that the sample contains semen cells where the defence argues that the sample contains skin cells. In these cases, traditional methods (e.g. a phosphatase test) can be used to examine the cell type contained in the sample. However, there are some drawbacks when using these methods. For instance, many of these techniques need to be carried out separately for each cell type and each of them requires part of the available sample, which reduces the amount that can be used for DNA analysis. Another option is messenger RNA (mRNA) evidence. mRNA expression levels vary among cell types and can be used to make (probability) statements about the cell type(s) present in a sample. Existing methods for the interpretation of RNA profiles as evidence for the presence of certain cell types aim at making categorical statements. Such statements limit the possibility to report the associated uncertainty. Some of these existing methods will be discussed. Most notably, a method based on a 'n/2' scoring rule (Lindenbergh et al.) and a method using marker values and cell type scoring thresholds (Roeder et al.). From a statistical point of view, a probabilistic approach is the most obvious choice. Two approaches (multinomial logistic regression and naïve Bayes') are suggested. All methods are compared, using two different datasets and several criteria regarding their ability to assess the evidential value of RNA profiles. We conclude that both the naïve Bayes' method and a method based on multinomial logistic regression, that produces a probabilistic statement as measure of the evidential value, are an important improvement of the existing methods. Besides a better performance

Metabolite profiling approach reveals the interface of primary and secondary metabolism in colored cauliflowers (Brassica oleracea L. ssp. botrytis).

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Park, Soo-Yun; Lim, Sun-Hyung; Ha, Sun-Hwa; Yeo, Yunsoo; Park, Woo Tae; Kwon, Do Yeon; Park, Sang Un; Kim, Jae Kwang

2013-07-17

In the present study, carotenoids, anthocyanins, and phenolic acids of cauliflowers ( Brassica oleracea L. ssp. botrytis) with various colored florets (white, yellow, green, and purple) were characterized to determine their phytochemical diversity. Additionally, 48 metabolites comprising amino acids, organic acids, sugars, and sugar alcohols were identified using gas chromatography-time-of-flight mass spectrometry (GC-TOFMS). Carotenoid content was considerably higher in green cauliflower; anthocyanins were detected only in purple cauliflower. Phenolic acids were higher in both green and purple cauliflower. Results of partial least-squares discriminant, Pearson correlation, and hierarchical clustering analyses showed that green cauliflower is distinct on the basis of the high levels of amino acids and clusters derived from common or closely related biochemical pathways. These results suggest that GC-TOFMS-based metabolite profiling, combined with chemometrics, is a useful tool for determining phenotypic variation and identifying metabolic networks connecting primary and secondary metabolism.

Application of xCELLigence RTCA Biosensor Technology for Revealing the Profile and Window of Drug Responsiveness in Real Time

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Dan Kho

2015-04-01

Full Text Available The xCELLigence technology is a real-time cellular biosensor, which measures the net adhesion of cells to high-density gold electrode arrays printed on custom-designed E-plates. The strength of cellular adhesion is influenced by a myriad of factors that include cell type, cell viability, growth, migration, spreading and proliferation. We therefore hypothesised that xCELLigence biosensor technology would provide a valuable platform for the measurement of drug responses in a multitude of different experimental, clinical or pharmacological contexts. In this manuscript, we demonstrate how xCELLigence technology has been invaluable in the identification of (1 not only if cells respond to a particular drug, but (2 the window of drug responsiveness. The latter aspect is often left to educated guess work in classical end-point assays, whereas biosensor technology reveals the temporal profile of the response in real time, which enables both acute responses and longer term responses to be profiled within the same assay. In our experience, the xCELLigence biosensor technology is suitable for highly targeted drug assessment and also low to medium throughput drug screening, which produces high content temporal data in real time.

Arabian Sea GEOSECS stations revisited: Tracer-depth profiles reveal temporal variations?

International Nuclear Information System (INIS)

Mulsow, S.; Povinec, P.P.; Somayajulu, B.L.K.

2002-01-01

In March-April 1998, the Physical Research Laboratory and the Regional Research Laboratory (Ahmedabad, India) together with the IAEA Marine Environment Laboratory, Monaco, participated in the research mission to visit GEOSECS (Geochemical Ocean Sections Study) stations in the Arabian Sea. The main objective was to reoccupy these stations which were sampled in the early seventies to observe possible time variations in trace behaviour in this region. It is generally accepted that both natural (climate variations) and anthropogenic (greenhouse effect) changes can cause modifications of the oceanic characteristics and properties of deep waters on yearly and decadal scales. For long time-scales (100 to 1000 years) one needs to look at the sediments where these changes are subtly recorded. Tracers such as 14 C and 3 H (deep waters) and 228 Ra surface waters are useful markers of water circulation patterns and changes. Also man-made radiotracers such as 90 Sr, 137 Cs, 99 Tc, 238 Pu, 239 , 240 Pu and 241 Am, can give information on air-sea exchange as well as penetration (vertical change) rates in the open ocean [2]. We visited GEOSECS stations 415 to 419. In each station, CTD profiles, 3 H, 14 C, 90 Sr, 137 Cs, Pu and Am profiles, nutrients, Be, TOC and oxygen were determined from surface to bottom. Also uranium and trace elements were sampled in function of the oxygen minimum zone. In this paper we report the findings on the physical properties as well as the variations in water circulation patterns and also vertical exchange rates in the Arabian Sea. PSU profiles collected in this mission compared with those PSU profiles measured in 1974 (GEOSECS) showed marked differences in those stations located in the southeast part of the Arabian Sea. In contrast, those located more towards the north (415-416) showed little temporal variation. We think these changes may be real given that the PSU values at depth are comparable and reflect the presence of deep Antarctic bottom

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

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

2014-07-07

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

Gene expression profiles of prostate cancer reveal involvement of multiple molecular pathways in the metastatic process

International Nuclear Information System (INIS)

Chandran, Uma R; Ma, Changqing; Dhir, Rajiv; Bisceglia, Michelle; Lyons-Weiler, Maureen; Liang, Wenjing; Michalopoulos, George; Becich, Michael; Monzon, Federico A

2007-01-01

Prostate cancer is characterized by heterogeneity in the clinical course that often does not correlate with morphologic features of the tumor. Metastasis reflects the most adverse outcome of prostate cancer, and to date there are no reliable morphologic features or serum biomarkers that can reliably predict which patients are at higher risk of developing metastatic disease. Understanding the differences in the biology of metastatic and organ confined primary tumors is essential for developing new prognostic markers and therapeutic targets. Using Affymetrix oligonucleotide arrays, we analyzed gene expression profiles of 24 androgen-ablation resistant metastatic samples obtained from 4 patients and a previously published dataset of 64 primary prostate tumor samples. Differential gene expression was analyzed after removing potentially uninformative stromal genes, addressing the differences in cellular content between primary and metastatic tumors. The metastatic samples are highly heterogenous in expression; however, differential expression analysis shows that 415 genes are upregulated and 364 genes are downregulated at least 2 fold in every patient with metastasis. The expression profile of metastatic samples reveals changes in expression of a unique set of genes representing both the androgen ablation related pathways and other metastasis related gene networks such as cell adhesion, bone remodelling and cell cycle. The differentially expressed genes include metabolic enzymes, transcription factors such as Forkhead Box M1 (FoxM1) and cell adhesion molecules such as Osteopontin (SPP1). We hypothesize that these genes have a role in the biology of metastatic disease and that they represent potential therapeutic targets for prostate cancer

Transcriptome profiling of the Plutella xylostella (Lepidoptera: Plutellidae) ovary reveals genes involved in oogenesis.

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Peng, Lu; Wang, Lei; Yang, Yi-Fan; Zou, Ming-Min; He, Wei-Yi; Wang, Yue; Wang, Qing; Vasseur, Liette; You, Min-Sheng

2017-12-30

As a specialized organ, the insect ovary performs valuable functions by ensuring fecundity and population survival. Oogenesis is the complex physiological process resulting in the production of mature eggs, which are involved in epigenetic programming, germ cell behavior, cell cycle regulation, etc. Identification of the genes involved in ovary development and oogenesis is critical to better understand the reproductive biology and screening for the potential molecular targets in Plutella xylostella, a worldwide destructive pest of economically major crops. Based on transcriptome sequencing, a total of 7.88Gb clean nucleotides was obtained, with 19,934 genes and 1861 new transcripts being identified. Expression profiling indicated that 61.7% of the genes were expressed (FPKM≥1) in the P. xylostella ovary. GO annotation showed that the pathways of multicellular organism reproduction and multicellular organism reproduction process, as well as gamete generation and chorion were significantly enriched. Processes that were most likely relevant to reproduction included the spliceosome, ubiquitin mediated proteolysis, endocytosis, PI3K-Akt signaling pathway, insulin signaling pathway, cAMP signaling pathway, and focal adhesion were identified in the top 20 'highly represented' KEGG pathways. Functional genes involved in oogenesis were further analyzed and validated by qRT-PCR to show their potential predominant roles in P. xylostella reproduction. Our newly developed P. xylostella ovary transcriptome provides an overview of the gene expression profiling in this specialized tissue and the functional gene network closely related to the ovary development and oogenesis. This is the first genome-wide transcriptome dataset of P. xylostella ovary that includes a subset of functionally activated genes. This global approach will be the basis for further studies on molecular mechanisms of P. xylostella reproduction aimed at screening potential molecular targets for integrated pest

Profiling physical activity motivation based on self-determination theory: a cluster analysis approach.

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Friederichs, Stijn Ah; Bolman, Catherine; Oenema, Anke; Lechner, Lilian

2015-01-01

In order to promote physical activity uptake and maintenance in individuals who do not comply with physical activity guidelines, it is important to increase our understanding of physical activity motivation among this group. The present study aimed to examine motivational profiles in a large sample of adults who do not comply with physical activity guidelines. The sample for this study consisted of 2473 individuals (31.4% male; age 44.6 ± 12.9). In order to generate motivational profiles based on motivational regulation, a cluster analysis was conducted. One-way analyses of variance were then used to compare the clusters in terms of demographics, physical activity level, motivation to be active and subjective experience while being active. Three motivational clusters were derived based on motivational regulation scores: a low motivation cluster, a controlled motivation cluster and an autonomous motivation cluster. These clusters differed significantly from each other with respect to physical activity behavior, motivation to be active and subjective experience while being active. Overall, the autonomous motivation cluster displayed more favorable characteristics compared to the other two clusters. The results of this study provide additional support for the importance of autonomous motivation in the context of physical activity behavior. The three derived clusters may be relevant in the context of physical activity interventions as individuals within the different clusters might benefit most from different intervention approaches. In addition, this study shows that cluster analysis is a useful method for differentiating between motivational profiles in large groups of individuals who do not comply with physical activity guidelines.

Global Transcription Profiling Reveals Comprehensive Insights into Hypoxic Response in Arabidopsis1[w

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Liu, Fenglong; VanToai, Tara; Moy, Linda P.; Bock, Geoffrey; Linford, Lara D.; Quackenbush, John

2005-01-01

Plants have evolved adaptation mechanisms to sense oxygen deficiency in their environments and make coordinated physiological and structural adjustments to enhance their hypoxic tolerance. To gain insight into how plants respond to low-oxygen stress, gene expression profiling using whole-genome DNA amplicon microarrays was carried out at seven time points over 24 h, in wild-type and transgenic PSAG12:ipt Arabidopsis (Arabidopsis thaliana) plants under normoxic and hypoxic conditions. Transcript levels of genes involved in glycolysis and fermentation pathways, ethylene synthesis and perception, calcium signaling, nitrogen utilization, trehalose metabolism, and alkaloid synthesis were significantly altered in response to oxygen limitation. Analysis based on gene ontology assignments suggested a significant down-regulation of genes whose functions are associated with cell walls, nucleosome structures, water channels, and ion transporters and a significant up-regulation of genes involved in transcriptional regulation, protein kinase activity, and auxin responses under conditions of oxygen shortage. Promoter analysis on a cluster of up-regulated genes revealed a significant overrepresentation of the AtMYB2-binding motif (GT motif), a sugar response element-like motif, and a G-box-related sequence, and also identified several putative anaerobic response elements. Finally, quantitative real-time polymerase chain reactions using 29 selected genes independently verified the microarray results. This study represents one of the most comprehensive analyses conducted to date investigating hypoxia-responsive transcriptional networks in plants. PMID:15734912

Deprivation profile in Cameroon: A combined analysis of Poverty and Social Exclusion

OpenAIRE

Miamo Wendji, Clovis

2015-01-01

In this study, we analyze the privations welfare in Cameroon considering poverty and social exclusion. The framework provided by the capability approach and construction of indicators of poverty and social exclusion by the fuzzy method from ECAM III survey data shows that the overall level of poverty and social exclusion (respectively 0.4008 and 0.2291), are still very high. The definition of two-dimensional profile of welfare deprivation reveals that the determinants of deprivation are diffe...

RASopathies are associated with a distinct personality profile.

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Bizaoui, Varoona; Gage, Jessica; Brar, Rita; Rauen, Katherine A; Weiss, Lauren A

2018-06-01

Personality is a complex, yet partially heritable, trait. Although some Mendelian diseases like Williams-Beuren syndrome are associated with a particular personality profile, studies have failed to assign the personality features to a single gene or pathway. As a family of monogenic disorders caused by mutations in the Ras/MAPK pathway known to influence social behavior, RASopathies are likely to provide insight into the genetic basis of personality. Eighty subjects diagnosed with cardiofaciocutaneous syndrome, Costello syndrome, neurofibromatosis type 1, and Noonan syndrome were assessed using a parent-report BFQ-C (Big Five Questionnaire for Children) evaluating agreeableness, extraversion, conscientiousness, intellect/openness, and neuroticism, along with 55 unaffected sibling controls. A short questionnaire was added to assess sense of humor. RASopathy subjects and sibling controls were compared for individual components of personality, multidimensional personality profiles, and individual questions using Student tests, analysis of variance, and principal component analysis. RASopathy subjects were given lower scores on average compared to sibling controls in agreeableness, extraversion, conscientiousness, openness, and sense of humor, and similar scores in neuroticism. When comparing the multidimensional personality profile between groups, RASopathies showed a distinct profile from unaffected siblings, but no difference in this global profile was found within RASopathies, revealing a common profile for the Ras/MAPK-related disorders. In addition, several syndrome-specific strengths or weaknesses were observed in individual domains. We describe for the first time an association between a single pathway and a specific personality profile, providing a better understanding of the genetics underlying personality, and new tools for tailoring educational and behavioral approaches for individuals with RASopathies. © 2018 Wiley Periodicals, Inc.

Proteomic Profiles Reveal the Function of Different Vegetative Tissues of Moringa oleifera.

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Wang, Lei; Zou, Qiong; Wang, Jinxing; Zhang, Junjie; Liu, Zeping; Chen, Xiaoyang

2016-12-01

Moringa oleifera is a rich source of bioactive compounds and is widely used in traditional medicine and food for its nutritional value; however, the protein and peptide components of different tissues are rarely discussed. Here, we describe the first investigation of M. oleifera proteomes using mass spectrometry and bioinformatics methods. We aimed to elucidate the protein profiles of M. oleifera leaves, stem, bark, and root. Totally 202 proteins were identified from four vegetative organs. We identified 101 proteins from leaves, 51 from stem, 94 from bark and 67 from root, finding that only five proteins existed in both four vegetative parts. The calculated pI of most of the proteins is distributed in 5-10 and the molecular weight distributed below 100 kDa. Functional classification analysis revealed that proteins which are involved in catalytic activities are the most abundant both in leaves, stem, bark and root. Identification of several heat shock proteins in four vegetative tissues might be adaptive for resistance to high temperature environmental stresses of tropical or subtropical areas. Some enzymes involved in antioxidant processes were also identified in M. oleifera leaves, stem, bark and root. Among the four tissues studies here, leaves protein content and molecular diversity were the highest. The identification of the flocculating protein MO2.1 and MO2.2 in the bark and root provides clue to clarify the antimicrobial molecular mechanisms of root and bark. This study provides information on the protein compositions of M. oleifera vegetative tissues that will be beneficial for potential drug and food supplement development and plant physiology research.

Personal summarization from profile networks

Institute of Scientific and Technical Information of China (English)

Zhongqing WANG; Shoushan LI; Guodong ZHOU

2017-01-01

Personal profile information on social media like Linkedln.com and Facebook.com is at the core of many interesting applications,such as talent recommendation and contextual advertising.However,personal profiles usually lack consistent organization confronted with the large amount of available information.Therefore,it is always a challenge for people to quickly find desired information from them.In this paper,we address the task of personal profile summarization by leveraging both textual information and social connection information in social networks from both unsupervised and supervised learning paradigms.Here,using social connection information is motivated by the intuition that people with similar academic,business or social background (e.g.,comajor,co-university,and co-corporation) tend to have similar experiences and should have similar summaries.For unsupervised learning,we propose a collective ranking approach,called SocialRank,to combine textual information in an individual profile and social context information from relevant profiles in generating a personal profile summary.For supervised learning,we propose a collective factor graph model,called CoFG,to summarize personal profiles with local textual attribute functions and social connection factors.Extensive evaluation on a large dataset from LinkedIn.com demonstrates the usefulness of social connection information in personal profile summarization and the effectiveness of our proposed unsupervised and supervised learning approaches.

YOUNG ATHLETES' MOTIVATIONAL PROFILES

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Juan Antonio Moreno Murcia

2007-06-01

Full Text Available The aim of this study was to examine the relationship between motivational characteristics and dispositional flow. In order to accomplish this goal, motivational profiles emerging from key constructs within Achievement Goal Theory and Self-Determination Theory were related to the dispositional flow measures. A sample of 413 young athletes (Age range 12 to 16 years completed the PMCSQ-2, POSQ, SMS and DFS measures. Cluster analysis results revealed three profiles: a "self-determined profile" characterised by higher scores on the task-involving climate perception and on the task orientation; a "non-self-determined profile", characterised by higher scores on ego-involving climate perception and ego orientation; and a "low self-determined and low non-self-determined profile" which had the lowest dispositional flow. No meaningful differences were found between the "self-determined profile" and the "non-self-determined profile" in dispositional flow. The "self-determined profile" was more commonly associated with females, athletes practising individual sports and those training more than three days a week. The "non-self-determined profile" was more customary of males and athletes practising team sports as well as those training just two or three days a week

Response-predictive gene expression profiling of glioma progenitor cells in vitro.

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Sylvia Moeckel

Full Text Available High-grade gliomas are amongst the most deadly human tumors. Treatment results are disappointing. Still, in several trials around 20% of patients respond to therapy. To date, diagnostic strategies to identify patients that will profit from a specific therapy do not exist.In this study, we used serum-free short-term treated in vitro cell cultures to predict treatment response in vitro. This approach allowed us (a to enrich specimens for brain tumor initiating cells and (b to confront cells with a therapeutic agent before expression profiling.As a proof of principle we analyzed gene expression in 18 short-term serum-free cultures of high-grade gliomas enhanced for brain tumor initiating cells (BTIC before and after in vitro treatment with the tyrosine kinase inhibitor Sunitinib. Profiles from treated progenitor cells allowed to predict therapy-induced impairment of proliferation in vitro.For the tyrosine kinase inhibitor Sunitinib used in this dataset, the approach revealed additional predictive information in comparison to the evaluation of classical signaling analysis.

Design of the tool for periodic not evolvent profiles

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Anisimov Roman

2017-01-01

Full Text Available The new approach to profiling of the tool for processing of parts with periodic not evolvent profiles are considered in the article The discriminatory analysis of periodic profiles including repetition of profile both in the plane of perpendicular axis of part, and in the plane of passing along part of axis is offered. In the basis of the offered profiling method the idea of space shaping by rated surface of product of tool surface lies. The big advantage of the offered approach in profiling is its combination with the analysis of parameters of process of engineering work. It allows to predict the accuracy and surface quality of product with not evolvent periodic profile. While using the offered approach the pinion cutter for processing of wheels with internal triangular teeths and mill for processing of the screw of the counter of consumption of liquid, complex profile of which consists of several formings, have been received

Global methylation profiling of lymphoblastoid cell lines reveals epigenetic contributions to autism spectrum disorders and a novel autism candidate gene, RORA, whose protein product is reduced in autistic brain

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Nguyen, AnhThu; Rauch, Tibor A.; Pfeifer, Gerd P.; Hu, Valerie W.

2010-01-01

Autism is currently considered a multigene disorder with epigenetic influences. To investigate the contribution of DNA methylation to autism spectrum disorders, we have recently completed large-scale methylation profiling by CpG island microarray analysis of lymphoblastoid cell lines derived from monozygotic twins discordant for diagnosis of autism and their nonautistic siblings. Methylation profiling revealed many candidate genes differentially methylated between discordant MZ twins as well as between both twins and nonautistic siblings. Bioinformatics analysis of the differentially methylated genes demonstrated enrichment for high-level functions including gene transcription, nervous system development, cell death/survival, and other biological processes implicated in autism. The methylation status of 2 of these candidate genes, BCL-2 and retinoic acid-related orphan receptor alpha (RORA), was further confirmed by bisulfite sequencing and methylation-specific PCR, respectively. Immunohistochemical analyses of tissue arrays containing slices of the cerebellum and frontal cortex of autistic and age- and sex-matched control subjects revealed decreased expression of RORA and BCL-2 proteins in the autistic brain. Our data thus confirm the role of epigenetic regulation of gene expression via differential DNA methylation in idiopathic autism, and furthermore link molecular changes in a peripheral cell model with brain pathobiology in autism.—Nguyen, A., Rauch, T. A., Pfeifer, G. P., Hu, V. W. Global methylation profiling of lymphoblastoid cell lines reveals epigenetic contributions to autism spectrum disorders and a novel autism candidate gene, RORA, whose protein product is reduced in autistic brain. PMID:20375269

Profiles of adolescent religiousness using latent profile analysis: Implications for psychopathology.

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Longo, Gregory S; Bray, Bethany C; Kim-Spoon, Jungmeen

2017-03-01

Prior research has documented robust associations between adolescent religiousness/spirituality (R/S) and psychopathology outcomes including externalizing and internalizing symptomatology, yet no previous studies have examined these associations with adolescent R/S profiles using a person-centred approach. We examined whether there are identifiable subgroups characterized by unique multidimensional patterns of R/S experiences and how these experiences may be related to externalizing and internalizing symptomatology. The sample consisted of 220 Appalachian adolescents between 12 and 18 years old who were primarily White and primarily Christian. Latent profile analysis revealed three profiles of adolescent R/S: high religiousness (28.4%), introjectors (47.6%), and low religiousness (24.0%). These profiles were differentially related to internalizing and externalizing symptomatology such that the high religiousness group was significantly lower than the introjectors with respect to internalizing and externalizing symptomatology and lower than the low religiousness group in externalizing symptomatology. Implications and suggestions for future research using person-centred approaches to better understand differential developmental trajectories of religious development are provided. Statement of contribution What is already known Prior research has demonstrated a negative relationship between adolescent religiousness and spirituality (R/S) and psychopathology. Numerous studies document the differential relationships between aspects of R/S and psychopathology; however, few have done so from a person-centred perspective. There are several theories that outline how R/S to study R/S when paying specific attention to culture. Saroglou's Big Four dimensions of religion (believing, bonding, behaving, and belonging) posits that these four dimensions (1) are able to delimit religion from proximal constructs; (2) translate major distinct dimensions of religiousness; (3) can be

Analyses in zebrafish embryos reveal that nanotoxicity profiles are dependent on surface-functionalization controlled penetrance of biological membranes.

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Paatero, Ilkka; Casals, Eudald; Niemi, Rasmus; Özliseli, Ezgi; Rosenholm, Jessica M; Sahlgren, Cecilia

2017-08-21

Mesoporous silica nanoparticles (MSNs) are extensively explored as drug delivery systems, but in depth understanding of design-toxicity relationships is still scarce. We used zebrafish (Danio rerio) embryos to study toxicity profiles of differently surface functionalized MSNs. Embryos with the chorion membrane intact, or dechoroniated embryos, were incubated or microinjected with amino (NH 2 -MSNs), polyethyleneimine (PEI-MSNs), succinic acid (SUCC-MSNs) or polyethyleneglycol (PEG-MSNs) functionalized MSNs. Toxicity was assessed by viability and cardiovascular function. NH 2 -MSNs, SUCC-MSNs and PEG-MSNs were well tolerated, 50 µg/ml PEI-MSNs induced 100% lethality 48 hours post fertilization (hpf). Dechoroniated embryos were more sensitive and 10 µg/ml PEI-MSNs reduced viability to 5% at 96hpf. Sensitivity to PEG- and SUCC-, but not NH 2 -MSNs, was also enhanced. Typically cardiovascular toxicity was evident prior to lethality. Confocal microscopy revealed that PEI-MSNs penetrated into the embryos whereas PEG-, NH2- and SUCC-MSNs remained aggregated on the skin surface. Direct exposure of inner organs by microinjecting NH 2 -MSNs and PEI-MSNs demonstrated that the particles displayed similar toxicity indicating that functionalization affects the toxicity profile by influencing penetrance through biological barriers. The data emphasize the need for careful analyses of toxicity mechanisms in relevant models and constitute an important knowledge step towards the development of safer and sustainable nanotherapies.

Transcription Profiles Reveal Sugar and Hormone Signaling Pathways Mediating Flower Induction in Apple (Malus domestica Borkh.).

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Xing, Li-Bo; Zhang, Dong; Li, You-Mei; Shen, Ya-Wen; Zhao, Cai-Ping; Ma, Juan-Juan; An, Na; Han, Ming-Yu

2015-10-01

Flower induction in apple (Malus domestica Borkh.) is regulated by complex gene networks that involve multiple signal pathways to ensure flower bud formation in the next year, but the molecular determinants of apple flower induction are still unknown. In this research, transcriptomic profiles from differentiating buds allowed us to identify genes potentially involved in signaling pathways that mediate the regulatory mechanisms of flower induction. A hypothetical model for this regulatory mechanism was obtained by analysis of the available transcriptomic data, suggesting that sugar-, hormone- and flowering-related genes, as well as those involved in cell-cycle induction, participated in the apple flower induction process. Sugar levels and metabolism-related gene expression profiles revealed that sucrose is the initiation signal in flower induction. Complex hormone regulatory networks involved in cytokinin (CK), abscisic acid (ABA) and gibberellic acid pathways also induce apple flower formation. CK plays a key role in the regulation of cell formation and differentiation, and in affecting flowering-related gene expression levels during these processes. Meanwhile, ABA levels and ABA-related gene expression levels gradually increased, as did those of sugar metabolism-related genes, in developing buds, indicating that ABA signals regulate apple flower induction by participating in the sugar-mediated flowering pathway. Furthermore, changes in sugar and starch deposition levels in buds can be affected by ABA content and the expression of the genes involved in the ABA signaling pathway. Thus, multiple pathways, which are mainly mediated by crosstalk between sugar and hormone signals, regulate the molecular network involved in bud growth and flower induction in apple trees. © The Author 2015. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists.

African-American esophageal squamous cell carcinoma expression profile reveals dysregulation of stress response and detox networks.

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Erkizan, Hayriye Verda; Johnson, Kory; Ghimbovschi, Svetlana; Karkera, Deepa; Trachiotis, Gregory; Adib, Houtan; Hoffman, Eric P; Wadleigh, Robert G

2017-06-19

Esophageal carcinoma is the third most common gastrointestinal malignancy worldwide and is largely unresponsive to therapy. African-Americans have an increased risk for esophageal squamous cell carcinoma (ESCC), the subtype that shows marked variation in geographic frequency. The molecular architecture of African-American ESCC is still poorly understood. It is unclear why African-American ESCC is more aggressive and the survival rate in these patients is worse than those of other ethnic groups. To begin to define genetic alterations that occur in African-American ESCC we conducted microarray expression profiling in pairs of esophageal squamous cell tumors and matched control tissues. We found significant dysregulation of genes encoding drug-metabolizing enzymes and stress response components of the NRF2- mediated oxidative damage pathway, potentially representing key genes in African-American esophageal squamous carcinogenesis. Loss of activity of drug metabolizing enzymes would confer increased sensitivity of esophageal cells to xenobiotics, such as alcohol and tobacco smoke, and may account for the high incidence and aggressiveness of ESCC in this ethnic group. To determine whether certain genes are uniquely altered in African-American ESCC we performed a meta-analysis of ESCC expression profiles in our African-American samples and those of several Asian samples. Down-regulation of TP53 pathway components represented the most common feature in ESCC of all ethnic groups. Importantly, this analysis revealed a potential distinctive molecular underpinning of African-American ESCC, that is, a widespread and prominent involvement of the NRF2 pathway. Taken together, these findings highlight the remarkable interplay of genetic and environmental factors in the pathogenesis of African-American ESCC.

Using a multifactorial approach to determine fall risk profiles in portuguese older adults.

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Moniz-Pereira, Vera; Carnide, Filomena; Ramalho, Fátima; André, Helô; Machado, Maria; Santos-Rocha, Rita; Veloso, António P

2013-01-01

The aim of this study was to use a multifactorial approach to characterize episodic and recurrent fallers risk profiles in Portuguese older adults. To accomplish the mentioned purpose, 1416 Portuguese older adults above 65 years were tested with three different field measurements: 1) health and falls questionnaire; 2) Physical Activity questionnaire and 3) a set of functional fitness tests. The subjects were divided in three different groups according to fall prevalence: non-fallers, subjects who did not report any falls during the previous year, episodic fallers, those who reported to have fallen only once during the previous year, and recurrent fallers, the ones that fell twice or more times during the previous year. Episodic and Recurrent fallers risk profiles were established using multifactorial logistic regression models in order to avoid confounding effects between the variables. The results showed that age was not a risk factor for either episodic or recurrent falling. In addition, health parameters were shown to be the factors distinguishing recurrent from episodic fallers. This may imply that, comparing with episodic falls, recurrent falls are more associated with higher presence of chronic conditions and are less likely to occur due to external factors. Furthermore, being a woman, having fear of falling and lower functional fitness levels were determinant factors for both episodic and recurrent falls. It is also important to note that, although total physical activity was only related with episodic falling, promoting physical activity and exercise may be the easiest and cheapest way to improve functional fitness and health levels and therefore, its role in fall prevention should not be underestimated. The results of this study reinforce the importance of using a multifactorial approach, not only focusing on cognitive-behavioral factors, but also on promoting physical activity and healthy lifestyles, when assessing fall risk or planning an intervention

Approximate Stokes Drift Profiles in Deep Water

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Breivik, Øyvind; Janssen, Peter A. E. M.; Bidlot, Jean-Raymond

2014-09-01

A deep-water approximation to the Stokes drift velocity profile is explored as an alternative to the monochromatic profile. The alternative profile investigated relies on the same two quantities required for the monochromatic profile, viz the Stokes transport and the surface Stokes drift velocity. Comparisons with parametric spectra and profiles under wave spectra from the ERA-Interim reanalysis and buoy observations reveal much better agreement than the monochromatic profile even for complex sea states. That the profile gives a closer match and a more correct shear has implications for ocean circulation models since the Coriolis-Stokes force depends on the magnitude and direction of the Stokes drift profile and Langmuir turbulence parameterizations depend sensitively on the shear of the profile. The alternative profile comes at no added numerical cost compared to the monochromatic profile.

Quantitative multi-target RNA profiling in Epstein-Barr virus infected tumor cells.

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Greijer, A E; Ramayanti, O; Verkuijlen, S A W M; Novalić, Z; Juwana, H; Middeldorp, J M

2017-03-01

Epstein-Barr virus (EBV) is etiologically linked to multiple acute, chronic and malignant diseases. Detection of EBV-RNA transcripts in tissues or biofluids besides EBV-DNA can help in diagnosing EBV related syndromes. Sensitive EBV transcription profiling yields new insights on its pathogenic role and may be useful for monitoring virus targeted therapy. Here we describe a multi-gene quantitative RT-PCR profiling method that simultaneously detects a broad spectrum (n=16) of crucial latent and lytic EBV transcripts. These transcripts include (but are not restricted to), EBNA1, EBNA2, LMP1, LMP2, BARTs, EBER1, BARF1 and ZEBRA, Rta, BGLF4 (PK), BXLF1 (TK) and BFRF3 (VCAp18) all of which have been implicated in EBV-driven oncogenesis and viral replication. With this method we determine the amount of RNA copies per infected (tumor) cell in bulk populations of various origin. While we confirm the expected RNA profiles within classic EBV latency programs, this sensitive quantitative approach revealed the presence of rare cells undergoing lytic replication. Inducing lytic replication in EBV tumor cells supports apoptosis and is considered as therapeutic approach to treat EBV-driven malignancies. This sensitive multi-primed quantitative RT-PCR approach can provide broader understanding of transcriptional activity in latent and lytic EBV infection and is suitable for monitoring virus-specific therapy responses in patients with EBV associated cancers. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Activity-Based Profiling of a Physiologic Aglycone Library Reveals Sugar Acceptor Promiscuity of Family 1 UDP-Glucosyltransferases from Grape1[W

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Bönisch, Friedericke; Frotscher, Johanna; Stanitzek, Sarah; Rühl, Ernst; Wüst, Matthias; Bitz, Oliver; Schwab, Wilfried

2014-01-01

Monoterpenols serve various biological functions and accumulate in grape (Vitis vinifera), where a major fraction occurs as nonvolatile glycosides. We have screened the grape genome for sequences with similarity to terpene URIDINE DIPHOSPHATE GLYCOSYLTRANSFERASES (UGTs) from Arabidopsis (Arabidopsis thaliana). A ripening-related expression pattern was shown for three candidates by spatial and temporal expression analyses in five grape cultivars. Transcript accumulation correlated with the production of monoterpenyl β-d-glucosides in grape exocarp during ripening and was low in vegetative tissue. Targeted functional screening of the recombinant UGTs for their biological substrates was performed by activity-based metabolite profiling (ABMP) employing a physiologic library of aglycones built from glycosides isolated from grape. This approach led to the identification of two UDP-glucose:monoterpenol β-d-glucosyltransferases. Whereas VvGT14a glucosylated geraniol, R,S-citronellol, and nerol with similar efficiency, the three allelic forms VvGT15a, VvGT15b, and VvGT15c preferred geraniol over nerol. Kinetic resolution of R,S-citronellol and R,S-linalool was shown for VvGT15a and VvGT14a, respectively. ABMP revealed geraniol as the major biological substrate but also disclosed that these UGTs may add to the production of further glycoconjugates in planta. ABMP of aglycone libraries provides a versatile tool to uncover novel biologically relevant substrates of small-molecule glycosyltransferases that often show broad sugar acceptor promiscuity. PMID:25073706

Do Energy Efficiency Standards Improve Quality? Evidence from a Revealed Preference Approach

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Houde, Sebastien [Univ. of Maryland, College Park, MD (United States); Spurlock, C. Anna [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

2015-06-01

Minimum energy efficiency standards have occupied a central role in U.S. energy policy for more than three decades, but little is known about their welfare effects. In this paper, we employ a revealed preference approach to quantify the impact of past revisions in energy efficiency standards on product quality. The micro-foundation of our approach is a discrete choice model that allows us to compute a price-adjusted index of vertical quality. Focusing on the appliance market, we show that several standard revisions during the period 2001-2011 have led to an increase in quality. We also show that these standards have had a modest effect on prices, and in some cases they even led to decreases in prices. For revision events where overall quality increases and prices decrease, the consumer welfare effect of tightening the standards is unambiguously positive. Finally, we show that after controlling for the effect of improvement in energy efficiency, standards have induced an expansion of quality in the non-energy dimension. We discuss how imperfect competition can rationalize these results.

A systems biology approach reveals that tissue tropism to West Nile virus is regulated by antiviral genes and innate immune cellular processes.

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Mehul S Suthar

2013-02-01

Full Text Available The actions of the RIG-I like receptor (RLR and type I interferon (IFN signaling pathways are essential for a protective innate immune response against the emerging flavivirus West Nile virus (WNV. In mice lacking RLR or IFN signaling pathways, WNV exhibits enhanced tissue tropism, indicating that specific host factors of innate immune defense restrict WNV infection and dissemination in peripheral tissues. However, the immune mechanisms by which the RLR and IFN pathways coordinate and function to impart restriction of WNV infection are not well defined. Using a systems biology approach, we defined the host innate immune response signature and actions that restrict WNV tissue tropism. Transcriptional profiling and pathway modeling to compare WNV-infected permissive (spleen and nonpermissive (liver tissues showed high enrichment for inflammatory responses, including pattern recognition receptors and IFN signaling pathways, that define restriction of WNV replication in the liver. Assessment of infected livers from Mavs(-/- × Ifnar(-/- mice revealed the loss of expression of several key components within the natural killer (NK cell signaling pathway, including genes associated with NK cell activation, inflammatory cytokine production, and NK cell receptor signaling. In vivo analysis of hepatic immune cell infiltrates from WT mice demonstrated that WNV infection leads to an increase in NK cell numbers with enhanced proliferation, maturation, and effector action. In contrast, livers from Mavs(-/- × Ifnar(-/- infected mice displayed reduced immune cell infiltration, including a significant reduction in NK cell numbers. Analysis of cocultures of dendritic and NK cells revealed both cell-intrinsic and -extrinsic roles for the RLR and IFN signaling pathways to regulate NK cell effector activity. Taken together, these observations reveal a complex innate immune signaling network, regulated by the RLR and IFN signaling pathways, that drives tissue

Expression profiling of a genetic animal model of depression reveals novel molecular pathways underlying depressive-like behaviours.

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Ekaterini Blaveri

2010-09-01

Full Text Available The Flinders model is a validated genetic rat model of depression that exhibits a number of behavioural, neurochemical and pharmacological features consistent with those observed in human depression.In this study we have used genome-wide microarray expression profiling of the hippocampus and prefrontal/frontal cortex of Flinders Depression Sensitive (FSL and control Flinders Depression Resistant (FRL lines to understand molecular basis for the differences between the two lines. We profiled two independent cohorts of Flinders animals derived from the same colony six months apart, each cohort statistically powered to allow independent as well as combined analysis. Using this approach, we were able to validate using real-time-PCR a core set of gene expression differences that showed statistical significance in each of the temporally distinct cohorts, representing consistently maintained features of the model. Small but statistically significant increases were confirmed for cholinergic (chrm2, chrna7 and serotonergic receptors (Htr1a, Htr2a in FSL rats consistent with known neurochemical changes in the model. Much larger gene changes were validated in a number of novel genes as exemplified by TMEM176A, which showed 35-fold enrichment in the cortex and 30-fold enrichment in hippocampus of FRL animals relative to FSL.These data provide significant insights into the molecular differences underlying the Flinders model, and have potential relevance to broader depression research.

Metabolomic profiling reveals mitochondrial-derived lipid biomarkers that drive obesity-associated inflammation.

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Brante P Sampey

Full Text Available Obesity has reached epidemic proportions worldwide. Several animal models of obesity exist, but studies are lacking that compare traditional lard-based high fat diets (HFD to "Cafeteria diets" (CAF consisting of nutrient poor human junk food. Our previous work demonstrated the rapid and severe obesogenic and inflammatory consequences of CAF compared to HFD including rapid weight gain, markers of Metabolic Syndrome, multi-tissue lipid accumulation, and dramatic inflammation. To identify potential mediators of CAF-induced obesity and Metabolic Syndrome, we used metabolomic analysis to profile serum, muscle, and white adipose from rats fed CAF, HFD, or standard control diets. Principle component analysis identified elevations in clusters of fatty acids and acylcarnitines. These increases in metabolites were associated with systemic mitochondrial dysfunction that paralleled weight gain, physiologic measures of Metabolic Syndrome, and tissue inflammation in CAF-fed rats. Spearman pairwise correlations between metabolites, physiologic, and histologic findings revealed strong correlations between elevated markers of inflammation in CAF-fed animals, measured as crown like structures in adipose, and specifically the pro-inflammatory saturated fatty acids and oxidation intermediates laurate and lauroyl carnitine. Treatment of bone marrow-derived macrophages with lauroyl carnitine polarized macrophages towards the M1 pro-inflammatory phenotype through downregulation of AMPK and secretion of pro-inflammatory cytokines. Results presented herein demonstrate that compared to a traditional HFD model, the CAF diet provides a robust model for diet-induced human obesity, which models Metabolic Syndrome-related mitochondrial dysfunction in serum, muscle, and adipose, along with pro-inflammatory metabolite alterations. These data also suggest that modifying the availability or metabolism of saturated fatty acids may limit the inflammation associated with obesity

Elemental microchemistry, fatty acid profile and geometric morphometrics signatures of goose barnacles (Pollicipes pollicipes reveal their place of origin

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Rui Albuquerque

2014-06-01

Full Text Available Seafood plays an important role in the socioeconomic, gastronomy and cultural heritage of Portuguese coastal communities. In the Iberian Peninsula, the goose barnacle Pollicipes pollicipes is the intertidal biological resource most heavily exploited by man, resulting on overexploitation of stocks. In the MPA of BNR P.pollicipes harvesting is however strictly regulated, making it a good example of marine resources management. Analytical methods able to identify the origin of goose barnacle would be an important tool to help the management of the trade. For such purpose, we investigated whether P. pollicipes have site-specific differences based on its elemental microchemistry (EM, fatty acid profile (FA and capitulum shape (CS. The analysis was performed on specimens collected from 3 sites in the BNR and 7 along a 300 km stretch of the Portuguese coast. For each individual we analysed the largest lateral shell for EM using ICP-MS, the FA content of the muscle using GC-FID, and the CS using geometric morphometrics. Discriminant function analyses (DFA for both EM and FA separately provided a high reclassification success (77.6% and 99% respectively, of cross-validated cases correctly classified, while for EM combined with FA allowed for a 100% reclassification success. DFA analysis based only on CS, revealed a low classification success (29.6%. These results show that EM and FA signatures can be a powerful tool to infer goose barnacles origin. Such “fingerprinting” approach can be used to track and identify goose barnacles origin, helping in establishing an origin certificate and increasing the potential value of biological resources from Portuguese MPAs.

The Promise of Systems Biology Approaches for Revealing Host Pathogen Interactions in Malaria

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Meghan Zuck

2017-11-01

Full Text Available Despite global eradication efforts over the past century, malaria remains a devastating public health burden, causing almost half a million deaths annually (WHO, 2016. A detailed understanding of the mechanisms that control malaria infection has been hindered by technical challenges of studying a complex parasite life cycle in multiple hosts. While many interventions targeting the parasite have been implemented, the complex biology of Plasmodium poses a major challenge, and must be addressed to enable eradication. New approaches for elucidating key host-parasite interactions, and predicting how the parasite will respond in a variety of biological settings, could dramatically enhance the efficacy and longevity of intervention strategies. The field of systems biology has developed methodologies and principles that are well poised to meet these challenges. In this review, we focus our attention on the Liver Stage of the Plasmodium lifecycle and issue a “call to arms” for using systems biology approaches to forge a new era in malaria research. These approaches will reveal insights into the complex interplay between host and pathogen, and could ultimately lead to novel intervention strategies that contribute to malaria eradication.

Use of an ecologically relevant modelling approach to improve remote sensing-based schistosomiasis risk profiling

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Yvonne Walz

2015-11-01

Full Text Available Schistosomiasis is a widespread water-based disease that puts close to 800 million people at risk of infection with more than 250 million infected, mainly in sub-Saharan Africa. Transmission is governed by the spatial distribution of specific freshwater snails that act as intermediate hosts and the frequency, duration and extent of human bodies exposed to infested water sources during human water contact. Remote sensing data have been utilized for spatially explicit risk profiling of schistosomiasis. Since schistosomiasis risk profiling based on remote sensing data inherits a conceptual drawback if school-based disease prevalence data are directly related to the remote sensing measurements extracted at the location of the school, because the disease transmission usually does not exactly occur at the school, we took the local environment around the schools into account by explicitly linking ecologically relevant environmental information of potential disease transmission sites to survey measurements of disease prevalence. Our models were validated at two sites with different landscapes in Côte d’Ivoire using high- and moderateresolution remote sensing data based on random forest and partial least squares regression. We found that the ecologically relevant modelling approach explained up to 70% of the variation in Schistosoma infection prevalence and performed better compared to a purely pixelbased modelling approach. Furthermore, our study showed that model performance increased as a function of enlarging the school catchment area, confirming the hypothesis that suitable environments for schistosomiasis transmission rarely occur at the location of survey measurements.

A study on online learner profile for supporting personalized learning

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Jie Yang

2013-09-01

Full Text Available Digital learning as a popular learning approach has received increasing attention in modern education. The learner profile in online learning plays a critical role in supporting personalized learning. This article uses an information flow-based approach to build the learner profile for supporting personalized learning. The learner profile includes the individual profile to capture the personal features and the community profile to capture the social features in online learning environment.

Evaluation of the methodologies used to generate random pavement profiles based on the power spectral density: An approach based on the International Roughness Index

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Boris Jesús Goenaga

2017-01-01

Full Text Available The pavement roughness is the main variable that produces the vertical excitation in vehicles. Pavement profiles are the main determinant of (i discomfort perception on users and (ii dynamic loads generated at the tire-pavement interface, hence its evaluation constitutes an essential step on a Pavement Management System. The present document evaluates two specific techniques used to simulate pavement profiles; these are the shaping filter and the sinusoidal approach, both based on the Power Spectral Density. Pavement roughness was evaluated using the International Roughness Index (IRI, which represents the most used index to characterize longitudinal road profiles. Appropriate parameters were defined in the simulation process to obtain pavement profiles with specific ranges of IRI values using both simulation techniques. The results suggest that using a sinusoidal approach one can generate random profiles with IRI values that are representative of different road types, therefore, one could generate a profile for a paved or an unpaved road, representing all the proposed categories defined by ISO 8608 standard. On the other hand, to obtain similar results using the shaping filter approximation a modification in the simulation parameters is necessary. The new proposed values allow one to generate pavement profiles with high levels of roughness, covering a wider range of surface types. Finally, the results of the current investigation could be used to further improve our understanding on the effect of pavement roughness on tire pavement interaction. The evaluated methodologies could be used to generate random profiles with specific levels of roughness to assess its effect on dynamic loads generated at the tire-pavement interface and user’s perception of road condition.

Motivational Profiles for Physical Activity Practice in Adults with Type 2 Diabetes: A Self-Determination Theory Perspective.

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Gourlan, Mathieu; Trouilloud, David; Boiché, Julie

2016-01-01

Drawing on Self-Determination Theory, this study explored the motivational profiles toward Physical Activity (PA) among adults with type 2 diabetes and the relationships between motivational profile, perceived competence and PA. Participants were 350 men and women (Mean age 62.77 years) who were interviewed on their motivations toward PA, perceived level of competence to practice, and PA practice. Cluster analyses reveal the existence of three distinct profiles: "High Combined" (ie, high scores on motivations ranging from intrinsic to external regulation, moderate level on amotivation), "Self-Determined" (ie, high scores on intrinsic, integrated, and identified regulations; low scores on other regulations), and "Moderate" (ie, moderate scores on all regulations). Participants with "High Combined" and "Self-Determined" profiles reported higher perceived competence and longer leisure-time PA practice in comparison to those with a "Moderate" profile. This study highlights the necessity of adopting a person-centered approach to better understand motivation toward PA among type 2 diabetics.

Metabolomic Profiling for Identification of Novel Potential Biomarkers in Cardiovascular Diseases

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Maria G. Barderas

2011-01-01

Full Text Available Metabolomics involves the identification and quantification of metabolites present in a biological system. Three different approaches can be used: metabolomic fingerprinting, metabolic profiling, and metabolic footprinting, in order to evaluate the clinical course of a disease, patient recovery, changes in response to surgical intervention or pharmacological treatment, as well as other associated features. Characteristic patterns of metabolites can be revealed that broaden our understanding of a particular disorder. In the present paper, common strategies and analytical techniques used in metabolomic studies are reviewed, particularly with reference to the cardiovascular field.

PROFIL KEMAMPUAN PENALARAN MATEMATIS SISWA DITINJAU DARI GAYA BELAJAR

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Muhamad Ridwan

2017-11-01

Full Text Available Students learn according to their learning style, and every learning styles are affecting the process of mathematical reasoning and learning outcomes. The combination of how to absorb, manage and process information is the definition of learning styles. To maximize the students' ability to absorb, manage and process information, first identified learning styles of the students are visual, auditory or kinesthetic (V-A-K. This research aims to reveal the profile of mathematical reasoning abilities of students in terms of learning styles visual, audio and kinesthetic on the material function composition and inverse function. This research is a qualitative descriptive approach ethnography and research subject is grade XI of senior high school. The results of the research of profile learning styles (V-A-K that profile visual students' mathematical reasoning skill, have the ability to manipulate, draw conclusions, giving reasons or evidence is sufficient. While the ability to deliver his argument lacking. Profile auditory students' mathematical reasoning skills, have the ability to manipulate, giving reason or evidence, and provide argument or the validity of the answer is both. While the ability gets conclusion to enough. Profile kinesthetic students' mathematical reasoning skills have the ability to manipulate and give reasons or evidence is sufficient. The ability to draw conclusions while the less, as well as the ability to provide an answer or the validity of the argument, he answered with a unique and clear

Circuit-wide Transcriptional Profiling Reveals Brain Region-Specific Gene Networks Regulating Depression Susceptibility.

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Bagot, Rosemary C; Cates, Hannah M; Purushothaman, Immanuel; Lorsch, Zachary S; Walker, Deena M; Wang, Junshi; Huang, Xiaojie; Schlüter, Oliver M; Maze, Ian; Peña, Catherine J; Heller, Elizabeth A; Issler, Orna; Wang, Minghui; Song, Won-Min; Stein, Jason L; Liu, Xiaochuan; Doyle, Marie A; Scobie, Kimberly N; Sun, Hao Sheng; Neve, Rachael L; Geschwind, Daniel; Dong, Yan; Shen, Li; Zhang, Bin; Nestler, Eric J

2016-06-01

Depression is a complex, heterogeneous disorder and a leading contributor to the global burden of disease. Most previous research has focused on individual brain regions and genes contributing to depression. However, emerging evidence in humans and animal models suggests that dysregulated circuit function and gene expression across multiple brain regions drive depressive phenotypes. Here, we performed RNA sequencing on four brain regions from control animals and those susceptible or resilient to chronic social defeat stress at multiple time points. We employed an integrative network biology approach to identify transcriptional networks and key driver genes that regulate susceptibility to depressive-like symptoms. Further, we validated in vivo several key drivers and their associated transcriptional networks that regulate depression susceptibility and confirmed their functional significance at the levels of gene transcription, synaptic regulation, and behavior. Our study reveals novel transcriptional networks that control stress susceptibility and offers fundamentally new leads for antidepressant drug discovery. Copyright © 2016 Elsevier Inc. All rights reserved.

Multiplexed activity-based protein profiling of the human pathogen Aspergillus fumigatus reveals large functional changes upon exposure to human serum.

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Wiedner, Susan D; Burnum, Kristin E; Pederson, LeeAnna M; Anderson, Lindsey N; Fortuin, Suereta; Chauvigné-Hines, Lacie M; Shukla, Anil K; Ansong, Charles; Panisko, Ellen A; Smith, Richard D; Wright, Aaron T

2012-09-28

Environmental adaptability is critical for survival of the fungal human pathogen Aspergillus fumigatus in the immunocompromised host lung. We hypothesized that exposure of the fungal pathogen to human serum would lead to significant alterations to the organism's physiology, including metabolic activity and stress response. Shifts in functional pathway and corresponding enzyme reactivity of A. fumigatus upon exposure to the human host may represent much needed prognostic indicators of fungal infection. To address this, we employed a multiplexed activity-based protein profiling (ABPP) approach coupled to quantitative mass spectrometry-based proteomics to measure broad enzyme reactivity of the fungus cultured with and without human serum. ABPP showed a shift from aerobic respiration to ethanol fermentation and utilization over time in the presence of human serum, which was not observed in serum-free culture. Our approach provides direct insight into this pathogen's ability to survive, adapt, and proliferate. Additionally, our multiplexed ABPP approach captured a broad swath of enzyme reactivity and functional pathways and provides a method for rapid assessment of the A. fumigatus response to external stimuli.

Multiplexed Activity-based Protein Profiling of the Human Pathogen Aspergillus fumigatus Reveals Large Functional Changes upon Exposure to Human Serum*

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Wiedner, Susan D.; Burnum, Kristin E.; Pederson, LeeAnna M.; Anderson, Lindsey N.; Fortuin, Suereta; Chauvigné-Hines, Lacie M.; Shukla, Anil K.; Ansong, Charles; Panisko, Ellen A.; Smith, Richard D.; Wright, Aaron T.

2012-01-01

Environmental adaptability is critical for survival of the fungal human pathogen Aspergillus fumigatus in the immunocompromised host lung. We hypothesized that exposure of the fungal pathogen to human serum would lead to significant alterations to the organism's physiology, including metabolic activity and stress response. Shifts in functional pathway and corresponding enzyme reactivity of A. fumigatus upon exposure to the human host may represent much needed prognostic indicators of fungal infection. To address this, we employed a multiplexed activity-based protein profiling (ABPP) approach coupled to quantitative mass spectrometry-based proteomics to measure broad enzyme reactivity of the fungus cultured with and without human serum. ABPP showed a shift from aerobic respiration to ethanol fermentation and utilization over time in the presence of human serum, which was not observed in serum-free culture. Our approach provides direct insight into this pathogen's ability to survive, adapt, and proliferate. Additionally, our multiplexed ABPP approach captured a broad swath of enzyme reactivity and functional pathways and provides a method for rapid assessment of the A. fumigatus response to external stimuli. PMID:22865858

Expression profile of the Schistosoma japonicum degradome reveals differential protease expression patterns and potential anti-schistosomal intervention targets.

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Shuai Liu

2014-10-01

Full Text Available Blood fluke proteases play pivotal roles in the processes of invasion, nutrition acquisition, immune evasion, and other host-parasite interactions. Hundreds of genes encoding putative proteases have been identified in the recently published schistosome genomes. However, the expression profiles of these proteases in Schistosoma species have not yet been systematically analyzed. We retrieved and culled the redundant protease sequences of Schistosoma japonicum, Schistosoma mansoni, Echinococcus multilocularis, and Clonorchis sinensis from public databases utilizing bioinformatic approaches. The degradomes of the four parasitic organisms and Homo sapiens were then comparatively analyzed. A total of 262 S. japonicum protease sequences were obtained and the expression profiles generated using whole-genome microarray. Four main clusters of protease genes with different expression patterns were identified: proteases up-regulated in hepatic schistosomula and adult worms, egg-specific or predominantly expressed proteases, cercaria-specific or predominantly expressed proteases, and constantly expressed proteases. A subset of protease genes with different expression patterns were further validated using real-time quantitative PCR. The present study represents the most comprehensive analysis of a degradome in Schistosoma species to date. These results provide a firm foundation for future research on the specific function(s of individual proteases and may help to refine anti-proteolytic strategies in blood flukes.

Microarray expression profiling of human dental pulp from single subject.

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Tete, Stefano; Mastrangelo, Filiberto; Scioletti, Anna Paola; Tranasi, Michelangelo; Raicu, Florina; Paolantonio, Michele; Stuppia, Liborio; Vinci, Raffaele; Gherlone, Enrico; Ciampoli, Cristian; Sberna, Maria Teresa; Conti, Pio

2008-01-01

Microarray is a recently developed simultaneous analysis of expression patterns of thousand of genes. The aim of this research was to evaluate the expression profile of human healthy dental pulp in order to find the presence of genes activated and encoding for proteins involved in the physiological process of human dental pulp. We report data obtained by analyzing expression profiles of human tooth pulp from single subjects, using an approach based on the amplification of the total RNA. Experiments were performed on a high-density array able to analyse about 21,000 oligonucleotide sequences of about 70 bases in duplicate, using an approach based on the amplification of the total RNA from the pulp of a single tooth. Obtained data were analyzed using the S.A.M. system (Significance Analysis of Microarray) and genes were merged according to their molecular functions and biological process by the Onto-Express software. The microarray analysis revealed 362 genes with specific pulp expression. Genes showing significant high expression were classified in genes involved in tooth development, protoncogenes, genes of collagen, DNAse, Metallopeptidases and Growth factors. We report a microarray analysis, carried out by extraction of total RNA from specimens of healthy human dental pulp tissue. This approach represents a powerful tool in the study of human normal and pathological pulp, allowing minimization of the genetic variability due to the pooling of samples from different individuals.

3D profile-based approach to proteome-wide discovery of novel human chemokines.

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Aurelie Tomczak

Full Text Available Chemokines are small secreted proteins with important roles in immune responses. They consist of a conserved three-dimensional (3D structure, so-called IL8-like chemokine fold, which is supported by disulfide bridges characteristic of this protein family. Sequence- and profile-based computational methods have been proficient in discovering novel chemokines by making use of their sequence-conserved cysteine patterns. However, it has been recently shown that some chemokines escaped annotation by these methods due to low sequence similarity to known chemokines and to different arrangement of cysteines in sequence and in 3D. Innovative methods overcoming the limitations of current techniques may allow the discovery of new remote homologs in the still functionally uncharacterized fraction of the human genome. We report a novel computational approach for proteome-wide identification of remote homologs of the chemokine family that uses fold recognition techniques in combination with a scaffold-based automatic mapping of disulfide bonds to define a 3D profile of the chemokine protein family. By applying our methodology to all currently uncharacterized human protein sequences, we have discovered two novel proteins that, without having significant sequence similarity to known chemokines or characteristic cysteine patterns, show strong structural resemblance to known anti-HIV chemokines. Detailed computational analysis and experimental structural investigations based on mass spectrometry and circular dichroism support our structural predictions and highlight several other chemokine-like features. The results obtained support their functional annotation as putative novel chemokines and encourage further experimental characterization. The identification of remote homologs of human chemokines may provide new insights into the molecular mechanisms causing pathologies such as cancer or AIDS, and may contribute to the development of novel treatments. Besides

Variations in Decision-Making Profiles by Age and Gender: A Cluster-Analytic Approach

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Delaney, Rebecca; Strough, JoNell; Parker, Andrew M.; de Bruin, Wandi Bruine

2015-01-01

Using cluster-analysis, we investigated whether rational, intuitive, spontaneous, dependent, and avoidant styles of decision making (Scott & Bruce, 1995) combined to form distinct decision-making profiles that differed by age and gender. Self-report survey data were collected from 1,075 members of RAND’s American Life Panel (56.2% female, 18–93 years, Mage = 53.49). Three decision-making profiles were identified: affective/experiential, independent/self-controlled, and an interpersonally-oriented dependent profile. Older people were less likely to be in the affective/experiential profile and more likely to be in the independent/self-controlled profile. Women were less likely to be in the affective/experiential profile and more likely to be in the interpersonally-oriented dependent profile. Interpersonally-oriented profiles are discussed as an overlooked but important dimension of how people make important decisions. PMID:26005238

Variations in Decision-Making Profiles by Age and Gender: A Cluster-Analytic Approach.

Science.gov (United States)

Delaney, Rebecca; Strough, JoNell; Parker, Andrew M; de Bruin, Wandi Bruine

2015-10-01

Using cluster-analysis, we investigated whether rational, intuitive, spontaneous, dependent, and avoidant styles of decision making (Scott & Bruce, 1995) combined to form distinct decision-making profiles that differed by age and gender. Self-report survey data were collected from 1,075 members of RAND's American Life Panel (56.2% female, 18-93 years, M age = 53.49). Three decision-making profiles were identified: affective/experiential, independent/self-controlled, and an interpersonally-oriented dependent profile. Older people were less likely to be in the affective/experiential profile and more likely to be in the independent/self-controlled profile. Women were less likely to be in the affective/experiential profile and more likely to be in the interpersonally-oriented dependent profile. Interpersonally-oriented profiles are discussed as an overlooked but important dimension of how people make important decisions.

Global minimum profile error (GMPE) - a least-squares-based approach for extracting macroscopic rate coefficients for complex gas-phase chemical reactions.

Science.gov (United States)

Duong, Minh V; Nguyen, Hieu T; Mai, Tam V-T; Huynh, Lam K

2018-01-03

Master equation/Rice-Ramsperger-Kassel-Marcus (ME/RRKM) has shown to be a powerful framework for modeling kinetic and dynamic behaviors of a complex gas-phase chemical system on a complicated multiple-species and multiple-channel potential energy surface (PES) for a wide range of temperatures and pressures. Derived from the ME time-resolved species profiles, the macroscopic or phenomenological rate coefficients are essential for many reaction engineering applications including those in combustion and atmospheric chemistry. Therefore, in this study, a least-squares-based approach named Global Minimum Profile Error (GMPE) was proposed and implemented in the MultiSpecies-MultiChannel (MSMC) code (Int. J. Chem. Kinet., 2015, 47, 564) to extract macroscopic rate coefficients for such a complicated system. The capability and limitations of the new approach were discussed in several well-defined test cases.

A Discrete Dynamical System Approach to Pathway Activation Profiles of Signaling Cascades.

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Catozzi, S; Sepulchre, J-A

2017-08-01

In living organisms, cascades of covalent modification cycles are one of the major intracellular signaling mechanisms, allowing to transduce physical or chemical stimuli of the external world into variations of activated biochemical species within the cell. In this paper, we develop a novel method to study the stimulus-response of signaling cascades and overall the concept of pathway activation profile which is, for a given stimulus, the sequence of activated proteins at each tier of the cascade. Our approach is based on a correspondence that we establish between the stationary states of a cascade and pieces of orbits of a 2D discrete dynamical system. The study of its possible phase portraits in function of the biochemical parameters, and in particular of the contraction/expansion properties around the fixed points of this discrete map, as well as their bifurcations, yields a classification of the cascade tiers into three main types, whose biological impact within a signaling network is examined. In particular, our approach enables to discuss quantitatively the notion of cascade amplification/attenuation from this new perspective. The method allows also to study the interplay between forward and "retroactive" signaling, i.e., the upstream influence of an inhibiting drug bound to the last tier of the cascade.

Profiling extracellular vesicle release by the filarial nematode Brugia malayi reveals sex-specific differences in cargo and a sensitivity to ivermectin.

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Hiruni Harischandra

2018-04-01

Full Text Available The filarial nematode Brugia malayi is an etiological agent of Lymphatic Filariasis. The capability of B. malayi and other parasitic nematodes to modulate host biology is recognized but the mechanisms by which such manipulation occurs are obscure. An emerging paradigm is the release of parasite-derived extracellular vesicles (EV containing bioactive proteins and small RNA species that allow secretion of parasite effector molecules and their potential trafficking to host tissues. We have previously described EV release from the infectious L3 stage B. malayi and here we profile vesicle release across all intra-mammalian life cycle stages (microfilariae, L3, L4, adult male and female worms. Nanoparticle Tracking Analysis was used to quantify and size EVs revealing discrete vesicle populations and indicating a secretory process that is conserved across the life cycle. Brugia EVs are internalized by murine macrophages with no preference for life stage suggesting a uniform mechanism for effector molecule trafficking. Further, the use of chemical uptake inhibitors suggests all life stage EVs are internalized by phagocytosis. Proteomic profiling of adult male and female EVs using nano-scale LC-MS/MS described quantitative and qualitative differences in the adult EV proteome, helping define the biogenesis of Brugia EVs and revealing sexual dimorphic characteristics in immunomodulatory cargo. Finally, ivermectin was found to rapidly inhibit EV release by all Brugia life stages. Further this drug effect was also observed in the related filarial nematode, the canine heartworm Dirofilaria immitis but not in an ivermectin-unresponsive field isolate of that parasite, highlighting a potential mechanism of action for this drug and suggesting new screening platforms for anti-filarial drug development.

Outcomes Assessment of Treating Completely Edentulous Patients with a Fixed Implant-Supported Profile Prosthesis Utilizing a Graftless Approach. Part 1: Clinically Related Outcomes.

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Alzoubi, Fawaz; Bedrossian, Edmond; Wong, Allen; Farrell, Douglas; Park, Chan; Indresano, Thomas

To assess outcomes of treating completely edentulous patients with a fixed implant-supported profile prosthesis utilizing a graftless approach for the maxilla and for the mandible, with emphasis on clinically related outcomes, specifically implant and prosthesis survival. This was a retrospective study with the following inclusion criteria: completely edentulous patients rehabilitated with a fixed implant-supported profile denture utilizing a graftless approach. Patients fulfilling the inclusion criteria were asked to participate in the study during their follow-up visits, and hence a consecutive sampling strategy was used. Data regarding implant and prosthesis cumulative survival rates (CSRs) were gathered and calculated. Thirty-four patients were identified with a total of 220 implants placed. An overall CSR of 98.2% was recorded with an observation of up to 10 years. For tilted, axial, and zygomatic implants, CSRs of 96.9%, 98.0%, and 100%, respectively, were observed for up to 10 years. For provisional prostheses, CSRs of 92.3% at 1 year, and 84.6% at 2 years were observed. For final prostheses, a CSR of 93.8% was observed at 10 years. The results suggest that treating completely edentulous patients with a fixed profile prosthesis utilizing a graftless approach in the maxilla and the mandible can be a reliable treatment option.

Existence of Inverted Profile in Chemically Responsive Molecular Pathways in the Zebrafish Liver

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Zhang, Xun; Li, Hu; Ma, Jing; Zhang, Louxin; Li, Baowen; Gong, Zhiyuan

2011-01-01

How a living organism maintains its healthy equilibrium in response to endless exposure of potentially harmful chemicals is an important question in current biology. By transcriptomic analysis of zebrafish livers treated by various chemicals, we defined hubs as molecular pathways that are frequently perturbed by chemicals and have high degree of functional connectivity to other pathways. Our network analysis revealed that these hubs were organized into two groups showing inverted functionality with each other. Intriguingly, the inverted activity profiles in these two groups of hubs were observed to associate only with toxicopathological states but not with physiological changes. Furthermore, these inverted profiles were also present in rat, mouse, and human under certain toxicopathological conditions. Thus, toxicopathological-associated anti-correlated profiles in hubs not only indicate their potential use in diagnosis but also development of systems-based therapeutics to modulate gene expression by chemical approach in order to rewire the deregulated activities of hubs back to normal physiology. PMID:22140468

Glycomic Analysis of Life Stages of the Human Parasite Schistosoma mansoni Reveals Developmental Expression Profiles of Functional and Antigenic Glycan Motifs.

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Smit, Cornelis H; van Diepen, Angela; Nguyen, D Linh; Wuhrer, Manfred; Hoffmann, Karl F; Deelder, André M; Hokke, Cornelis H

2015-07-01

Glycans present on glycoproteins and glycolipids of the major human parasite Schistosoma mansoni induce innate as well as adaptive immune responses in the host. To be able to study the molecular characteristics of schistosome infections it is therefore required to determine the expression profiles of glycans and antigenic glycan-motifs during a range of critical stages of the complex schistosome lifecycle. We performed a longitudinal profiling study covering schistosome glycosylation throughout worm- and egg-development using a mass spectrometry-based glycomics approach. Our study revealed that during worm development N-glycans with Galβ1-4(Fucα1-3)GlcNAc (LeX) and core-xylose motifs were rapidly lost after cercariae to schistosomula transformation, whereas GalNAcβ1-4GlcNAc (LDN)-motifs gradually became abundant and predominated in adult worms. LeX-motifs were present on glycolipids up to 2 weeks of schistosomula development, whereas glycolipids with mono- and multifucosylated LDN-motifs remained present up to the adult worm stage. In contrast, expression of complex O-glycans diminished to undetectable levels within days after transformation. During egg development, a rich diversity of N-glycans with fucosylated motifs was expressed, but with α3-core fucose and a high degree of multifucosylated antennae only in mature eggs and miracidia. N-glycan antennae were exclusively LDN-based in miracidia. O-glycans in the mature eggs were also diverse and contained LeX- and multifucosylated LDN, but none of these were associated with miracidia in which we detected only the Galβ1-3(Galβ1-6)GalNAc core glycan. Immature eggs also exhibited short O-glycan core structures only, suggesting that complex fucosylated O-glycans of schistosome eggs are derived primarily from glycoproteins produced by the subshell envelope in the developed egg. Lipid glycans with multifucosylated GlcNAc repeats were present throughout egg development, but with the longer highly fucosylated

Comprehensive evaluation of genome-wide 5-hydroxymethylcytosine profiling approaches in human DNA.

Science.gov (United States)

Skvortsova, Ksenia; Zotenko, Elena; Luu, Phuc-Loi; Gould, Cathryn M; Nair, Shalima S; Clark, Susan J; Stirzaker, Clare

2017-01-01

The discovery that 5-methylcytosine (5mC) can be oxidized to 5-hydroxymethylcytosine (5hmC) by the ten-eleven translocation (TET) proteins has prompted wide interest in the potential role of 5hmC in reshaping the mammalian DNA methylation landscape. The gold-standard bisulphite conversion technologies to study DNA methylation do not distinguish between 5mC and 5hmC. However, new approaches to mapping 5hmC genome-wide have advanced rapidly, although it is unclear how the different methods compare in accurately calling 5hmC. In this study, we provide a comparative analysis on brain DNA using three 5hmC genome-wide approaches, namely whole-genome bisulphite/oxidative bisulphite sequencing (WG Bis/OxBis-seq), Infinium HumanMethylation450 BeadChip arrays coupled with oxidative bisulphite (HM450K Bis/OxBis) and antibody-based immunoprecipitation and sequencing of hydroxymethylated DNA (hMeDIP-seq). We also perform loci-specific TET-assisted bisulphite sequencing (TAB-seq) for validation of candidate regions. We show that whole-genome single-base resolution approaches are advantaged in providing precise 5hmC values but require high sequencing depth to accurately measure 5hmC, as this modification is commonly in low abundance in mammalian cells. HM450K arrays coupled with oxidative bisulphite provide a cost-effective representation of 5hmC distribution, at CpG sites with 5hmC levels >~10%. However, 5hmC analysis is restricted to the genomic location of the probes, which is an important consideration as 5hmC modification is commonly enriched at enhancer elements. Finally, we show that the widely used hMeDIP-seq method provides an efficient genome-wide profile of 5hmC and shows high correlation with WG Bis/OxBis-seq 5hmC distribution in brain DNA. However, in cell line DNA with low levels of 5hmC, hMeDIP-seq-enriched regions are not detected by WG Bis/OxBis or HM450K, either suggesting misinterpretation of 5hmC calls by hMeDIP or lack of sensitivity of the latter methods. We

Do dental hygiene students fit the learning profile of the millennial student?

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Blue, Christine M

2009-12-01

Differences in learning and the cultural context of our students' life experiences are important variables that faculty members need to understand in order to be effective in the classroom. Faculty members are finding that millennial students' approaches to learning are often vastly different from their own and as a result feel frustrated in their ability to help these students with their learning needs. Cultivating awareness of how today's dental hygiene student learns as well as the millennial learner profile can help faculty members address this educational challenge. The purpose of this study was to identify the learning styles of three groups of dental hygiene students and determine if they fit the learning profile of the millennial student as measured by the Learning Type Measure. Given this new generation of learners, it was hypothesized that dental hygiene students' learning style preferences would fit the learning profile of the millennial student. The Learning Type Measure was administered to 101 dental hygiene students at the University of Minnesota, University of Arizona, and Virginia Commonwealth University. The results from the study revealed that dental hygiene students do exhibit learning style preferences consistent with the millennial learner profile.

Peptide profiling of bovine kefir reveals 236 unique peptides released from caseins during its production by starter culture or kefir grains.

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Ebner, Jennifer; Aşçı Arslan, Ayşe; Fedorova, Maria; Hoffmann, Ralf; Küçükçetin, Ahmet; Pischetsrieder, Monika

2015-03-18

composition of the peptide profile can be controlled by the applied microflora (grains or starter culture). On the other hand, a considerable portion of the peptide profile was identified to be typical for kefir in general and independent from production parameters. In summary, the generated kefir peptide profile helped to reveal its origin and to identify bioactive peptides in kefir, which may advance the understanding of health benefits of this food product. The results further indicate that subsets of the kefir peptide list can be used as markers to control food authenticity, for example, to distinguish different types of kefir. Copyright © 2015 Elsevier B.V. All rights reserved.

Substrate channel in nitrogenase revealed by a molecular dynamics approach.

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

2014-04-15

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

Metabolomic Profiling as a Possible Reverse Engineering Tool for Estimating Processing Conditions of Dry-Cured Hams.

Science.gov (United States)

Sugimoto, Masahiro; Obiya, Shinichi; Kaneko, Miku; Enomoto, Ayame; Honma, Mayu; Wakayama, Masataka; Soga, Tomoyoshi; Tomita, Masaru

2017-01-18

Dry-cured hams are popular among consumers. To increase the attractiveness of the product, objective analytical methods and algorithms to evaluate the relationship between observable properties and consumer acceptability are required. In this study, metabolomics, which is used for quantitative profiling of hundreds of small molecules, was applied to 12 kinds of dry-cured hams from Japan and Europe. In total, 203 charged metabolites, including amino acids, organic acids, nucleotides, and peptides, were successfully identified and quantified. Metabolite profiles were compared for the samples with different countries of origin and processing methods (e.g., smoking or use of a starter culture). Principal component analysis of the metabolite profiles with sensory properties revealed significant correlations for redness, homogeneity, and fat whiteness. This approach could be used to design new ham products by objective evaluation of various features.

Environmental Pollution, Toxicity Profile and Treatment Approaches for Tannery Wastewater and Its Chemical Pollutants.

Science.gov (United States)

Saxena, Gaurav; Chandra, Ram; Bharagava, Ram Naresh

Leather industries are key contributors in the economy of many developing countries, but unfortunately they are facing serious challenges from the public and governments due to the associated environmental pollution. There is a public outcry against the industry due to the discharge of potentially toxic wastewater having alkaline pH, dark brown colour, unpleasant odour, high biological and chemical oxygen demand, total dissolved solids and a mixture of organic and inorganic pollutants. Various environment protection agencies have prioritized several chemicals as hazardous and restricted their use in leather processing however; many of these chemicals are used and discharged in wastewater. Therefore, it is imperative to adequately treat/detoxify the tannery wastewater for environmental safety. This paper provides a detail review on the environmental pollution and toxicity profile of tannery wastewater and chemicals. Furthermore, the status and advances in the existing treatment approaches used for the treatment and/or detoxification of tannery wastewater at both laboratory and pilot/industrial scale have been reviewed. In addition, the emerging treatment approaches alone or in combination with biological treatment approaches have also been considered. Moreover, the limitations of existing and emerging treatment approaches have been summarized and potential areas for further investigations have been discussed. In addition, the clean technologies for waste minimization, control and management are also discussed. Finally, the international legislation scenario on discharge limits for tannery wastewater and chemicals has also been discussed country wise with discharge standards for pollution prevention due to tannery wastewater.

Household electricity demand profiles

DEFF Research Database (Denmark)

Marszal, Anna Joanna; Heiselberg, Per Kvols; Larsen, Olena Kalyanova

2016-01-01

Highlights •A 1-min resolution household electricity load model is presented. •Model adapts a bottom-up approach with single appliance as the main building block. •Load profiles are used to analyse the flexibility potential of household appliances. •Load profiles can be applied in other domains, .......g. building energy simulations. •The demand level of houses with different number of occupants is well captured....

Construction of Multi-Year Time-Series Profiles of Suspended Particulate Inorganic Matter Concentrations Using Machine Learning Approach

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Pannimpullath R. Renosh

2017-12-01

Full Text Available Hydro-sedimentary numerical models have been widely employed to derive suspended particulate matter (SPM concentrations in coastal and estuarine waters. These hydro-sedimentary models are computationally and technically expensive in nature. Here we have used a computationally less-expensive, well-established methodology of self-organizing maps (SOMs along with a hidden Markov model (HMM to derive profiles of suspended particulate inorganic matter (SPIM. The concept of the proposed work is to benefit from all available data sets through the use of fusion methods and machine learning approaches that are able to process a growing amount of available data. This approach is applied to two different data sets entitled “Hidden” and “Observable”. The hidden data are composed of 15 months (27 September 2007 to 30 December 2008 of hourly SPIM profiles extracted from the Regional Ocean Modeling System (ROMS. The observable data include forcing parameter variables such as significant wave heights ( H s and H s 50 (50 days from the Wavewatch 3-HOMERE database and barotropic currents ( U b a r and V b a r from the Iberian–Biscay–Irish (IBI reanalysis data. These observable data integrate hourly surface samples from 1 February 2002 to 31 December 2012. The time-series profiles of the SPIM have been derived from four different stations in the English Channel by considering 15 months of output hidden data from the ROMS as a statistical representation of the ocean for ≈11 years. The derived SPIM profiles clearly show seasonal and tidal fluctuations in accordance with the parent numerical model output. The surface SPIM concentrations of the derived model have been validated with satellite remote sensing data. The time series of the modeled SPIM and satellite-derived SPIM show similar seasonal fluctuations. The ranges of concentrations for the four stations are also in good agreement with the corresponding satellite data. The high accuracy of the

Expanded metabolomics approach to profiling endogenous carbohydrates in the serum of ovarian cancer patients.

Science.gov (United States)

Cheng, Yu; Li, Li; Zhu, Bangjie; Liu, Feng; Wang, Yan; Gu, Xue; Yan, Chao

2016-01-01

We applied hydrophilic interaction liquid chromatography coupled with tandem mass spectrometry to the quantitative analysis of serum from 58 women, including ovarian cancer patients, ovarian benign tumor patients, and healthy controls. All of these ovarian cancer and ovarian benign tumor patients have elevated cancer antigen 125, which makes them clinically difficult to differentiate the malignant from the benign. All of the 16 endogenous carbohydrates were quantitatively detected in the human sera, of which, eight endogenous carbohydrates were significantly different (P-value carbohydrates in the expanded metabolomics approach after the global metabolic profiling are characterized and are potential biomarkers for the early diagnosis of ovarian cancer. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Gene Expression Profiles in Paired Gingival Biopsies from Periodontitis-Affected and Healthy Tissues Revealed by Massively Parallel Sequencing

Science.gov (United States)

Båge, Tove; Lagervall, Maria; Jansson, Leif; Lundeberg, Joakim; Yucel-Lindberg, Tülay

2012-01-01

Periodontitis is a chronic inflammatory disease affecting the soft tissue and bone that surrounds the teeth. Despite extensive research, distinctive genes responsible for the disease have not been identified. The objective of this study was to elucidate transcriptome changes in periodontitis, by investigating gene expression profiles in gingival tissue obtained from periodontitis-affected and healthy gingiva from the same patient, using RNA-sequencing. Gingival biopsies were obtained from a disease-affected and a healthy site from each of 10 individuals diagnosed with periodontitis. Enrichment analysis performed among uniquely expressed genes for the periodontitis-affected and healthy tissues revealed several regulated pathways indicative of inflammation for the periodontitis-affected condition. Hierarchical clustering of the sequenced biopsies demonstrated clustering according to the degree of inflammation, as observed histologically in the biopsies, rather than clustering at the individual level. Among the top 50 upregulated genes in periodontitis-affected tissues, we investigated two genes which have not previously been demonstrated to be involved in periodontitis. These included interferon regulatory factor 4 and chemokine (C-C motif) ligand 18, which were also expressed at the protein level in gingival biopsies from patients with periodontitis. In conclusion, this study provides a first step towards a quantitative comprehensive insight into the transcriptome changes in periodontitis. We demonstrate for the first time site-specific local variation in gene expression profiles of periodontitis-affected and healthy tissues obtained from patients with periodontitis, using RNA-seq. Further, we have identified novel genes expressed in periodontitis tissues, which may constitute potential therapeutic targets for future treatment strategies of periodontitis. PMID:23029519

An analytical approach to characterize morbidity profile dissimilarity between distinct cohorts using electronic medical records.

Science.gov (United States)

Schildcrout, Jonathan S; Basford, Melissa A; Pulley, Jill M; Masys, Daniel R; Roden, Dan M; Wang, Deede; Chute, Christopher G; Kullo, Iftikhar J; Carrell, David; Peissig, Peggy; Kho, Abel; Denny, Joshua C

2010-12-01

We describe a two-stage analytical approach for characterizing morbidity profile dissimilarity among patient cohorts using electronic medical records. We capture morbidities using the International Statistical Classification of Diseases and Related Health Problems (ICD-9) codes. In the first stage of the approach separate logistic regression analyses for ICD-9 sections (e.g., "hypertensive disease" or "appendicitis") are conducted, and the odds ratios that describe adjusted differences in prevalence between two cohorts are displayed graphically. In the second stage, the results from ICD-9 section analyses are combined into a general morbidity dissimilarity index (MDI). For illustration, we examine nine cohorts of patients representing six phenotypes (or controls) derived from five institutions, each a participant in the electronic MEdical REcords and GEnomics (eMERGE) network. The phenotypes studied include type II diabetes and type II diabetes controls, peripheral arterial disease and peripheral arterial disease controls, normal cardiac conduction as measured by electrocardiography, and senile cataracts. Copyright © 2010 Elsevier Inc. All rights reserved.

From the profile of position to the profile of competences in human talent management

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Marianela Bermejo-Salmon

2017-12-01

Full Text Available The objective of this study was the application of a methodology for the making of a position profile by competences with a holistic approach from the position of school director or engineering career of enterprises of the Faculty of Enterprises Administration in the Higher Polytechnical School of Chimborazo of Ecuador. Theoretical and empirical methods were used such as: Dialectical and Historical Materialism as a method that allows to establish the didactic logic in treating processes, the Delphi method and the holistic and integrated approach and techniques used were: group work, direct observation, functional analysis, psychological tests and interviews. As result, the application of this methodology to integrate the position profile and profile of labor competences as a unique system and insert them to other contexts outside the Cuban frontier from its adequacy to the particularities that characterize the negotiation of the human talent in the selected place.

Urinary proteomic profiling reveals diclofenac-induced renal injury and hepatic regeneration in mice

Energy Technology Data Exchange (ETDEWEB)

Swelm, Rachel P.L. van [Department of Pharmacology and Toxicology, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen (Netherlands); Laarakkers, Coby M.M. [Department of Laboratory Medicine, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen (Netherlands); Pertijs, Jeanne C.L.M.; Verweij, Vivienne; Masereeuw, Rosalinde [Department of Pharmacology and Toxicology, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen (Netherlands); Russel, Frans G.M., E-mail: F.Russel@pharmtox.umcn.nl [Department of Pharmacology and Toxicology, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen (Netherlands)

2013-06-01

Diclofenac (DF) is a widely used non-steroidal anti-inflammatory drug for the treatment of rheumatic disorders, but is often associated with liver injury. We applied urinary proteomic profiling using MALDI-TOF MS to identify biomarkers for DF-induced hepatotoxicity in mice. Female CH3/HeOUJIco mice were treated with 75 mg/kg bw DF by oral gavage and 24 h urine was collected. Proteins identified in urine of DF-treated mice included epidermal growth factor, transthyretin, kallikrein, clusterin, fatty acid binding protein 1 and urokinase, which are related to liver regeneration but also to kidney injury. Both organs showed enhanced levels of oxidative stress (TBARS, p < 0.01). Kidney injury was confirmed by histology and increased Kim1 and Il-6 mRNA expression levels (p < 0.001 and p < 0.01). Liver histology and plasma ALT levels in DF-treated mice were not different from control, but mRNA expression of Stat3 (p < 0.001) and protein expression of PCNA (p < 0.05) were increased, indicating liver regeneration. In conclusion, urinary proteome analysis revealed that DF treatment in mice induced kidney and liver injury. Within 24 h, however, the liver was able to recover by activating tissue regeneration processes. Hence, the proteins found in urine of DF-treated mice represent kidney damage rather than hepatic injury. - Highlights: • The urinary proteome shows biological processes involved in adverse drug reactions. • Urine proteins of DF-treated mice relate to kidney injury rather than liver injury. • Liver regeneration, not liver injury, is apparent 24h after oral DF administration. • Pretreatment with LPS does not enhance DF-induced liver injury in mice.

Energy Profiles of an Agricultural Frontier: The American Great Plains, 1860-2000.

Science.gov (United States)

Cunfer, Geoff; Watson, Andrew; MacFadyen, Joshua

2018-04-01

Agro-ecosystem energy profiles reveal energy flows into, within, and out of U.S. Great Plains farm communities across 140 years. This study evaluates external energy inputs such as human labor, machinery, fuel, and fertilizers. It tracks the energy content of land produce, including crops, grazed pasture, and firewood, and also accounts unharvested energy that remains available for wildlife. It estimates energy redirected through livestock feed into draft power, meat, and milk, and estimates the energy content of final produce available for local consumption or market sale. The article presents energy profiles for three case studies in Kansas in 1880, 1930, 1954, and 1997. Two energy transformations occurred during that time. The first, agricultural colonization , saw farm communities remake the landscape, turning native grassland into a mosaic of cropland and pasture, a process that reduced overall landscape energy productivity. A second energy transition occurred in the mid-twentieth century, characterized by fossil fuel energy imports. That outside energy raised harvested and unharvested energy flows, reused biomass energy, and also final produce. This socio-ecological transition increased landscape energy productivity by 33 to 45 percent above pre-settlement conditions in grain-growing regions. These energy developments were not uniform across the plains. Variations in rainfall and soil quality constrained or favored energy productivity in different places. The case studies reveal the spatial variation of energy profiles in Great Plains agro-ecosystems, while the longitudinal approach tracks temporal change.

Gene expression profiling reveals multiple toxicity endpoints induced by hepatotoxicants

Energy Technology Data Exchange (ETDEWEB)

Huang Qihong; Jin Xidong; Gaillard, Elias T.; Knight, Brian L.; Pack, Franklin D.; Stoltz, James H.; Jayadev, Supriya; Blanchard, Kerry T

2004-05-18

Microarray technology continues to gain increased acceptance in the drug development process, particularly at the stage of toxicology and safety assessment. In the current study, microarrays were used to investigate gene expression changes associated with hepatotoxicity, the most commonly reported clinical liability with pharmaceutical agents. Acetaminophen, methotrexate, methapyrilene, furan and phenytoin were used as benchmark compounds capable of inducing specific but different types of hepatotoxicity. The goal of the work was to define gene expression profiles capable of distinguishing the different subtypes of hepatotoxicity. Sprague-Dawley rats were orally dosed with acetaminophen (single dose, 4500 mg/kg for 6, 24 and 72 h), methotrexate (1 mg/kg per day for 1, 7 and 14 days), methapyrilene (100 mg/kg per day for 3 and 7 days), furan (40 mg/kg per day for 1, 3, 7 and 14 days) or phenytoin (300 mg/kg per day for 14 days). Hepatic gene expression was assessed using toxicology-specific gene arrays containing 684 target genes or expressed sequence tags (ESTs). Principal component analysis (PCA) of gene expression data was able to provide a clear distinction of each compound, suggesting that gene expression data can be used to discern different hepatotoxic agents and toxicity endpoints. Gene expression data were applied to the multiplicity-adjusted permutation test and significantly changed genes were categorized and correlated to hepatotoxic endpoints. Repression of enzymes involved in lipid oxidation (acyl-CoA dehydrogenase, medium chain, enoyl CoA hydratase, very long-chain acyl-CoA synthetase) were associated with microvesicular lipidosis. Likewise, subsets of genes associated with hepatotocellular necrosis, inflammation, hepatitis, bile duct hyperplasia and fibrosis have been identified. The current study illustrates that expression profiling can be used to: (1) distinguish different hepatotoxic endpoints; (2) predict the development of toxic endpoints; and

Comparative mRNA and microRNA expression profiling of three genitourinary cancers reveals common hallmarks and cancer-specific molecular events.

Directory of Open Access Journals (Sweden)

Xianxin Li

Full Text Available Genome-wide gene expression profile using deep sequencing technologies can drive the discovery of cancer biomarkers and therapeutic targets. Such efforts are often limited to profiling the expression signature of either mRNA or microRNA (miRNA in a single type of cancer.Here we provided an integrated analysis of the genome-wide mRNA and miRNA expression profiles of three different genitourinary cancers: carcinomas of the bladder, kidney and testis.Our results highlight the general or cancer-specific roles of several genes and miRNAs that may serve as candidate oncogenes or suppressors of tumor development. Further comparative analyses at the systems level revealed that significant aberrations of the cell adhesion process, p53 signaling, calcium signaling, the ECM-receptor and cell cycle pathways, the DNA repair and replication processes and the immune and inflammatory response processes were the common hallmarks of human cancers. Gene sets showing testicular cancer-specific deregulation patterns were mainly implicated in processes related to male reproductive function, and general disruptions of multiple metabolic pathways and processes related to cell migration were the characteristic molecular events for renal and bladder cancer, respectively. Furthermore, we also demonstrated that tumors with the same histological origins and genes with similar functions tended to group together in a clustering analysis. By assessing the correlation between the expression of each miRNA and its targets, we determined that deregulation of 'key' miRNAs may result in the global aberration of one or more pathways or processes as a whole.This systematic analysis deciphered the molecular phenotypes of three genitourinary cancers and investigated their variations at the miRNA level simultaneously. Our results provided a valuable source for future studies and highlighted some promising genes, miRNAs, pathways and processes that may be useful for diagnostic or

Gender Profiles of Workplace Individual and Organizational Deviance

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Lily Chernyak-Hai

2018-03-01

Full Text Available Employees’ workplace deviant behaviors have a harmful potential for organizations in many respects. Past research has indicated that individual variables may account for personal differences in work deviance. One of the prevalent findings is that men display direct aggression more frequently than women. Yet, most of the past studies have reported results providing information on the magnitude of a general behavioral tendency of each gender, leading to rough distinctions. Unlike the previous studies, we focused on examining profiles of the role of gender in interpersonal and organizational deviance, utilizing Profile Analysis via Multidimensional Scaling that allowed us to compare specific deviance behavior indicators between males and females included in the profiles. The current exploratory study reveals that gender differences in aggressive workplace behavior are not only those apparent in inter-personal relations but also when directed towards the organization. Moreover, the reported results point to specific behavioral profiles of men and women that could not be revealed using the mean difference analyses.

Automatic identification approach for high-performance liquid chromatography-multiple reaction monitoring fatty acid global profiling.

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Tie, Cai; Hu, Ting; Jia, Zhi-Xin; Zhang, Jin-Lan

2015-08-18

Fatty acids (FAs) are a group of lipid molecules that are essential to organisms. As potential biomarkers for different diseases, FAs have attracted increasing attention from both biological researchers and the pharmaceutical industry. A sensitive and accurate method for globally profiling and identifying FAs is required for biomarker discovery. The high selectivity and sensitivity of high-performance liquid chromatography-multiple reaction monitoring (HPLC-MRM) gives it great potential to fulfill the need to identify FAs from complicated matrices. This paper developed a new approach for global FA profiling and identification for HPLC-MRM FA data mining. Mathematical models for identifying FAs were simulated using the isotope-induced retention time (RT) shift (IRS) and peak area ratios between parallel isotope peaks for a series of FA standards. The FA structures were predicated using another model based on the RT and molecular weight. Fully automated FA identification software was coded using the Qt platform based on these mathematical models. Different samples were used to verify the software. A high identification efficiency (greater than 75%) was observed when 96 FA species were identified in plasma. This FAs identification strategy promises to accelerate FA research and applications.

Criticality: static profiling for real-time programs

DEFF Research Database (Denmark)

Brandner, Florian; Hepp, Stefan; Jordan, Alexander

2014-01-01

With the increasing performance demand in real-time systems it becomes more and more important to provide feedback to programmers and software development tools on the performance-relevant code parts of a real-time program. So far, this information was limited to an estimation of the worst....... Experiments using well-established real-time benchmark programs show an interesting distribution of the criticality values, revealing considerable amounts of highly critical as well as uncritical code. The metric thus provides ideal information to programmers and software development tools to optimize...... view covering the entire code base, tools in the spirit of program profiling are required. This work proposes an efficient approach to compute worst-case timing information for all code parts of a program using a complementary metric, called criticality. Every statement of a program is assigned...

Microarray glycan profiling reveals algal fucoidan epitopes in diverse marine metazoans

DEFF Research Database (Denmark)

Asunción Salmeán, Armando; Hervé, Cécile; Jørgensen, Bodil

2017-01-01

Despite the biological importance and pharmacological potential of glycans from marine organisms, there are many unanswered questions regarding their distribution, function, and evolution. Here we describe microarray-based glycan profiling of a diverse selection of marine animals using antibodies...... raised against fucoidan isolated from a brown alga. We demonstrate the presence of two fucoidan epitopes in six animals belonging to three phyla including Porifera, Molusca, and Chordata. We studied the spatial distribution of these epitopes in Cliona celata ("boring sponge") and identified...

Circular RNA expression profiling of human granulosa cells during maternal aging reveals novel transcripts associated with assisted reproductive technology outcomes.

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Jing Cheng

Full Text Available Circular RNAs (circRNAs are a unique class of endogenous RNAs which could be used as potential diagnostic and prognostic biomarkers of many diseases. Our study aimed to investigate circRNA profiles in human granulosa cells (GCs during maternal aging and to uncover age-related circRNA variations that potentially reflect decreased oocyte competence. CircRNAs in GCs from in vitro fertilization (IVF patients with young age (YA, ≤ 30 years and advanced age (AA, ≥ 38 years were profiled by microarray, and validated in 20 paired samples. The correlation between circRNAs expression and clinical characteristics was analyzed in additional 80 samples. Chip-based analysis revealed 46 up-regulated and 11 down-regulated circRNAs in AA samples (fold change > 2.0. Specifically, circRNA_103829, circRNA_103827 and circRNA_104816 were validated to be up-regulated, while circRNA_101889 was down-regulated in AA samples. After adjustment for gonadotropin treatment, only circRNA_103827 and circRNA_104816 levels were positively associated with maternal age (partial r = 0.332, P = 0.045; partial r = 0.473, P = 0.003; respectively. Moreover, circRNA_103827 and circRNA_104816 expressions in GCs were negatively correlated with the number of top quality embryos (r = -0.235, P = 0.036; r = -0.221, P = 0.049; respectively. Receiver operating characteristic (ROC curve analysis indicated that the performance of circRNA_103827 for live birth prediction reached 0.698 [0.570-0.825], with 77.2% sensitivity and 60.9% specificity (P = 0.006, and that of circRNA_104816 was 0.645 [0.507-0.783] (P = 0.043. Bioinformatics analysis revealed that both circRNAs were potentially involved in glucose metabolism, mitotic cell cycle, and ovarian steroidogenesis. Therefore, age-related up-regulation of circRNA_103827 and circRNA_104816 might be potential indicators of compromised follicular micro-environment which could be used to predict IVF prognosis, and improve female infertility

Peptidomic and transcriptomic profiling of four distinct spider venoms.

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Vera Oldrati

Full Text Available Venom based research is exploited to find novel candidates for the development of innovative pharmacological tools, drug candidates and new ingredients for cosmetic and agrochemical industries. Moreover, venomics, as a well-established approach in systems biology, helps to elucidate the genetic mechanisms of the production of such a great molecular biodiversity. Today the advances made in the proteomics, transcriptomics and bioinformatics fields, favor venomics, allowing the in depth study of complex matrices and the elucidation even of minor compounds present in minute biological samples. The present study illustrates a rapid and efficient method developed for the elucidation of venom composition based on NextGen mRNA sequencing of venom glands and LC-MS/MS venom proteome profiling. The analysis of the comprehensive data obtained was focused on cysteine rich peptide toxins from four spider species originating from phylogenetically distant families for comparison purposes. The studied species were Heteropoda davidbowie (Sparassidae, Poecilotheria formosa (Theraphosidae, Viridasius fasciatus (Viridasiidae and Latrodectus mactans (Theridiidae. This led to a high resolution profiling of 284 characterized cysteine rich peptides, 111 of which belong to the Inhibitor Cysteine Knot (ICK structural motif. The analysis of H. davidbowie venom revealed a high richness in term of venom diversity: 95 peptide sequences were identified; out of these, 32 peptides presented the ICK structural motif and could be classified in six distinct families. The profiling of P. formosa venom highlighted the presence of 126 peptide sequences, with 52 ICK toxins belonging to three structural distinct families. V. fasciatus venom was shown to contain 49 peptide sequences, out of which 22 presented the ICK structural motif and were attributed to five families. The venom of L. mactans, until now studied for its large neurotoxins (Latrotoxins, revealed the presence of 14

Barcode DNA length polymorphisms vs fatty acid profiling for adulteration detection in olive oil.

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Uncu, Ali Tevfik; Uncu, Ayse Ozgur; Frary, Anne; Doganlar, Sami

2017-04-15

The aim of this study was to compare the performance of a DNA-barcode assay with fatty acid profile analysis to authenticate the botanical origin of olive oil. To achieve this aim, we performed a PCR-capillary electrophoresis (PCR-CE) approach on olive oil: seed oil blends using the plastid trnL (UAA) intron barcode. In parallel to genomic analysis, we subjected the samples to gas chromatography analysis of fatty acid composition. While the PCR-CE assay proved equally efficient as gas chromatography analysis in detecting adulteration with soybean, palm, rapeseed, sunflower, sesame, cottonseed and peanut oils, it was superior to the widely utilized analytical chemistry approach in revealing the adulterant species and detecting small quantities of corn and safflower oils in olive oil. Moreover, the DNA-based test correctly identified all tested olive oil: hazelnut oil blends whereas it was not feasible to detect hazelnut oil adulteration through fatty acid profile analysis. Thus, the present research has shown the feasibility of a PCR-CE barcode assay to detect adulteration in olive oil. Copyright © 2016 Elsevier Ltd. All rights reserved.

Latent Profiles of Perceived Time Adequacy for Paid Work, Parenting, and Partner Roles

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Lee, Soomi; Almeida, David M.; Davis, Kelly D.; King, Rosalind B.; Hammer, Leslie B.; Kelly, Erin L.

2015-01-01

This study examined feelings of having enough time (i.e., perceived time adequacy) in a sample of employed parents (N=880) in information technology and extended-care industries. Adapting a person-centered latent profile approach, we identified three profiles of perceived time adequacy for paid work, parenting, and partner roles: Family Time Protected, Family Time Sacrificed, and Time Balanced. Drawing upon the Conservation of Resources theory (Hobfòll, 1989), we examined the associations of stressors and resources with the time adequacy profiles. Parents in the Family Time Sacrificed profile were more likely to be younger, women, have younger children, work in the extended-care industry, and have nonstandard work schedules compared to those in the Family Time Protected profile. Results from multinomial logistic regression analyses revealed that, with the Time Balanced profile as the reference group, having fewer stressors and more resources in the family context (less parent-child conflict and more partner support), work context (longer company tenure, higher schedule control and job satisfaction), and work-family interface (lower work-to-family conflict) was linked to a higher probability of membership in the Family Time Protected profile. By contrast, having more stressors and fewer resources, in the forms of less partner support and higher work-to-family conflict, predicted a higher likelihood of being in the Family Time Sacrificed profile. Our findings suggest that low work-to-family conflict is the most critical predictor of membership in the Family Time Protected profile, whereas lack of partner support is the most important factor to be included in the Family Time Sacrificed profile. PMID:26075739

Latent profiles of perceived time adequacy for paid work, parenting, and partner roles.

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Lee, Soomi; Almeida, David M; Davis, Kelly D; King, Rosalind B; Hammer, Leslie B; Kelly, Erin L

2015-10-01

This study examined feelings of having enough time (i.e., perceived time adequacy) in a sample of employed parents (N = 880) in information technology and extended-care industries. Adapting a person-centered latent profile approach, we identified 3 profiles of perceived time adequacy for paid work, parenting, and partner roles: family time protected, family time sacrificed, and time balanced. Drawing upon the conservation of resources theory (Hobfòll, 1989), we examined the associations of stressors and resources with the time adequacy profiles. Parents in the family time sacrificed profile were more likely to be younger, women, have younger children, work in the extended-care industry, and have nonstandard work schedules compared to those in the family time protected profile. Results from multinomial logistic regression analyses revealed that, with the time balanced profile as the reference group, having fewer stressors and more resources in the family context (less parent-child conflict and more partner support), work context (longer company tenure, higher schedule control and job satisfaction), and work-family interface (lower work-to-family conflict) was linked to a higher probability of membership in the family time protected profile. By contrast, having more stressors and fewer resources, in the forms of less partner support and higher work-to-family conflict, predicted a higher likelihood of being in the family time sacrificed profile. Our findings suggest that low work-to-family conflict is the most critical predictor of membership in the family time protected profile, whereas lack of partner support is the most important factor to be included in the family time sacrificed profile. (c) 2015 APA, all rights reserved).

Achievement goal profiles, trait-anxiety and state-emotion of young ...

African Journals Online (AJOL)

-emotion in competitive horse riding. The profile that was high in the approach orientations and low in the avoidant orientations emerged as the most emotionally robust profile. It was also the most competitively successful profile. The profiles ...

Educational games for brain health: revealing their unexplored potential through a neurocognitive approach

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Patrick eFissler

2015-07-01

Full Text Available Educational games link the motivational nature of games with learning of knowledge and skills. Here, we go beyond effects on these learning outcomes. We review two lines of evidence which indicate the currently unexplored potential of educational games to promote brain health: First, gaming with specific neurocognitive demands (e.g., executive control, and second, educational learning experiences (e.g., studying foreign languages improve brain health markers. These markers include cognitive ability, brain function, and brain structure. As educational games allow the combination of specific neurocognitive demands with educational learning experiences, they seem to be optimally suited for promoting brain health. We propose a neurocognitive approach to reveal this unexplored potential of educational games in future research.

EG-09EPIGENETIC PROFILING REVEALS A CpG HYPERMETHYLATION PHENOTYPE (CIMP) ASSOCIATED WITH WORSE PROGRESSION-FREE SURVIVAL IN MENINGIOMA

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Olar, Adriana; Wani, Khalida; Mansouri, Alireza; Zadeh, Gelareh; Wilson, Charmaine; DeMonte, Franco; Fuller, Gregory; Jones, David; Pfister, Stefan; von Deimling, Andreas; Sulman, Erik; Aldape, Kenneth

2014-01-01

BACKGROUND: Methylation profiling of solid tumors has revealed biologic subtypes, often with clinical implications. Methylation profiles of meningioma and their clinical implications are not well understood. METHODS: Ninety-two meningioma samples (n = 44 test set and n = 48 validation set) were profiled using the Illumina HumanMethylation450 BeadChip. Unsupervised clustering and analyses for recurrence-free survival (RFS) were performed. RESULTS: Unsupervised clustering of the test set using approximately 900 highly variable markers identified two clearly defined methylation subgroups. One of the groups (n = 19) showed global hypermethylation of a set of markers, analogous to CpG island methylator phenotype (CIMP). These findings were reproducible in the validation set, with 18/48 samples showing the CIMP-positive phenotype. Importantly, of 347 highly variable markers common to both the test and validation set analyses, 107 defined CIMP in the test set and 94 defined CIMP in the validation set, with an overlap of 83 markers between the two datasets. This number is much greater than expected by chance indicating reproducibly of the hypermethylated markers that define CIMP in meningioma. With respect to clinical correlation, the 37 CIMP-positive cases displayed significantly shorter RFS compared to the 55 non-CIMP cases (hazard ratio 2.9, p = 0.013). In an effort to develop a preliminary outcome predictor, a 155-marker subset correlated with RFS was identified in the test dataset. When interrogated in the validation dataset, this 155-marker subset showed a statistical trend (p < 0.1) towards distinguishing survival groups. CONCLUSIONS: This study defines the existence of a CIMP phenotype in meningioma, which involves a substantial proportion (37/92, 40%) of samples with clinical implications. Ongoing work will expand this cohort and examine identification of additional biologic differences (mutational and DNA copy number analysis) to further characterize the aberrant

Statistical modelling of transcript profiles of differentially regulated genes

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Sergeant Martin J

2008-07-01

Full Text Available Abstract Background The vast quantities of gene expression profiling data produced in microarray studies, and the more precise quantitative PCR, are often not statistically analysed to their full potential. Previous studies have summarised gene expression profiles using simple descriptive statistics, basic analysis of variance (ANOVA and the clustering of genes based on simple models fitted to their expression profiles over time. We report the novel application of statistical non-linear regression modelling techniques to describe the shapes of expression profiles for the fungus Agaricus bisporus, quantified by PCR, and for E. coli and Rattus norvegicus, using microarray technology. The use of parametric non-linear regression models provides a more precise description of expression profiles, reducing the "noise" of the raw data to produce a clear "signal" given by the fitted curve, and describing each profile with a small number of biologically interpretable parameters. This approach then allows the direct comparison and clustering of the shapes of response patterns between genes and potentially enables a greater exploration and interpretation of the biological processes driving gene expression. Results Quantitative reverse transcriptase PCR-derived time-course data of genes were modelled. "Split-line" or "broken-stick" regression identified the initial time of gene up-regulation, enabling the classification of genes into those with primary and secondary responses. Five-day profiles were modelled using the biologically-oriented, critical exponential curve, y(t = A + (B + CtRt + ε. This non-linear regression approach allowed the expression patterns for different genes to be compared in terms of curve shape, time of maximal transcript level and the decline and asymptotic response levels. Three distinct regulatory patterns were identified for the five genes studied. Applying the regression modelling approach to microarray-derived time course data

A Network Biology Approach to Discover the Molecular Biomarker Associated with Hepatocellular Carcinoma

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Liwei Zhuang

2014-01-01

Full Text Available In recent years, high throughput technologies such as microarray platform have provided a new avenue for hepatocellular carcinoma (HCC investigation. Traditionally, gene sets enrichment analysis of survival related genes is commonly used to reveal the underlying functional mechanisms. However, this approach usually produces too many candidate genes and cannot discover detailed signaling transduction cascades, which greatly limits their clinical application such as biomarker development. In this study, we have proposed a network biology approach to discover novel biomarkers from multidimensional omics data. This approach effectively combines clinical survival data with topological characteristics of human protein interaction networks and patients expression profiling data. It can produce novel network based biomarkers together with biological understanding of molecular mechanism. We have analyzed eighty HCC expression profiling arrays and identified that extracellular matrix and programmed cell death are the main themes related to HCC progression. Compared with traditional enrichment analysis, this approach can provide concrete and testable hypothesis on functional mechanism. Furthermore, the identified subnetworks can potentially be used as suitable targets for therapeutic intervention in HCC.

An Andean-type retro-arc foreland system beneath northwest South China revealed by SINOPROBE profiling

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Li, Jianhua; Dong, Shuwen; Cawood, Peter A.; Zhao, Guochun; Johnston, Stephen T.; Zhang, Yueqiao; Xin, Yujia

2018-05-01

In the Mesozoic, South China was situated along the convergent margin between the Asian and Pacific plates, providing an excellent laboratory to understand the interactions between deformation, sedimentation and magmatism in a retroarc environment. The crustal architecture of northwest South China is displayed along the ∼600-km-long SINOPROBE deep seismic reflection profiles and reveals from east to west: (1) highly folded and truncated reflectors in the upper crust of the Yangtze Fold Zone, which correspond to thin- and thick-skinned thrust systems, and document large-scale intraplate structural imbrication and shortening; (2) a crustal-scale flat-ramp-flat structure, termed the Main Yangtze decollement, which forms a weak, viscous layer to accommodate strain decoupling and material transport in the thin- and thick-skinned systems; and (3) nearly flat-lying reflectors in the Sichuan Basin, which support interpretation of the basin as a weakly deformed depocentre. The Yangtze Fold Zone and the Sichuan Basin represent a retro-arc foreland basin system that is >800 km away from the continental-margin magmatic arc. We suggest that tectonic processes across the arc and retro-arc systems, including arc magma flare-up, basin sedimentation, retroarc thrust propagation, lithosphere underthrusting, root foundering, and extension-related magmatism were interrelated and governed mass transfer. Age data and geological relations link the tectonic processes to evolving geodynamics of the subducting Paleo-Pacific plate.

Integrative analysis and expression profiling of secondary cell wall genes in C4 biofuel model Setaria italica reveals targets for lignocellulose bioengineering

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Mehanathan eMuthamilarasan

2015-11-01

Full Text Available Several underutilized grasses have excellent potential for use as bioenergy feedstock due to their lignocellulosic biomass. Genomic tools have enabled identification of lignocellulose biosynthesis genes in several sequenced plants. However, the non-availability of whole genome sequence of bioenergy grasses hinders the study on bioenergy genomics and their genomics-assisted crop improvement. Foxtail millet (Setaria italica L.; Si is a model crop for studying systems biology of bioenergy grasses. In the present study, a systematic approach has been used for identification of gene families involved in cellulose (CesA/Csl, callose (Gsl and monolignol biosynthesis (PAL, C4H, 4CL, HCT, C3H, CCoAOMT, F5H, COMT, CCR, CAD and construction of physical map of foxtail millet. Sequence alignment and phylogenetic analysis of identified proteins showed that monolignol biosynthesis proteins were highly diverse, whereas CesA/Csl and Gsl proteins were homologous to rice and Arabidopsis. Comparative mapping of foxtail millet lignocellulose biosynthesis genes with other C4 panicoid genomes revealed maximum homology with switchgrass, followed by sorghum and maize. Expression profiling of candidate lignocellulose genes in response to different abiotic stresses and hormone treatments showed their differential expression pattern, with significant higher expression of SiGsl12, SiPAL2, SiHCT1, SiF5H2 and SiCAD6 genes. Further, due to the evolutionary conservation of grass genomes, the insights gained from the present study could be extrapolated for identifying genes involved in lignocellulose biosynthesis in other biofuel species for further characterization.

Integrative analysis and expression profiling of secondary cell wall genes in C4 biofuel model Setaria italica reveals targets for lignocellulose bioengineering.

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Muthamilarasan, Mehanathan; Khan, Yusuf; Jaishankar, Jananee; Shweta, Shweta; Lata, Charu; Prasad, Manoj

2015-01-01

Several underutilized grasses have excellent potential for use as bioenergy feedstock due to their lignocellulosic biomass. Genomic tools have enabled identification of lignocellulose biosynthesis genes in several sequenced plants. However, the non-availability of whole genome sequence of bioenergy grasses hinders the study on bioenergy genomics and their genomics-assisted crop improvement. Foxtail millet (Setaria italica L.; Si) is a model crop for studying systems biology of bioenergy grasses. In the present study, a systematic approach has been used for identification of gene families involved in cellulose (CesA/Csl), callose (Gsl) and monolignol biosynthesis (PAL, C4H, 4CL, HCT, C3H, CCoAOMT, F5H, COMT, CCR, CAD) and construction of physical map of foxtail millet. Sequence alignment and phylogenetic analysis of identified proteins showed that monolignol biosynthesis proteins were highly diverse, whereas CesA/Csl and Gsl proteins were homologous to rice and Arabidopsis. Comparative mapping of foxtail millet lignocellulose biosynthesis genes with other C4 panicoid genomes revealed maximum homology with switchgrass, followed by sorghum and maize. Expression profiling of candidate lignocellulose genes in response to different abiotic stresses and hormone treatments showed their differential expression pattern, with significant higher expression of SiGsl12, SiPAL2, SiHCT1, SiF5H2, and SiCAD6 genes. Further, due to the evolutionary conservation of grass genomes, the insights gained from the present study could be extrapolated for identifying genes involved in lignocellulose biosynthesis in other biofuel species for further characterization.

Lateral energy band profile modulation in tunnel field effect transistors based on gate structure engineering

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Ning Cui

2012-06-01

Full Text Available Choosing novel materials and structures is important for enhancing the on-state current in tunnel field-effect transistors (TFETs. In this paper, we reveal that the on-state performance of TFETs is mainly determined by the energy band profile of the channel. According to this interpretation, we present a new concept of energy band profile modulation (BPM achieved with gate structure engineering. It is believed that this approach can be used to suppress the ambipolar effect. Based on this method, a Si TFET device with a symmetrical tri-material-gate (TMG structure is proposed. Two-dimensional numerical simulations demonstrated that the special band profile in this device can boost on-state performance, and it also suppresses the off-state current induced by the ambipolar effect. These unique advantages are maintained over a wide range of gate lengths and supply voltages. The BPM concept can serve as a guideline for improving the performance of nanoscale TFET devices.

Integrative structural modeling with small angle X-ray scattering profiles

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Schneidman-Duhovny Dina

2012-07-01

Full Text Available Abstract Recent technological advances enabled high-throughput collection of Small Angle X-ray Scattering (SAXS profiles of biological macromolecules. Thus, computational methods for integrating SAXS profiles into structural modeling are needed more than ever. Here, we review specifically the use of SAXS profiles for the structural modeling of proteins, nucleic acids, and their complexes. First, the approaches for computing theoretical SAXS profiles from structures are presented. Second, computational methods for predicting protein structures, dynamics of proteins in solution, and assembly structures are covered. Third, we discuss the use of SAXS profiles in integrative structure modeling approaches that depend simultaneously on several data types.

Safety profile of solid lipid nanoparticles loaded with rosmarinic acid for oral use: in vitro and animal approaches.

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Madureira, Ana Raquel; Nunes, Sara; Campos, Débora A; Fernandes, João C; Marques, Cláudia; Zuzarte, Monica; Gullón, Beatriz; Rodríguez-Alcalá, Luís M; Calhau, Conceição; Sarmento, Bruno; Gomes, Ana Maria; Pintado, Maria Manuela; Reis, Flávio

2016-01-01

Rosmarinic acid (RA) possesses several protective bioactivities that have attracted increasing interest by nutraceutical/pharmaceutical industries. Considering the reduced bioavailability after oral use, effective (and safe) delivery systems are crucial to protect RA from gastrointestinal degradation. This study aims to characterize the safety profile of solid lipid nanoparticles produced with Witepsol and Carnauba waxes and loaded with RA, using in vitro and in vivo approaches, focused on genotoxicity and cytotoxicity assays, redox status markers, hematological and biochemical profile, liver and kidney function, gut bacterial microbiota, and fecal fatty acids composition. Free RA and sage extract, empty nanoparticles, or nanoparticles loaded with RA or sage extract (0.15 and 1.5 mg/mL) were evaluated for cell (lymphocytes) viability, necrosis and apoptosis, and antioxidant/prooxidant effects upon DNA. Wistar rats were orally treated for 14 days with vehicle (control) and with Witepsol or Carnauba nanoparticles loaded with RA at 1 and 10 mg/kg body weight/d. Blood, urine, feces, and several tissues were collected for analysis. Free and loaded RA, at 0.15 mg/mL, presented a safe profile, while genotoxic potential was found for the higher dose (1.5 mg/mL), mainly by necrosis. Our data suggest that both types of nanoparticles are safe when loaded with moderate concentrations of RA, without in vitro genotoxicity and cytotoxicity and with an in vivo safety profile in rats orally treated, thus opening new avenues for use in nutraceutical applications.

Similarity between neonatal profile and socioeconomic index: a spatial approach

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d'Orsi Eleonora

2005-01-01

Full Text Available This study aims to compare neonatal characteristics and socioeconomic conditions in Rio de Janeiro city neighborhoods in order to identify priority areas for intervention. The study design was ecological. Two databases were used: the Brazilian Population Census and the Live Birth Information System, aggregated by neighborhoods. Spatial analysis, multivariate cluster classification, and Moran's I statistics for detection of spatial clustering were used. A similarity index was created to compare socioeconomic clusters with the neonatal profile in each neighborhood. The proportions of Apgar score above 8 and cesarean sections showed positive spatial correlation and high similarity with the socioeconomic index. The proportion of low birth weight infants showed a random spatial distribution, indicating that at this scale of analysis, birth weight is not sufficiently sensitive to discriminate subtler differences among population groups. The observed relationship between the neighborhoods' neonatal profile (particularly Apgar score and mode of delivery and socioeconomic conditions shows evidence of a change in infant health profile, where the possibility for intervention shifts to medical services and the Apgar score assumes growing significance as a risk indicator.

Dual Transcriptome Profiling of Leishmania-Infected Human Macrophages Reveals Distinct Reprogramming Signatures.

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Fernandes, Maria Cecilia; Dillon, Laura A L; Belew, Ashton Trey; Bravo, Hector Corrada; Mosser, David M; El-Sayed, Najib M

2016-05-10

Macrophages are mononuclear phagocytes that constitute a first line of defense against pathogens. While lethal to many microbes, they are the primary host cells of Leishmania spp. parasites, the obligate intracellular pathogens that cause leishmaniasis. We conducted transcriptomic profiling of two Leishmania species and the human macrophage over the course of intracellular infection by using high-throughput RNA sequencing to characterize the global gene expression changes and reprogramming events that underlie the interactions between the pathogen and its host. A systematic exclusion of the generic effects of large-particle phagocytosis revealed a vigorous, parasite-specific response of the human macrophage early in the infection that was greatly tempered at later time points. An analogous temporal expression pattern was observed with the parasite, suggesting that much of the reprogramming that occurs as parasites transform into intracellular forms generally stabilizes shortly after entry. Following that, the parasite establishes an intracellular niche within macrophages, with minimal communication between the parasite and the host cell later during the infection. No significant difference was observed between parasite species transcriptomes or in the transcriptional response of macrophages infected with each species. Our comparative analysis of gene expression changes that occur as mouse and human macrophages are infected by Leishmania spp. points toward a general signature of the Leishmania-macrophage infectome. Little is known about the transcriptional changes that occur within mammalian cells harboring intracellular pathogens. This study characterizes the gene expression signatures of Leishmania spp. parasites and the coordinated response of infected human macrophages as the pathogen enters and persists within them. After accounting for the generic effects of large-particle phagocytosis, we observed a parasite-specific response of the human macrophages early in

Transcriptional profiling reveals the expression of novel genes in response to various stimuli in the human dermatophyte Trichophyton rubrum

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Aquino-Ferreira Roseli

2010-02-01

Full Text Available Abstract Background Cutaneous mycoses are common human infections among healthy and immunocompromised hosts, and the anthropophilic fungus Trichophyton rubrum is the most prevalent microorganism isolated from such clinical cases worldwide. The aim of this study was to determine the transcriptional profile of T. rubrum exposed to various stimuli in order to obtain insights into the responses of this pathogen to different environmental challenges. Therefore, we generated an expressed sequence tag (EST collection by constructing one cDNA library and nine suppression subtractive hybridization libraries. Results The 1388 unigenes identified in this study were functionally classified based on the Munich Information Center for Protein Sequences (MIPS categories. The identified proteins were involved in transcriptional regulation, cellular defense and stress, protein degradation, signaling, transport, and secretion, among other functions. Analysis of these unigenes revealed 575 T. rubrum sequences that had not been previously deposited in public databases. Conclusion In this study, we identified novel T. rubrum genes that will be useful for ORF prediction in genome sequencing and facilitating functional genome analysis. Annotation of these expressed genes revealed metabolic adaptations of T. rubrum to carbon sources, ambient pH shifts, and various antifungal drugs used in medical practice. Furthermore, challenging T. rubrum with cytotoxic drugs and ambient pH shifts extended our understanding of the molecular events possibly involved in the infectious process and resistance to antifungal drugs.

Differential metabolic profiles associated to movement behaviour of stream-resident brown trout (Salmo trutta.

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Neus Oromi

Full Text Available The mechanisms that can contribute in the fish movement strategies and the associated behaviour can be complex and related to the physiology, genetic and ecology of each species. In the case of the brown trout (Salmo trutta, in recent research works, individual differences in mobility have been observed in a population living in a high mountain river reach (Pyrenees, NE Spain. The population is mostly sedentary but a small percentage of individuals exhibit a mobile behavior, mainly upstream movements. Metabolomics can reflect changes in the physiological process and can determine different profiles depending on behaviour. Here, a non-targeted metabolomics approach was used to find possible changes in the blood metabolomic profile of S. trutta related to its movement behaviour, using a minimally invasive sampling. Results showed a differentiation in the metabolomic profiles of the trouts and different level concentrations of some metabolites (e.g. cortisol according to the home range classification (pattern of movements: sedentary or mobile. The change in metabolomic profiles can generally occur during the upstream movement and probably reflects the changes in metabolite profile from the non-mobile season to mobile season. This study reveals the contribution of the metabolomic analyses to better understand the behaviour of organisms.

Differential metabolic profiles associated to movement behaviour of stream-resident brown trout (Salmo trutta).

Science.gov (United States)

Oromi, Neus; Jové, Mariona; Pascual-Pons, Mariona; Royo, Jose Luis; Rocaspana, Rafel; Aparicio, Enric; Pamplona, Reinald; Palau, Antoni; Sanuy, Delfi; Fibla, Joan; Portero-Otin, Manuel

2017-01-01

The mechanisms that can contribute in the fish movement strategies and the associated behaviour can be complex and related to the physiology, genetic and ecology of each species. In the case of the brown trout (Salmo trutta), in recent research works, individual differences in mobility have been observed in a population living in a high mountain river reach (Pyrenees, NE Spain). The population is mostly sedentary but a small percentage of individuals exhibit a mobile behavior, mainly upstream movements. Metabolomics can reflect changes in the physiological process and can determine different profiles depending on behaviour. Here, a non-targeted metabolomics approach was used to find possible changes in the blood metabolomic profile of S. trutta related to its movement behaviour, using a minimally invasive sampling. Results showed a differentiation in the metabolomic profiles of the trouts and different level concentrations of some metabolites (e.g. cortisol) according to the home range classification (pattern of movements: sedentary or mobile). The change in metabolomic profiles can generally occur during the upstream movement and probably reflects the changes in metabolite profile from the non-mobile season to mobile season. This study reveals the contribution of the metabolomic analyses to better understand the behaviour of organisms.

A QC approach to the determination of day-to-day reproducibility and robustness of LC-MS methods for global metabolite profiling in metabonomics/metabolomics.

Science.gov (United States)

Gika, Helen G; Theodoridis, Georgios A; Earll, Mark; Wilson, Ian D

2012-09-01

An approach to the determination of day-to-day analytical robustness of LC-MS-based methods for global metabolic profiling using a pooled QC sample is presented for the evaluation of metabonomic/metabolomic data. A set of 60 urine samples were repeatedly analyzed on five different days and the day-to-day reproducibility of the data obtained was determined. Multivariate statistical analysis was performed with the aim of evaluating variability and selected peaks were assessed and validated in terms of retention time stability, mass accuracy and intensity. The methodology enables the repeatability/reproducibility of extended analytical runs in large-scale studies to be determined, allowing the elimination of analytical (as opposed to biological) variability, in order to discover true patterns and correlations within the data. The day-to-day variability of the data revealed by this process suggested that, for this particular system, 3 days continuous operation was possible without the need for maintenance and cleaning. Variation was generally based on signal intensity changes over the 7-day period of the study, and was mainly a result of source contamination.

Size Matters: Penis Size and Sexual Position in Gay Porn Profiles.

Science.gov (United States)

Brennan, Joseph

2018-01-01

This article combines qualitative and quantitative textual approaches to the representation of penis size and sexual position of performers in 10 of the most visited gay pornography Web sites currently in operation. Specifically, in excess of 6,900 performer profiles sourced from 10 commercial Web sites are analyzed. Textual analysis of the profile descriptions is combined with a quantitative representation of disclosed penis size and sexual position, which is presented visually by two figures. The figures confirm that these sites generally market themselves as featuring penises that are extraordinarily large and find a sample-wide correlation between smaller penis sizes (5-6.5 inches) and receptive sexual acts (bottoming), and larger (8.5-13 inches) with penetrative acts (topping). These observations are supported through the qualitative textual readings of how the performers are described on these popular sites, revealing the narratives and marketing strategies that shape the construction of popular porn brands, performers, and profitable fantasies.

Regional two-dimensional magnetotelluric profile in West Bohemia/Vogtland reveals deep conductive channel into the earthquake swarm region

Science.gov (United States)

Muñoz, Gerard; Weckmann, Ute; Pek, Josef; Kováčiková, Světlana; Klanica, Radek

2018-03-01

The West Bohemia/Vogtland region, characterized by the intersection of the Eger (Ohře) Rift and the Mariánské Lázně fault, is a geodynamically active area exhibiting repeated occurrence of earthquake swarms, massive CO2 emanations and mid Pleistocene volcanism. The Eger Rift is the only known intra-continental region in Europe where such deep seated, active lithospheric processes currently take place. We present an image of electrical resistivity obtained from two-dimensional inversion of magnetotelluric (MT) data acquired along a regional profile crossing the Eger Rift. At the near surface, the Cheb basin and the aquifer feeding the mofette fields of Bublák and Hartoušov have been imaged as part of a region of very low resistivity. The most striking resistivity feature, however, is a deep reaching conductive channel which extends from the surface into the lower crust spatially correlated with the hypocentres of the seismic events of the Nový Kostel Focal Zone. This channel has been interpreted as imaging a pathway from a possible mid-crustal fluid reservoir to the surface. The resistivity model reinforces the relation between the fluid circulation along deep-reaching faults and the generation of the earthquakes. Additionally, a further conductive channel has been revealed to the south of the profile. This other feature could be associated to fossil hydrothermal alteration related to Mýtina and/or Neualbenreuth Maar structures or alternatively could be the signature of a structure associated to the suture between the Saxo-Thuringian and Teplá-Barrandian zones, whose surface expression is located only a few kilometres away.

Deep RNA-Seq profile reveals biodiversity, plant-microbe interactions and a large family of NBS-LRR resistance genes in walnut (Juglans regia) tissues.

Science.gov (United States)

Chakraborty, Sandeep; Britton, Monica; Martínez-García, P J; Dandekar, Abhaya M

2016-03-01

Deep RNA-Seq profiling, a revolutionary method used for quantifying transcriptional levels, often includes non-specific transcripts from other co-existing organisms in spite of stringent protocols. Using the recently published walnut genome sequence as a filter, we present a broad analysis of the RNA-Seq derived transcriptome profiles obtained from twenty different tissues to extract the biodiversity and possible plant-microbe interactions in the walnut ecosystem in California. Since the residual nature of the transcripts being analyzed does not provide sufficient information to identify the exact strain, inferences made are constrained to the genus level. The presence of the pathogenic oomycete Phytophthora was detected in the root through the presence of a glyceraldehyde-3-phosphate dehydrogenase. Cryptococcus, the causal agent of cryptococcosis, was found in the catkins and vegetative buds, corroborating previous work indicating that the plant surface supported the sexual cycle of this human pathogen. The RNA-Seq profile revealed several species of the endophytic nitrogen fixing Actinobacteria. Another bacterial species implicated in aerobic biodegradation of methyl tert-butyl ether (Methylibium petroleiphilum) is also found in the root. RNA encoding proteins from the pea aphid were found in the leaves and vegetative buds, while a serine protease from mosquito with significant homology to a female reproductive tract protease from Drosophila mojavensis in the vegetative bud suggests egg-laying activities. The comprehensive analysis of RNA-seq data present also unraveled detailed, tissue-specific information of ~400 transcripts encoded by the largest family of resistance (R) genes (NBS-LRR), which possibly rationalizes the resistance of the specific walnut plant to the pathogens detected. Thus, we elucidate the biodiversity and possible plant-microbe interactions in several walnut (Juglans regia) tissues in California using deep RNA-Seq profiling.

Metabolite Profiling of Red Sea Corals

KAUST Repository

Ortega, Jovhana Alejandra

2016-01-01

that provide insights into the specific nature of the symbiosis. Our analysis also revealed aquatic pollutants, which suggests that metabolite profiling might be used for monitoring pollution levels and assessing environmental impact.

Serum proteome profiling in canine idiopathic dilated cardiomyopathy using TMT-based quantitative proteomics approach.

Science.gov (United States)

Bilić, Petra; Guillemin, Nicolas; Kovačević, Alan; Beer Ljubić, Blanka; Jović, Ines; Galan, Asier; Eckersall, Peter David; Burchmore, Richard; Mrljak, Vladimir

2018-05-15

Idiopathic dilated cardiomyopathy (iDCM) is a primary myocardial disorder with an unknown aetiology, characterized by reduced contractility and ventricular dilation of the left or both ventricles. Naturally occurring canine iDCM was used herein to identify serum proteomic signature of the disease compared to the healthy state, providing an insight into underlying mechanisms and revealing proteins with biomarker potential. To achieve this, we used high-throughput label-based quantitative LC-MS/MS proteomics approach and bioinformatics analysis of the in silico inferred interactome protein network created from the initial list of differential proteins. To complement the proteomic analysis, serum biochemical parameters and levels of know biomarkers of cardiac function were measured. Several proteins with biomarker potential were identified, such as inter-alpha-trypsin inhibitor heavy chain H4, microfibril-associated glycoprotein 4 and apolipoprotein A-IV, which were validated using an independent method (Western blotting) and showed high specificity and sensitivity according to the receiver operating characteristic curve analysis. Bioinformatics analysis revealed involvement of different pathways in iDCM, such as complement cascade activation, lipoprotein particles dynamics, elastic fibre formation, GPCR signalling and respiratory electron transport chain. Idiopathic dilated cardiomyopathy is a severe primary myocardial disease of unknown cause, affecting both humans and dogs. This study is a contribution to the canine heart disease research by means of proteomic and bioinformatic state of the art analyses, following similar approach in human iDCM research. Importantly, we used serum as non-invasive and easily accessible biological source of information and contributed to the scarce data on biofluid proteome research on this topic. Bioinformatics analysis revealed biological pathways modulated in canine iDCM with potential of further targeted research. Also, several

Quantitative 1D saturation profiles on chalk by NMR

DEFF Research Database (Denmark)

Olsen, Dan; Topp, Simon; Stensgaard, Anders

1996-01-01

Quantitative one-dimensional saturation profiles showing the distribution of water and oil in chalk core samples are calculated from NMR measurements utilizing a 1D CSI spectroscopy pulse sequence. Saturation profiles may be acquired under conditions of fluid flow through the sample. Results reveal...

Kompetenční profil kaskadéra

OpenAIRE

Šittová, Magdalena

2017-01-01

Title: Competency profile of stuntman Objectives: The main aim of this thesis is to create the competency profile of the ideal stuntman. This competency profile should reveal key personality traits, qual- ities and abilities and in the future should help to choose a new stunt people. Methods: The thesis uses interviews with leading Czech stuntmen. The list of competencies based on interviews and written sources was distributed by questionnaires. To as- sess the importance has been selected 4 ...

An examination of the spatial variability of CO2 in the profile of managed forest soils

International Nuclear Information System (INIS)

Black, M.; Kellman, L.; Beltrami, H.

2005-01-01

Soil carbon dioxide (CO 2 ) profiles are typically used in soil-gas exchange studies. Although surface flux measuring methods may be more efficient for deriving surface soil CO 2 exchange budgets, they do not provide enough information about the generation of gas through depth. This poses a challenge in quantifying the CO 2 generated from different zones and soil carbon pools through time. The combination of subsurface concentration profiles and estimates of soil diffusivity reveal where CO 2 is being generated in the soil. This combined approach offers greater awareness into processes controlling CO 2 production in soils through depth, and clarifies how soil CO 2 exchange processes in these ecosystems can be changed by management regimes and climate change. Although information about spatial variability in subsurface concentrations within forested soils is limited, it is assumed to be high because of the high spatial variability in soil CO 2 flux estimates and the large variation in vegetation distribution and topography within sites. In this study, the soil CO 2 profile was monitored during the fall of 2004 at depths of 0, 5, 20 and 35 cm at 10 microsites of a clear-cut and an 80 year old intact mixed forest in Atlantic Canada. Microsites were about 10 meters apart and represented a range of microtopographical conditions that typically encompass extremes in soil CO 2 profile patterns. Preliminary results reveal predictable patterns in concentration profiles through depth, and increasing CO 2 concentration with depth, consistent with a large soil source of CO 2 . The significant variability in the soil carbon profile between microsites in the clear-cut and intact forest sites will be investigated to determine if distinct microsite patterns can be identified. The feasibility of using this method for providing process-based versus soil C exchange budgeting information at forested sites will also be examined

Improved EDELWEISS-III sensitivity for low-mass WIMPs using a profile likelihood approach

Energy Technology Data Exchange (ETDEWEB)

Hehn, L. [Karlsruher Institut fuer Technologie, Institut fuer Kernphysik, Karlsruhe (Germany); Armengaud, E.; Boissiere, T. de; Gros, M.; Navick, X.F.; Nones, C.; Paul, B. [CEA Saclay, DSM/IRFU, Gif-sur-Yvette Cedex (France); Arnaud, Q. [Univ Lyon, Universite Claude Bernard Lyon 1, CNRS/IN2P3, Institut de Physique Nucleaire de Lyon, Lyon (France); Queen' s University, Kingston (Canada); Augier, C.; Billard, J.; Cazes, A.; Charlieux, F.; Jesus, M. de; Gascon, J.; Juillard, A.; Queguiner, E.; Sanglard, V.; Vagneron, L. [Univ Lyon, Universite Claude Bernard Lyon 1, CNRS/IN2P3, Institut de Physique Nucleaire de Lyon, Lyon (France); Benoit, A.; Camus, P. [Institut Neel, CNRS/UJF, Grenoble (France); Berge, L.; Chapellier, M.; Dumoulin, L.; Giuliani, A.; Le-Sueur, H.; Marnieros, S.; Olivieri, E.; Poda, D. [CSNSM, Univ. Paris-Sud, CNRS/IN2P3, Universite Paris-Saclay, Orsay (France); Bluemer, J. [Karlsruher Institut fuer Technologie, Institut fuer Kernphysik, Karlsruhe (Germany); Karlsruher Institut fuer Technologie, Institut fuer Experimentelle Kernphysik, Karlsruhe (Germany); Broniatowski, A. [CSNSM, Univ. Paris-Sud, CNRS/IN2P3, Universite Paris-Saclay, Orsay (France); Karlsruher Institut fuer Technologie, Institut fuer Experimentelle Kernphysik, Karlsruhe (Germany); Eitel, K.; Kozlov, V.; Siebenborn, B. [Karlsruher Institut fuer Technologie, Institut fuer Kernphysik, Karlsruhe (Germany); Foerster, N.; Heuermann, G.; Scorza, S. [Karlsruher Institut fuer Technologie, Institut fuer Experimentelle Kernphysik, Karlsruhe (Germany); Jin, Y. [Laboratoire de Photonique et de Nanostructures, CNRS, Route de Nozay, Marcoussis (France); Kefelian, C. [Univ Lyon, Universite Claude Bernard Lyon 1, CNRS/IN2P3, Institut de Physique Nucleaire de Lyon, Lyon (France); Karlsruher Institut fuer Technologie, Institut fuer Experimentelle Kernphysik, Karlsruhe (Germany); Kleifges, M.; Tcherniakhovski, D.; Weber, M. [Karlsruher Institut fuer Technologie, Institut fuer Prozessdatenverarbeitung und Elektronik, Karlsruhe (Germany); Kraus, H. [University of Oxford, Department of Physics, Oxford (United Kingdom); Kudryavtsev, V.A. [University of Sheffield, Department of Physics and Astronomy, Sheffield (United Kingdom); Pari, P. [CEA Saclay, DSM/IRAMIS, Gif-sur-Yvette (France); Piro, M.C. [CSNSM, Univ. Paris-Sud, CNRS/IN2P3, Universite Paris-Saclay, Orsay (France); Rensselaer Polytechnic Institute, Troy, NY (United States); Rozov, S.; Yakushev, E. [JINR, Laboratory of Nuclear Problems, Dubna, Moscow Region (Russian Federation); Schmidt, B. [Karlsruher Institut fuer Technologie, Institut fuer Kernphysik, Karlsruhe (Germany); Lawrence Berkeley National Laboratory, Berkeley, CA (United States)

2016-10-15

We report on a dark matter search for a Weakly Interacting Massive Particle (WIMP) in the mass range m{sub χ} element of [4, 30] GeV/c{sup 2} with the EDELWEISS-III experiment. A 2D profile likelihood analysis is performed on data from eight selected detectors with the lowest energy thresholds leading to a combined fiducial exposure of 496 kg-days. External backgrounds from γ- and β-radiation, recoils from {sup 206}Pb and neutrons as well as detector intrinsic backgrounds were modelled from data outside the region of interest and constrained in the analysis. The basic data selection and most of the background models are the same as those used in a previously published analysis based on boosted decision trees (BDT) [1]. For the likelihood approach applied in the analysis presented here, a larger signal efficiency and a subtraction of the expected background lead to a higher sensitivity, especially for the lowest WIMP masses probed. No statistically significant signal was found and upper limits on the spin-independent WIMP-nucleon scattering cross section can be set with a hypothesis test based on the profile likelihood test statistics. The 90 % C.L. exclusion limit set for WIMPs with m{sub χ} = 4 GeV/c{sup 2} is 1.6 x 10{sup -39} cm{sup 2}, which is an improvement of a factor of seven with respect to the BDT-based analysis. For WIMP masses above 15 GeV/c{sup 2} the exclusion limits found with both analyses are in good agreement. (orig.)

Volatile profiling reveals intracellular metabolic changes in Aspergillus parasiticus: veA regulates branched chain amino acid and ethanol metabolism

Directory of Open Access Journals (Sweden)

Roze Ludmila V

2010-08-01

Full Text Available Abstract Background Filamentous fungi in the genus Aspergillus produce a variety of natural products, including aflatoxin, the most potent naturally occurring carcinogen known. Aflatoxin biosynthesis, one of the most highly characterized secondary metabolic pathways, offers a model system to study secondary metabolism in eukaryotes. To control or customize biosynthesis of natural products we must understand how secondary metabolism integrates into the overall cellular metabolic network. By applying a metabolomics approach we analyzed volatile compounds synthesized by Aspergillus parasiticus in an attempt to define the association of secondary metabolism with other metabolic and cellular processes. Results Volatile compounds were examined using solid phase microextraction - gas chromatography/mass spectrometry. In the wild type strain Aspergillus parasiticus SU-1, the largest group of volatiles included compounds derived from catabolism of branched chain amino acids (leucine, isoleucine, and valine; we also identified alcohols, esters, aldehydes, and lipid-derived volatiles. The number and quantity of the volatiles produced depended on media composition, time of incubation, and light-dark status. A block in aflatoxin biosynthesis or disruption of the global regulator veA affected the volatile profile. In addition to its multiple functions in secondary metabolism and development, VeA negatively regulated catabolism of branched chain amino acids and synthesis of ethanol at the transcriptional level thus playing a role in controlling carbon flow within the cell. Finally, we demonstrated that volatiles generated by a veA disruption mutant are part of the complex regulatory machinery that mediates the effects of VeA on asexual conidiation and sclerotia formation. Conclusions 1 Volatile profiling provides a rapid, effective, and powerful approach to identify changes in intracellular metabolic networks in filamentous fungi. 2 VeA coordinates the

Lateral facial profile may reveal the risk for sleep disordered breathing in children--the PANIC-study.

Science.gov (United States)

Ikävalko, Tiina; Närhi, Matti; Lakka, Timo; Myllykangas, Riitta; Tuomilehto, Henri; Vierola, Anu; Pahkala, Riitta

2015-01-01

To evaluate the lateral view photography of the face as a tool for assessing morphological properties (i.e. facial convexity) as a risk factor for sleep disordered breathing (SDB) in children and to test how reliably oral health and non-oral healthcare professionals can visually discern the lateral profile of the face from the photographs. The present study sample consisted of 382 children 6-8 years of age who were participants in the Physical Activity and Nutrition in Children (PANIC) Study. Sleep was assessed by a sleep questionnaire administered by the parents. SDB was defined as apnoeas, frequent or loud snoring or nocturnal mouth breathing observed by the parents. The facial convexity was assessed with three different methods. First, it was clinically evaluated by the reference orthodontist (T.I.). Second, lateral view photographs were taken to visually sub-divide the facial profile into convex, normal or concave. The photos were examined by a reference orthodontist and seven different healthcare professionals who work with children and also by a dental student. The inter- and intra-examiner consistencies were calculated by Kappa statistics. Three soft tissue landmarks of the facial profile, soft tissue Glabella (G`), Subnasale (Sn) and soft tissue Pogonion (Pg`) were digitally identified to analyze convexity of the face and the intra-examiner reproducibility of the reference orthodontist was determined by calculating intra-class correlation coefficients (ICCs). The third way to express the convexity of the face was to calculate the angle of facial convexity (G`-Sn-Pg`) and to group it into quintiles. For analysis the lowest quintile (≤164.2°) was set to represent the most convex facial profile. The prevalence of the SDB in children with the most convex profiles expressed with the lowest quintile of the angle G`-Sn-Pg` (≤164.2°) was almost 2-fold (14.5%) compared to those with normal profile (8.1%) (p = 0.084). The inter-examiner Kappa values between the

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

Science.gov (United States)

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

2015-01-01

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

A Transformational Approach to Parametric Accumulated-Cost Static Profiling

DEFF Research Database (Denmark)

Haemmerlé, Rémy; López García, Pedro; Liqat, Umer

2016-01-01

Traditional static resource analyses estimate the total resource usage of a program, without executing it. In this paper we present a novel resource analysis whose aim is instead the static profiling of accumulated cost, i.e., to discover, for selected parts of the program, an estimate or bound...... of the resource usage accumulated in each of those parts. Traditional resource analyses are parametric in the sense that the results can be functions on input data sizes. Our static profiling is also parametric, i.e., our accumulated cost estimates are also parameterized by input data sizes. Our proposal is based...... on the concept of cost centers and a program transformation that allows the static inference of functions that return bounds on these accumulated costs depending on input data sizes, for each cost center of interest. Such information is much more useful to the software developer than the traditional resource...

Road profile estimation of city roads using DTPS

Science.gov (United States)

Wang, Qi; McDaniel, J. Gregory; Sun, Nian X.; Wang, Ming L.

2013-04-01

This work presents a non-destructive and non-contact acoustic sensing approach for measuring road profile of road and bridge deck with vehicles running at normal speed without stopping traffic. This approach uses an instantaneous and real-time dynamic tire pressure sensor (DTPS) that can measure dynamic response of the tire-road interaction and increases the efficiency of currently used road profile measuring systems with vehicle body-mounted profilers and axle-mounted accelerometers. In this work, a prototype of real-time DTPS system has been developed and demonstrated on a testing van at speeds from 5 to 80 miles per hour (mph). A data analysis algorithm has been developed to remove axle dynamic motions from the measured DTPS data and to find the transfer function between dynamic tire pressure change and the road profile. Field test has been performed to estimate road profiles. The road profile resolution is approximately 5 to 10 cm in width and sensitivity is 0. 3 cm for the height road surface features at driving speeds of 5 to 80 mph.

Flash Study Analysis and the Music Learning Pro-Files Project

Science.gov (United States)

Cremata, Radio; Pignato, Joseph; Powell, Bryan; Smith, Gareth Dylan

2016-01-01

This paper introduces the Music Learning Profiles Project, and its methodological approach, flash study analysis. Flash study analysis is a method that draws heavily on extant qualitative approaches to education research, to develop broad understandings of music learning in diverse contexts. The Music Learning Profiles Project (MLPP) is an…

From the SAIN,LIM system to the SENS algorithm: a review of a French approach of nutrient profiling.

Science.gov (United States)

Tharrey, Marion; Maillot, Matthieu; Azaïs-Braesco, Véronique; Darmon, Nicole

2017-08-01

Nutrient profiling aims to classify or rank foods according to their nutritional composition to assist policies aimed at improving the nutritional quality of foods and diets. The present paper reviews a French approach of nutrient profiling by describing the SAIN,LIM system and its evolution from its early draft to the simplified nutrition labelling system (SENS) algorithm. Considered in 2010 by WHO as the 'French model' of nutrient profiling, SAIN,LIM classifies foods into four classes based on two scores: a nutrient density score (NDS) called SAIN and a score of nutrients to limit called LIM, and one threshold on each score. The system was first developed by the French Food Standard Agency in 2008 in response to the European regulation on nutrition and health claims (European Commission (EC) 1924/2006) to determine foods that may be eligible for bearing claims. Recently, the European regulation (EC 1169/2011) on the provision of food information to consumers allowed simplified nutrition labelling to facilitate consumer information and help them make fully informed choices. In that context, the SAIN,LIM was adapted to obtain the SENS algorithm, a system able to rank foods for simplified nutrition labelling. The implementation of the algorithm followed a step-by-step, systematic, transparent and logical process where shortcomings of the SAIN,LIM were addressed by integrating specificities of food categories in the SENS, reducing the number of nutrients, ordering the four classes and introducing European reference intakes. Through the French example, this review shows how an existing nutrient profiling system can be specifically adapted to support public health nutrition policies.

Label-free proteome profiling reveals developmental-dependent patterns in young barley grains.

Science.gov (United States)

Kaspar-Schoenefeld, Stephanie; Merx, Kathleen; Jozefowicz, Anna Maria; Hartmann, Anja; Seiffert, Udo; Weschke, Winfriede; Matros, Andrea; Mock, Hans-Peter

2016-06-30

Due to its importance as a cereal crop worldwide, high interest in the determination of factors influencing barley grain quality exists. This study focusses on the elucidation of protein networks affecting early grain developmental processes. NanoLC-based separation coupled to label-free MS detection was applied to gain insights into biochemical processes during five different grain developmental phases (pre-storage until storage phase, 3days to 16days after flowering). Multivariate statistics revealed two distinct developmental patterns during the analysed grain developmental phases: proteins showed either highest abundance in the middle phase of development - in the transition phase - or at later developmental stages - within the storage phase. Verification of developmental patterns observed by proteomic analysis was done by applying hypothesis-driven approaches, namely Western Blot analysis and enzyme assays. High general metabolic activity of the grain with regard to protein synthesis, cell cycle regulation, defence against oxidative stress, and energy production via photosynthesis was observed in the transition phase. Proteins upregulated in the storage phase are related towards storage protein accumulation, and interestingly to the defence of storage reserves against pathogens. A mixed regulatory pattern for most enzymes detected in our study points to regulatory mechanisms at the level of protein isoforms. In-depth understanding of early grain developmental processes of cereal caryopses is of high importance as they influence final grain weight and quality. Our knowledge about these processes is still limited, especially on proteome level. To identify key mechanisms in early barley grain development, a label-free data-independent proteomics acquisition approach has been applied. Our data clearly show, that proteins either exhibit highest expression during cellularization and the switch to the storage phase (transition phase, 5-7 DAF), or during storage

Quantitative high dynamic range beam profiling for fluorescence microscopy

International Nuclear Information System (INIS)

Mitchell, T. J.; Saunter, C. D.; O’Nions, W.; Girkin, J. M.; Love, G. D.

2014-01-01

Modern developmental biology relies on optically sectioning fluorescence microscope techniques to produce non-destructive in vivo images of developing specimens at high resolution in three dimensions. As optimal performance of these techniques is reliant on the three-dimensional (3D) intensity profile of the illumination employed, the ability to directly record and analyze these profiles is of great use to the fluorescence microscopist or instrument builder. Though excitation beam profiles can be measured indirectly using a sample of fluorescent beads and recording the emission along the microscope detection path, we demonstrate an alternative approach where a miniature camera sensor is used directly within the illumination beam. Measurements taken using our approach are solely concerned with the illumination optics as the detection optics are not involved. We present a miniature beam profiling device and high dynamic range flux reconstruction algorithm that together are capable of accurately reproducing quantitative 3D flux maps over a large focal volume. Performance of this beam profiling system is verified within an optical test bench and demonstrated for fluorescence microscopy by profiling the low NA illumination beam of a single plane illumination microscope. The generality and success of this approach showcases a widely flexible beam amplitude diagnostic tool for use within the life sciences

Community-aware user profile enrichment in folksonomy.

Science.gov (United States)

Xie, Haoran; Li, Qing; Mao, Xudong; Li, Xiaodong; Cai, Yi; Rao, Yanghui

2014-10-01

In the era of big data, collaborative tagging (a.k.a. folksonomy) systems have proliferated as a consequence of the growth of Web 2.0 communities. Constructing user profiles from folksonomy systems is useful for many applications such as personalized search and recommender systems. The identification of latent user communities is one way to better understand and meet user needs. The behavior of users is highly influenced by the behavior of their neighbors or community members, and this can be utilized in constructing user profiles. However, conventional user profiling techniques often encounter data sparsity problems as data from a single user is insufficient to build a powerful profile. Hence, in this paper we propose a method of enriching user profiles based on latent user communities in folksonomy data. Specifically, the proposed approach contains four sub-processes: (i) tag-based user profiles are extracted from a folksonomy tripartite graph; (ii) a multi-faceted folksonomy graph is constructed by integrating tag and image affinity subgraphs with the folksonomy tripartite graph; (iii) random walk distance is used to unify various relationships and measure user similarities; (iv) a novel prototype-based clustering method based on user similarities is used to identify user communities, which are further used to enrich the extracted user profiles. To evaluate the proposed method, we conducted experiments using a public dataset, the results of which show that our approach outperforms previous ones in user profile enrichment. Copyright © 2014 Elsevier Ltd. All rights reserved.

Signal process and profile reconstruction of stress corrosion crack by eddy current test

International Nuclear Information System (INIS)

Zhang Siquan; Chen Tiequn; Liu Guixiong

2008-01-01

The reconstruction of crack profiles is very important in the NDE (nondestructive evaluation) of critical structures, such as pressure vessel and tubes in heat exchangers. First a wavelet transform signal processing technique is used to reduce noise and other non-defect signals from the signals of crack, and then based on an artificial neural network method, the crack profiles are reconstructed. Although the results reveal that this method is with many advantages such as a short CPU time and precision for reconstruction,it does have some drawbacks, for example, the database generation and network training is a much time consuming work. Moreover, this approach does not expressly reconstruct the distribution of conductivity inside a crack, so the reliability of a reconstructed crack shape is unknown. But in practical application, if we do not consider the multiple cracks, this method can be used to reconstruct the natural crack. (authors)

Comprehensive genomic profiling reveals inactivating SMARCA4 mutations and low tumor mutational burden in small cell carcinoma of the ovary, hypercalcemic-type.

Science.gov (United States)

Lin, Douglas I; Chudnovsky, Yakov; Duggan, Bridget; Zajchowski, Deborah; Greenbowe, Joel; Ross, Jeffrey S; Gay, Laurie M; Ali, Siraj M; Elvin, Julia A

2017-12-01

Small cell carcinoma of the ovary, hypercalcemic-type (SCCOHT) is a rare, extremely aggressive neoplasm that usually occurs in young women and is characterized by deleterious germline or somatic SMARCA4 mutations. We performed comprehensive genomic profiling (CGP) to potentially identify additional clinically and pathophysiologically relevant genomic alterations in SCCOHT. CGP assessment of all classes of coding alterations in up to 406 genes commonly altered in cancer and intronic regions for up to 31 genes commonly rearranged in cancer was performed on 18 SCCOHT cases (16 exhibiting classic morphology and 2 cases exhibiting exclusive a large cell variant morphology). In addition, a retrospective database search for clinically advanced ovarian tumors with genomic profiles similar to SCCOHT yielded 3 additional cases originally diagnosed as non-SCCOHT. CGP revealed inactivating SMARCA4 alterations and low tumor mutational burden (TMB) (<6mutations/Mb) in 94% (15/16) of SCCOHT with classic morphology. In contrast, both (2/2) cases exhibiting only large cell variant morphology were hypermutated (TMB scores of 90 and 360mut/Mb) and were wildtype for SMARCA4. In our retrospective search, an index ovarian cancer patient harboring inactivating SMARCA4 alterations, initially diagnosed as endometrioid carcinoma, was re-classified as SCCOHT and responded to an SCCOHT chemotherapy regimen. The vast majority of SCCOHT demonstrate genomic SMARCA4 loss with only rare co-occurring alterations. Our data support a role for CGP in the diagnosis and management of SCCOHT and of other lesions with overlapping histological and clinical features, since identifying the former by genomic profile suggests benefit from an appropriate regimen and treatment decisions, as illustrated by an index patient. Copyright © 2017 Elsevier Inc. All rights reserved.

Crustal structure revealed by a deep seismic sounding profile of Baijing-Gaoming-Jinwan in the Pearl River Delta

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Zhang, Xiang; Ye, Xiuwei; Lv, Jinshui; Sun, Jinlong; Wang, Xiaona

2018-02-01

The Pearl River Estuary area, located in the middle part of the southern China coastal seismic belt, has long been considered a potential source of strong earthquakes above magnitude 7.0. To scientifically assess the potential strong earthquake risk in this area, a three-dimensional artificial seismic sounding experiment, consisting of a receiving array and seabed seismograph, was performed to reveal the deep crustal structure in this region. We used artificial ship-borne air-gun excitation shots as sources, and fixed and mobile stations as receivers to record seismic data from May to August 2015. This paper presents results along a line from the western side of the Pearl River Estuary to the western side of the Baijing-Gaoming-Jinwan profile. A two-dimensional velocity structure was constructed using seismic travel-time tomography. The inversion results show that the Moho depth is 27 km in the coastal area and 30 km in the northwest of the Pearl River Estuary area, indicating that the crust thins from land to sea. Two structural discontinuities and multiple low-velocity anomalies appear in the crustal section. Inside both discontinuity zones, a low-velocity layer, with a minimum velocity of 6.05 km s-1, exists at a depth of about 15 km, and another, with a minimum velocity of 6.37 km s-1, exists at a depth of about 21.5 km between the middle and lower crust. These low velocities suggest that the discontinuities may consist of partly molten material. Earthquakes with magnitudes higher than 5.0 occurred in the low-velocity layer along the profile. The deep Kaiping-Enping fault, rooted in the crust, may be one of the most important channels for deep material upwelling and is related to tectonic movement since the Cretaceous in the Pearl River Delta tectonic rift basin.

Corrosion issues of powder coated AA6060 aluminium profiles

DEFF Research Database (Denmark)

Din, Rameez Ud; Valgarðsson, Smári; Jellesen, Morten Stendahl

2015-01-01

In this study detailed microstructural investigation of the reason for unexpected corrosion of powder coated aluminium alloy AA6060 windows profiles has been performed. The results from this study reveals that the failure of the window profiles was originated from the surface defects present...... on the extruded AA6060 aluminium profile after metallurgical process prior to powder coating. Surface defects are produced due to intermetallic particles in the alloy, which disturb the flow during the extrusion process. The corrosion mechanism leading to the failure of the powder coated AA6060 aluminium profiles...

Gas-Chromatography Mass-Spectrometry (GC-MS Based Metabolite Profiling Reveals Mannitol as a Major Storage Carbohydrate in the Coccolithophorid Alga Emiliania huxleyi

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Alisdair R. Fernie

2013-03-01

Full Text Available Algae are divergent organisms having a wide variety of evolutional histories. Although most of them share photosynthetic activity, their pathways of primary carbon metabolism are rather diverse among species. Here we developed a method for gas chromatography-mass spectroscopy (GC-MS based metabolite profiling for the coccolithophorid alga Emiliania huxleyi, which is one of the most abundant microalgae in the ocean, in order to gain an overview of the pathway of primary metabolism within this alga. Following method optimization, twenty-six metabolites could be detected by this method. Whilst most proteogenic amino acids were detected, no peaks corresponding to malate and fumarate were found. The metabolite profile of E. huxleyi was, however, characterized by a prominent accumulation of mannitol reaching in excess of 14 nmol 106 cells−1. Similarly, the accumulation of the 13C label during short term H13CO3− feeding revealed a massive redistribution of label into mannitol as well as rapid but saturating label accumulation into glucose and several amino acids including aspartate, glycine and serine. These results provide support to previous work suggesting that this species adopts C3 photosynthesis and that mannitol functions as a carbon store in E. huxleyi.

Integration of miRNA and protein profiling reveals coordinated neuroadaptations in the alcohol-dependent mouse brain.

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Giorgio Gorini

Full Text Available The molecular mechanisms underlying alcohol dependence involve different neurochemical systems and are brain region-dependent. Chronic Intermittent Ethanol (CIE procedure, combined with a Two-Bottle Choice voluntary drinking paradigm, represents one of the best available animal models for alcohol dependence and relapse drinking. MicroRNAs, master regulators of the cellular transcriptome and proteome, can regulate their targets in a cooperative, combinatorial fashion, ensuring fine tuning and control over a large number of cellular functions. We analyzed cortex and midbrain microRNA expression levels using an integrative approach to combine and relate data to previous protein profiling from the same CIE-subjected samples, and examined the significance of the data in terms of relative contribution to alcohol consumption and dependence. MicroRNA levels were significantly altered in CIE-exposed dependent mice compared with their non-dependent controls. More importantly, our integrative analysis identified modules of coexpressed microRNAs that were highly correlated with CIE effects and predicted target genes encoding differentially expressed proteins. Coexpressed CIE-relevant proteins, in turn, were often negatively correlated with specific microRNA modules. Our results provide evidence that microRNA-orchestrated translational imbalances are driving the behavioral transition from alcohol consumption to dependence. This study represents the first attempt to combine ex vivo microRNA and protein expression on a global scale from the same mammalian brain samples. The integrative systems approach used here will improve our understanding of brain adaptive changes in response to drug abuse and suggests the potential therapeutic use of microRNAs as tools to prevent or compensate multiple neuroadaptations underlying addictive behavior.

Ultra-high performance liquid chromatography coupled with quadrupole/time of flight mass spectrometry based chemical profiling approach for the holistic quality control of complex Kang-Jing formula preparations.

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Yang, Xiao-Huan; Cheng, Xiao-Lan; Qin, Bing; Cai, Zhuo-Ya; Cai, Xiong; Liu, Shao; Wang, Qi; Qin, Yong

2016-05-30

The Kang-Jing (KJ) formula is a compound preparation made from 12 kinds of herbs. So far, four different methods (M1-M4) have been documented for KJ preparation, but the influence of preparation methods on the holistic quality of KJ have remained unknown. In this study, a strategy was proposed to investigate the influence of different preparation methods on the holistic quality of KJ using ultra-high performance liquid chromatography coupled with quadrupole/time of flight mass spectrometry (UHPLC-QTOF-MS/MS) based chemical profiling. A total of 101 compounds mainly belonging to flavonoids, tanshinones, monoterpene glycosides, triterpenoid saponins, alkaloids, phenolic acids and volatile oils, were identified. Among these compounds, glaucine was detected only in M3/M4 samples, while two dehydrocorydaline isomers merely detected in M2/M3/M4 samples. Tetrahydrocolumbamine, ethylic lithospermic acid, salvianolic acid E and rosmarimic acid were only detected in M1/M3/M4 samples. In the subsequent quantitative analysis, 12 major compounds were determined by UHPLC-MS/MS. The proposed method was validated with respect to linearity, accuracy, precision and recovery. It was found that the contents of marker compounds varied significantly in samples prepared by different methods. These results demonstrated that preparation method does significantly affect the holistic quality of KJ. UHPLC-QTOF-MS/MS based chemical profiling approach is efficient and reliable for comprehensive quality evaluation of KJ. Collectively, this study provide the chemical evidence for revealing the material basis of KJ, and establish a simple and accurate chemical profiling method for its quality control. Copyright © 2016 Elsevier B.V. All rights reserved.

Gene array analysis of PD-1H overexpressing monocytes reveals a pro-inflammatory profile

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Preeti Bharaj

2018-02-01

Full Text Available We have previously reported that overexpression of Programmed Death -1 Homolog (PD-1H in human monocytes leads to activation and spontaneous secretion of multiple pro inflammatory cytokines. Here we evaluate changes in monocytes gene expression after enforced PD-1H expression by gene array. The results show that there are significant alterations in 51 potential candidate genes that relate to immune response, cell adhesion and metabolism. Genes corresponding to pro-inflammatory cytokines showed the highest upregulation, 7, 3.2, 3.0, 5.8, 4.4 and 3.1 fold upregulation of TNF-α, IL-1 β, IFN-α, γ, λ and IL-27 relative to vector control. The data are in agreement with cytometric bead array analysis showing induction of proinflammatory cytokines, IL-6, IL-1β and TNF-α by PD-1H. Other genes related to inflammation, include transglutaminase 2 (TG2, NF-κB (p65 and p50 and toll like receptors (TLR 3 and 4 were upregulated 5, 4.5 and 2.5 fold, respectively. Gene set enrichment analysis (GSEA also revealed that signaling pathways related to inflammatory response, such as NFκB, AT1R, PYK2, MAPK, RELA, TNFR1, MTOR and proteasomal degradation, were significantly upregulated in response to PD-1H overexpression. We validated the results utilizing a standard inflammatory sepsis model in humanized BLT mice, finding that PD-1H expression was highly correlated with proinflammatory cytokine production. We therefore conclude that PD-1H functions to enhance monocyte activation and the induction of a pro-inflammatory gene expression profile.

Transcriptome profiling of a curdlan-producing Agrobacterium reveals conserved regulatory mechanisms of exopolysaccharide biosynthesis

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Ruffing Anne M

2012-02-01

Full Text Available Abstract Background The ability to synthesize exopolysaccharides (EPS is widespread among microorganisms, and microbial EPS play important roles in biofilm formation, pathogen persistence, and applications in the food and medical industries. Although it is well established that EPS synthesis is invariably in response to environmental cues, it remains largely unknown how various environmental signals trigger activation of the biochemical synthesis machinery. Results We report here the transcriptome profiling of Agrobacterium sp. ATCC 31749, a microorganism that produces large amounts of a glucose polymer known as curdlan under nitrogen starvation. Transcriptome analysis revealed a nearly 100-fold upregulation of the curdlan synthesis operon upon transition to nitrogen starvation, thus establishing the prominent role that transcriptional regulation plays in the EPS synthesis. In addition to known mechanisms of EPS regulation such as activation by c-di-GMP, we identify novel mechanisms of regulation in ATCC 31749, including RpoN-independent NtrC regulation and intracellular pH regulation by acidocalcisomes. Furthermore, we show evidence that curdlan synthesis is also regulated by conserved cell stress responses, including polyphosphate accumulation and the stringent response. In fact, the stringent response signal, pppGpp, appears to be indispensible for transcriptional activation of curdlan biosynthesis. Conclusions This study identifies several mechanisms regulating the synthesis of curdlan, an EPS with numerous applications. These mechanisms are potential metabolic engineering targets for improving the industrial production of curdlan from Agrobacterium sp. ATCC 31749. Furthermore, many of the genes identified in this study are highly conserved across microbial genomes, and we propose that the molecular elements identified in this study may serve as universal regulators of microbial EPS synthesis.

miRNome Expression Analysis Reveals New Players on Leprosy Immune Physiopathology

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Claudio Guedes Salgado

2018-03-01

Full Text Available Leprosy remains as a public health problem and its physiopathology is still not fully understood. MicroRNAs (miRNA are small RNA non-coding that can interfere with mRNA to regulate gene expression. A few studies using DNA chip microarrays have explored the expression of miRNA in leprosy patients using a predetermined set of genes as targets, providing interesting findings regarding the regulation of immune genes. However, using a predetermined set of genes restricted the possibility of finding new miRNAs that might be involved in different mechanisms of disease. Thus, we examined the miRNome of tuberculoid (TT and lepromatous (LL patients using both blood and lesional biopsies from classical leprosy patients (LP who visited the Dr. Marcello Candia Reference Unit in Sanitary Dermatology in the State of Pará and compared them with healthy subjects. Using a set of tools to correlate significantly differentially expressed miRNAs with their gene targets, we identified possible interactions and networks of miRNAs that might be involved in leprosy immunophysiopathology. Using this approach, we showed that the leprosy miRNA profile in blood is distinct from that in lesional skin as well as that four main groups of genes are the targets of leprosy miRNA: (1 recognition and phagocytosis, with activation of immune effector cells, where the immunosuppressant profile of LL and immunoresponsive profile of TT are clearly affected by miRNA expression; (2 apoptosis, with supportive data for an antiapoptotic leprosy profile based on BCL2, MCL1, and CASP8 expression; (3 Schwann cells (SCs, demyelination and epithelial–mesenchymal transition (EMT, supporting a role for different developmental or differentiation gene families, such as Sox, Zeb, and Hox; and (4 loss of sensation and neuropathic pain, revealing that RHOA, ROCK1, SIGMAR1, and aquaporin-1 (AQP1 may be involved in the loss of sensation or leprosy pain, indicating possible new therapeutic targets

Serum profiling of healthy aging identifies phospho- and sphingolipid species as markers of human longevity.

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Montoliu, Ivan; Scherer, Max; Beguelin, Fiona; DaSilva, Laeticia; Mari, Daniela; Salvioli, Stefano; Martin, Francois-Pierre J; Capri, Miriam; Bucci, Laura; Ostan, Rita; Garagnani, Paolo; Monti, Daniela; Biagi, Elena; Brigidi, Patrizia; Kussmann, Martin; Rezzi, Serge; Franceschi, Claudio; Collino, Sebastiano

2014-01-01

As centenarians well represent the model of healthy aging, there are many important implications in revealing the underlying molecular mechanisms behind such successful aging. By combining NMR metabonomics and shot-gun lipidomics in serum we analyzed metabolome and lipidome composition of a group of centenarians with respect to elderly individuals. Specifically, NMR metabonomics profiling of serum revealed that centenarians are characterized by a metabolic phenotype distinct from that of elderly subjects, in particular regarding amino acids and lipid species. Shot- gun lipidomics approach displays unique changes in lipids biosynthesis in centenarians, with 41 differently abundant lipid species with respect to elderly subjects. These findings reveal phospho/sphingolipids as putative markers and biological modulators of healthy aging, in humans. Considering the particular actions of these metabolites, these data are suggestive of a better counteractive antioxidant capacity and a well-developed membrane lipid remodelling process in the healthy aging phenotype.

Partial venom gland transcriptome of a Drosophila parasitoid wasp, Leptopilina heterotoma, reveals novel and shared bioactive profiles with stinging Hymenoptera

Science.gov (United States)

Heavner, Mary E.; Gueguen, Gwenaelle; Rajwani, Roma; Pagan, Pedro E.; Small, Chiyedza; Govind, Shubha

2013-01-01

Analysis of natural host-parasite relationships reveals the evolutionary forces that shape the delicate and unique specificity characteristic of such interactions. The accessory long gland-reservoir complex of the wasp Leptopilina heterotoma (Figitidae) produces venom with virus-like particles. Upon delivery, venom components delay host larval development and completely block host immune responses. The host range of this Drosophila endoparasitoid notably includes the highly-studied model organism, Drosophila melanogaster. Categorization of 827 unigenes, using similarity as an indicator of putative homology, reveals that approximately 25% are novel or classified as hypothetical proteins. Most of the remaining unigenes are related to processes involved in signaling, cell cycle, and cell physiology including detoxification, protein biogenesis, and hormone production. Analysis of L. heterotoma’s predicted venom gland proteins demonstrates conservation among endo- and ectoparasitoids within the Apocrita (e.g., this wasp and the jewel wasp Nasonia vitripennis) and stinging aculeates (e.g., the honey bee and ants). Enzyme and KEGG pathway profiling predicts that kinases, esterases, and hydrolases may contribute to venom activity in this unique wasp. To our knowledge, this investigation marks the first functional genomic study for a natural parasitic wasp of Drosophila. Our findings will help explain how L. heterotoma shuts down its hosts’ immunity and shed light on the molecular basis of a natural arms race between these insects. PMID:23688557

Metabolome and proteome profiling of complex I deficiency induced by rotenone.

Science.gov (United States)

Gielisch, Ina; Meierhofer, David

2015-01-02

Complex I (CI; NADH dehydrogenase) deficiency causes mitochondrial diseases, including Leigh syndrome. A variety of clinical symptoms of CI deficiency are known, including neurodegeneration. Here, we report an integrative study combining liquid chromatography-mass spectrometry (LC-MS)-based metabolome and proteome profiling in CI deficient HeLa cells. We report a rapid LC-MS-based method for the relative quantification of targeted metabolome profiling with an additional layer of confidence by applying multiple reaction monitoring (MRM) ion ratios for further identity confirmation and robustness. The proteome was analyzed by label-free quantification (LFQ). More than 6000 protein groups were identified. Pathway and network analyses revealed that the respiratory chain was highly deregulated, with metabolites such as FMN, FAD, NAD(+), and ADP, direct players of the OXPHOS system, and metabolites of the TCA cycle decreased up to 100-fold. Synthesis of functional iron-sulfur clusters, which are of central importance for the electron transfer chain, and degradation products like bilirubin were also significantly reduced. Glutathione metabolism on the pathway level, as well as individual metabolite components such as NADPH, glutathione (GSH), and oxidized glutathione (GSSG), was downregulated. Overall, metabolome and proteome profiles in CI deficient cells correlated well, supporting our integrated approach.

The 'revealed preferences' theory: Assumptions and conjectures

International Nuclear Information System (INIS)

Green, C.H.

1983-01-01

Being kind of intuitive psychology the 'Revealed-Preferences'- theory based approaches towards determining the acceptable risks are a useful method for the generation of hypotheses. In view of the fact that reliability engineering develops faster than methods for the determination of reliability aims the Revealed-Preferences approach is a necessary preliminary help. Some of the assumptions on which the 'Revealed-Preferences' theory is based will be identified and analysed and afterwards compared with experimentally obtained results. (orig./DG) [de

Classifying and profiling Social Networking Site users: a latent segmentation approach.

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Alarcón-del-Amo, María-del-Carmen; Lorenzo-Romero, Carlota; Gómez-Borja, Miguel-Ángel

2011-09-01

Social Networking Sites (SNSs) have showed an exponential growth in the last years. The first step for an efficient use of SNSs stems from an understanding of the individuals' behaviors within these sites. In this research, we have obtained a typology of SNS users through a latent segmentation approach, based on the frequency by which users perform different activities within the SNSs, sociodemographic variables, experience in SNSs, and dimensions related to their interaction patterns. Four different segments have been obtained. The "introvert" and "novel" users are the more occasional. They utilize SNSs mainly to communicate with friends, although "introverts" are more passive users. The "versatile" user performs different activities, although occasionally. Finally, the "expert-communicator" performs a greater variety of activities with a higher frequency. They tend to perform some marketing-related activities such as commenting on ads or gathering information about products and brands as well as commenting ads. The companies can take advantage of these segmentation schemes in different ways: first, by tracking and monitoring information interchange between users regarding their products and brands. Second, they should match the SNS users' profiles with their market targets to use SNSs as marketing tools. Finally, for most business, the expert users could be interesting opinion leaders and potential brand influencers.

Label-free protein profiling of formalin-fixed paraffin-embedded (FFPE) heart tissue reveals immediate mitochondrial impairment after ionising radiation.

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Azimzadeh, Omid; Scherthan, Harry; Yentrapalli, Ramesh; Barjaktarovic, Zarko; Ueffing, Marius; Conrad, Marcus; Neff, Frauke; Calzada-Wack, Julia; Aubele, Michaela; Buske, Christian; Atkinson, Michael J; Hauck, Stefanie M; Tapio, Soile

2012-04-18

Qualitative proteome profiling of formalin-fixed, paraffin-embedded (FFPE) tissue is advancing the field of clinical proteomics. However, quantitative proteome analysis of FFPE tissue is hampered by the lack of an efficient labelling method. The usage of conventional protein labelling on FFPE tissue has turned out to be inefficient. Classical labelling targets lysine residues that are blocked by the formalin treatment. The aim of this study was to establish a quantitative proteomics analysis of FFPE tissue by combining the label-free approach with optimised protein extraction and separation conditions. As a model system we used FFPE heart tissue of control and exposed C57BL/6 mice after total body irradiation using a gamma ray dose of 3 gray. We identified 32 deregulated proteins (p≤0.05) in irradiated hearts 24h after the exposure. The proteomics data were further evaluated and validated by bioinformatics and immunoblotting investigation. In good agreement with our previous results using fresh-frozen tissue, the analysis indicated radiation-induced alterations in three main biological pathways: respiratory chain, lipid metabolism and pyruvate metabolism. The label-free approach enables the quantitative measurement of radiation-induced alterations in FFPE tissue and facilitates retrospective biomarker identification using clinical archives. Copyright © 2012 Elsevier B.V. All rights reserved.

Integrative proteomics, genomics, and translational immunology approaches reveal mutated forms of Proteolipid Protein 1 (PLP1) and mutant-specific immune response in multiple sclerosis.

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Qendro, Veneta; Bugos, Grace A; Lundgren, Debbie H; Glynn, John; Han, May H; Han, David K

2017-03-01

In order to gain mechanistic insights into multiple sclerosis (MS) pathogenesis, we utilized a multi-dimensional approach to test the hypothesis that mutations in myelin proteins lead to immune activation and central nervous system autoimmunity in MS. Mass spectrometry-based proteomic analysis of human MS brain lesions revealed seven unique mutations of PLP1; a key myelin protein that is known to be destroyed in MS. Surprisingly, in-depth genomic analysis of two MS patients at the genomic DNA and mRNA confirmed mutated PLP1 in RNA, but not in the genomic DNA. Quantification of wild type and mutant PLP RNA levels by qPCR further validated the presence of mutant PLP RNA in the MS patients. To seek evidence linking mutations in abundant myelin proteins and immune-mediated destruction of myelin, specific immune response against mutant PLP1 in MS patients was examined. Thus, we have designed paired, wild type and mutant peptide microarrays, and examined antibody response to multiple mutated PLP1 in sera from MS patients. Consistent with the idea of different patients exhibiting unique mutation profiles, we found that 13 out of 20 MS patients showed antibody responses against specific but not against all the mutant-PLP1 peptides. Interestingly, we found mutant PLP-directed antibody response against specific mutant peptides in the sera of pre-MS controls. The results from integrative proteomic, genomic, and immune analyses reveal a possible mechanism of mutation-driven pathogenesis in human MS. The study also highlights the need for integrative genomic and proteomic analyses for uncovering pathogenic mechanisms of human diseases. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

On Active Current Selection for Lagrangian Profilers

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J. Jouffroy

2013-01-01

Full Text Available Autonomous Lagrangian profilers are now widely used as measurement and monitoring platforms, notably in observation programs as Argo. In a typical mode of operation, the profilers drift passively at their parking depthbefore making a vertical profile to go back to the surface. This paperpresents simple and computationally-efficient control strategies to activelyselect and use ocean currents so that a profiler can autonomously reach adesired destination. After briefly presenting a typical profiler andpossible mechanical modifications for a coastal environment, we introducesimple mathematical models for the profiler and the currents it will use. Wethen present simple feedback controllers that, using the direction of thecurrents and taking into account the configuration of the environment(coastal or deep-sea, is able to steer the profiler to any desiredhorizontal location. To illustrate the approach, a few results are presentedusing both simulated currents and real current velocity profiles from theNorth Sea.

Convolution based profile fitting

International Nuclear Information System (INIS)

Kern, A.; Coelho, A.A.; Cheary, R.W.

2002-01-01

diffractometers (e.g. BM16 at ESRF and Station 2.3 at Daresbury). In the literature, convolution based profile fitting is normally associated with microstructure analysis where the sample contribution needs to be separated from the instrument contribution in an observed profile. This is no longer the case. Convolution based profile fitting can be also performed on a fully empirical basis to provide better fits to data and a greater variety of profile shapes. With convolution based profile fitting virtually any peak shape and its angular dependence can be modelled. The approach may be based on a physical model (FPA) or performed empirically. The quality of fit by convolution is normally better than using other methods. The uncertainty in derived parameters is therefore reduced. The number of parameters required to describe a pattern is normally smaller than the 'analytical function approach' and therefore parameter correlation is reduced significantly, therefore, increasing profile complexity does not necessarily require an increasing number of parameters. Copyright (2002) Australian X-ray Analytical Association Inc

A Scalable Permutation Approach Reveals Replication and Preservation Patterns of Network Modules in Large Datasets.

Science.gov (United States)

Ritchie, Scott C; Watts, Stephen; Fearnley, Liam G; Holt, Kathryn E; Abraham, Gad; Inouye, Michael

2016-07-01

Network modules-topologically distinct groups of edges and nodes-that are preserved across datasets can reveal common features of organisms, tissues, cell types, and molecules. Many statistics to identify such modules have been developed, but testing their significance requires heuristics. Here, we demonstrate that current methods for assessing module preservation are systematically biased and produce skewed p values. We introduce NetRep, a rapid and computationally efficient method that uses a permutation approach to score module preservation without assuming data are normally distributed. NetRep produces unbiased p values and can distinguish between true and false positives during multiple hypothesis testing. We use NetRep to quantify preservation of gene coexpression modules across murine brain, liver, adipose, and muscle tissues. Complex patterns of multi-tissue preservation were revealed, including a liver-derived housekeeping module that displayed adipose- and muscle-specific association with body weight. Finally, we demonstrate the broader applicability of NetRep by quantifying preservation of bacterial networks in gut microbiota between men and women. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Targeted and untargeted-metabolite profiling to track the compositional integrity of ginger during processing using digitally-enhanced HPTLC pattern recognition analysis.

Science.gov (United States)

Ibrahim, Reham S; Fathy, Hoda

2018-03-30

Tracking the impact of commonly applied post-harvesting and industrial processing practices on the compositional integrity of ginger rhizome was implemented in this work. Untargeted metabolite profiling was performed using digitally-enhanced HPTLC method where the chromatographic fingerprints were extracted using ImageJ software then analysed with multivariate Principal Component Analysis (PCA) for pattern recognition. A targeted approach was applied using a new, validated, simple and fast HPTLC image analysis method for simultaneous quantification of the officially recognized markers 6-, 8-, 10-gingerol and 6-shogaol in conjunction with chemometric Hierarchical Clustering Analysis (HCA). The results of both targeted and untargeted metabolite profiling revealed that peeling, drying in addition to storage employed during processing have a great influence on ginger chemo-profile, the different forms of processed ginger shouldn't be used interchangeably. Moreover, it deemed necessary to consider the holistic metabolic profile for comprehensive evaluation of ginger during processing. Copyright © 2018. Published by Elsevier B.V.

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

International Nuclear Information System (INIS)

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

2015-01-01

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

Genome Wide Expression Profiling of Cancer Cell Lines Cultured in Microgravity Reveals Significant Dysregulation of Cell Cycle and MicroRNA Gene Networks.

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Prasanna Vidyasekar

Full Text Available Zero gravity causes several changes in metabolic and functional aspects of the human body and experiments in space flight have demonstrated alterations in cancer growth and progression. This study reports the genome wide expression profiling of a colorectal cancer cell line-DLD-1, and a lymphoblast leukemic cell line-MOLT-4, under simulated microgravity in an effort to understand central processes and cellular functions that are dysregulated among both cell lines. Altered cell morphology, reduced cell viability and an aberrant cell cycle profile in comparison to their static controls were observed in both cell lines under microgravity. The process of cell cycle in DLD-1 cells was markedly affected with reduced viability, reduced colony forming ability, an apoptotic population and dysregulation of cell cycle genes, oncogenes, and cancer progression and prognostic markers. DNA microarray analysis revealed 1801 (upregulated and 2542 (downregulated genes (>2 fold in DLD-1 cultures under microgravity while MOLT-4 cultures differentially expressed 349 (upregulated and 444 (downregulated genes (>2 fold under microgravity. The loss in cell proliferative capacity was corroborated with the downregulation of the cell cycle process as demonstrated by functional clustering of DNA microarray data using gene ontology terms. The genome wide expression profile also showed significant dysregulation of post transcriptional gene silencing machinery and multiple microRNA host genes that are potential tumor suppressors and proto-oncogenes including MIR22HG, MIR17HG and MIR21HG. The MIR22HG, a tumor-suppressor gene was one of the highest upregulated genes in the microarray data showing a 4.4 log fold upregulation under microgravity. Real time PCR validated the dysregulation in the host gene by demonstrating a 4.18 log fold upregulation of the miR-22 microRNA. Microarray data also showed dysregulation of direct targets of miR-22, SP1, CDK6 and CCNA2.

Bioinformatics Approach Based Research of Profile Protein Carbonic Anhydrase II Analysis as a Potential Candidate Cause Autism for The Variation of Learning Subjects Biotechnology

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Dian Eka A. F. Ningrum

2017-03-01

Full Text Available This study aims to determine the needs of learning variations on Biotechnology courses using bioinformatics approaches. One example of applied use of bioinformatics in biotechnology course is the analysis of protein profiles carbonic anhydrase II as a potential cause of autism candidate. This research is a qualitative descriptive study consisted of two phases. The first phase of the data obtained from observations of learning, student questionnaires, and questionnaires lecturer. Results from the first phase, namely the need for variations learning in Biotechnology course using bioinformatics. Collecting data on the second stage uses three webserver to predict the target protein and scientific articles. Visualization of proteins using PyMOL software. 3 based webserver which is used, the candidate of target proteins associated with autism is carbonic anhydrase II. The survey results revealed that the protein carbonic anhydrase II as a potential candidate for the cause of autism classified metaloenzim are able to bind with heavy metals. The content of heavy metals in autistic patients high that affect metabolism. This prediction of protein candidate cause autism is applied use to solve the problem in society, so that can achieve the learning outcome in biotechnology course.

Discrepancy between WISC-III and WISC-IV Cognitive Profile in Autism Spectrum: What Does It Reveal about Autistic Cognition?

Science.gov (United States)

Nader, Anne-Marie; Jelenic, Patricia; Soulières, Isabelle

2015-01-01

The cognitive profile and measured intellectual level vary according to assessment tools in children on the autism spectrum, much more so than in typically developing children. The recent inclusion of intellectual functioning in the diagnostic process for autism spectrum disorders leads to the crucial question on how to assess intelligence in autism, especially as some tests and subtests seem more sensitive to certain neurodevelopmental conditions. Our first aim was to examine the cognitive profile on the current version of the most widely used test, the Wechsler Intelligence Scales for Children (WISC-IV), for a homogenous subgroup of children on the autism spectrum, i.e. corresponding to DSM-IV diagnosis of “autism”. The second aim was to compare cognitive profiles obtained on the third edition versus 4th edition of WISC, in order to verify whether the WISC-IV yields a more distinctive cognitive profile in autistic children. The third aim was to examine the impact of the WISC-IV on the cognitive profile of another subgroup, children with Asperger’s Syndrome. 51 autistic, 15 Asperger and 42 typically developing children completed the WISC-IV and were individually matched to children who completed the WISC-III. Divergent WISC-IV profiles were observed despite no significant intelligence quotient difference between groups. Autistic children scored significantly higher on the Perceptual Reasoning Index than on the Verbal Comprehension Index, a discrepancy that nearly tripled in comparison to WISC-III results. Asperger children scored higher on the VCI than on other indexes, with the lowest score found on the Processing Speed Index. WISC-IV cognitive profiles were consistent with, but more pronounced than WISC-III profiles. Cognitive profiles are a valuable diagnostic tool for differential diagnosis, keeping in mind that children on the autism spectrum might be more sensitive to the choice of subtests used to assess intelligence. PMID:26673881

Discrepancy between WISC-III and WISC-IV Cognitive Profile in Autism Spectrum: What Does It Reveal about Autistic Cognition?

Science.gov (United States)

Nader, Anne-Marie; Jelenic, Patricia; Soulières, Isabelle

2015-01-01

The cognitive profile and measured intellectual level vary according to assessment tools in children on the autism spectrum, much more so than in typically developing children. The recent inclusion of intellectual functioning in the diagnostic process for autism spectrum disorders leads to the crucial question on how to assess intelligence in autism, especially as some tests and subtests seem more sensitive to certain neurodevelopmental conditions. Our first aim was to examine the cognitive profile on the current version of the most widely used test, the Wechsler Intelligence Scales for Children (WISC-IV), for a homogenous subgroup of children on the autism spectrum, i.e. corresponding to DSM-IV diagnosis of "autism". The second aim was to compare cognitive profiles obtained on the third edition versus 4th edition of WISC, in order to verify whether the WISC-IV yields a more distinctive cognitive profile in autistic children. The third aim was to examine the impact of the WISC-IV on the cognitive profile of another subgroup, children with Asperger's Syndrome. 51 autistic, 15 Asperger and 42 typically developing children completed the WISC-IV and were individually matched to children who completed the WISC-III. Divergent WISC-IV profiles were observed despite no significant intelligence quotient difference between groups. Autistic children scored significantly higher on the Perceptual Reasoning Index than on the Verbal Comprehension Index, a discrepancy that nearly tripled in comparison to WISC-III results. Asperger children scored higher on the VCI than on other indexes, with the lowest score found on the Processing Speed Index. WISC-IV cognitive profiles were consistent with, but more pronounced than WISC-III profiles. Cognitive profiles are a valuable diagnostic tool for differential diagnosis, keeping in mind that children on the autism spectrum might be more sensitive to the choice of subtests used to assess intelligence.

Discrepancy between WISC-III and WISC-IV Cognitive Profile in Autism Spectrum: What Does It Reveal about Autistic Cognition?

Directory of Open Access Journals (Sweden)

Anne-Marie Nader

Full Text Available The cognitive profile and measured intellectual level vary according to assessment tools in children on the autism spectrum, much more so than in typically developing children. The recent inclusion of intellectual functioning in the diagnostic process for autism spectrum disorders leads to the crucial question on how to assess intelligence in autism, especially as some tests and subtests seem more sensitive to certain neurodevelopmental conditions. Our first aim was to examine the cognitive profile on the current version of the most widely used test, the Wechsler Intelligence Scales for Children (WISC-IV, for a homogenous subgroup of children on the autism spectrum, i.e. corresponding to DSM-IV diagnosis of "autism". The second aim was to compare cognitive profiles obtained on the third edition versus 4th edition of WISC, in order to verify whether the WISC-IV yields a more distinctive cognitive profile in autistic children. The third aim was to examine the impact of the WISC-IV on the cognitive profile of another subgroup, children with Asperger's Syndrome. 51 autistic, 15 Asperger and 42 typically developing children completed the WISC-IV and were individually matched to children who completed the WISC-III. Divergent WISC-IV profiles were observed despite no significant intelligence quotient difference between groups. Autistic children scored significantly higher on the Perceptual Reasoning Index than on the Verbal Comprehension Index, a discrepancy that nearly tripled in comparison to WISC-III results. Asperger children scored higher on the VCI than on other indexes, with the lowest score found on the Processing Speed Index. WISC-IV cognitive profiles were consistent with, but more pronounced than WISC-III profiles. Cognitive profiles are a valuable diagnostic tool for differential diagnosis, keeping in mind that children on the autism spectrum might be more sensitive to the choice of subtests used to assess intelligence.

A Standardized Narrative Profile Approach to Self-Reflection and Assessment of Cross-Cultural Communication

Directory of Open Access Journals (Sweden)

Kyle J Wilby

2017-03-01

Full Text Available Objectives: 1 to explore clinical assessor’s values regarding behaviours related to cultural aspects of care, 2 to generate standardized narrative profiles regarding cultural behavioural outcomes within clinical teaching settings, and 3 to rank order standardized narrative profiles according to performance expectations. Methods: Ten interviews were completed with clinicians to determine values and performance expectations for culturally competent behaviours. Transcripts were produced and coded. Six narrative profiles were developed based on data obtained. Twenty clinicians categorized profiles according to performance expectations and rank ordered. Intraclass correlation coefficients (ICCs determined inter-rater reliability. Clinicians rated usability of profiles in clinical training settings. Results: Eighteen categories were coded with communication, awareness and ability most frequently reported with each ranging from 9.6-11.5% of the utterances. Consensus for categorization of all profiles was achieved at a level of 70% (ICC = 0.837, 95% CI 0.654-0.969. High inter-rater reliability was achieved for rank ordering (ICC = 0.815, 95% CI 0.561 to 0.984. Seventeen (85% clinicians agreed that the profiles would be usable in clinical training settings. Conclusions: Standardized narrative profiles may aid assessment and self-reflection for student performance within culturally diverse interactions. Conflict of Interest We declare no conflicts of interest or financial interests that the authors or members of their immediate families have in any product or service discussed in the manuscript, including grants (pending or received, employment, gifts, stock holdings or options, honoraria, consultancies, expert testimony, patents and royalties.   Type: Original Research

Comprehensive gene expression profiling reveals synergistic functional networks in cerebral vessels after hypertension or hypercholesterolemia.

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Wei-Yi Ong

Full Text Available Atherosclerotic stenosis of cerebral arteries or intracranial large artery disease (ICLAD is a major cause of stroke especially in Asians, Hispanics and Africans, but relatively little is known about gene expression changes in vessels at risk. This study compares comprehensive gene expression profiles in the middle cerebral artery (MCA of New Zealand White rabbits exposed to two stroke risk factors i.e. hypertension and/or hypercholesterolemia, by the 2-Kidney-1-Clip method, or dietary supplementation with cholesterol. Microarray and Ingenuity Pathway Analyses of the MCA of the hypertensive rabbits showed up-regulated genes in networks containing the node molecules: UBC (ubiquitin, P38 MAPK, ERK, NFkB, SERPINB2, MMP1 and APP (amyloid precursor protein; and down-regulated genes related to MAPK, ERK 1/2, Akt, 26 s proteasome, histone H3 and UBC. The MCA of hypercholesterolemic rabbits showed differentially expressed genes that are surprisingly, linked to almost the same node molecules as the hypertensive rabbits, despite a relatively low percentage of 'common genes' (21 and 7% between the two conditions. Up-regulated common genes were related to: UBC, SERPINB2, TNF, HNF4A (hepatocyte nuclear factor 4A and APP, and down-regulated genes, related to UBC. Increased HNF4A message and protein were verified in the aorta. Together, these findings reveal similar nodal molecules and gene pathways in cerebral vessels affected by hypertension or hypercholesterolemia, which could be a basis for synergistic action of risk factors in the pathogenesis of ICLAD.

Comprehensive Gene Expression Profiling Reveals Synergistic Functional Networks in Cerebral Vessels after Hypertension or Hypercholesterolemia

Science.gov (United States)

Ong, Wei-Yi; Ng, Mary Pei-Ern; Loke, Sau-Yeen; Jin, Shalai; Wu, Ya-Jun; Tanaka, Kazuhiro; Wong, Peter Tsun-Hon

2013-01-01

Atherosclerotic stenosis of cerebral arteries or intracranial large artery disease (ICLAD) is a major cause of stroke especially in Asians, Hispanics and Africans, but relatively little is known about gene expression changes in vessels at risk. This study compares comprehensive gene expression profiles in the middle cerebral artery (MCA) of New Zealand White rabbits exposed to two stroke risk factors i.e. hypertension and/or hypercholesterolemia, by the 2-Kidney-1-Clip method, or dietary supplementation with cholesterol. Microarray and Ingenuity Pathway Analyses of the MCA of the hypertensive rabbits showed up-regulated genes in networks containing the node molecules: UBC (ubiquitin), P38 MAPK, ERK, NFkB, SERPINB2, MMP1 and APP (amyloid precursor protein); and down-regulated genes related to MAPK, ERK 1/2, Akt, 26 s proteasome, histone H3 and UBC. The MCA of hypercholesterolemic rabbits showed differentially expressed genes that are surprisingly, linked to almost the same node molecules as the hypertensive rabbits, despite a relatively low percentage of ‘common genes’ (21 and 7%) between the two conditions. Up-regulated common genes were related to: UBC, SERPINB2, TNF, HNF4A (hepatocyte nuclear factor 4A) and APP, and down-regulated genes, related to UBC. Increased HNF4A message and protein were verified in the aorta. Together, these findings reveal similar nodal molecules and gene pathways in cerebral vessels affected by hypertension or hypercholesterolemia, which could be a basis for synergistic action of risk factors in the pathogenesis of ICLAD. PMID:23874591

Profile of organic food consumers

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Kranjac Mirjana

2017-01-01

Full Text Available The aim of this study is to prove that profile of organic food consumers is dependent on their socio-demographic characteristics as well as to shape universal organic food consumer profile. The survey included 398 consumers in Serbia. Results indicate existence of typical consumer's profile. The findings could be generalized proving that socio-demographic profiles in a larger population are strictly related to the decision to utilize organic food. The study finally contributes to the stakeholders in general, since the knowledge of the attributes can help all of them to play more active role in this supply chain. It should stimulate the personalized approach to the particular groups of consumers based on socio-demographic characteristics in order to intensify consumption of organic food and to create different marketing plans dependent on the particular countries or areas.

Personalized Proteome Profiles of Healthy and Tumor Human Colon Organoids Reveal Both Individual Diversity and Basic Features of Colorectal Cancer.

Science.gov (United States)

Cristobal, Alba; van den Toorn, Henk W P; van de Wetering, Marc; Clevers, Hans; Heck, Albert J R; Mohammed, Shabaz

2017-01-03

Diseases at the molecular level are complex and patient dependent, necessitating development of strategies that enable precision treatment to optimize clinical outcomes. Organoid technology has recently been shown to have the potential to recapitulate the in vivo characteristics of the original individual's tissue in a three-dimensional in vitro culture system. Here, we present a quantitative mass-spectrometry-based proteomic analysis and a comparative transcriptomic analysis of human colorectal tumor and healthy organoids derived, in parallel, from seven patients. Although gene and protein signatures can be derived to distinguish the tumor organoid population from healthy organoids, our data clearly reveal that each patient possesses a distinct organoid signature at the proteomic level. We demonstrate that a personalized patient-specific organoid proteome profile can be related to the diagnosis of a patient and with future development contribute to the generation of personalized therapies. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Molecular profiling of interspecific lowland rice populations derived ...

African Journals Online (AJOL)

STORAGESEVER

2008-12-03

Dec 3, 2008 ... Molecular profiling of interspecific lowland rice populations ... Both cluster and principal component analyses revealed two major groups ...... simulations. Theor ... inheritance, chromosomal location, and population dynamics.

Beneficial Phytochemicals with Anti-Tumor Potential Revealed through Metabolic Profiling of New Red Pigmented Lettuces (Lactuca sativa L.

Directory of Open Access Journals (Sweden)

Xiao-Xiao Qin

2018-04-01

Full Text Available The present study aimed to compare polyphenols among red lettuce cultivars and identify suitable cultivars for the development and utilization of healthy vegetables. Polyphenols, mineral elements, and antioxidant activity were analyzed in the leaves of six red pigmented lettuce (Lactuca sativa L. cultivars; thereafter, we assessed the anti-tumor effects of cultivar B-2, which displayed the highest antioxidant activity. Quadrupole–Orbitrap mass spectrometry analysis revealed four classes of polyphenols in these cultivars. The composition and contents of these metabolites varied significantly among cultivars and primarily depended on leaf color. The B-2 cultivar had the highest antioxidant potential than others because it contained the highest levels of polyphenols, especially anthocyanin, flavone, and phenolic acid; furthermore, this cultivar displayed anti-tumor effects against the human lung adenocarcinoma cell line A549, human hepatoma cell line Bel7402, human cancer colorectal adenoma cell line HCT-8, and HT-29 human colon cancer cell line. Hence, the new red-leaf lettuce cultivar B-2 has a distinct metabolite profile, with high potential for development and utilization of natural phytochemical and mineral resources in lettuces and can be used as a nutrient-dense food product.

Beneficial Phytochemicals with Anti-Tumor Potential Revealed through Metabolic Profiling of New Red Pigmented Lettuces (Lactuca sativa L.).

Science.gov (United States)

Qin, Xiao-Xiao; Zhang, Ming-Yue; Han, Ying-Yan; Hao, Jing-Hong; Liu, Chao-Jie; Fan, Shuang-Xi

2018-04-11

The present study aimed to compare polyphenols among red lettuce cultivars and identify suitable cultivars for the development and utilization of healthy vegetables. Polyphenols, mineral elements, and antioxidant activity were analyzed in the leaves of six red pigmented lettuce ( Lactuca sativa L.) cultivars; thereafter, we assessed the anti-tumor effects of cultivar B-2, which displayed the highest antioxidant activity. Quadrupole-Orbitrap mass spectrometry analysis revealed four classes of polyphenols in these cultivars. The composition and contents of these metabolites varied significantly among cultivars and primarily depended on leaf color. The B-2 cultivar had the highest antioxidant potential than others because it contained the highest levels of polyphenols, especially anthocyanin, flavone, and phenolic acid; furthermore, this cultivar displayed anti-tumor effects against the human lung adenocarcinoma cell line A549, human hepatoma cell line Bel7402, human cancer colorectal adenoma cell line HCT-8, and HT-29 human colon cancer cell line. Hence, the new red-leaf lettuce cultivar B-2 has a distinct metabolite profile, with high potential for development and utilization of natural phytochemical and mineral resources in lettuces and can be used as a nutrient-dense food product.

Gene Expression Profiling Reveals a Massive, Aneuploidy-Dependent Transcriptional Deregulation and Distinct Differences between Lymph Node–Negative and Lymph Node–Positive Colon Carcinomas

Science.gov (United States)

Grade, Marian; Hörmann, Patrick; Becker, Sandra; Hummon, Amanda B.; Wangsa, Danny; Varma, Sudhir; Simon, Richard; Liersch, Torsten; Becker, Heinz; Difilippantonio, Michael J.; Ghadimi, B. Michael; Ried, Thomas

2016-01-01

To characterize patterns of global transcriptional deregulation in primary colon carcinomas, we did gene expression profiling of 73 tumors [Unio Internationale Contra Cancrum stage II (n = 33) and stage III (n = 40)] using oligonucleotide microarrays. For 30 of the tumors, expression profiles were compared with those from matched normal mucosa samples. We identified a set of 1,950 genes with highly significant deregulation between tumors and mucosa samples (P 5-fold average expression difference between normal colon mucosa and carcinomas, including up-regulation of MYC and of HMGA1, a putative oncogene. Furthermore, we identified 68 genes that were significantly differentially expressed between lymph node–negative and lymph node–positive tumors (P deregulated genes were validated using quantitative real-time reverse transcription-PCR in >40 tumor and normal mucosa samples with good concordance between the techniques. Finally, we established a relationship between specific genomic imbalances, which were mapped for 32 of the analyzed colon tumors by comparative genomic hybridization, and alterations of global transcriptional activity. Previously, we had conducted a similar analysis of primary rectal carcinomas. The systematic comparison of colon and rectal carcinomas revealed a significant overlap of genomic imbalances and transcriptional deregulation, including activation of the Wnt/β-catenin signaling cascade, suggesting similar pathogenic pathways. PMID:17210682

A Novel Index for Online Voltage Stability Assessment Based on Correlation Characteristic of Voltage Profiles

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M. R. Aghamohammadi

2011-06-01

Full Text Available Abstract: Voltage instability is a major threat for security of power systems. Preserving voltage security margin at a certain limit is a vital requirement for today’s power systems. Assessment of voltage security margin is a challenging task demanding sophisticated indices. In this paper, for the purpose of on line voltage security assessment a new index based on the correlation characteristic of network voltage profile is proposed. Voltage profile comprising all bus voltages contains the effect of network structure, load-generation patterns and reactive power compensation on the system behaviour and voltage security margin. Therefore, the proposed index is capable to clearly reveal the effect of system characteristics and events on the voltage security margin. The most attractive feature for this index is its fast and easy calculation from synchronously measured voltage profile without any need to system modelling and simulation and without any dependency on network size. At any instant of system operation by merely measuring network voltage profile and no further simulation calculation this index could be evaluated with respect to a specific reference profile. The results show that the behaviour of this index with respect to the change in system security is independent of the selected reference profile. The simplicity and easy calculation make this index very suitable for on line application. The proposed approach has been demonstrated on IEEE 39 bus test system with promising results showing its effectiveness and applicability.

Microarray Glycan Profiling Reveals Algal Fucoidan Epitopes in Diverse Marine Metazoans

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Armando A. Salmeán

2017-09-01

Full Text Available Despite the biological importance and pharmacological potential of glycans from marine organisms, there are many unanswered questions regarding their distribution, function, and evolution. Here we describe microarray-based glycan profiling of a diverse selection of marine animals using antibodies raised against fucoidan isolated from a brown alga. We demonstrate the presence of two fucoidan epitopes in six animals belonging to three phyla including Porifera, Molusca, and Chordata. We studied the spatial distribution of these epitopes in Cliona celata (“boring sponge” and identified their restricted localization on the surface of internal chambers. Our results show the potential of high-throughput screening and probes commonly used in plant and algal cell wall biology to study the diversity and distribution of glycan structures in metazoans.

Criminal profiling as expert witness evidence: The implications of the profiler validity research.

Science.gov (United States)

Kocsis, Richard N; Palermo, George B

The use and development of the investigative tool colloquially known as criminal profiling has steadily increased over the past five decades throughout the world. Coupled with this growth has been a diversification in the suggested range of applications for this technique. Possibly the most notable of these has been the attempted transition of the technique from a tool intended to assist police investigations into a form of expert witness evidence admissible in legal proceedings. Whilst case law in various jurisdictions has considered with mutual disinclination the evidentiary admissibility of criminal profiling, a disjunction has evolved between these judicial examinations and the scientifically vetted research testing the accuracy (i.e., validity) of the technique. This article offers an analysis of the research directly testing the validity of the criminal profiling technique and the extant legal principles considering its evidentiary admissibility. This analysis reveals that research findings concerning the validity of criminal profiling are surprisingly compatible with the extant legal principles. The overall conclusion is that a discrete form of crime behavioural analysis is supported by the profiler validity research and could be regarded as potentially admissible expert witness evidence. Finally, a number of theoretical connections are also identified concerning the skills and qualifications of individuals who may feasibly provide such expert testimony. Copyright © 2016 Elsevier Ltd. All rights reserved.

Marine Actinobacteria as a source of compounds for phytopathogen control: An integrative metabolic-profiling / bioactivity and taxonomical approach.

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Luz A Betancur

Full Text Available Marine bacteria are considered as promising sources for the discovery of novel biologically active compounds. In this study, samples of sediment, invertebrate and algae were collected from the Providencia and Santa Catalina coral reef (Colombian Caribbean Sea with the aim of isolating Actinobateria-like strain able to produce antimicrobial and quorum quenching compounds against pathogens. Several approaches were used to select actinobacterial isolates, obtaining 203 strains from all samples. According to their 16S rRNA gene sequencing, a total of 24 strains was classified within Actinobacteria represented by three genera: Streptomyces, Micromonospora, and Gordonia. In order to assess their metabolic profiles, the actinobacterial strains were grown in liquid cultures, and LC-MS-based analyses from ethyl acetate fractions were performed. Based on taxonomical classification, screening information of activity against phytopathogenic strains and quorum quenching activity, as well as metabolic profiling, six out of the 24 isolates were selected for follow-up with chemical isolation and structure identification analyses of putative metabolites involved in antimicrobial activities.

Marine Actinobacteria as a source of compounds for phytopathogen control: An integrative metabolic-profiling / bioactivity and taxonomical approach

Science.gov (United States)

Betancur, Luz A.; Naranjo-Gaybor, Sandra J.; Vinchira-Villarraga, Diana M.; Moreno-Sarmiento, Nubia C.; Maldonado, Luis A.; Suarez-Moreno, Zulma R.; Acosta-González, Alejandro; Padilla-Gonzalez, Gillermo F.; Puyana, Mónica; Castellanos, Leonardo; Ramos, Freddy A.

2017-01-01

Marine bacteria are considered as promising sources for the discovery of novel biologically active compounds. In this study, samples of sediment, invertebrate and algae were collected from the Providencia and Santa Catalina coral reef (Colombian Caribbean Sea) with the aim of isolating Actinobateria-like strain able to produce antimicrobial and quorum quenching compounds against pathogens. Several approaches were used to select actinobacterial isolates, obtaining 203 strains from all samples. According to their 16S rRNA gene sequencing, a total of 24 strains was classified within Actinobacteria represented by three genera: Streptomyces, Micromonospora, and Gordonia. In order to assess their metabolic profiles, the actinobacterial strains were grown in liquid cultures, and LC-MS-based analyses from ethyl acetate fractions were performed. Based on taxonomical classification, screening information of activity against phytopathogenic strains and quorum quenching activity, as well as metabolic profiling, six out of the 24 isolates were selected for follow-up with chemical isolation and structure identification analyses of putative metabolites involved in antimicrobial activities. PMID:28225766

Hidden profiles and concealed information: strategic information sharing and use in group decision making.

Science.gov (United States)

Toma, Claudia; Butera, Fabrizio

2009-06-01

Two experiments investigated the differential impact of cooperation and competition on strategic information sharing and use in a three-person group decision-making task. Information was distributed in order to create a hidden profile so that disconfirmation of group members' initial preferences was required to solve the task. Experiment 1 revealed that competition, compared to cooperation, led group members to withhold unshared information, a difference that was not significant for shared information. In competition, compared to cooperation, group members were also more reluctant to disconfirm their initial preferences. Decision quality was lower in competition than in cooperation, this effect being mediated by disconfirmation use and not by information sharing. Experiment 2 replicated these findings and revealed the role of mistrust in predicting strategic information sharing and use in competition. These results support a motivated information processing approach of group decision making.

Revealing conceptual understanding of international business

NARCIS (Netherlands)

Sue Ashley; Dr. Harmen Schaap; Prof.Dr. Elly de Bruijn

2017-01-01

This study aims to identify an adequate approach for revealing conceptual understanding in higher professional education. Revealing students’ conceptual understanding is an important step towards developing effective curricula, assessment and aligned teaching strategies to enhance conceptual

Carbon profiles of remote Australian Indigenous communities: A base for opportunities

International Nuclear Information System (INIS)

Stewart, J.; Anda, M.; Harper, R.J.

2016-01-01

A decision-making model was constructed to assist remote Australian Indigenous communities select appropriate climate change mitigation programs. The Resilient Community and Livelihood Asset Integration Model (ReCLAIM) comprises six steps that focus on community assets and aspirations. The second of these steps is to determine the baseline carbon profiles of communities based on six sources of carbon emissions: materials, construction processes, stationary energy, transport, water systems and waste. The methodology employed an annualised lifecycle analysis of housing materials and construction, and an annual inventory of other emission sources. Profiles were calculated for two remote communities and compared to the Australian average and also average electricity consumption by remote communities in the Northern Territory. The results, expressed in tonnes of carbon dioxide equivalent (tCO_2-e), showed that average household carbon profiles of the two communities (6.3 and 4.1 tCO_2-e/capita/yr) were generally lower than the Australian average (7.3 tCO_2-e/capita/yr). The stationary energy results revealed that infrastructure and building design could raise fuel consumption and costs, and therefore carbon emissions, despite modest lifestyles. The carbon emission categories differed between the two communities highlighting the need for an individualised approach to understanding the drivers of carbon emissions and mitigation responses. - Highlights: •We model carbon profiles of two remote Aboriginal communities. •Community carbon profiles were lower than the Australian average. •We compare stationary energy with a 72-community sample average. •Low-carbon communities are possible with renewable energy systems. •Building design and energy source can impact significantly on emissions.

Can a surgery-first orthognathic approach reduce the total treatment time?

Science.gov (United States)

Jeong, Woo Shik; Choi, Jong Woo; Kim, Do Yeon; Lee, Jang Yeol; Kwon, Soon Man

2017-04-01

Although pre-surgical orthodontic treatment has been accepted as a necessary process for stable orthognathic correction in the traditional orthognathic approach, recent advances in the application of miniscrews and in the pre-surgical simulation of orthodontic management using dental models have shown that it is possible to perform a surgery-first orthognathic approach without pre-surgical orthodontic treatment. This prospective study investigated the surgical outcomes of patients with diagnosed skeletal class III dentofacial deformities who underwent orthognathic surgery between December 2007 and December 2014. Cephalometric landmark data for patients undergoing the surgery-first approach were analyzed in terms of postoperative changes in vertical and horizontal skeletal pattern, dental pattern, and soft tissue profile. Forty-five consecutive Asian patients with skeletal class III dentofacial deformities who underwent surgery-first orthognathic surgery and 52 patients who underwent conventional two-jaw orthognathic surgery were included. The analysis revealed that the total treatment period for the surgery-first approach averaged 14.6 months, compared with 22.0 months for the orthodontics-first approach. Comparisons between the immediate postoperative and preoperative and between the postoperative and immediate postoperative cephalometric data revealed factors that correlated with the total treatment duration. The surgery-first orthognathic approach can dramatically reduce the total treatment time, with no major complications. Copyright © 2016 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Diagnostic approach to neurotransmitter monoamine disorders: experience from clinical, biochemical, and genetic profiles.

Science.gov (United States)

Kuster, Alice; Arnoux, Jean-Baptiste; Barth, Magalie; Lamireau, Delphine; Houcinat, Nada; Goizet, Cyril; Doray, Bérénice; Gobin, Stéphanie; Schiff, Manuel; Cano, Aline; Amsallem, Daniel; Barnerias, Christine; Chaumette, Boris; Plaze, Marion; Slama, Abdelhamid; Ioos, Christine; Desguerre, Isabelle; Lebre, Anne-Sophie; de Lonlay, Pascale; Christa, Laurence

2018-01-01

To improve the diagnostic work-up of patients with diverse neurological diseases, we have elaborated specific clinical and CSF neurotransmitter patterns. Neurotransmitter determinations in CSF from 1200 patients revealed abnormal values in 228 (19%) cases. In 54/228 (24%) patients, a final diagnosis was identified. We have reported primary (30/54, 56%) and secondary (24/54, 44%) monoamine neurotransmitter disorders. For primary deficiencies, the most frequently mutated gene was DDC (n = 9), and the others included PAH with neuropsychiatric features (n = 4), PTS (n = 5), QDPR (n = 3), SR (n = 1), and TH (n = 1). We have also identified mutations in SLC6A3, FOXG1 (n = 1 of each), MTHFR (n = 3), FOLR1, and MTHFD (n = 1 of each), for dopamine transporter, neuronal development, and folate metabolism disorders, respectively. For secondary deficiencies, we have identified POLG (n = 3), ACSF3 (n = 1), NFU1, and SDHD (n = 1 of each), playing a role in mitochondrial function. Other mutated genes included: ADAR, RNASEH2B, RNASET2, SLC7A2-IT1 A/B lncRNA, and EXOSC3 involved in nuclear and cytoplasmic metabolism; RanBP2 and CASK implicated in post-traductional and scaffolding modifications; SLC6A19 regulating amino acid transport; MTM1, KCNQ2 (n = 2), and ATP1A3 playing a role in nerve cell electrophysiological state. Chromosome abnormalities, del(8)(p23)/dup(12) (p23) (n = 1), del(6)(q21) (n = 1), dup(17)(p13.3) (n = 1), and non-genetic etiologies (n = 3) were also identified. We have classified the final 54 diagnoses in 11 distinctive biochemical profiles and described them through 20 clinical features. To identify the specific molecular cause of abnormal NT profiles, (targeted) genomics might be used, to improve diagnosis and allow early treatment of complex and rare neurological genetic diseases.

High-Throughput Data of Circular RNA Profiles in Human Temporal Cortex Tissue Reveals Novel Insights into Temporal Lobe Epilepsy.

Science.gov (United States)

Li, Jiaxin; Lin, Haijun; Sun, Zhenrong; Kong, Guanyi; Yan, Xu; Wang, Yujiao; Wang, Xiaoxuan; Wen, Yanhua; Liu, Xiang; Zheng, Hongkun; Jia, Mei; Shi, Zhongfang; Xu, Rong; Yang, Shaohua; Yuan, Fang

2018-01-01

Circular RNAs (circRNAs) are a class of long noncoding RNAs with a closed loop structure that regulate gene expression as microRNA sponges. CircRNAs are more enriched in brain tissue, but knowledge of the role of circRNAs in temporal lobe epilepsy (TLE) has remained limited. This study is the first to identify the global expression profiles and characteristics of circRNAs in human temporal cortex tissue from TLE patients. Temporal cortices were collected from 17 TLE patients and 17 non-TLE patients. Total RNA was isolated, and high-throughput sequencing was used to profile the transcriptome of dysregulated circRNAs. Quantitative PCR was performed for the validation of changed circRNAs. In total, 78983 circRNAs, including 15.29% known and 84.71% novel circRNAs, were detected in this study. Intriguingly, 442 circRNAs were differentially expressed between the TLE and non-TLE groups (fold change≥2.0 and FDR≤0.05). Of these circRNAs, 188 were up-regulated, and 254 were down-regulated in the TLE patient group. Eight circRNAs were validated by real-time PCR. Remarkably, circ-EFCAB2 was intensely up-regulated, while circ-DROSHA expression was significantly lower in the TLE group than in the non-TLE group (P<0.05). Bioinformatic analysis revealed that circ-EFCAB2 binds to miR-485-5p to increase the expression level of the ion channel CLCN6, while circ-DROSHA interacts with miR-1252-5p to decrease the expression level of ATP1A2. The dysregulations of circRNAs may reflect the pathogenesis of TLE and circ-EFCAB2 and circ-DROSHA might be potential therapeutic targets and biomarkers in TLE patients. © 2018 The Author(s). Published by S. Karger AG, Basel.

Protein expression profiling of inflammatory mediators in human temporal lobe epilepsy reveals co-activation of multiple chemokines and cytokines

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Kan Anne A

2012-08-01

Full Text Available Abstract Mesial temporal lobe epilepsy (mTLE is a chronic and often treatment-refractory brain disorder characterized by recurrent seizures originating from the hippocampus. The pathogenic mechanisms underlying mTLE remain largely unknown. Recent clinical and experimental evidence supports a role of various inflammatory mediators in mTLE. Here, we performed protein expression profiling of 40 inflammatory mediators in surgical resection material from mTLE patients with and without hippocampal sclerosis, and autopsy controls using a multiplex bead-based immunoassay. In mTLE patients we identified 21 upregulated inflammatory mediators, including 10 cytokines and 7 chemokines. Many of these upregulated mediators have not previously been implicated in mTLE (for example, CCL22, IL-7 and IL-25. Comparing the three patient groups, two main hippocampal expression patterns could be distinguished, pattern I (for example, IL-10 and IL-25 showing increased expression in mTLE + HS patients compared to mTLE-HS and controls, and pattern II (for example, CCL4 and IL-7 showing increased expression in both mTLE groups compared to controls. Upregulation of a subset of inflammatory mediators (for example, IL-25 and IL-7 could not only be detected in the hippocampus of mTLE patients, but also in the neocortex. Principle component analysis was used to cluster the inflammatory mediators into several components. Follow-up analyses of the identified components revealed that the three patient groups could be discriminated based on their unique expression profiles. Immunocytochemistry showed that IL-25 IR (pattern I and CCL4 IR (pattern II were localized in astrocytes and microglia, whereas IL-25 IR was also detected in neurons. Our data shows co-activation of multiple inflammatory mediators in hippocampus and neocortex of mTLE patients, indicating activation of multiple pro- and anti-epileptogenic immune pathways in this disease.

Integrated microRNA and gene expression profiling reveals the crucial miRNAs in curcumin anti-lung cancer cell invasion.

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Zhan, Jian-Wei; Jiao, De-Min; Wang, Yi; Song, Jia; Wu, Jin-Hong; Wu, Li-Jun; Chen, Qing-Yong; Ma, Sheng-Lin

2017-09-01

Curcumin (diferuloylmethane) has chemopreventive and therapeutic properties against many types of tumors, both in vitro and in vivo. Previous reports have shown that curcumin exhibits anti-invasive activities, but the mechanisms remain largely unclear. In this study, both microRNA (miRNA) and messenger RNA (mRNA) expression profiles were used to characterize the anti-metastasis mechanisms of curcumin in human non-small cell lung cancer A549 cell line. Microarray analysis revealed that 36 miRNAs were differentially expressed between the curcumin-treated and control groups. miR-330-5p exhibited maximum upregulation, while miR-25-5p exhibited maximum downregulation in the curcumin treatment group. mRNA expression profiles and functional analysis indicated that 226 differentially expressed mRNAs belonged to different functional categories. Significant pathway analysis showed that mitogen-activated protein kinase, transforming growth factor-β, and Wnt signaling pathways were significantly downregulated. At the same time, axon guidance, glioma, and ErbB tyrosine kinase receptor signaling pathways were significantly upregulated. We constructed a miRNA gene network that contributed to the curcumin inhibition of metastasis in lung cancer cells. let-7a-3p, miR-1262, miR-499a-5p, miR-1276, miR-331-5p, and miR-330-5p were identified as key microRNA regulators in the network. Finally, using miR-330-5p as an example, we confirmed the role of miR-330-5p in mediating the anti-migration effect of curcumin, suggesting the importance of miRNAs in the regulation of curcumin biological activity. Our findings provide new insights into the anti-metastasis mechanism of curcumin in lung cancer. © 2017 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Analytical approach for determining beam profiles in water phantom of symmetric and asymmetric fields of wedged, blocked, and open photon beams.

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Tahmasebi Birgani, Mohamad Javad; Chegeni, Nahid; Arvandi, Shole; Razmjoo Ghalaee, Sasan; Zabihzadeh, Mansoor; Khezerloo, Davood

2013-11-04

Nowadays, in most radiotherapy departments, the commercial treatment planning systems (TPS) used to calculate dose distributions needs to be verified; therefore, quick, easy-to-use, and low-cost dose distribution algorithms are desirable to test and verify the performance of the TPS. In this paper, we put forth an analytical method to calculate the phantom scatter contribution and depth dose on the central axis based on the equivalent square concept. Then, this method was generalized to calculate the profiles at any depth and for several field shapes - regular or irregular fields - under symmetry and asymmetry photon beam conditions. Varian 2100 C/D and Siemens Primus Plus linacs with 6 and 18 MV photon beam were used for irradiations. Percentage depth doses (PDDs) were measured for a large number of square fields for both energies and for 45° wedge, which were employed to obtain the profiles in any depth. To assess the accuracy of the calculated profiles, several profile measurements were carried out for some treatment fields. The calculated and measured profiles were compared by gamma-index calculation. All γ-index calculations were based on a 3% dose criterion and a 3 mm dose-to-agreement (DTA) acceptance criterion. The γ values were less than 1 at most points. However, the maximum γ observed was about 1.10 in the penumbra region in most fields and in the central area for the asymmetric fields. This analytical approach provides a generally quick and fairly accurate algorithm to calculate dose distribution for some treatment fields in conventional radiotherapy.

Family Profiles of Cohesion and Parenting Practices and Latino Youth Adjustment.

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Bámaca-Colbert, Mayra Y; Gonzales-Backen, Melinda; Henry, Carolyn S; Kim, Peter S Y; Roblyer, Martha Zapata; Plunkett, Scott W; Sands, Tovah

2017-08-10

Using a sample of 279 (52% female) Latino youth in 9th grade (M = 14.57, SD = .56), we examined profiles of family cohesion and parenting practices and their relation to youth adjustment. The results of latent profile analyses revealed four family profiles: Engaged, Supportive, Intrusive, and Disengaged. Latino youth in the Supportive family profile showed most positive adjustment (highest self-esteem and lowest depressive symptoms), followed by youth in the Engaged family profile. Youth in the Intrusive and Disengaged profiles showed the lowest levels of positive adjustment. The findings contribute to the current literature on family dynamics, family profiles, and youth psychological adjustment within specific ethnic groups. © 2017 Family Process Institute.

Adaptive User Profiles in Pervasive Advertising Environments

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Alt, Florian; Balz, Moritz; Kristes, Stefanie; Shirazi, Alireza Sahami; Mennenöh, Julian; Schmidt, Albrecht; Schröder, Hendrik; Goedicke, Michael

Nowadays modern advertising environments try to provide more efficient ads by targeting costumers based on their interests. Various approaches exist today as to how information about the users' interests can be gathered. Users can deliberately and explicitly provide this information or user's shopping behaviors can be analyzed implicitly. We implemented an advertising platform to simulate an advertising environment and present adaptive profiles, which let users setup profiles based on a self-assessment, and enhance those profiles with information about their real shopping behavior as well as about their activity intensity. Additionally, we explain how pervasive technologies such as Bluetooth can be used to create a profile anonymously and unobtrusively.

Transcriptional profiling in response to terminal drought stress reveals differential responses along the wheat genome

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Ferrari Francesco

2009-06-01

Full Text Available Abstract Background Water stress during grain filling has a marked effect on grain yield, leading to a reduced endosperm cell number and thus sink capacity to accumulate dry matter. The bread wheat cultivar Chinese Spring (CS, a Chinese Spring terminal deletion line (CS_5AL-10 and the durum wheat cultivar Creso were subjected to transcriptional profiling after exposure to mild and severe drought stress at the grain filling stage to find evidences of differential stress responses associated to different wheat genome regions. Results The transcriptome analysis of Creso, CS and its deletion line revealed 8,552 non redundant probe sets with different expression levels, mainly due to the comparisons between the two species. The drought treatments modified the expression of 3,056 probe sets. Besides a set of genes showing a similar drought response in Creso and CS, cluster analysis revealed several drought response features that can be associated to the different genomic structure of Creso, CS and CS_5AL-10. Some drought-related genes were expressed at lower level (or not expressed in Creso (which lacks the D genome or in the CS_5AL-10 deletion line compared to CS. The chromosome location of a set of these genes was confirmed by PCR-based mapping on the D genome (or the 5AL-10 region. Many clusters were characterized by different level of expression in Creso, CS and CS_AL-10, suggesting that the different genome organization of the three genotypes may affect plant adaptation to stress. Clusters with similar expression trend were grouped and functional classified to mine the biological mean of their activation or repression. Genes involved in ABA, proline, glycine-betaine and sorbitol pathways were found up-regulated by drought stress. Furthermore, the enhanced expression of a set of transposons and retrotransposons was detected in CS_5AL-10. Conclusion Bread and durum wheat genotypes were characterized by a different physiological reaction to water

MicroRNA profiling in Muc2 knockout mice of colitis-associated cancer model reveals epigenetic alterations during chronic colitis malignant transformation.

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Yonghua Bao

Full Text Available Our previous studies have demonstrated that genetic deletion of the Muc2 gene causes colorectal cancers in mice. The current study further showed that at the early stage (3 months the mice exhibited colorectal cancer, including a unique phenotype of rectal prolapsed (rectal severe inflammation and adenocarcinoma. Thus, the age of 3 months might be the key point of the transition from chronic inflammation to cancer. To determine the mechanisms of the malignant transformation, we conducted miRNA array on the colonic epithelial cells from the 3-month Muc2-/- and +/+ mice. MicroRNA profiling showed differential expression of miRNAs (i.e. lower or higher expression enrichments in Muc2-/- mice. 15 of them were validated by quantitative PCR. Based on relevance to cytokine and cancer, 4 miRNAs (miR-138, miR-145, miR-146a, and miR-150 were validate and were found significantly downregulated in human colitis and colorectal cancer tissues. The network of the targets of these miRNAs was characterized, and interestedly, miRNA-associated cytokines were significantly increased in Muc2-/-mice. This is the first to reveal the importance of aberrant expression of miRNAs in dynamically transformation from chronic colitis to colitis-associated cancer. These findings shed light on revealing the mechanisms of chronic colitis malignant transformation.

RNA profiles of porcine embryos during genome activation reveal complex metabolic switch sensitive to in vitro conditions

DEFF Research Database (Denmark)

Østrup, Olga; Olbricht, Gayla; Østrup, Esben

2013-01-01

produced in vitro. Overall, our data are in good accordance with previously published, genome-wide profiling data in other species. Moreover, comparison with mouse and human embryos showed striking overlap in functional annotation of transcripts during the EGA, suggesting conserved basic mechanisms...... a handful of reports characterize changing transcriptome profiles and resulting metabolic changes in cleavage stage embryos. The aims of the current study were to investigate RNA profiles of in vivo developed (ivv) and in vitro produced (ivt) porcine embryos before (2-cell stage) and after (late 4-cell...... from oocyte and are imposed either before oocyte aspiration or during in vitro maturation. IVT embryos have altered content of apoptotic factors, cell cycle regulation factors and spindle components, and transcription factors, which all may contribute to reduced developmental competence of embryos...

Accelerated Profile HMM Searches.

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Sean R Eddy

2011-10-01

Full Text Available Profile hidden Markov models (profile HMMs and probabilistic inference methods have made important contributions to the theory of sequence database homology search. However, practical use of profile HMM methods has been hindered by the computational expense of existing software implementations. Here I describe an acceleration heuristic for profile HMMs, the "multiple segment Viterbi" (MSV algorithm. The MSV algorithm computes an optimal sum of multiple ungapped local alignment segments using a striped vector-parallel approach previously described for fast Smith/Waterman alignment. MSV scores follow the same statistical distribution as gapped optimal local alignment scores, allowing rapid evaluation of significance of an MSV score and thus facilitating its use as a heuristic filter. I also describe a 20-fold acceleration of the standard profile HMM Forward/Backward algorithms using a method I call "sparse rescaling". These methods are assembled in a pipeline in which high-scoring MSV hits are passed on for reanalysis with the full HMM Forward/Backward algorithm. This accelerated pipeline is implemented in the freely available HMMER3 software package. Performance benchmarks show that the use of the heuristic MSV filter sacrifices negligible sensitivity compared to unaccelerated profile HMM searches. HMMER3 is substantially more sensitive and 100- to 1000-fold faster than HMMER2. HMMER3 is now about as fast as BLAST for protein searches.

Metabolite Profiling of Red Sea Corals

KAUST Repository

Ortega, Jovhana Alejandra

2016-12-01

Looking at the metabolite profile of an organism provides insights into the metabolomic state of a cell and hence also into pathways employed. Little is known about the metabolites produced by corals and their algal symbionts. In particular, corals from the central Red Sea are understudied, but interesting study objects, as they live in one of the warmest and most saline environments and can provide clues as to the adjustment of corals to environmental change. In this study, we applied gas chromatography – mass spectrometry (GC–MS) metabolite profiling to analyze the metabolic profile of four coral species and their associated symbionts: Fungia granulosa, Acropora hemprichii, Porites lutea, and Pocillopora verrucosa. We identified and quantified 102 compounds among primary and secondary metabolites across all samples. F. granulosa and its symbiont showed a total of 59 metabolites which were similar to the 51 displayed by P. verrucosa. P. lutea and A. hemprichii both harbored 40 compounds in conjunction with their respective isolated algae. Comparing across species, 28 metabolites were exclusively present in algae, while 38 were exclusive to corals. A principal component and cluster analyses revealed that metabolite profiles clustered between corals and algae, but each species harbored a distinct catalog of metabolites. The major classes of compounds were carbohydrates and amino acids. Taken together, this study provides a first description of metabolites of Red Sea corals and their associated symbionts. As expected, the metabolites of coral hosts differ from their algal symbionts, but each host and algal species harbor a unique set of metabolites. This corroborates that host-symbiont species pairs display a fine-tuned complementary metabolism that provide insights into the specific nature of the symbiosis. Our analysis also revealed aquatic pollutants, which suggests that metabolite profiling might be used for monitoring pollution levels and assessing

In silico activity profiling reveals the mechanism of action of antimalarials discovered in a high-throughput screen

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Plouffe, David; Brinker, Achim; McNamara, Case; Henson, Kerstin; Kato, Nobutaka; Kuhen, Kelli; Nagle, Advait; Adrián, Francisco; Matzen, Jason T.; Anderson, Paul; Nam, Tae-gyu; Gray, Nathanael S.; Chatterjee, Arnab; Janes, Jeff; Yan, S. Frank; Trager, Richard; Caldwell, Jeremy S.; Schultz, Peter G.; Zhou, Yingyao; Winzeler, Elizabeth A.

2008-01-01

The growing resistance to current first-line antimalarial drugs represents a major health challenge. To facilitate the discovery of new antimalarials, we have implemented an efficient and robust high-throughput cell-based screen (1,536-well format) based on proliferation of Plasmodium falciparum (Pf) in erythrocytes. From a screen of ≈1.7 million compounds, we identified a diverse collection of ≈6,000 small molecules comprised of >530 distinct scaffolds, all of which show potent antimalarial activity (antimalarials were identified in this screen, thus validating our approach. In addition, we identified many novel chemical scaffolds, which likely act through both known and novel pathways. We further show that in some cases the mechanism of action of these antimalarials can be determined by in silico compound activity profiling. This method uses large datasets from unrelated cellular and biochemical screens and the guilt-by-association principle to predict which cellular pathway and/or protein target is being inhibited by select compounds. In addition, the screening method has the potential to provide the malaria community with many new starting points for the development of biological probes and drugs with novel antiparasitic activities. PMID:18579783

Multidimensional profiles of health locus of control in Hispanic Americans.

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Champagne, Brian R; Fox, Rina S; Mills, Sarah D; Sadler, Georgia Robins; Malcarne, Vanessa L

2016-10-01

Latent profile analysis identified health locus of control profiles among 436 Hispanic Americans who completed the Multidimensional Health Locus of Control scales. Results revealed four profiles: Internally Oriented-Weak, -Moderate, -Strong, and Externally Oriented. The profile groups were compared on sociocultural and demographic characteristics, health beliefs and behaviors, and physical and mental health outcomes. The Internally Oriented-Strong group had less cancer fatalism, religiosity, and equity health attributions, and more alcohol consumption than the other three groups; the Externally Oriented group had stronger equity health attributions and less alcohol consumption. Deriving multidimensional health locus of control profiles through latent profile analysis allows examination of the relationships of health locus of control subtypes to health variables. © The Author(s) 2015.

Proteomic profiling during the pre-competent to competent transition of the biofouling polychaete Hydroides elegans

KAUST Repository

Zhang, Yu

2014-08-22

The polychaete, Hydroides elegans, is a tube-building worm that is widely distributed in tropical and subtropical seas. It is a dominant fouling species and thus a major target organism in antifouling research. Here, the first high-throughput proteomic profiling of pre-competent and competent larvae of H. elegans is reported with the identification of 1,519 and 1,322 proteins, respectively. These proteins were associated with a variety of biological processes. However, a large proportion was involved in energy metabolism, redox homeostasis, and microtubule-based processes. A comparative analysis revealed 21 proteins that were differentially regulated in larvae approaching competency.

Proteomic profiling during the pre-competent to competent transition of the biofouling polychaete Hydroides elegans

KAUST Repository

Zhang, Yu; Sun, Jin; Zhang, Huoming; Chandramouli, Kondethimmanahalli; Xu, Ying; He, Lisheng; Ravasi, Timothy; Qian, Peiyuan

2014-01-01

The polychaete, Hydroides elegans, is a tube-building worm that is widely distributed in tropical and subtropical seas. It is a dominant fouling species and thus a major target organism in antifouling research. Here, the first high-throughput proteomic profiling of pre-competent and competent larvae of H. elegans is reported with the identification of 1,519 and 1,322 proteins, respectively. These proteins were associated with a variety of biological processes. However, a large proportion was involved in energy metabolism, redox homeostasis, and microtubule-based processes. A comparative analysis revealed 21 proteins that were differentially regulated in larvae approaching competency.

Proteomic profiling during the pre-competent to competent transition of the biofouling polychaete Hydroides elegans.

Science.gov (United States)

Zhang, Yu; Sun, Jin; Zhang, Huoming; Chandramouli, Kondethimmanahalli H; Xu, Ying; He, Li-Sheng; Ravasi, Timothy; Qian, Pei-Yuan

2014-09-01

The polychaete, Hydroides elegans, is a tube-building worm that is widely distributed in tropical and subtropical seas. It is a dominant fouling species and thus a major target organism in antifouling research. Here, the first high-throughput proteomic profiling of pre-competent and competent larvae of H. elegans is reported with the identification of 1,519 and 1,322 proteins, respectively. These proteins were associated with a variety of biological processes. However, a large proportion was involved in energy metabolism, redox homeostasis, and microtubule-based processes. A comparative analysis revealed 21 proteins that were differentially regulated in larvae approaching competency.

Understanding Biases in Ribosome Profiling Experiments Reveals Signatures of Translation Dynamics in Yeast.

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Jeffrey A Hussmann

2015-12-01

Full Text Available Ribosome profiling produces snapshots of the locations of actively translating ribosomes on messenger RNAs. These snapshots can be used to make inferences about translation dynamics. Recent ribosome profiling studies in yeast, however, have reached contradictory conclusions regarding the average translation rate of each codon. Some experiments have used cycloheximide (CHX to stabilize ribosomes before measuring their positions, and these studies all counterintuitively report a weak negative correlation between the translation rate of a codon and the abundance of its cognate tRNA. In contrast, some experiments performed without CHX report strong positive correlations. To explain this contradiction, we identify unexpected patterns in ribosome density downstream of each type of codon in experiments that use CHX. These patterns are evidence that elongation continues to occur in the presence of CHX but with dramatically altered codon-specific elongation rates. The measured positions of ribosomes in these experiments therefore do not reflect the amounts of time ribosomes spend at each position in vivo. These results suggest that conclusions from experiments in yeast using CHX may need reexamination. In particular, we show that in all such experiments, codons decoded by less abundant tRNAs were in fact being translated more slowly before the addition of CHX disrupted these dynamics.

Antifungal susceptibility profiles of 1698 yeast reference strains revealing potential emerging human pathogens.

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Marie Desnos-Ollivier

Full Text Available New molecular identification techniques and the increased number of patients with various immune defects or underlying conditions lead to the emergence and/or the description of novel species of human and animal fungal opportunistic pathogens. Antifungal susceptibility provides important information for ecological, epidemiological and therapeutic issues. The aim of this study was to assess the potential risk of the various species based on their antifungal drug resistance, keeping in mind the methodological limitations. Antifungal susceptibility profiles to the five classes of antifungal drugs (polyens, azoles, echinocandins, allylamines and antimetabolites were determined for 1698 yeast reference strains belonging to 992 species (634 Ascomycetes and 358 Basidiomycetes. Interestingly, geometric mean minimum inhibitory concentrations (MICs of all antifungal drugs tested were significantly higher for Basidiomycetes compared to Ascomycetes (p<0.001. Twenty four strains belonging to 23 species of which 19 were Basidiomycetes seem to be intrinsically "resistant" to all drugs. Comparison of the antifungal susceptibility profiles of the 4240 clinical isolates and the 315 reference strains belonging to 53 shared species showed similar results. Even in the absence of demonstrated in vitro/in vivo correlation, knowing the in vitro susceptibility to systemic antifungal agents and the putative intrinsic resistance of yeast species present in the environment is important because they could become opportunistic pathogens.

Optimized Estimation of Surface Layer Characteristics from Profiling Measurements

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Doreene Kang

2016-01-01

Full Text Available New sampling techniques such as tethered-balloon-based measurements or small unmanned aerial vehicles are capable of providing multiple profiles of the Marine Atmospheric Surface Layer (MASL in a short time period. It is desirable to obtain surface fluxes from these measurements, especially when direct flux measurements are difficult to obtain. The profiling data is different from the traditional mean profiles obtained at two or more fixed levels in the surface layer from which surface fluxes of momentum, sensible heat, and latent heat are derived based on Monin-Obukhov Similarity Theory (MOST. This research develops an improved method to derive surface fluxes and the corresponding MASL mean profiles of wind, temperature, and humidity with a least-squares optimization method using the profiling measurements. This approach allows the use of all available independent data. We use a weighted cost function based on the framework of MOST with the cost being optimized using a quasi-Newton method. This approach was applied to seven sets of data collected from the Monterey Bay. The derived fluxes and mean profiles show reasonable results. An empirical bias analysis is conducted using 1000 synthetic datasets to evaluate the robustness of the method.

Toxicological effects of benzo(a)pyrene, DDT and their mixture on the green mussel Perna viridis revealed by proteomic and metabolomic approaches.

Science.gov (United States)

Song, Qinqin; Chen, Hao; Li, Yuhu; Zhou, Hailong; Han, Qian; Diao, Xiaoping

2016-02-01

Benzo(a)pyrene (BaP) and dichlorodiphenyltrichloroethane (DDT) are persistent organic pollutants and environmental estrogens (EEs) with known toxicity towards the green mussel, Perna viridis. In this study, the toxic effects of BaP (10 µg/L) and DDT (10 µg/L) and their mixture were assessed in green mussel gills with proteomic and metabolomic approaches. Metabolic responses indicated that BaP mainly caused disturbance in osmotic regulation by significantly decrease in branched chain amino acids, dimethylamine and dimethylglycine in gills of male green mussels after exposure for 7 days. DDT mainly caused disturbance in osmotic regulation and energy metabolism by differential alteration of betaine, dimethylamine, dimethylglycine, amino acids, and succinate in gills of male green mussels. However, the mixture of BaP and DDT didn't show obvious metabolite changes. Proteomic analysis showed different protein expression profiles between different treatment groups, which demonstrated that BaP, DDT and their mixture may have different modes of action. Proteomic responses revealed that BaP induced cell apoptosis, disturbance in protein digestion and energy metabolism in gills of green mussels, whereas DDT exposure altered proteins that were associated with oxidative stress, cytoskeleton and cell structure, protein digestion and energy metabolism. However, the mixture of BaP and DDT affected proteins related to the oxidative stress, cytoskeleton and cell structure, protein biosynthesis and modification, energy metabolism, growth and apoptosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Psychological profile: the problem of modeling the unknown criminal personality

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Г. М. Гетьман

2013-10-01

Full Text Available The article investigates the problem of modeling an unknown person in the preparation of criminal psychological profile. Some approaches to the concept of "psychological profile" and "psychological portrait", in particular the proposed delineation of these terms. We consider the system steps in the development of the psychological profile of an unknown perpetrator.

Ion channel profile of TRPM8 cold receptors reveals a novel role of TASK-3 potassium channels in thermosensation

Science.gov (United States)

Morenilla-Palao, Cruz; Luis, Enoch; Fernández-Peña, Carlos; Quintero, Eva; Weaver, Janelle L.; Bayliss, Douglas A.; Viana, Félix

2017-01-01

Summary Animals sense cold ambient temperatures through the activation of peripheral thermoreceptors that express TRPM8, a cold- and menthol-activated ion channel. These receptors can discriminate a very wide range of temperatures from innocuous to noxious. The molecular mechanism responsible for the variable sensitivity of individual cold receptors to temperature is unclear. To address this question, we performed a detailed ion channel expression analysis of cold sensitive neurons, combining BAC transgenesis with a molecular profiling approach in FACS purified TRPM8 neurons. We found that TASK-3 leak potassium channels are highly enriched in a subpopulation of these sensory neurons. The thermal threshold of TRPM8 cold neurons is decreased during TASK-3 blockade and in mice lacking TASK-3 and, most importantly, these mice display hypersensitivity to cold. Our results demonstrate a novel role of TASK-3 channels in thermosensation, showing that a channel-based combinatorial strategy in TRPM8 cold thermoreceptors leads to molecular specialization and functional diversity. PMID:25199828

An Integrated Cell Purification and Genomics Strategy Reveals Multiple Regulators of Pancreas Development

Science.gov (United States)

Benitez, Cecil M.; Qu, Kun; Sugiyama, Takuya; Pauerstein, Philip T.; Liu, Yinghua; Tsai, Jennifer; Gu, Xueying; Ghodasara, Amar; Arda, H. Efsun; Zhang, Jiajing; Dekker, Joseph D.; Tucker, Haley O.; Chang, Howard Y.; Kim, Seung K.

2014-01-01

The regulatory logic underlying global transcriptional programs controlling development of visceral organs like the pancreas remains undiscovered. Here, we profiled gene expression in 12 purified populations of fetal and adult pancreatic epithelial cells representing crucial progenitor cell subsets, and their endocrine or exocrine progeny. Using probabilistic models to decode the general programs organizing gene expression, we identified co-expressed gene sets in cell subsets that revealed patterns and processes governing progenitor cell development, lineage specification, and endocrine cell maturation. Purification of Neurog3 mutant cells and module network analysis linked established regulators such as Neurog3 to unrecognized gene targets and roles in pancreas development. Iterative module network analysis nominated and prioritized transcriptional regulators, including diabetes risk genes. Functional validation of a subset of candidate regulators with corresponding mutant mice revealed that the transcription factors Etv1, Prdm16, Runx1t1 and Bcl11a are essential for pancreas development. Our integrated approach provides a unique framework for identifying regulatory genes and functional gene sets underlying pancreas development and associated diseases such as diabetes mellitus. PMID:25330008

An integrated cell purification and genomics strategy reveals multiple regulators of pancreas development.

Directory of Open Access Journals (Sweden)

Cecil M Benitez

2014-10-01

Full Text Available The regulatory logic underlying global transcriptional programs controlling development of visceral organs like the pancreas remains undiscovered. Here, we profiled gene expression in 12 purified populations of fetal and adult pancreatic epithelial cells representing crucial progenitor cell subsets, and their endocrine or exocrine progeny. Using probabilistic models to decode the general programs organizing gene expression, we identified co-expressed gene sets in cell subsets that revealed patterns and processes governing progenitor cell development, lineage specification, and endocrine cell maturation. Purification of Neurog3 mutant cells and module network analysis linked established regulators such as Neurog3 to unrecognized gene targets and roles in pancreas development. Iterative module network analysis nominated and prioritized transcriptional regulators, including diabetes risk genes. Functional validation of a subset of candidate regulators with corresponding mutant mice revealed that the transcription factors Etv1, Prdm16, Runx1t1 and Bcl11a are essential for pancreas development. Our integrated approach provides a unique framework for identifying regulatory genes and functional gene sets underlying pancreas development and associated diseases such as diabetes mellitus.

Lipidomic profiling reveals distinct differences in plasma lipid composition in healthy, prediabetic, and type 2 diabetic individuals

Science.gov (United States)

Zhong, Huanzi; Fang, Chao; Fan, Yanqun; Lu, Yan; Wen, Bo; Ren, Huahui; Hou, Guixue; Yang, Fangming; Xie, Hailiang; Jie, Zhuye; Peng, Ye; Ye, Zhiqiang; Wu, Jiegen; Zi, Jin; Zhao, Guoqing; Chen, Jiayu; Bao, Xiao; Hu, Yihe; Gao, Yan; Zhang, Jun; Yang, Huanming; Wang, Jian; Madsen, Lise; Kristiansen, Karsten

2017-01-01

Abstract The relationship between dyslipidemia and type 2 diabetes mellitus (T2D) has been extensively reported, but the global lipid profiles, especially in the East Asia population, associated with the development of T2D remain to be characterized. Liquid chromatography coupled to tandem mass spectrometry was applied to detect the global lipidome in the fasting plasma of 293 Chinese individuals, including 114 T2D patients, 81 prediabetic subjects, and 98 individuals with normal glucose tolerance (NGT). Both qualitative and quantitative analyses revealed a gradual change in plasma lipid features with T2D patients exhibiting characteristics close to those of prediabetic individuals, whereas they differed significantly from individuals with NGT. We constructed and validated a random forest classifier with 28 lipidomic features that effectively discriminated T2D from NGT or prediabetes. Most of the selected features significantly correlated with diabetic clinical indices. Hydroxybutyrylcarnitine was positively correlated with fasting plasma glucose, 2-hour postprandial glucose, glycated hemoglobin, and insulin resistance index (HOMA-IR). Lysophosphatidylcholines such as lysophosphatidylcholine (18:0), lysophosphatidylcholine (18:1), and lysophosphatidylcholine (18:2) were all negatively correlated with HOMA-IR. The altered plasma lipidome in Chinese T2D and prediabetic subjects suggests that lipid features may play a role in the pathogenesis of T2D and that such features may provide a basis for evaluating risk and monitoring disease development. PMID:28505362

Revealing Conceptual Understanding of International Business

Science.gov (United States)

Ashley, Sue; Schaap, Harmen; de Bruijn, Elly

2017-01-01

This study aims to identify an adequate approach for revealing conceptual understanding in higher professional education. Revealing students' conceptual understanding is an important step towards developing effective curricula, assessment and aligned teaching strategies to enhance conceptual understanding in higher education. Essays and concept…

Targeted Metabolomics Approach To Detect the Misuse of Steroidal Aromatase Inhibitors in Equine Sports by Biomarker Profiling.

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Chan, George Ho Man; Ho, Emmie Ngai Man; Leung, David Kwan Kon; Wong, Kin Sing; Wan, Terence See Ming

2016-01-05

The use of anabolic androgenic steroids (AAS) is prohibited in both human and equine sports. The conventional approach in doping control testing for AAS (as well as other prohibited substances) is accomplished by the direct detection of target AAS or their characteristic metabolites in biological samples using hyphenated techniques such as gas chromatography or liquid chromatography coupled with mass spectrometry. Such an approach, however, falls short when dealing with unknown designer steroids where reference materials and their pharmacokinetics are not available. In addition, AASs with fast elimination times render the direct detection approach ineffective as the detection window is short. A targeted metabolomics approach is a plausible alternative to the conventional direct detection approach for controlling the misuse of AAS in sports. Because the administration of AAS of the same class may trigger similar physiological responses or effects in the body, it may be possible to detect such administrations by monitoring changes in the endogenous steroidal expression profile. This study attempts to evaluate the viability of using the targeted metabolomics approach to detect the administration of steroidal aromatase inhibitors, namely androst-4-ene-3,6,17-trione (6-OXO) and androsta-1,4,6-triene-3,17-dione (ATD), in horses. Total (free and conjugated) urinary concentrations of 31 endogenous steroids were determined by gas chromatography-tandem mass spectrometry for a group of 2 resting and 2 in-training thoroughbred geldings treated with either 6-OXO or ATD. Similar data were also obtained from a control (untreated) group of in-training thoroughbred geldings (n = 28). Statistical processing and chemometric procedures using principle component analysis and orthogonal projection to latent structures-discriminant analysis (OPLS-DA) have highlighted 7 potential biomarkers that could be used to differentiate urine samples obtained from the control and the treated groups

Proanthocyanidin profile of cowpea (Vigna unguiculata) reveals catechin-O-glucoside as the dominant compound.

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Ojwang, Leonnard O; Yang, Liyi; Dykes, Linda; Awika, Joseph

2013-08-15

Proanthocyanidin (PA) profile and content can have important nutritional and health implications on plant foods. Six diverse cowpea phenotypes (black, red, green, white, light-brown and golden-brown) were investigated for PA composition using normal-phase HPLC and reversed-phase UPLC-TQD-MS. Catechin and (epi)afzelechin were the major flavan-3-ol units. Unusual composition was observed in all cowpea phenotypes with significant degrees of glycosylation in the monomers and dimers. The PA content of cowpea (dry basis) ranged between 2.2 and 6.3 mg/g. Monomeric flavan-3-ols were the largest group of PA (36-69%) in cowpea, with catechin-7-O-glucoside accounting for most (about 88%) of the monomers. The oligomers with degree of polymerization (DP) 2-4 ranged from 0.41 to 1.3 mg/g (15-20%), whereas DP>10 polymers accounted for only 13.5% of PA. Future studies that highlight the impact of the unusual cowpea PA profile on nutritional and bioactive properties of this important legume are warranted. Copyright © 2013 Elsevier Ltd. All rights reserved.

Antioxidant profiling of native Andean potato tubers (Solanum tuberosum L.) reveals cultivars with high levels of beta-carotene, alpha-tocopherol, chlorogenic acid, and petanin.

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Andre, Christelle M; Oufir, Mouhssin; Guignard, Cédric; Hoffmann, Lucien; Hausman, Jean-François; Evers, Danièle; Larondelle, Yvan

2007-12-26

The antioxidant profile of 23 native Andean potato cultivars has been investigated from a human nutrition perspective. The main carotenoid and tocopherol compounds were studied using high-performance liquid chromatography coupled with a diode array detector (HPLC-DAD) and a fluorescence detector, respectively, whereas polyphenols (including anthocyanins in colored tubers) were identified by means of both HPLC-mass spectrometry and HPLC-DAD. Antioxidant profiling revealed significant genotypic variations as well as cultivars of particular interest from a nutritional point of view. Concentrations of the health-promoting carotenoids, lutein and zeaxanthin, ranged from 1.12 to 17.69 microg g(-1) of dry weight (DW) and from 0 to 17.7 microg g(-1) of DW, with cultivars 704353 and 702472 showing the highest levels in lutein and zeaxanthin, respectively. Whereas beta-carotene is rarely reported in potato tubers, remarkable levels of this dietary provitamin A carotenoid were detected in 16 native varieties, ranging from 0.42 to 2.19 microg g(-1) of DW. The amounts of alpha-tocopherol found in Andean potato tubers, extending from 2.73 to 20.80 microg g(-1) of DW, were clearly above the quantities generally reported for commercial varieties. Chlorogenic acid and its isomers dominated the polyphenolic profile of each cultivar. Dark purple-fleshed tubers from the cultivar 704429 contained exceptionally high levels of total anthocyanins (16.33 mg g(-1) of DW). The main anthocyanin was identified as petanin (petunidin-3-p-coumaroyl-rutinoside-5-glucoside). The results suggest that Andean potato cultivars should be exploited in screening and breeding programs for the development of potato varieties with enhanced health and nutritional benefits.

Data Transfer Advisor with Transport Profiling Optimization

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Rao, Nageswara S. [ORNL; Liu, Qiang [ORNL; Yun, Daqing [Harrisburg University; Wu, Chase Qishi [New Jersey Institute of Technology; Kettimuthu, R. [Argonne National Laboratory (ANL); Jung, Eun-sung [Argonne National Laboratory (ANL)

2017-11-01

The network infrastructures have been rapidly upgraded in many high-performance networks (HPNs). However, such infrastructure investment has not led to corresponding performance improvement in big data transfer, especially at the application layer, largely due to the complexity of optimizing transport control on end hosts. We design and implement ProbData, a PRofiling Optimization Based DAta Transfer Advisor, to help users determine the most effective data transfer method with the most appropriate control parameter values to achieve the best data transfer performance. ProbData employs a profiling optimization based approach to exploit the optimal operational zone of various data transfer methods in support of big data transfer in extreme scale scientific applications. We present a theoretical framework of the optimized profiling approach employed in ProbData as wellas its detailed design and implementation. The advising procedure and performance benefits of ProbData are illustrated and evaluated by proof-of-concept experiments in real-life networks.

Active Tectonics Revealed by River Profiles along the Puqu Fault

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Ping Lu

2015-04-01

Full Text Available The Puqu Fault is situated in Southern Tibet. It is influenced by the eastward extrusion of Northern Tibet and carries the clockwise rotation followed by the southward extrusion. Thus, the Puqu Fault is bounded by the principal dynamic zones and the tectonic evolution remains active alongside. This study intends to understand the tectonic activity in the Puqu Fault Region from the river profiles obtained from the remotely sensed satellite imagery. A medium resolution Digital Elevation Model (DEM, 20 m was generated from an Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER stereo pair of images and the stream network in this region was extracted from this DEM. The indices of slope and drainage area were subsequently calculated from this ASTER DEM. Based on the stream power law, the area-slope plots of the streams were delineated to derive the indices of channel concavity and steepness, which are closely related to tectonic activity. The results show the active tectonics varying significantly along the Puqu Fault, although the potential influence of glaciations may exist. These results are expected to be useful for a better understanding of tectonic evolution in Southeastern Tibet.

Transcriptional Profiling of Egg Allergy and Relationship to Disease Phenotype.

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Roman Kosoy

Full Text Available Egg allergy is one of the most common food allergies of childhood. There is a lack of information on the immunologic basis of egg allergy beyond the role of IgE.To use transcriptional profiling as a novel approach to uncover immunologic processes associated with different phenotypes of egg allergy.Peripheral blood mononuclear cells (PBMCs were obtained from egg-allergic children who were defined as reactive (BER or tolerant (BET to baked egg, and from food allergic controls (AC who were egg non-allergic. PBMCs were stimulated with egg white protein. Gene transcription was measured by microarray after 24 h, and cytokine secretion by multiplex assay after 5 days.The transcriptional response of PBMCs to egg protein differed between BER and BET versus AC subjects. Compared to the AC group, the BER group displayed increased expression of genes associated with allergic inflammation as well as corresponding increased secretion of IL-5, IL-9 and TNF-α. A similar pattern was observed for the BET group. Further similarities in gene expression patterns between BER and BET groups, as well as some important differences, were revealed using a novel Immune Annotation resource developed for this project. This approach identified several novel processes not previously associated with egg allergy, including positive associations with TLR4-stimulated myeloid cells and activated NK cells, and negative associations with an induced Treg signature. Further pathway analysis of differentially expressed genes comparing BER to BET subjects showed significant enrichment of IFN-α and IFN-γ response genes, as well as genes associated with virally-infected DCs.Transcriptional profiling identified several novel pathways and processes that differed when comparing the response to egg allergen in BET, BER, and AC groups. We conclude that this approach is a useful hypothesis-generating mechanism to identify novel immune processes associated with allergy and tolerance to forms

Global Expression Profiling and Pathway Analysis of Mouse Mammary Tumor Reveals Strain and Stage Specific Dysregulated Pathways in Breast Cancer Progression.

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Mei, Yan; Yang, Jun-Ping; Lang, Yan-Hong; Peng, Li-Xia; Yang, Ming-Ming; Liu, Qin; Meng, Dong-Fang; Zheng, Li-Sheng; Qiang, Yuan-Yuan; Xu, Liang; Li, Chang-Zhi; Wei, Wen-Wen; Niu, Ting; Peng, Xing-Si; Yang, Qin; Lin, Fen; Hu, Hao; Xu, Hong-Fa; Huang, Bi-Jun; Wang, Li-Jing; Qian, Chao-Nan

2018-05-01

It is believed that the alteration of tissue microenvironment would affect cancer initiation and progression. However, little is known in terms of the underlying molecular mechanisms that would affect the initiation and progression of breast cancer. In the present study, we use two murine mammary tumor models with different speeds of tumor initiation and progression for whole genome expression profiling to reveal the involved genes and signaling pathways. The pathways regulating PI3K-Akt signaling and Ras signaling were activated in Fvb mice and promoted tumor progression. Contrastingly, the pathways regulating apoptosis and cellular senescence were activated in Fvb.B6 mice and suppressed tumor progression. We identified distinct patterns of oncogenic pathways activation at different stages of breast cancer, and uncovered five oncogenic pathways that were activated in both human and mouse breast cancers. The genes and pathways discovered in our study would be useful information for other researchers and drug development.

Comprehensive Genomic Profiling of 282 Pediatric Low- and High-Grade Gliomas Reveals Genomic Drivers, Tumor Mutational Burden, and Hypermutation Signatures.

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Johnson, Adrienne; Severson, Eric; Gay, Laurie; Vergilio, Jo-Anne; Elvin, Julia; Suh, James; Daniel, Sugganth; Covert, Mandy; Frampton, Garrett M; Hsu, Sigmund; Lesser, Glenn J; Stogner-Underwood, Kimberly; Mott, Ryan T; Rush, Sarah Z; Stanke, Jennifer J; Dahiya, Sonika; Sun, James; Reddy, Prasanth; Chalmers, Zachary R; Erlich, Rachel; Chudnovsky, Yakov; Fabrizio, David; Schrock, Alexa B; Ali, Siraj; Miller, Vincent; Stephens, Philip J; Ross, Jeffrey; Crawford, John R; Ramkissoon, Shakti H

2017-12-01

Pediatric brain tumors are the leading cause of death for children with cancer in the U.S. Incorporating next-generation sequencing data for both pediatric low-grade (pLGGs) and high-grade gliomas (pHGGs) can inform diagnostic, prognostic, and therapeutic decision-making. We performed comprehensive genomic profiling on 282 pediatric gliomas (157 pHGGs, 125 pLGGs), sequencing 315 cancer-related genes and calculating the tumor mutational burden (TMB; mutations per megabase [Mb]). In pLGGs, we detected genomic alterations (GA) in 95.2% (119/125) of tumors. BRAF was most frequently altered (48%; 60/125), and FGFR1 missense (17.6%; 22/125), NF1 loss of function (8.8%; 11/125), and TP53 (5.6%; 7/125) mutations were also detected. Rearrangements were identified in 35% of pLGGs, including KIAA1549-BRAF , QKI-RAF1 , FGFR3-TACC3 , CEP85L-ROS1 , and GOPC-ROS1 fusions. Among pHGGs, GA were identified in 96.8% (152/157). The genes most frequently mutated were TP53 (49%; 77/157), H3F3A (37.6%; 59/157), ATRX (24.2%; 38/157), NF1 (22.2%; 35/157), and PDGFRA (21.7%; 34/157). Interestingly, most H3F3A mutations (81.4%; 35/43) were the variant K28M. Midline tumor analysis revealed H3F3A mutations (40%; 40/100) consisted solely of the K28M variant. Pediatric high-grade gliomas harbored oncogenic EML4-ALK , DGKB-ETV1 , ATG7-RAF1 , and EWSR1-PATZ1 fusions. Six percent (9/157) of pHGGs were hypermutated (TMB >20 mutations per Mb; range 43-581 mutations per Mb), harboring mutations deleterious for DNA repair in MSH6, MSH2, MLH1, PMS2, POLE , and POLD1 genes (78% of cases). Comprehensive genomic profiling of pediatric gliomas provides objective data that promote diagnostic accuracy and enhance clinical decision-making. Additionally, TMB could be a biomarker to identify pediatric glioblastoma (GBM) patients who may benefit from immunotherapy. By providing objective data to support diagnostic, prognostic, and therapeutic decision-making, comprehensive genomic profiling is necessary for

Gene expression profiling during asexual development of the late blight pathogen Phytophthora infestans reveals a highly dynamic transcriptome.

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Judelson, Howard S; Ah-Fong, Audrey M V; Aux, George; Avrova, Anna O; Bruce, Catherine; Cakir, Cahid; da Cunha, Luis; Grenville-Briggs, Laura; Latijnhouwers, Maita; Ligterink, Wilco; Meijer, Harold J G; Roberts, Samuel; Thurber, Carrie S; Whisson, Stephen C; Birch, Paul R J; Govers, Francine; Kamoun, Sophien; van West, Pieter; Windass, John

2008-04-01

Much of the pathogenic success of Phytophthora infestans, the potato and tomato late blight agent, relies on its ability to generate from mycelia large amounts of sporangia, which release zoospores that encyst and form infection structures. To better understand these stages, Affymetrix GeneChips based on 15,650 unigenes were designed and used to profile the life cycle. Approximately half of P. infestans genes were found to exhibit significant differential expression between developmental transitions, with approximately (1)/(10) being stage-specific and most changes occurring during zoosporogenesis. Quantitative reverse-transcription polymerase chain reaction assays confirmed the robustness of the array results and showed that similar patterns of differential expression were obtained regardless of whether hyphae were from laboratory media or infected tomato. Differentially expressed genes encode potential cellular regulators, especially protein kinases; metabolic enzymes such as those involved in glycolysis, gluconeogenesis, or the biosynthesis of amino acids or lipids; regulators of DNA synthesis; structural proteins, including predicted flagellar proteins; and pathogenicity factors, including cell-wall-degrading enzymes, RXLR effector proteins, and enzymes protecting against plant defense responses. Curiously, some stage-specific transcripts do not appear to encode functional proteins. These findings reveal many new aspects of oomycete biology, as well as potential targets for crop protection chemicals.

Label-Free LC-MS Profiling of Skeletal Muscle Reveals Heart-Type Fatty Acid Binding Protein as a Candidate Biomarker of Aerobic Capacity

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Zulezwan A. Malik

2013-12-01

.54-fold (p = 0.0064 more abundant in HCR than LCR soleus. This discovery was verified using selective reaction monitoring (SRM of the y5 ion (551.21 m/z of the doubly-charged peptide SLGVGFATR (454.19 m/z of residues 23–31 of FABPH. SRM was conducted on technical replicates of each biological sample and exhibited a coefficient of variation of 20%. The abundance of FABPH measured by SRM was 2.84-fold greater (p = 0.0095 in HCR muscle. In addition, SRM of FABPH was performed in vastus lateralis samples of young and elderly humans with different habitual activity levels (collected during a previous study finding FABPH abundance was 2.23-fold greater (p = 0.0396 in endurance-trained individuals regardless of differences in age. In summary, our findings in HCR/LCR rats provide protein-level confirmation for earlier transcriptome profiling work and show LC-MS is a viable means of profiling the abundance of almost all major metabolic enzymes of skeletal muscle in a highly parallel manner. Moreover, our approach is relatively more time efficient than techniques relying on orthogonal separations, and we demonstrate LC-MS profiling of the HCR/LCR selection model was able to highlight biomarkers that also exhibit differences in trained and untrained human muscle.

A Sorghum bicolor expression atlas reveals dynamic genotype-specific expression profiles for vegetative tissues of grain, sweet and bioenergy sorghums

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Shakoor, N; Nair, R; Crasta, O; Morris, G; Feltus, A; Kresovich, S

2014-01-23

Background: Effective improvement in sorghum crop development necessitates a genomics-based approach to identify functional genes and QTLs. Sequenced in 2009, a comprehensive annotation of the sorghum genome and the development of functional genomics resources is key to enable the discovery and deployment of regulatory and metabolic genes and gene networks for crop improvement. Results: This study utilizes the first commercially available whole-transcriptome sorghum microarray (Sorgh-WTa520972F) to identify tissue and genotype-specific expression patterns for all identified Sorghum bicolor exons and UTRs. The genechip contains 1,026,373 probes covering 149,182 exons (27,577 genes) across the Sorghum bicolor nuclear, chloroplast, and mitochondrial genomes. Specific probesets were also included for putative non-coding RNAs that may play a role in gene regulation (e. g., microRNAs), and confirmed functional small RNAs in related species (maize and sugarcane) were also included in our array design. We generated expression data for 78 samples with a combination of four different tissue types (shoot, root, leaf and stem), two dissected stem tissues (pith and rind) and six diverse genotypes, which included 6 public sorghum lines (R159, Atlas, Fremont, PI152611, AR2400 and PI455230) representing grain, sweet, forage, and high biomass ideotypes. Conclusions: Here we present a summary of the microarray dataset, including analysis of tissue-specific gene expression profiles and associated expression profiles of relevant metabolic pathways. With an aim to enable identification and functional characterization of genes in sorghum, this expression atlas presents a new and valuable resource to the research community.

Bifactor Approach to Modeling Multidimensionality of Physical Self-Perception Profile

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Chung, ChihMing; Liao, Xiaolan; Song, Hairong; Lee, Taehun

2016-01-01

The multi-dimensionality of Physical Self-Perception Profile (PSPP) has been acknowledged by the use of correlated-factor model and second-order model. In this study, the authors critically endorse the bifactor model, as a substitute to address the multi-dimensionality of PSPP. To cross-validate the models, analyses are conducted first in…

Deducing hybrid performance from parental metabolic profiles of young primary roots of maize by using a multivariate diallel approach.

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Kristen Feher

Full Text Available Heterosis, the greater vigor of hybrids compared to their parents, has been exploited in maize breeding for more than 100 years to produce ever better performing elite hybrids of increased yield. Despite extensive research, the underlying mechanisms shaping the extent of heterosis are not well understood, rendering the process of selecting an optimal set of parental lines tedious. This study is based on a dataset consisting of 112 metabolite levels in young roots of four parental maize inbred lines and their corresponding twelve hybrids, along with the roots' biomass as a heterotic trait. Because the parental biomass is a poor predictor for hybrid biomass, we established a model framework to deduce the biomass of the hybrid from metabolite profiles of its parental lines. In the proposed framework, the hybrid metabolite levels are expressed relative to the parental levels by incorporating the standard concept of additivity/dominance, which we name the Combined Relative Level (CRL. Our modeling strategy includes a feature selection step on the parental levels which are demonstrated to be predictive of CRL across many hybrid metabolites. We demonstrate that these selected parental metabolites are further predictive of hybrid biomass. Our approach directly employs the diallel structure in a multivariate fashion, whereby we attempt to not only predict macroscopic phenotype (biomass, but also molecular phenotype (metabolite profiles. Therefore, our study provides the first steps for further investigations of the genetic determinants to metabolism and, ultimately, growth. Finally, our success on the small-scale experiments implies a valid strategy for large-scale experiments, where parental metabolite profiles may be used together with profiles of selected hybrids as a training set to predict biomass of all possible hybrids.

The impact of time perspective latent profiles on college drinking: a multidimensional approach.

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Braitman, Abby L; Henson, James M

2015-04-01

Zimbardo and Boyd's(1) time perspective, or the temporal framework individuals use to process information, has been shown to predict health behaviors such as alcohol use. Previous studies supported the predictive validity of individual dimensions of time perspective, with some dimensions acting as protective factors and others as risk factors. However, some studies produced findings contrary to the general body of literature. In addition, time perspective is a multidimensional construct, and the combination of perspectives may be more predictive than individual dimensions in isolation; consequently, multidimensional profiles are a more accurate measure of individual differences and more appropriate for predicting health behaviors. The current study identified naturally occurring profiles of time perspective and examined their association with risky alcohol use. Data were collected from a college student sample (n = 431, mean age = 20.41 years) using an online survey. Time perspective profiles were identified using latent profile analysis. Bootstrapped regression models identified a protective class that engaged in significantly less overall drinking (β = -0.254) as well as engaging in significantly less episodic high risk drinking (β = -0.274). There was also emerging evidence of a high risk time perspective profile that was linked to more overall drinking (β = 0.198) and engaging in more high risk drinking (β = 0.245), though these differences were not significant. CONCLUSIONS/IMPORTANCE: These findings support examining time perspective in a multidimensional framework rather than individual dimensions in isolation. Implications include identifying students most in need of interventions, and tailoring interventions to target temporal framing in decision-making.

Protein profiles of CCL5, HPGDS, and NPSR1 in plasma reveal association with childhood asthma.

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Hamsten, C; Häggmark, A; Grundström, J; Mikus, M; Lindskog, C; Konradsen, J R; Eklund, A; Pershagen, G; Wickman, M; Grunewald, J; Melén, E; Hedlin, G; Nilsson, P; van Hage, M

2016-09-01

Asthma is a common chronic childhood disease with many different phenotypes that need to be identified. We analyzed a broad range of plasma proteins in children with well-characterized asthma phenotypes to identify potential markers of childhood asthma. Using an affinity proteomics approach, plasma levels of 362 proteins covered by antibodies from the Human Protein Atlas were investigated in a total of 154 children with persistent or intermittent asthma and controls. After screening, chemokine ligand 5 (CCL5) hematopoietic prostaglandin D synthase (HPGDS) and neuropeptide S receptor 1 (NPSR1) were selected for further investigation. Significantly lower levels of both CCL5 and HPGDS were found in children with persistent asthma, while NPSR1 was found at higher levels in children with mild intermittent asthma compared to healthy controls. In addition, the protein levels were investigated in another respiratory disease, sarcoidosis, showing significantly higher NPSR1 levels in sera from sarcoidosis patients compared to healthy controls. Immunohistochemical staining of healthy tissues revealed high cytoplasmic expression of HPGDS in mast cells, present in stroma of both airway epithelia, lung as well as in other organs. High expression of NPSR1 was observed in neuroendocrine tissues, while no expression was observed in airway epithelia or lung. In conclusion, we have utilized a broad-scaled affinity proteomics approach to identify three proteins with altered plasma levels in asthmatic children, representing one of the first evaluations of HPGDS and NPSR1 protein levels in plasma. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chemogenomics profiling of drug targets of peptidoglycan biosynthesis pathway in Leptospira interrogans by virtual screening approaches.

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Bhattacharjee, Biplab; Simon, Rose Mary; Gangadharaiah, Chaithra; Karunakar, Prashantha

2013-06-28

Leptospirosis is a worldwide zoonosis of global concern caused by Leptospira interrogans. The availability of ligand libraries has facilitated the search for novel drug targets using chemogenomics approaches, compared with the traditional method of drug discovery, which is time consuming and yields few leads with little intracellular information for guiding target selection. Recent subtractive genomics studies have revealed the putative drug targets in peptidoglycan biosynthesis pathways in Leptospira interrogans. Aligand library for the murD ligase enzyme in the peptidoglycan pathway has also been identified. Our approach in this research involves screening of the pre-existing ligand library of murD with related protein family members in the putative drug target assembly in the peptidoglycan biosynthesis pathway. A chemogenomics approach has been implemented here, which involves screening of known ligands of a protein family having analogous domain architecture for identification of leads for existing druggable protein family members. By means of this approach, one murC and one murF inhibitor were identified, providing a platform for developing an antileptospirosis drug targeting the peptidoglycan biosynthesis pathway. Given that the peptidoglycan biosynthesis pathway is exclusive to bacteria, the in silico identified mur ligase inhibitors are expected to be broad-spectrum Gram-negative inhibitors if synthesized and tested in in vitro and in vivo assays.

Simultaneous profiling of seed-associated bacteria and fungi reveals antagonistic interactions between microorganisms within a shared epiphytic microbiome on Triticum and Brassica seeds

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Links, Matthew G; Demeke, Tigst; Gräfenhan, Tom; Hill, Janet E; Hemmingsen, Sean M; Dumonceaux, Tim J

2014-01-01

In order to address the hypothesis that seeds from ecologically and geographically diverse plants harbor characteristic epiphytic microbiota, we characterized the bacterial and fungal microbiota associated with Triticum and Brassica seed surfaces. The total microbial complement was determined by amplification and sequencing of a fragment of chaperonin 60 (cpn60). Specific microorganisms were quantified by qPCR. Bacteria and fungi corresponding to operational taxonomic units (OTU) that were identified in the sequencing study were isolated and their interactions examined. A total of 5477 OTU were observed from seed washes. Neither total epiphytic bacterial load nor community richness/evenness was significantly different between the seed types; 578 OTU were shared among all samples at a variety of abundances. Hierarchical clustering revealed that 203 were significantly different in abundance on Triticum seeds compared with Brassica. Microorganisms isolated from seeds showed 99–100% identity between the cpn60 sequences of the isolates and the OTU sequences from this shared microbiome. Bacterial strains identified as Pantoea agglomerans had antagonistic properties toward one of the fungal isolates (Alternaria sp.), providing a possible explanation for their reciprocal abundances on both Triticum and Brassica seeds. cpn60 enabled the simultaneous profiling of bacterial and fungal microbiota and revealed a core seed-associated microbiota shared between diverse plant genera. PMID:24444052

Large-scale expression analysis reveals distinct microRNA profiles at different stages of human neurodevelopment.

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Brandon Smith

Full Text Available BACKGROUND: MicroRNAs (miRNAs are short non-coding RNAs predicted to regulate one third of protein coding genes via mRNA targeting. In conjunction with key transcription factors, such as the repressor REST (RE1 silencing transcription factor, miRNAs play crucial roles in neurogenesis, which requires a highly orchestrated program of gene expression to ensure the appropriate development and function of diverse neural cell types. Whilst previous studies have highlighted select groups of miRNAs during neural development, there remains a need for amenable models in which miRNA expression and function can be analyzed over the duration of neurogenesis. PRINCIPAL FINDINGS: We performed large-scale expression profiling of miRNAs in human NTera2/D1 (NT2 cells during retinoic acid (RA-induced transition from progenitors to fully differentiated neural phenotypes. Our results revealed dynamic changes of miRNA patterns, resulting in distinct miRNA subsets that could be linked to specific neurodevelopmental stages. Moreover, the cell-type specific miRNA subsets were very similar in NT2-derived differentiated cells and human primary neurons and astrocytes. Further analysis identified miRNAs as putative regulators of REST, as well as candidate miRNAs targeted by REST. Finally, we confirmed the existence of two predicted miRNAs; pred-MIR191 and pred-MIR222 associated with SLAIN1 and FOXP2, respectively, and provided some evidence of their potential co-regulation. CONCLUSIONS: In the present study, we demonstrate that regulation of miRNAs occurs in precise patterns indicative of their roles in cell fate commitment, progenitor expansion and differentiation into neurons and glia. Furthermore, the similarity between our NT2 system and primary human cells suggests their roles in molecular pathways critical for human in vivo neurogenesis.

Multiway real-time PCR gene expression profiling in yeast Saccharomyces cerevisiae reveals altered transcriptional response of ADH-genes to glucose stimuli.

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Ståhlberg, Anders; Elbing, Karin; Andrade-Garda, José Manuel; Sjögreen, Björn; Forootan, Amin; Kubista, Mikael

2008-04-16

The large sensitivity, high reproducibility and essentially unlimited dynamic range of real-time PCR to measure gene expression in complex samples provides the opportunity for powerful multivariate and multiway studies of biological phenomena. In multiway studies samples are characterized by their expression profiles to monitor changes over time, effect of treatment, drug dosage etc. Here we perform a multiway study of the temporal response of four yeast Saccharomyces cerevisiae strains with different glucose uptake rates upon altered metabolic conditions. We measured the expression of 18 genes as function of time after addition of glucose to four strains of yeast grown in ethanol. The data are analyzed by matrix-augmented PCA, which is a generalization of PCA for 3-way data, and the results are confirmed by hierarchical clustering and clustering by Kohonen self-organizing map. Our approach identifies gene groups that respond similarly to the change of nutrient, and genes that behave differently in mutant strains. Of particular interest is our finding that ADH4 and ADH6 show a behavior typical of glucose-induced genes, while ADH3 and ADH5 are repressed after glucose addition. Multiway real-time PCR gene expression profiling is a powerful technique which can be utilized to characterize functions of new genes by, for example, comparing their temporal response after perturbation in different genetic variants of the studied subject. The technique also identifies genes that show perturbed expression in specific strains.

Multiway real-time PCR gene expression profiling in yeast Saccharomyces cerevisiae reveals altered transcriptional response of ADH-genes to glucose stimuli

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Andrade-Garda José

2008-04-01

Full Text Available Abstract Background The large sensitivity, high reproducibility and essentially unlimited dynamic range of real-time PCR to measure gene expression in complex samples provides the opportunity for powerful multivariate and multiway studies of biological phenomena. In multiway studies samples are characterized by their expression profiles to monitor changes over time, effect of treatment, drug dosage etc. Here we perform a multiway study of the temporal response of four yeast Saccharomyces cerevisiae strains with different glucose uptake rates upon altered metabolic conditions. Results We measured the expression of 18 genes as function of time after addition of glucose to four strains of yeast grown in ethanol. The data are analyzed by matrix-augmented PCA, which is a generalization of PCA for 3-way data, and the results are confirmed by hierarchical clustering and clustering by Kohonen self-organizing map. Our approach identifies gene groups that respond similarly to the change of nutrient, and genes that behave differently in mutant strains. Of particular interest is our finding that ADH4 and ADH6 show a behavior typical of glucose-induced genes, while ADH3 and ADH5 are repressed after glucose addition. Conclusion Multiway real-time PCR gene expression profiling is a powerful technique which can be utilized to characterize functions of new genes by, for example, comparing their temporal response after perturbation in different genetic variants of the studied subject. The technique also identifies genes that show perturbed expression in specific strains.

Expression profiling on soybean leaves reveals integration of ER- and osmotic-stress pathways

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Dewey Ralph E

2007-11-01

Full Text Available Abstract Background Despite the potential of the endoplasmic reticulum (ER stress response to accommodate adaptive pathways, its integration with other environmental-induced responses is poorly understood in plants. We have previously demonstrated that the ER-stress sensor binding protein (BiP from soybean exhibits an unusual response to drought. The members of the soybean BiP gene family are differentially regulated by osmotic stress and soybean BiP confers tolerance to drought. While these results may reflect crosstalk between the osmotic and ER-stress signaling pathways, the lack of mutants, transcriptional response profiles to stresses and genome sequence information of this relevant crop has limited our attempts to identify integrated networks between osmotic and ER stress-induced adaptive responses. As a fundamental step towards this goal, we performed global expression profiling on soybean leaves exposed to polyethylene glycol treatment (osmotic stress or to ER stress inducers. Results The up-regulated stress-specific changes unmasked the major branches of the ER-stress response, which include enhancing protein folding and degradation in the ER, as well as specific osmotically regulated changes linked to cellular responses induced by dehydration. However, a small proportion (5.5% of total up-regulated genes represented a shared response that seemed to integrate the two signaling pathways. These co-regulated genes were considered downstream targets based on similar induction kinetics and a synergistic response to the combination of osmotic- and ER-stress-inducing treatments. Genes in this integrated pathway with the strongest synergistic induction encoded proteins with diverse roles, such as plant-specific development and cell death (DCD domain-containing proteins, an ubiquitin-associated (UBA protein homolog and NAC domain-containing proteins. This integrated pathway diverged further from characterized specific branches of ER-stress as

ADME-Tox profiles of some food additives and pesticides

Science.gov (United States)

Craciun, Dana; Modra, Dorina; Isvoran, Adriana

2015-12-01

Within this study we compute the Absorption, Distribution, Metabolism, Excretion and Toxicity (ADME-Tox) profiles of several commonly used food additives and some pesticides. As expected, all the food additives considered in this study provided to be safe, their ADME-Tox profiles indicating that they have a good oral bioavailability and they do not produce phosphoslipidosis. The ADME-Tox profiles of the pesticides indicate that, with a few exceptions, they are highly toxic (some of them being not approved in the EU, but still used in other countries) and may cause many diseases. Our results are in good agreement with published data concerning the considered food additives and pesticides revealing that the ADME-Tox profiling method may be successfully used to test other chemicals than drug candidates.

Single-cell multiplexed cytokine profiling of CD19 CAR-T cells reveals a diverse landscape of polyfunctional antigen-specific response.

Science.gov (United States)

Xue, Qiong; Bettini, Emily; Paczkowski, Patrick; Ng, Colin; Kaiser, Alaina; McConnell, Timothy; Kodrasi, Olja; Quigley, Máire F; Heath, James; Fan, Rong; Mackay, Sean; Dudley, Mark E; Kassim, Sadik H; Zhou, Jing

2017-11-21

It remains challenging to characterize the functional attributes of chimeric antigen receptor (CAR)-engineered T cell product targeting CD19 related to potency and immunotoxicity ex vivo, despite promising in vivo efficacy in patients with B cell malignancies. We employed a single-cell, 16-plex cytokine microfluidics device and new analysis techniques to evaluate the functional profile of CD19 CAR-T cells upon antigen-specific stimulation. CAR-T cells were manufactured from human PBMCs transfected with the lentivirus encoding the CD19-BB-z transgene and expanded with anti-CD3/anti-CD28 coated beads. The enriched CAR-T cells were stimulated with anti-CAR or control IgG beads, stained with anti-CD4 RPE and anti-CD8 Alexa Fluor 647 antibodies, and incubated for 16 h in a single-cell barcode chip (SCBC). Each SCBC contains ~12,000 microchambers, covered with a glass slide that was pre-patterned with a complete copy of a 16-plex antibody array. Protein secretions from single CAR-T cells were captured and subsequently analyzed using proprietary software and new visualization methods. We demonstrate a new method for single-cell profiling of CD19 CAR-T pre-infusion products prepared from 4 healthy donors. CAR-T single cells exhibited a marked heterogeneity of cytokine secretions and polyfunctional (2+ cytokine) subsets specific to anti-CAR bead stimulation. The breadth of responses includes anti-tumor effector (Granzyme B, IFN-γ, MIP-1α, TNF-α), stimulatory (GM-CSF, IL-2, IL-8), regulatory (IL-4, IL-13, IL-22), and inflammatory (IL-6, IL-17A) functions. Furthermore, we developed two new bioinformatics tools for more effective polyfunctional subset visualization and comparison between donors. Single-cell, multiplexed, proteomic profiling of CD19 CAR-T product reveals a diverse landscape of immune effector response of CD19 CAR-T cells to antigen-specific challenge, providing a new platform for capturing CAR-T product data for correlative analysis. Additionally, such high

Revealing metabolite biomarkers for acupuncture treatment by linear programming based feature selection.

Science.gov (United States)

Wang, Yong; Wu, Qiao-Feng; Chen, Chen; Wu, Ling-Yun; Yan, Xian-Zhong; Yu, Shu-Guang; Zhang, Xiang-Sun; Liang, Fan-Rong

2012-01-01

Acupuncture has been practiced in China for thousands of years as part of the Traditional Chinese Medicine (TCM) and has gradually accepted in western countries as an alternative or complementary treatment. However, the underlying mechanism of acupuncture, especially whether there exists any difference between varies acupoints, remains largely unknown, which hinders its widespread use. In this study, we develop a novel Linear Programming based Feature Selection method (LPFS) to understand the mechanism of acupuncture effect, at molecular level, by revealing the metabolite biomarkers for acupuncture treatment. Specifically, we generate and investigate the high-throughput metabolic profiles of acupuncture treatment at several acupoints in human. To select the subsets of metabolites that best characterize the acupuncture effect for each meridian point, an optimization model is proposed to identify biomarkers from high-dimensional metabolic data from case and control samples. Importantly, we use nearest centroid as the prototype to simultaneously minimize the number of selected features and the leave-one-out cross validation error of classifier. We compared the performance of LPFS to several state-of-the-art methods, such as SVM recursive feature elimination (SVM-RFE) and sparse multinomial logistic regression approach (SMLR). We find that our LPFS method tends to reveal a small set of metabolites with small standard deviation and large shifts, which exactly serves our requirement for good biomarker. Biologically, several metabolite biomarkers for acupuncture treatment are revealed and serve as the candidates for further mechanism investigation. Also biomakers derived from five meridian points, Zusanli (ST36), Liangmen (ST21), Juliao (ST3), Yanglingquan (GB34), and Weizhong (BL40), are compared for their similarity and difference, which provide evidence for the specificity of acupoints. Our result demonstrates that metabolic profiling might be a promising method to

Ribosome Profiling Reveals Pervasive Translation Outside of Annotated Protein-Coding Genes

Directory of Open Access Journals (Sweden)

Nicholas T. Ingolia

2014-09-01

Full Text Available Ribosome profiling suggests that ribosomes occupy many regions of the transcriptome thought to be noncoding, including 5′ UTRs and long noncoding RNAs (lncRNAs. Apparent ribosome footprints outside of protein-coding regions raise the possibility of artifacts unrelated to translation, particularly when they occupy multiple, overlapping open reading frames (ORFs. Here, we show hallmarks of translation in these footprints: copurification with the large ribosomal subunit, response to drugs targeting elongation, trinucleotide periodicity, and initiation at early AUGs. We develop a metric for distinguishing between 80S footprints and nonribosomal sources using footprint size distributions, which validates the vast majority of footprints outside of coding regions. We present evidence for polypeptide production beyond annotated genes, including the induction of immune responses following human cytomegalovirus (HCMV infection. Translation is pervasive on cytosolic transcripts outside of conserved reading frames, and direct detection of this expanded universe of translated products enables efforts at understanding how cells manage and exploit its consequences.

Novel approach for quantitatively estimating element retention and material balances in soil profiles of recharge basins used for wastewater reclamation

Energy Technology Data Exchange (ETDEWEB)

Eshel, Gil, E-mail: eshelgil@gmail.com [Soil Erosion Research Station, Ministry of Agriculture and Rural Development, HaMaccabim Road, Rishon-Lezion. P.O.B. 30, Beit-Dagan, 50250 (Israel); Lin, Chunye [School of Environment, Beijing Normal University, 19 Xinjiekouwaidajie St., Beijing, 100875 (China); Banin, Amos [Department of Soil and Water Sciences, Faculty of Agricultural, Food and Environmental Quality Sciences, The Hebrew University of Jerusalem, P.O. Box 12, Rehovot (Israel)

2015-01-01

We investigated changes in element content and distribution in soil profiles in a study designed to monitor the geochemical changes accruing in soil due to long-term secondary effluent recharge, and its impact on the sustainability of the Soil Aquifer Treatment (SAT) system. Since the initial elemental contents of the soils at the studied site were not available, we reconstructed them using scandium (Sc) as a conservative tracer. By using this approach, we were able to produce a mass-balance for 18 elements and evaluate the geochemical changes resulting from 19 years of effluent recharge. This approach also provides a better understanding of the role of soils as an adsorption filter for the heavy metals contained in the effluent. The soil mass balance suggests 19 years of effluent recharge cause for a significant enrichment in Cu, Cr, Ni, Zn, Mg, K, Na, S and P contents in the upper 4 m of the soil profile. Combining the elements lode record during the 19 years suggest that Cr, Ni, and P inputs may not reach the groundwater (20 m deep), whereas the other elements may. Conversely, we found that 58, 60, and 30% of the initial content of Mn, Ca and Co respectively leached from the upper 2-m of the soil profile. These high percentages of Mn and Ca depletion from the basin soils may reduce the soil's ability to buffer decreases in redox potential pe and pH, respectively, which could initiate a reduction in the soil's holding capacity for heavy metals. - Highlights: • Sc proved as a reliable tracer for reconstructing the initial soil elemental contents. • Mass-balance for 18 elements resulting from 19 years of SAT operation is presented. • After 19 years of operation Cr, Ni, and P inputs may not reach the groundwater. • The inputs of other 15 elements may reach the groundwater. • 58, 60, 30% of initial soil content of Mn, Ca, Co res. leached from the upper 2-m.

Predicting the oral pharmacokinetic profiles of multiple-unit (pellet) dosage forms using a modeling and simulation approach coupled with biorelevant dissolution testing: case example diclofenac sodium.

Science.gov (United States)

Kambayashi, Atsushi; Blume, Henning; Dressman, Jennifer B

2014-07-01

The objective of this research was to characterize the dissolution profile of a poorly soluble drug, diclofenac, from a commercially available multiple-unit enteric coated dosage form, Diclo-Puren® capsules, and to develop a predictive model for its oral pharmacokinetic profile. The paddle method was used to obtain the dissolution profiles of this dosage form in biorelevant media, with the exposure to simulated gastric conditions being varied in order to simulate the gastric emptying behavior of pellets. A modified Noyes-Whitney theory was subsequently fitted to the dissolution data. A physiologically-based pharmacokinetic (PBPK) model for multiple-unit dosage forms was designed using STELLA® software and coupled with the biorelevant dissolution profiles in order to simulate the plasma concentration profiles of diclofenac from Diclo-Puren® capsule in both the fasted and fed state in humans. Gastric emptying kinetics relevant to multiple-units pellets were incorporated into the PBPK model by setting up a virtual patient population to account for physiological variations in emptying kinetics. Using in vitro biorelevant dissolution coupled with in silico PBPK modeling and simulation it was possible to predict the plasma profile of this multiple-unit formulation of diclofenac after oral administration in both the fasted and fed state. This approach might be useful to predict variability in the plasma profiles for other drugs housed in multiple-unit dosage forms. Copyright © 2014 Elsevier B.V. All rights reserved.

Interpreting Power-Force-Velocity Profiles for Individualized and Specific Training.

Science.gov (United States)

Morin, Jean-Benoît; Samozino, Pierre

2016-03-01

Recent studies have brought new insights into the evaluation of power-force-velocity profiles in both ballistic push-offs (eg, jumps) and sprint movements. These are major physical components of performance in many sports, and the methods the authors developed and validated are based on data that are now rather simple to obtain in field conditions (eg, body mass, jump height, sprint times, or velocity). The promising aspect of these approaches is that they allow for more individualized and accurate evaluation, monitoring, and training practices, the success of which is highly dependent on the correct collection, generation, and interpretation of athletes' mechanical outputs. The authors therefore wanted to provide a practical vade mecum to sports practitioners interested in implementing these power-force-velocity-profiling approaches. After providing a summary of theoretical and practical definitions for the main variables, the authors first detail how vertical profiling can be used to manage ballistic push-off performance, with emphasis on the concept of optimal force-velocity profile and the associated force-velocity imbalance. Furthermore, they discuss these same concepts with regard to horizontal profiling in the management of sprinting performance. These sections are illustrated by typical examples from the authors' practice. Finally, they provide a practical and operational synthesis and outline future challenges that will help further develop these approaches.

Tamarix microRNA Profiling Reveals New Insight into Salt Tolerance

Directory of Open Access Journals (Sweden)

Jianwen Wang

2018-04-01

Full Text Available The halophyte tamarisk (Tamarix is extremely salt tolerant, making it an ideal material for salt tolerance-related studies. Although many salt-responsive genes of Tamarix were identified in previous studies, there are no reports on the role of post-transcriptional regulation in its salt tolerance. We constructed six small RNA libraries of Tamarix chinensis roots with NaCl treatments. High-throughput sequencing of the six libraries was performed and microRNA expression profiles were constructed. We investigated salt-responsive microRNAs to uncover the microRNA-mediated genes regulation. From these analyses, 251 conserved and 18 novel microRNA were identified from all small RNAs. From 191 differentially expressed microRNAs, 74 co-expressed microRNAs were identified as salt-responsive candidate microRNAs. The most enriched GO (gene ontology terms for the 157 genes targeted by differentially expressed microRNAs suggested that transcriptions factors were highly active. Two hub microRNAs (miR414, miR5658, which connected by several target genes into an organic microRNA regulatory network, appeared to be the key regulators of post-transcriptional salt-stress responses. As the first survey on the tamarisk small RNAome, this study improves the understanding of tamarisk salt-tolerance mechanisms and will contribute to the molecular-assisted resistance breeding.

Data-driven approach for auditory profiling

DEFF Research Database (Denmark)

Sanchez Lopez, Raul; Bianchi, Federica; Fereczkowski, Michal

2017-01-01

Nowadays, the pure-tone audiogram is the main tool used to characterizehearing loss and to fit hearing aids. However, the perceptual consequencesof hearing loss are typically not only associated with a loss of sensitivity, butalso with a clarity loss that is not captured by the audiogram. A detai......-in-noise perception. The current approach is promising for analyzingother existing data sets in order to select the most relevant tests for auditoryprofiling....

Impurity profiling of a chemical weapon precursor for possible forensic signatures by comprehensive two-dimensional gas chromatography/mass spectrometry and chemometrics.

Science.gov (United States)

Hoggard, Jamin C; Wahl, Jon H; Synovec, Robert E; Mong, Gary M; Fraga, Carlos G

2010-01-15

In this report we present the feasibility of using analytical and chemometric methodologies to reveal and exploit the chemical impurity profiles from commercial dimethyl methylphosphonate (DMMP) samples to illustrate the type of forensic information that may be obtained from chemical-attack evidence. Using DMMP as a model compound of a toxicant that may be used in a chemical attack, we used comprehensive two-dimensional gas chromatography/time-of-flight mass spectrometry (GC x GC/TOF-MS) to detect and identify trace organic impurities in six samples of commercially acquired DMMP. The GC x GC/TOF-MS data was analyzed to produce impurity profiles for all six DMMP samples using 29 analyte impurities. The use of PARAFAC for the mathematical resolution of overlapped GC x GC peaks ensured clean spectra for the identification of many of the detected analytes by spectral library matching. The use of statistical pairwise comparison revealed that there were trace impurities that were quantitatively similar and different among five of the six DMMP samples. Two of the DMMP samples were revealed to have identical impurity profiles by this approach. The use of nonnegative matrix factorization indicated that there were five distinct DMMP sample types as illustrated by the clustering of the multiple DMMP analyses into five distinct clusters in the scores plots. The two indistinguishable DMMP samples were confirmed by their chemical supplier to be from the same bulk source. Sample information from the other chemical suppliers supported the idea that the other four DMMP samples were likely from different bulk sources. These results demonstrate that the matching of synthesized products from the same source is possible using impurity profiling. In addition, the identified impurities common to all six DMMP samples provide strong evidence that basic route information can be obtained from impurity profiles. Finally, impurities that may be unique to the sole bulk manufacturer of DMMP were

Dangers resulting from DNA profiling of biological materials derived from patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT with regard to forensic genetic analysis

Directory of Open Access Journals (Sweden)

Renata Jacewicz

2016-07-01

Full Text Available The study documents the risk that comes with DNA analysis of materials derived from patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT in forensic genetics. DNA chimerism was studied in 30 patients after allo-HSCT, based on techniques applied in contemporary forensic genetics, i.e. real-time PCR and multiplex PCR-STR with the use of autosomal DNA as well as Y-DNA markers. The results revealed that the DNA profile of the recipient’s blood was identical with the donor’s in the majority of cases. Therefore, blood analysis can lead to false conclusions in personal identification as well as kinship analysis. An investigation of buccal swabs revealed a mixture of DNA in the majority of recipients. Consequently, personal identification on the basis of stain analysis of the same origin may be impossible. The safest (but not ideal material turned out to be the hair root. Its analysis based on autosomal DNA revealed 100% of the recipient’s profile. However, an analysis based on Y-chromosome markers performed in female allo-HSCT recipients with male donors demonstrated the presence of donor DNA in hair cells – similarly to the blood and buccal swabs. In the light of potential risks arising from DNA profiling of biological materials derived from persons after allotransplantation in judicial aspects, certain procedures were proposed to eliminate such dangers. The basic procedures include abandoning the approach based exclusively on blood collection, both for kinship analysis and personal identification; asking persons who are to be tested about their history of allo-HSCT before sample collection and profile entry in the DNA database, and verification of DNA profiling based on hair follicles in uncertain cases.

Density-matrix approach for the electroluminescence of molecules in a scanning tunneling microscope.

Science.gov (United States)

Tian, Guangjun; Liu, Ji-Cai; Luo, Yi

2011-04-29

The electroluminescence (EL) of molecules confined inside a nanocavity in the scanning tunneling microscope possesses many intriguing but unexplained features. We present here a general theoretical approach based on the density-matrix formalism to describe the EL from molecules near a metal surface induced by both electron tunneling and localized surface plasmon excitations simultaneously. It reveals the underlying physical mechanism for the external bias dependent EL. The important role played by the localized surface plasmon on the EL is highlighted. Calculations for porphyrin derivatives have reproduced corresponding experimental spectra and nicely explained the observed unusual large variation of emission spectral profiles. This general theoretical approach can find many applications in the design of molecular electronic and photonic devices.

Oak protein profile alterations upon root colonization by an ectomycorrhizal fungus

DEFF Research Database (Denmark)

Sebastiana, Mónica; Martins, Joana; Figueiredo, Andreia

2017-01-01

in the roots. Consistent with the results of the biochemical analysis, the proteome analysis of the mycorrhizal roots suggests a decreasing utilization of sucrose for the metabolic activity of mycorrhizal roots which is consistent with an increased allocation of carbohydrates from the plant to the fungus...... to ectomycorrhizae formation using a proteomics approach complemented by biochemical analysis of carbohydrate levels. Comparative proteome analysis between mycorrhizal and nonmycorrhizal cork oak plants revealed no differences at the foliar level. However, the protein profile of 34 unique oak proteins was altered...... in order to sustain the symbiosis. In addition, a promotion of protein unfolding mechanisms, attenuation of defense reactions, increased nutrient mobilization from the plant-fungus interface (N and P), as well as cytoskeleton rearrangements and induction of plant cell wall loosening for fungal root...

tRNA modification profiles of the fast-proliferating cancer cells

Energy Technology Data Exchange (ETDEWEB)

Dong, Chao; Niu, Leilei; Song, Wei [State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Department of Obstetrics and Gynecology, Peking University Third Hospital, Peking University, Beijing 100191 (China); Xiong, Xin; Zhang, Xianhua [Departmentof Pharmacy, Peking University Third Hospital, Peking University, Beijing 100191 (China); Zhang, Zhenxi; Yang, Yi; Yi, Fan [State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Department of Obstetrics and Gynecology, Peking University Third Hospital, Peking University, Beijing 100191 (China); Zhan, Jun; Zhang, Hongquan [Department of Anatomy, Histology and Embryology, Laboratory of Molecular Cell Biology and Tumor Biology, Peking University, Beijing 100191 (China); Yang, Zhenjun; Zhang, Li-He [State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Department of Obstetrics and Gynecology, Peking University Third Hospital, Peking University, Beijing 100191 (China); Zhai, Suodi [Departmentof Pharmacy, Peking University Third Hospital, Peking University, Beijing 100191 (China); Li, Hua, E-mail: huali88@sina.com [State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Department of Obstetrics and Gynecology, Peking University Third Hospital, Peking University, Beijing 100191 (China); Ye, Min, E-mail: yemin@bjmu.edu.cn [State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Department of Obstetrics and Gynecology, Peking University Third Hospital, Peking University, Beijing 100191 (China); Du, Quan, E-mail: quan.du@pku.edu.cn [State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Department of Obstetrics and Gynecology, Peking University Third Hospital, Peking University, Beijing 100191 (China)

2016-08-05

Despite the recent progress in RNA modification study, a comprehensive modification profile is still lacking for mammalian cells. Using a quantitative HPLC/MS/MS assay, we present here a study where RNA modifications are examined in term of the major RNA species. With paired slow- and fast-proliferating cell lines, distinct RNA modification profiles are first revealed for diverse RNA species. Compared to mRNAs, increased ribose and nucleobase modifications are shown for the highly-structured tRNAs and rRNAs, lending support to their contribution to the formation of high-order structures. This study also reveals a dynamic tRNA modification profile in the fast-proliferating cells. In addition to cultured cells, this unique tRNA profile has been further confirmed with endometrial cancers and their adjacent normal tissues. Taken together, the results indicate that tRNA is a actively regulated RNA species in the fast-proliferating cancer cells, and suggest that they may play a more active role in biological process than expected. -- Highlights: •RNA modifications were first examined in term of the major RNA species. •A dynamic tRNA modifications was characterized for the fast-proliferating cells. •The unique tRNA profile was confirmed with endometrial cancers and their adjacent normal tissues. •tRNA was predicted as an actively regulated RNA species in the fast-proliferating cancer cells.

tRNA modification profiles of the fast-proliferating cancer cells

International Nuclear Information System (INIS)

Dong, Chao; Niu, Leilei; Song, Wei; Xiong, Xin; Zhang, Xianhua; Zhang, Zhenxi; Yang, Yi; Yi, Fan; Zhan, Jun; Zhang, Hongquan; Yang, Zhenjun; Zhang, Li-He; Zhai, Suodi; Li, Hua; Ye, Min; Du, Quan

2016-01-01

Despite the recent progress in RNA modification study, a comprehensive modification profile is still lacking for mammalian cells. Using a quantitative HPLC/MS/MS assay, we present here a study where RNA modifications are examined in term of the major RNA species. With paired slow- and fast-proliferating cell lines, distinct RNA modification profiles are first revealed for diverse RNA species. Compared to mRNAs, increased ribose and nucleobase modifications are shown for the highly-structured tRNAs and rRNAs, lending support to their contribution to the formation of high-order structures. This study also reveals a dynamic tRNA modification profile in the fast-proliferating cells. In addition to cultured cells, this unique tRNA profile has been further confirmed with endometrial cancers and their adjacent normal tissues. Taken together, the results indicate that tRNA is a actively regulated RNA species in the fast-proliferating cancer cells, and suggest that they may play a more active role in biological process than expected. -- Highlights: •RNA modifications were first examined in term of the major RNA species. •A dynamic tRNA modifications was characterized for the fast-proliferating cells. •The unique tRNA profile was confirmed with endometrial cancers and their adjacent normal tissues. •tRNA was predicted as an actively regulated RNA species in the fast-proliferating cancer cells.

The demographic and academic profile of Irish dental school faculty members.

LENUS (Irish Health Repository)

O'Sullivan, Eleanor M

2010-04-23

AIM: This paper reviews the demographic, academic and professional profile of Irish dental school faculty members. Faculty duties are explored. METHODS AND MATERIALS: Custom-designed questionnaires were distributed to faculty members for self-completion, adopting a \\'mixed-method\\' approach with quantitative and qualitative components. Response rate was 64.60%. RESULTS: Demographic profile reveals a male-dominated regime (64%). Males also occupy a disproportionate number of senior academic positions. The age profile mirrors international trends with 75% of staff over 40 and c.33% over 50, including 78% of professorial staff (p < 0.001). Dental school faculties are comprised of highly educated professionals with the following qualifications: 89% BDS, 43% FDS, 39% Masters, 16% Doctorates. Most (77%) have 10+ years of clinical experience, while 47% have over 20 years\\' experience. Clinical experience varied by age, rank (p < 0.001) and gender (p < 0.05). A review of contractual agreements and duties confirms the major role of part-time clinical staff in dental education, comprising the largest single group (48%) delivering the bulk of the clinical teaching. However, 54% of part-time clinical staff have less than five years teaching experience. This study also explores staff views of various faculty roles. CONCLUSIONS: This report provides a benchmark profile of Irish dental school faculty members. It reflects on the heavily skewed age groups of our current dental educators and the impending retirement of many senior academics. Educational organisations need to explore ways to make a career in dental education financially and sociologically attractive and provide adequate support for existing faculty to ensure their development during these challenging times.

Seabed resident event driven profiling system (SREP). Concept, design and tests

Digital Repository Service at National Institute of Oceanography (India)

Mascarenhas, A.A.M.Q.; Afzulpurkar, S.; Maurya, P.K.; Fernandes, L.; Madhan, R.; Desa, E.S.; Dabolkar, N.A.; Navelkar, G.S.; Naik, L.; Shetye, V.G.; Shetty, N.B.; Prabhudesai, S.P.; Nagvekar, S.; Vimalakumari, D.

The seabed resident event driven profiling system (SREP) described here offers a novel, optimized approach to profiling in coastal waters from seabed to sea surface during the rough seas encountered in the southwest monsoon season (June...

[Search for potential gastric cancer biomarkers using low molecular weight blood plasma proteome profiling by mass spectrometry].

Science.gov (United States)

Shevchenko, V E; Arnotskaia, N E; Ogorodnikova, E V; Davydov, M M; Ibraev, M A; Turkin, I N; Davydov, M I

2014-01-01

Gastric cancer, one of the most widespread malignant tumors, still lacks reliable serum/plasma biomarkers of its early detection. In this study we have developed, unified, and tested a new methodology for search of gastric cancer biomarkers based on profiling of low molecular weight proteome (LMWP) (1-17 kDa). This approach included three main components: sample pre-fractionation, matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS), data analysis by a bioinformatics software package. Applicability and perspectives of the developed approach for detection of potential gastric cancer markers during LMWP analysis have been demonstrated using 69 plasma samples from patients with gastric cancer (stages I-IV) and 238 control samples. The study revealed peptides/polypeptides, which may be potentially used for detection of this pathology.

A novel approach for honey pollen profile assessment using an electronic tongue and chemometric tools

Energy Technology Data Exchange (ETDEWEB)

Dias, Luís G., E-mail: ldias@ipb.pt [Escola Superior Agrária, Instituto Politécnico de Bragança, Campus Santa Apolónia, 5301-855 Bragança (Portugal); CQ-VR, Centro de Química – Vila Real, University of Trás-os-Montes e Alto Douro, Apartado 1013, 5001-801 Vila Real (Portugal); Veloso, Ana C.A. [Instituto Politécnico de Coimbra, ISEC, DEQB, Rua Pedro Nunes, Quinta da Nora, 3030-199 Coimbra (Portugal); CEB-Centre of Biological Engineering, University of Minho, Campus de Gualtar, 4710-057 Braga (Portugal); Sousa, Mara E.B.C.; Estevinho, Letícia [CIMO-Escola Superior Agrária, Instituto Politécnico de Bragança, Campus Santa Apolónia, 5301-855 Bragança (Portugal); Machado, Adélio A.S.C. [LAQUIPAI – Laboratório de Química Inorgânica Pura e de Aplicação Interdisciplinar, Departamento de Química, Faculdade de Ciências da, Universidade do Porto, Rua Campo Alegre n°. 687, 4169-007 Porto (Portugal); and others

2015-11-05

Nowadays the main honey producing countries require accurate labeling of honey before commercialization, including floral classification. Traditionally, this classification is made by melissopalynology analysis, an accurate but time-consuming task requiring laborious sample pre-treatment and high-skilled technicians. In this work the potential use of a potentiometric electronic tongue for pollinic assessment is evaluated, using monofloral and polyfloral honeys. The results showed that after splitting honeys according to color (white, amber and dark), the novel methodology enabled quantifying the relative percentage of the main pollens (Castanea sp., Echium sp., Erica sp., Eucaliptus sp., Lavandula sp., Prunus sp., Rubus sp. and Trifolium sp.). Multiple linear regression models were established for each type of pollen, based on the best sensors' sub-sets selected using the simulated annealing algorithm. To minimize the overfitting risk, a repeated K-fold cross-validation procedure was implemented, ensuring that at least 10–20% of the honeys were used for internal validation. With this approach, a minimum average determination coefficient of 0.91 ± 0.15 was obtained. Also, the proposed technique enabled the correct classification of 92% and 100% of monofloral and polyfloral honeys, respectively. The quite satisfactory performance of the novel procedure for quantifying the relative pollen frequency may envisage its applicability for honey labeling and geographical origin identification. Nevertheless, this approach is not a full alternative to the traditional melissopalynologic analysis; it may be seen as a practical complementary tool for preliminary honey floral classification, leaving only problematic cases for pollinic evaluation. - Highlights: • Honey's floral origin labeling is a legal requirement. • Melissopalynology analysis usually used to evaluate pollens profile is laborious. • A novel E-tongue based approach is applied to assess pollens

A novel approach for honey pollen profile assessment using an electronic tongue and chemometric tools

International Nuclear Information System (INIS)

Dias, Luís G.; Veloso, Ana C.A.; Sousa, Mara E.B.C.; Estevinho, Letícia; Machado, Adélio A.S.C.

2015-01-01

Nowadays the main honey producing countries require accurate labeling of honey before commercialization, including floral classification. Traditionally, this classification is made by melissopalynology analysis, an accurate but time-consuming task requiring laborious sample pre-treatment and high-skilled technicians. In this work the potential use of a potentiometric electronic tongue for pollinic assessment is evaluated, using monofloral and polyfloral honeys. The results showed that after splitting honeys according to color (white, amber and dark), the novel methodology enabled quantifying the relative percentage of the main pollens (Castanea sp., Echium sp., Erica sp., Eucaliptus sp., Lavandula sp., Prunus sp., Rubus sp. and Trifolium sp.). Multiple linear regression models were established for each type of pollen, based on the best sensors' sub-sets selected using the simulated annealing algorithm. To minimize the overfitting risk, a repeated K-fold cross-validation procedure was implemented, ensuring that at least 10–20% of the honeys were used for internal validation. With this approach, a minimum average determination coefficient of 0.91 ± 0.15 was obtained. Also, the proposed technique enabled the correct classification of 92% and 100% of monofloral and polyfloral honeys, respectively. The quite satisfactory performance of the novel procedure for quantifying the relative pollen frequency may envisage its applicability for honey labeling and geographical origin identification. Nevertheless, this approach is not a full alternative to the traditional melissopalynologic analysis; it may be seen as a practical complementary tool for preliminary honey floral classification, leaving only problematic cases for pollinic evaluation. - Highlights: • Honey's floral origin labeling is a legal requirement. • Melissopalynology analysis usually used to evaluate pollens profile is laborious. • A novel E-tongue based approach is applied to assess pollens relative

Wind profiling for a coherent wind Doppler lidar by an auto-adaptive background subtraction approach.

Science.gov (United States)

Wu, Yanwei; Guo, Pan; Chen, Siying; Chen, He; Zhang, Yinchao

2017-04-01

Auto-adaptive background subtraction (AABS) is proposed as a denoising method for data processing of the coherent Doppler lidar (CDL). The method is proposed specifically for a low-signal-to-noise-ratio regime, in which the drifting power spectral density of CDL data occurs. Unlike the periodogram maximum (PM) and adaptive iteratively reweighted penalized least squares (airPLS), the proposed method presents reliable peaks and is thus advantageous in identifying peak locations. According to the analysis results of simulated and actually measured data, the proposed method outperforms the airPLS method and the PM algorithm in the furthest detectable range. The proposed method improves the detection range approximately up to 16.7% and 40% when compared to the airPLS method and the PM method, respectively. It also has smaller mean wind velocity and standard error values than the airPLS and PM methods. The AABS approach improves the quality of Doppler shift estimates and can be applied to obtain the whole wind profiling by the CDL.

A two-time-scale dynamic-model approach for magnetic and kinetic profile control in advanced tokamak scenarios on JET

International Nuclear Information System (INIS)

Moreau, D.; Mazon, D.; Ariola, M.; Tommasi, G. De; Laborde, L.; Piccolo, F.; Sartori, F.; Zabeo, L.; Boboc, A.; Brix, M.; Challis, C.D.; Felton, R.; Hawkes, N.; Tala, T.; Bouvier, E.; Cordoliani, V.; Brzozowski, J.; Cocilovo, V.; Crisanti, F.; Luna, E. de la

2008-01-01

experiments, and typical results are shown. Finally, in the last section of the paper, the first experimental results using this dynamic-model approach to control the plasma current and the safety factor profile on JET, either with the three H and CD systems or also with the PF system as an additional actuator, are presented and discussed. (special topic)

Image-based compound profiling reveals a dual inhibitor of tyrosine kinase and microtubule polymerization

OpenAIRE

Tanabe, Kenji

2016-01-01

Small-molecule compounds are widely used as biological research tools and therapeutic drugs. Therefore, uncovering novel targets of these compounds should provide insights that are valuable in both basic and clinical studies. I developed a method for image-based compound profiling by quantitating the effects of compounds on signal transduction and vesicle trafficking of epidermal growth factor receptor (EGFR). Using six signal transduction molecules and two markers of vesicle trafficking, 570...

Carotenoid metabolic profiling and transcriptome-genome mining reveal functional equivalence among blue-pigmented copepods and appendicularia

KAUST Repository

Mojib, Nazia; Amad, Maan H.; Thimma, Manjula; Aldanondo, Naroa; Kumaran, Mande; Irigoien, Xabier

2014-01-01

The tropical oligotrophic oceanic areas are characterized by high water transparency and annual solar radiation. Under these conditions, a large number of phylogenetically diverse mesozooplankton species living in the surface waters (neuston) are found to be blue pigmented. In the present study, we focused on understanding the metabolic and genetic basis of the observed blue phenotype functional equivalence between the blue-pigmented organisms from the phylum Arthropoda, subclass Copepoda (Acartia fossae) and the phylum Chordata, class Appendicularia (Oikopleura dioica) in the Red Sea. Previous studies have shown that carotenoid–protein complexes are responsible for blue coloration in crustaceans. Therefore, we performed carotenoid metabolic profiling using both targeted and nontargeted (high-resolution mass spectrometry) approaches in four different blue-pigmented genera of copepods and one blue-pigmented species of appendicularia. Astaxanthin was found to be the principal carotenoid in all the species. The pathway analysis showed that all the species can synthesize astaxanthin from β-carotene, ingested from dietary sources, via 3-hydroxyechinenone, canthaxanthin, zeaxanthin, adonirubin or adonixanthin. Further, using de novo assembled transcriptome of blue A. fossae (subclass Copepoda), we identified highly expressed homologous β-carotene hydroxylase enzymes and putative carotenoid-binding proteins responsible for astaxanthin formation and the blue phenotype. In blue O. dioica (class Appendicularia), corresponding putative genes were identified from the reference genome. Collectively, our data provide molecular evidences for the bioconversion and accumulation of blue astaxanthin–protein complexes underpinning the observed ecological functional equivalence and adaptive convergence among neustonic mesozooplankton.

Carotenoid metabolic profiling and transcriptome-genome mining reveal functional equivalence among blue-pigmented copepods and appendicularia

KAUST Repository

Mojib, Nazia

2014-06-01

The tropical oligotrophic oceanic areas are characterized by high water transparency and annual solar radiation. Under these conditions, a large number of phylogenetically diverse mesozooplankton species living in the surface waters (neuston) are found to be blue pigmented. In the present study, we focused on understanding the metabolic and genetic basis of the observed blue phenotype functional equivalence between the blue-pigmented organisms from the phylum Arthropoda, subclass Copepoda (Acartia fossae) and the phylum Chordata, class Appendicularia (Oikopleura dioica) in the Red Sea. Previous studies have shown that carotenoid–protein complexes are responsible for blue coloration in crustaceans. Therefore, we performed carotenoid metabolic profiling using both targeted and nontargeted (high-resolution mass spectrometry) approaches in four different blue-pigmented genera of copepods and one blue-pigmented species of appendicularia. Astaxanthin was found to be the principal carotenoid in all the species. The pathway analysis showed that all the species can synthesize astaxanthin from β-carotene, ingested from dietary sources, via 3-hydroxyechinenone, canthaxanthin, zeaxanthin, adonirubin or adonixanthin. Further, using de novo assembled transcriptome of blue A. fossae (subclass Copepoda), we identified highly expressed homologous β-carotene hydroxylase enzymes and putative carotenoid-binding proteins responsible for astaxanthin formation and the blue phenotype. In blue O. dioica (class Appendicularia), corresponding putative genes were identified from the reference genome. Collectively, our data provide molecular evidences for the bioconversion and accumulation of blue astaxanthin–protein complexes underpinning the observed ecological functional equivalence and adaptive convergence among neustonic mesozooplankton.

Investigating the Correspondence Between Transcriptomic and Proteomic Expression Profiles Using Coupled Cluster Models

International Nuclear Information System (INIS)

Rogers, Simon; Girolami, Mark; Kolch, Walter; Waters, Katrina M.; Liu, Tao; Thrall, Brian D.; Wiley, H. S.

2008-01-01

Modern transcriptomics and proteomics enable us to survey the expression of RNAs and proteins at large scales. While these data are usually generated and analyzed separately, there is an increasing interest in comparing and co-analyzing transcriptome and proteome expression data. A major open question is whether transcriptome and proteome expression is linked and how it is coordinated. Results: Here we have developed a probabilistic clustering model that permits analysis of the links between transcriptomic and proteomic profiles in a sensible and flexible manner. Our coupled mixture model defines a prior probability distribution over the component to which a protein profile should be assigned conditioned on which component the associated mRNA profile belongs to. By providing probabilistic assignments this approach sits between the two extremes of concatenating the data on the assumption that mRNA and protein clusters would have a one-to-one relationship, and independent clustering where the mRNA profile provides no information on the protein profile and vice-versa. We apply this approach to a large dataset of quantitative transcriptomic and proteomic expression data obtained from a human breast epithelial cell line (HMEC) stimulated by epidermal growth factor (EGF) over a series of timepoints corresponding to one cell cycle. The results reveal a complex relationship between transcriptome and proteome with most mRNA clusters linked to at least two protein clusters, and vice versa. A more detailed analysis incorporating information on gene function from the gene ontology database shows that a high correlation of mRNA and protein expression is limited to the components of some molecular machines, such as the ribosome, cell adhesion complexes and the TCP-1 chaperonin involved in protein folding. Conclusions: The dynamic regulation of the transcriptome and proteome in mammalian cells in response to an acute mitogenic stimulus appears largely independent with very little

A Chinese Herbal Decoction, Danggui Buxue Tang, Stimulates Proliferation, Differentiation and Gene Expression of Cultured Osteosarcoma Cells: Genomic Approach to Reveal Specific Gene Activation

Directory of Open Access Journals (Sweden)

Roy C. Y. Choi

2011-01-01

Full Text Available Danggui Buxue Tang (DBT, a Chinese herbal decoction used to treat ailments in women, contains Radix Astragali (Huangqi; RA and Radix Angelicae Sinensis (Danggui; RAS. When DBT was applied onto cultured MG-63 cells, an increase of cell proliferation and differentiation of MG-63 cell were revealed: both of these effects were significantly higher in DBT than RA or RAS extract. To search for the biological markers that are specifically regulated by DBT, DNA microarray was used to reveal the gene expression profiling of DBT in MG-63 cells as compared to that of RA- or RAS-treated cells. Amongst 883 DBT-regulated genes, 403 of them are specifically regulated by DBT treatment, including CCL-2, CCL-7, CCL-8, and galectin-9. The signaling cascade of this DBT-regulated gene expression was also elucidated in cultured MG-63 cells. The current results reveal the potential usage of this herbal decoction in treating osteoporosis and suggest the uniqueness of Chinese herbal decoction that requires a well-defined formulation. The DBT-regulated genes in the culture could serve as biological responsive markers for quality assurance of the herbal preparation.

Carotta: Revealing Hidden Confounder Markers in Metabolic Breath Profiles

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Anne-Christin Hauschild

2015-06-01

Full Text Available Computational breath analysis is a growing research area aiming at identifying volatile organic compounds (VOCs in human breath to assist medical diagnostics of the next generation. While inexpensive and non-invasive bioanalytical technologies for metabolite detection in exhaled air and bacterial/fungal vapor exist and the first studies on the power of supervised machine learning methods for profiling of the resulting data were conducted, we lack methods to extract hidden data features emerging from confounding factors. Here, we present Carotta, a new cluster analysis framework dedicated to uncovering such hidden substructures by sophisticated unsupervised statistical learning methods. We study the power of transitivity clustering and hierarchical clustering to identify groups of VOCs with similar expression behavior over most patient breath samples and/or groups of patients with a similar VOC intensity pattern. This enables the discovery of dependencies between metabolites. On the one hand, this allows us to eliminate the effect of potential confounding factors hindering disease classification, such as smoking. On the other hand, we may also identify VOCs associated with disease subtypes or concomitant diseases. Carotta is an open source software with an intuitive graphical user interface promoting data handling, analysis and visualization. The back-end is designed to be modular, allowing for easy extensions with plugins in the future, such as new clustering methods and statistics. It does not require much prior knowledge or technical skills to operate. We demonstrate its power and applicability by means of one artificial dataset. We also apply Carotta exemplarily to a real-world example dataset on chronic obstructive pulmonary disease (COPD. While the artificial data are utilized as a proof of concept, we will demonstrate how Carotta finds candidate markers in our real dataset associated with confounders rather than the primary disease (COPD

Gene expression profiles of prohibitin in testes of Octopus tankahkeei (ot-phb) revealing its possible role during spermiogenesis.

Science.gov (United States)

Mao, Hai-Tao; Wang, Da-Hui; Lan, Zhou; Zhou, Hong; Yang, Wan-Xi

2012-05-01

Prohibitin is essential for intracellular homeostasis and stabilization of mitochondrial respiratory chain complexes. To explore its functions during spermiogenesis of Octopus tankahkeei (O. tankahkeei), we have cloned and sequenced the cDNA of this mammalian PHB homologue (termed ot-PHB) from the testes of O. tankahkeei. The 1165 bp ot-phb cDNA contains a 100 bp 5' UTR, a 882 bp open reading frame and a 183 bp 3' UTR. The putative ot-PHB protein owns a transmembrane domain from 6 to 31 amino acid (aa) and a putative PHB domain from 26 to 178 aa. Protein alignment demonstrated that ot-PHB had 73.3, 73.6, 74.0, 75.1, and 45.4% identity with its homologues in Homo sapiens, Mus muculus, Danio rerio, Xenopus tropicalis and Trypanosoma brucei, respectively. Tissue distribution profile analysis revealed its presence in all the tissues examined. In situ hybridization in spermiogenic cells demonstrated that ot-phb was expressed moderately at the beginning of the spermiogenesis. The abundance of transcripts increased in intermediate spermatids and in drastically remodeling final spermatids. In mature spermatozoa, the residuary transcripts concentrated around the chondriosomal mantle where mitochondria assemble around. In summary, the expression of ot-phb during spermiogenesis implicates a potential function of this protein during mitochondrial ubiquitination. It is the first time to implicate the role of prohibitin in cephalopod spermiogenesis.

CRISPR/Cas9 cleavages in budding yeast reveal templated insertions and strand-specific insertion/deletion profiles.

Science.gov (United States)

Lemos, Brenda R; Kaplan, Adam C; Bae, Ji Eun; Ferrazzoli, Alexander E; Kuo, James; Anand, Ranjith P; Waterman, David P; Haber, James E

2018-02-27

Harnessing CRISPR-Cas9 technology provides an unprecedented ability to modify genomic loci via DNA double-strand break (DSB) induction and repair. We analyzed nonhomologous end-joining (NHEJ) repair induced by Cas9 in budding yeast and found that the orientation of binding of Cas9 and its guide RNA (gRNA) profoundly influences the pattern of insertion/deletions (indels) at the site of cleavage. A common indel created by Cas9 is a 1-bp (+1) insertion that appears to result from Cas9 creating a 1-nt 5' overhang that is filled in by a DNA polymerase and ligated. The origin of +1 insertions was investigated by using two gRNAs with PAM sequences located on opposite DNA strands but designed to cleave the same sequence. These templated +1 insertions are dependent on the X-family DNA polymerase, Pol4. Deleting Pol4 also eliminated +2 and +3 insertions, which are biased toward homonucleotide insertions. Using inverted PAM sequences, we also found significant differences in overall NHEJ efficiency and repair profiles, suggesting that the binding of the Cas9:gRNA complex influences subsequent NHEJ processing. As with events induced by the site-specific HO endonuclease, CRISPR-Cas9-mediated NHEJ repair depends on the Ku heterodimer and DNA ligase 4. Cas9 events are highly dependent on the Mre11-Rad50-Xrs2 complex, independent of Mre11's nuclease activity. Inspection of the outcomes of a large number of Cas9 cleavage events in mammalian cells reveals a similar templated origin of +1 insertions in human cells, but also a significant frequency of similarly templated +2 insertions.

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

Science.gov (United States)

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

2013-12-19

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

Bifurcation-based approach reveals synergism and optimal combinatorial perturbation.

Science.gov (United States)

Liu, Yanwei; Li, Shanshan; Liu, Zengrong; Wang, Ruiqi

2016-06-01

Cells accomplish the process of fate decisions and form terminal lineages through a series of binary choices in which cells switch stable states from one branch to another as the interacting strengths of regulatory factors continuously vary. Various combinatorial effects may occur because almost all regulatory processes are managed in a combinatorial fashion. Combinatorial regulation is crucial for cell fate decisions because it may effectively integrate many different signaling pathways to meet the higher regulation demand during cell development. However, whether the contribution of combinatorial regulation to the state transition is better than that of a single one and if so, what the optimal combination strategy is, seem to be significant issue from the point of view of both biology and mathematics. Using the approaches of combinatorial perturbations and bifurcation analysis, we provide a general framework for the quantitative analysis of synergism in molecular networks. Different from the known methods, the bifurcation-based approach depends only on stable state responses to stimuli because the state transition induced by combinatorial perturbations occurs between stable states. More importantly, an optimal combinatorial perturbation strategy can be determined by investigating the relationship between the bifurcation curve of a synergistic perturbation pair and the level set of a specific objective function. The approach is applied to two models, i.e., a theoretical multistable decision model and a biologically realistic CREB model, to show its validity, although the approach holds for a general class of biological systems.

Atmospheric turbulence profiling with unknown power spectral density

Science.gov (United States)

Helin, Tapio; Kindermann, Stefan; Lehtonen, Jonatan; Ramlau, Ronny

2018-04-01

Adaptive optics (AO) is a technology in modern ground-based optical telescopes to compensate for the wavefront distortions caused by atmospheric turbulence. One method that allows to retrieve information about the atmosphere from telescope data is so-called SLODAR, where the atmospheric turbulence profile is estimated based on correlation data of Shack-Hartmann wavefront measurements. This approach relies on a layered Kolmogorov turbulence model. In this article, we propose a novel extension of the SLODAR concept by including a general non-Kolmogorov turbulence layer close to the ground with an unknown power spectral density. We prove that the joint estimation problem of the turbulence profile above ground simultaneously with the unknown power spectral density at the ground is ill-posed and propose three numerical reconstruction methods. We demonstrate by numerical simulations that our methods lead to substantial improvements in the turbulence profile reconstruction compared to the standard SLODAR-type approach. Also, our methods can accurately locate local perturbations in non-Kolmogorov power spectral densities.

Estimating Mixing Heights Using Microwave Temperature Profiler

Science.gov (United States)

Nielson-Gammon, John; Powell, Christina; Mahoney, Michael; Angevine, Wayne

2008-01-01

A paper describes the Microwave Temperature Profiler (MTP) for making measurements of the planetary boundary layer thermal structure data necessary for air quality forecasting as the Mixing Layer (ML) height determines the volume in which daytime pollution is primarily concentrated. This is the first time that an airborne temperature profiler has been used to measure the mixing layer height. Normally, this is done using a radar wind profiler, which is both noisy and large. The MTP was deployed during the Texas 2000 Air Quality Study (TexAQS-2000). An objective technique was developed and tested for estimating the ML height from the MTP vertical temperature profiles. In order to calibrate the technique and evaluate the usefulness of this approach, estimates from a variety of measurements during the TexAQS-2000 were compared. Estimates of ML height were used from radiosondes, radar wind profilers, an aerosol backscatter lidar, and in-situ aircraft measurements in addition to those from the MTP.

Metabolite profiling reveals a role for atypical cinnamyl alcohol dehydrogenase CAD1 in the synthesis of coniferyl alcohol in tobacco xylem.

Science.gov (United States)

Damiani, Isabelle; Morreel, Kris; Danoun, Saïda; Goeminne, Geert; Yahiaoui, Nabila; Marque, Christiane; Kopka, Joachim; Messens, Eric; Goffner, Deborah; Boerjan, Wout; Boudet, Alain-Michel; Rochange, Soizic

2005-11-01

In angiosperms, lignin is built from two main monomers, coniferyl and sinapyl alcohol, which are incorporated respectively as G and S units in the polymer. The last step of their synthesis has so far been considered to be performed by a family of dimeric cinnamyl alcohol dehydrogenases (CAD2). However, previous studies on Eucalyptus gunnii xylem showed the presence of an additional, structurally unrelated, monomeric CAD form named CAD1. This form reduces coniferaldehyde to coniferyl alcohol, but is inactive on sinapaldehyde. In this paper, we report the functional characterization of CAD1 in tobacco (Nicotiana tabacum L.). Transgenic tobacco plants with reduced CAD1 expression were obtained through an RNAi strategy. These plants displayed normal growth and development, and detailed biochemical studies were needed to reveal a role for CAD1. Lignin analyses showed that CAD1 down-regulation does not affect Klason lignin content, and has a moderate impact on G unit content of the non-condensed lignin fraction. However, comparative metabolic profiling of the methanol-soluble phenolic fraction from basal xylem revealed significant differences between CAD1 down-regulated and wild-type plants. Eight compounds were less abundant in CAD1 down-regulated lines, five of which were identified as dimers or trimers of monolignols, each containing at least one moiety derived from coniferyl alcohol. In addition, 3-trans-caffeoyl quinic acid accumulated in the transgenic plants. Together, our results support a significant contribution of CAD1 to the synthesis of coniferyl alcohol in planta, along with the previously characterized CAD2 enzymes.

Expression Profiling of Mitogen-Activated Protein Kinase Genes Reveals Their Evolutionary and Functional Diversity in Different Rubber Tree (Hevea brasiliensis Cultivars

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Xiang Jin

2017-10-01

Full Text Available Rubber tree (Hevea brasiliensis is the only commercially cultivated plant for producing natural rubber, one of the most essential industrial raw materials. Knowledge of the evolutionary and functional characteristics of kinases in H. brasiliensis is limited because of the long growth period and lack of well annotated genome information. Here, we reported mitogen-activated protein kinases in H. brasiliensis (HbMPKs by manually checking and correcting the rubber tree genome. Of the 20 identified HbMPKs, four members were validated by proteomic data. Protein motif and phylogenetic analyses classified these members into four known groups comprising Thr-Glu-Tyr (TEY and Thr-Asp-Tyr (TDY domains, respectively. Evolutionary and syntenic analyses suggested four duplication events: HbMPK3/HbMPK6, HbMPK8/HbMPK9/HbMPK15, HbMPK10/HbMPK12 and HbMPK11/HbMPK16/HbMPK19. Expression profiling of the identified HbMPKs in roots, stems, leaves and latex obtained from three cultivars with different latex yield ability revealed tissue- and variety-expression specificity of HbMPK paralogues. Gene expression patterns under osmotic, oxidative, salt and cold stresses, combined with cis-element distribution analyses, indicated different regulation patterns of HbMPK paralogues. Further, Ka/Ks and Tajima analyses suggested an accelerated evolutionary rate in paralogues HbMPK10/12. These results revealed HbMPKs have diverse functions in natural rubber biosynthesis, and highlighted the potential possibility of using MPKs to improve stress tolerance in future rubber tree breeding.

Functional profiles reveal unique ecological roles of various biological soil crust organisms

Science.gov (United States)

Bowker, M.A.; Mau, R.L.; Maestre, F.T.; Escolar, C.; Castillo-Monroy, A. P.

2011-01-01

1. At the heart of the body of research on biodiversity effects on ecosystem function is the debate over whether different species tend to be functionally singular or redundant. When we consider ecosystem multi-function, the provision of multiple ecosystem functions simultaneously, we may find that seemingly redundant species may in fact play unique roles in ecosystems. 2. Over the last few decades, the significance of biological soil crusts (BSCs) as ecological boundaries and ecosystem engineers, and their multi-functional nature, has become increasingly well documented. We compiled 'functional profiles' of the organisms in this understudied community, to determine whether functional singularity emerges when multiple ecosystem functions are considered. 3. In two data sets, one representing multiple sites around the semi-arid regions of Spain (regional scale), and another from a single site in central Spain (local scale), we examined correlations between the abundance or frequency of BSC species in a community, and multiple surrogates of ecosystem functioning. There was a wide array of apparent effects of species on specific functions. 4. Notably, in gypsiferous soils and at regional scale, we found that indicators of carbon (C) and phosphorus cycling were apparently suppressed and promoted by the lichens Diploschistes diacapsis and Squamarina lentigera, respectively. The moss Pleurochaete squarrosa appears to promote C cycling in calcareous soils at this spatial scale. At the local scale in gypsiferous soils, D. diacapsis positively correlated with carbon cycling, but negatively with nitrogen cycling, whereas numerous lichens exhibited the opposite profile. 5. We found a high degree of functional singularity, i.e. that species were highly individualistic in their effects on multiple functions. Many functional attributes were not easily predictable from existing functional grouping systems based primarily on morphology. 6. Our results suggest that maintaining

Approaching nanometre accuracy in measurement of the profile deviation of a large plane mirror

International Nuclear Information System (INIS)

Müller, Andreas; Hofmann, Norbert; Manske, Eberhard

2012-01-01

The interferometric nanoprofilometer (INP), developed at the Institute of Process Measurement and Sensor Technology at the Ilmenau University of Technology, is a precision device for measuring the profile deviations of plane mirrors with a profile length of up to 250 mm at the nanometre scale. As its expanded uncertainty of U(l) = 7.8 nm at a confidence level of p = 95% (k = 2) was mainly influenced by the uncertainty of the straightness standard (3.6 nm) and the uncertainty caused by the signal and demodulation errors of the interferometer signals (1.2 nm), these two sources of uncertainty have been the subject of recent analyses and modifications. To measure the profile deviation of the standard mirror we performed a classic three-flat test using the INP. The three-flat test consists of a combination of measurements between three different test flats. The shape deviations of the three flats can then be determined by applying a least-squares solution of the resulting equation system. The results of this three-flat test showed surprisingly good consistency, enabling us to correct this systematic error in profile deviation measurements and reducing the uncertainty component of the standard mirror to 0.4 nm. Another area of research is the signal and demodulation error arising during the interpretation of the interferometer signals. In the case of the interferometric nanoprofilometer, the special challenge is that the maximum path length differences are too small during the scan of the entire profile deviation over perfectly aligned 250 mm long mirrors for proper interpolation and correction since they do not yet cover even half of an interference fringe. By applying a simple method of weighting to the interferometer data the common ellipse fitting could be performed successfully and the demodulation error was greatly reduced. The remaining uncertainty component is less than 0.5 nm. In summary we were successful in greatly reducing two major systematic errors. The

Effects of sex, age, and fasting conditions on plasma lipidomic profiles of fasted Sprague-Dawley rats.

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Kosuke Saito

Full Text Available Circulating lipid molecules reflect biological processes in the body and, thus, are useful tools for preclinical estimation of the efficacy and safety of newly developed drugs. However, background information on profiles of circulating lipid molecules in preclinical animal models is limited. Therefore, we examined the effects of multiple factors such as sex (fasted male vs. female, age (fasted 10 vs. 30 weeks old, and feeding conditions (feeding vs. fasting, 16 vs. 22 hr fasting, 10 AM vs. 4 PM blood collection, on the global profiles of lipid molecules in plasma from Sprague-Dawley rats by using a lipidomic approach. Our assay platform determined 262 lipid molecules (68 phospholipids, 20 sphingolipids, 138 neutral lipids, and 36 polyunsaturated fatty acids and their metabolites in rat plasma. Multivariate discriminant analysis (orthogonal partial least squares discriminant analysis and heat maps of statistically significant lipid molecules revealed that the plasma lipid profiles in rats are predominantly influenced by feeding conditions, followed by sex and age. In addition, the fasting duration (16 vs. 22 hr fasting or the time of blood collection (10 AM vs. 4 PM blood collection has limited or no contribution on the profiles of lipid molecules in rat plasma. Our results provide useful, fundamental information for exploring and validating biomarkers in future preclinical studies and may help to establish regulatory standards for such studies.

Global Metabolomics of the Placenta Reveals Distinct Metabolic Profiles between Maternal and Fetal Placental Tissues Following Delivery in Non-Labored Women

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Jacquelyn M. Walejko

2018-01-01

Full Text Available We evaluated the metabolic alterations in maternal and fetal placental tissues from non-labored women undergoing cesarean section using samples collected from 5 min to 24 h following delivery. Using 1H-NMR, we identified 14 metabolites that significantly differed between maternal and fetal placental tissues (FDR-corrected p-value < 0.05, with 12 metabolites elevated in the maternal tissue, reflecting the flux of these metabolites from mother to fetus. In the maternal tissue, 4 metabolites were significantly altered at 15 min, 10 metabolites at 30 min, and 16 metabolites at 1 h postdelivery, while 11 metabolites remained stable over 24 h. In contrast, in the fetal placenta tissue, 1 metabolite was significantly altered at 15 min, 2 metabolites at 30 min, and 4 metabolites at 1 h postdelivery, while 22 metabolites remained stable over 24 h. Our study provides information on the metabolic profiles of maternal and fetal placental tissues delivered by cesarean section and reveals that there are different metabolic alterations in the maternal and fetal tissues of the placenta following delivery.

Profiling of REST-dependent microRNAs reveals dynamic modes of expression

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Zhengliang eGao

2012-05-01

Full Text Available Multipotent neural stem cells (NSCs possess the ability to self-renew and differentiate into both neurons and glia. However, the detailed mechanisms underlying NSC fate decisions are not well understood. Recent work suggest that the interaction between cell-type specific transcription factors and microRNAs (miRNAs is important as resident neural stem/progenitor cells give rise to functionally mature neurons. Recently, we demonstrated that the transcriptional repressor REST (RE1-silencing transcription factor is essential to prevent precocious neuronal differentiation and maintain NSC self-renewal in the adult hippocampus. Here we show that REST is required for orchestrating the expression of distinct subsets of miRNAs in primary mouse NSC cultures, a physiologically relevant cell type. Using miRNA array profiling, we identified known REST-regulated miRNA genes, as well as previously uncharacterized REST-dependent miRNAs. Interestingly, REST-regulated miRNAs undergo dynamic expression changes under differentiation conditions over time, but not under proliferation conditions. These results suggest that REST functions in a context-dependent manner through its target miRNAs for mediating neuronal production.

Approximate Stokes Drift Profiles and their use in Ocean Modelling

Science.gov (United States)

Breivik, Oyvind; Bidlot, Jea-Raymond; Janssen, Peter A. E. M.; Mogensen, Kristian

2016-04-01

Deep-water approximations to the Stokes drift velocity profile are explored as alternatives to the monochromatic profile. The alternative profiles investigated rely on the same two quantities required for the monochromatic profile, viz the Stokes transport and the surface Stokes drift velocity. Comparisons against parametric spectra and profiles under wave spectra from the ERA-Interim reanalysis and buoy observations reveal much better agreement than the monochromatic profile even for complex sea states. That the profiles give a closer match and a more correct shear has implications for ocean circulation models since the Coriolis-Stokes force depends on the magnitude and direction of the Stokes drift profile and Langmuir turbulence parameterizations depend sensitively on the shear of the profile. Of the two Stokes drift profiles explored here, the profile based on the Phillips spectrum is by far the best. In particular, the shear near the surface is almost identical to that influenced by the f-5 tail of spectral wave models. The NEMO general circulation ocean model was recently extended to incorporate the Stokes-Coriolis force along with two other wave-related effects. The ECWMF coupled atmosphere-wave-ocean ensemble forecast system now includes these wave effects in the ocean model component (NEMO).

Label-Free LC-MS Profiling of Skeletal Muscle Reveals Heart-Type Fatty Acid Binding Protein as a Candidate Biomarker of Aerobic Capacity.

Science.gov (United States)

Malik, Zulezwan Ab; Cobley, James N; Morton, James P; Close, Graeme L; Edwards, Ben J; Koch, Lauren G; Britton, Steven L; Burniston, Jatin G

2013-12-01

earlier transcriptome profiling work and show LC-MS is a viable means of profiling the abundance of almost all major metabolic enzymes of skeletal muscle in a highly parallel manner. Moreover, our approach is relatively more time efficient than techniques relying on orthogonal separations, and we demonstrate LC-MS profiling of the HCR/LCR selection model was able to highlight biomarkers that also exhibit differences in trained and untrained human muscle.

New dynamic NNORSY ozone profile climatology

Science.gov (United States)

Kaifel, A. K.; Felder, M.; Declercq, C.; Lambert, J.-C.

2012-01-01

Climatological ozone profile data are widely used as a-priori information for total ozone using DOAS type retrievals as well as for ozone profile retrieval using optimal estimation, for data assimilation or evaluation of 3-D chemistry-transport models and a lot of other applications in atmospheric sciences and remote sensing. For most applications it is important that the climatology represents not only long term mean values but also the links between ozone and dynamic input parameters. These dynamic input parameters should be easily accessible from auxiliary datasets or easily measureable, and obviously should have a high correlation with ozone. For ozone profile these parameters are mainly total ozone column and temperature profile data. This was the outcome of a user consultation carried out in the framework of developing a new, dynamic ozone profile climatology. The new ozone profile climatology is based on the Neural Network Ozone Retrieval System (NNORSY) widely used for ozone profile retrieval from UV and IR satellite sounder data. NNORSY allows implicit modelling of any non-linear correspondence between input parameters (predictors) and ozone profile target vector. This paper presents the approach, setup and validation of a new family of ozone profile climatologies with static as well as dynamic input parameters (total ozone and temperature profile). The neural network training relies on ozone profile measurement data of well known quality provided by ground based (ozonesondes) and satellite based (SAGE II, HALOE, and POAM-III) measurements over the years 1995-2007. In total, four different combinations (modes) for input parameters (date, geolocation, total ozone column and temperature profile) are available. The geophysical validation spans from pole to pole using independent ozonesonde, lidar and satellite data (ACE-FTS, AURA-MLS) for individual and time series comparisons as well as for analysing the vertical and meridian structure of different modes of

A new method for depth profiling reconstruction in confocal microscopy

Science.gov (United States)

Esposito, Rosario; Scherillo, Giuseppe; Mensitieri, Giuseppe

2018-05-01

Confocal microscopy is commonly used to reconstruct depth profiles of chemical species in multicomponent systems and to image nuclear and cellular details in human tissues via image intensity measurements of optical sections. However, the performance of this technique is reduced by inherent effects related to wave diffraction phenomena, refractive index mismatch and finite beam spot size. All these effects distort the optical wave and cause an image to be captured of a small volume around the desired illuminated focal point within the specimen rather than an image of the focal point itself. The size of this small volume increases with depth, thus causing a further loss of resolution and distortion of the profile. Recently, we proposed a theoretical model that accounts for the above wave distortion and allows for a correct reconstruction of the depth profiles for homogeneous samples. In this paper, this theoretical approach has been adapted for describing the profiles measured from non-homogeneous distributions of emitters inside the investigated samples. The intensity image is built by summing the intensities collected from each of the emitters planes belonging to the illuminated volume, weighed by the emitters concentration. The true distribution of the emitters concentration is recovered by a new approach that implements this theoretical model in a numerical algorithm based on the Maximum Entropy Method. Comparisons with experimental data and numerical simulations show that this new approach is able to recover the real unknown concentration distribution from experimental profiles with an accuracy better than 3%.

High frequency longitudinal profiling reveals hydrologic controls on solute sourcing, transport and processing in a karst river

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Hensley, R. T.; Cohen, M. J.; Spangler, M.; Gooseff, M. N.

2017-12-01

The lower Santa Fe River is a large, karst river of north Florida, fed by numerous artesian springs and also containing multiple sink-rise systems. We performed repeated longitudinal profiles collecting very high frequency measurements of multiple stream parameters including temperature, dissolved oxygen, carbon dioxide, pH, dissolved organic matter, nitrate, ammonium, phosphate and turbidity. This high frequency dataset provided a spatially explicit understanding of solute sources and coupled biogeochemical processing rates along the 25 km study reach. We noted marked changes in river profiles as the river transitioned from low to high flow during the onset of the wet season. The role of lateral inflow from springs as the primary solute source was greatly reduced under high flow conditions. Effects of sink-rise systems, which under low flow conditions allow the majority of flow to bypass several kilometer long sections of the main channel, virtually disappeared under high flow conditions. Impeded light transmittance at high flow reduced primary production and by extension assimilatory nutrient uptake. This study demonstrates how high frequency longitudinal profiling can be used to observe how hydrologic conditions can alter groundwater-surface water interactions and modulate the sourcing, transport and biogeochemical processing of stream solutes.

Profiling Patients’ Healthcare Needs to Support Integrated, Person-Centered Models for Long-Term Disease Management (Profile: Research Design

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Arianne MJ Elissen

2016-04-01

Full Text Available Background: This article presents the design of PROFILe, a study investigating which (biomedical and non-(biomedical patient characteristics should guide more tailored chronic care. Based on this insight, the project aims to develop and validate ‘patient profiles’ that can be used in practice to determine optimal treatment strategies for subgroups of chronically ill with similar healthcare needs and preferences. Methods/Design: PROFILe is a practice-based research comprising four phases. The project focuses on patients with type 2 diabetes. During the first study phase, patient profiles are drafted based on a systematic literature research, latent class growth modeling, and expert collaboration. In phase 2, the profiles are validated from a clinical, patient-related and statistical perspective. Phase 3 involves a discrete choice experiment to gain insight into the patient preferences that exist per profile. In phase 4, the results from all analyses are integrated and recommendations formulated on which patient characteristics should guide tailored chronic care. Discussion: PROFILe is an innovative study which uses a uniquely holistic approach to assess the healthcare needs and preferences of chronically ill. The patient profiles resulting from this project must be tested in practice to investigate the effects of tailored management on patient experience, population health and costs.

Root profile in Multi-layered Dehesas: an approach to plant-to-plant Interaction

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Rolo, V.; Moreno, G.

2009-04-01

Assessing plant-to-plant relationship is a key issue in agroforestry systems. Due to the sessile feature of plants most of these interactions take place within a restricted space, so characterizing the zone where the plant alters its environment is important to find overlapping areas where the facilitation or competition could occur. Main part of plan-to-plant interactions in the dehesa are located at belowground level, thus the main limited resources in Mediterranean ecosystems are soil nutrient and water. Hence a better knowledge of rooting plant profile can be useful to understand the functioning of the dehesa. The Iberian dehesa has always been considered as a silvopastoral system where, at least, two strata of vegetation coexist: native grasses and trees. However the dehesa is also a diverse system where cropland and encroached territories have been systematically combined, more or less periodically, with native pasture in order to obtain agricultural, pastoral and forestry outputs. These multipurpose mosaic-type systems generate several scenarios where the plant influence zone may be overlapped and the interaction, competition or facilitation, between plants can play an important role in the ecosystem functioning in terms of productivity and stability. In the present study our aim was to characterize the rooting profile of multi-layered dehesas in order to understand the competitive, and/or facilitative, relationships within the different plant strata. The root profile of Quercus ilex subsp. ballota, Cistus ladanifer, Retama spaherocarpa and natural grasses was studied. So 48 trenches, up to 2 meters deep, were excavated in 4 different environments: (i) grass; (ii) tree-grass; (iii) tree-shrub and (iv) tree-shrub-grass (12 trenches in each environment). The study was carried out in 4 dehesas, 2 encroached with C. ladanifer and 2 with R. spaherocarpa. In every trench soil samples were taken each 20 cm. Subsequently, all samples were sieved using different mesh

A research-based profile of a Dutch excellent facility manager

NARCIS (Netherlands)

Roos-Mink, Anke; Offringa, Johan; de Boer, Esther; Heijne-Penninga, Marjolein; Mobach, Mark P.; Wolfensberger, Marca; Balslev Nielsen, S.; Anker Jensen, P.

2016-01-01

Purpose - This paper aims to establish the profile of an excellent facility manager in The Netherlands.Design/methodology/approach − As part of a large-scale study on profiles of excellent professionals, a study was carried out to find the key characteristics of an excellent facility manager. Three

Genome-Wide Identification and Expression Profiling of ATP-Binding Cassette (ABC) Transporter Gene Family in Pineapple (Ananas comosus (L.) Merr.) Reveal the Role of AcABCG38 in Pollen Development.

Science.gov (United States)

Chen, Piaojuan; Li, Yi; Zhao, Lihua; Hou, Zhimin; Yan, Maokai; Hu, Bingyan; Liu, Yanhui; Azam, Syed Muhammad; Zhang, Ziyan; Rahman, Zia Ur; Liu, Liping; Qin, Yuan

2017-01-01

Pineapple ( Ananas comosus L .) cultivation commonly relies on asexual reproduction which is easily impeded by many factors in agriculture production. Sexual reproduction might be a novel approach to improve the pineapple planting. However, genes controlling pineapple sexual reproduction are still remain elusive. In different organisms a conserved superfamily proteins known as ATP binding cassette (ABC) participate in various biological processes. Whereas, till today the ABC gene family has not been identified in pineapple. Here 100 ABC genes were identified in the pineapple genome and grouped into eight subfamilies (5 ABCAs , 20 ABCB s, 16 ABCCs , 2 ABCDs , one ABCEs , 5 ABCFs , 42 ABCGs and 9 ABCIs ). Gene expression profiling revealed the dynamic expression pattern of ABC gene family in various tissues and different developmental stages. AcABCA5, AcABCB6, AcABCC4 , AcABCC7 , AcABCC9 , AcABCG26 , AcABCG38 and AcABCG42 exhibited preferential expression in ovule and stamen. Over-expression of AcABCG38 in the Arabidopsis double mutant abcg1-2abcg16-2 partially restored its pollen abortion defects, indicating that AcABCG38 plays important roles in pollen development. Our study on ABC gene family in pineapple provides useful information for developing sexual pineapple plantation which could be utilized to improve pineapple agricultural production.

Secretome profiling of oral squamous cell carcinoma-associated fibroblasts reveals organization and disassembly of extracellular matrix and collagen metabolic process signatures.

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Bagordakis, Elizabete; Sawazaki-Calone, Iris; Macedo, Carolina Carneiro Soares; Carnielli, Carolina M; de Oliveira, Carine Ervolino; Rodrigues, Priscila Campioni; Rangel, Ana Lucia C A; Dos Santos, Jean Nunes; Risteli, Juha; Graner, Edgard; Salo, Tuula; Paes Leme, Adriana Franco; Coletta, Ricardo D

2016-07-01

An important role has been attributed to cancer-associated fibroblasts (CAFs) in the tumorigenesis of oral squamous cell carcinoma (OSCC), the most common tumor of the oral cavity. Previous studies demonstrated that CAF-secreted molecules promote the proliferation and invasion of OSCC cells, inducing a more aggressive phenotype. In this study, we searched for differences in the secretome of CAFs and normal oral fibroblasts (NOF) using mass spectrometry-based proteomics and biological network analysis. Comparison of the secretome profiles revealed that upregulated proteins involved mainly in extracellular matrix organization and disassembly and collagen metabolism. Among the upregulated proteins were fibronectin type III domain-containing 1 (FNDC1), serpin peptidase inhibitor type 1 (SERPINE1), and stanniocalcin 2 (STC2), the upregulation of which was validated by quantitative PCR and ELISA in an independent set of CAF cell lines. The transition of transforming growth factor beta 1 (TGF-β1)-mediating NOFs into CAFs was accompanied by significant upregulation of FNDC1, SERPINE1, and STC2, confirming the participation of these proteins in the CAF-derived secretome. Type I collagen, the main constituent of the connective tissue, was also associated with several upregulated biological processes. The immunoexpression of type I collagen N-terminal propeptide (PINP) was significantly correlated in vivo with CAFs in the tumor front and was associated with significantly shortened survival of OSCC patients. Presence of CAFs in the tumor stroma was also an independent prognostic factor for OSCC disease-free survival. These results demonstrate the value of secretome profiling for evaluating the role of CAFs in the tumor microenvironment and identify potential novel therapeutic targets such as FNDC1, SERPINE1, and STC2. Furthermore, type I collagen expression by CAFs, represented by PINP levels, may be a prognostic marker of OSCC outcome.

Regulators of Long-Term Memory Revealed by Mushroom Body-Specific Gene Expression Profiling in Drosophila melanogaster.

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Widmer, Yves F; Bilican, Adem; Bruggmann, Rémy; Sprecher, Simon G

2018-06-20

Memory formation is achieved by genetically tightly controlled molecular pathways that result in a change of synaptic strength and synapse organization. While for short-term memory traces rapidly acting biochemical pathways are in place, the formation of long-lasting memories requires changes in the transcriptional program of a cell. Although many genes involved in learning and memory formation have been identified, little is known about the genetic mechanisms required for changing the transcriptional program during different phases of long-term memory formation. With Drosophila melanogaster as a model system we profiled transcriptomic changes in the mushroom body, a memory center in the fly brain, at distinct time intervals during appetitive olfactory long-term memory formation using the targeted DamID technique. We describe the gene expression profiles during these phases and tested 33 selected candidate genes for deficits in long-term memory formation using RNAi knockdown. We identified 10 genes that enhance or decrease memory when knocked-down in the mushroom body. For vajk-1 and hacd1 , the two strongest hits, we gained further support for their crucial role in appetitive learning and forgetting. These findings show that profiling gene expression changes in specific cell-types harboring memory traces provides a powerful entry point to identify new genes involved in learning and memory. The presented transcriptomic data may further be used as resource to study genes acting at different memory phases. Copyright © 2018, Genetics.

Metabolomics reveals distinct neurochemical profiles associated with stress resilience

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Brooke N. Dulka

2017-12-01

Full Text Available Acute social defeat represents a naturalistic form of conditioned fear and is an excellent model in which to investigate the biological basis of stress resilience. While there is growing interest in identifying biomarkers of stress resilience, until recently, it has not been feasible to associate levels of large numbers of neurochemicals and metabolites to stress-related phenotypes. The objective of the present study was to use an untargeted metabolomics approach to identify known and unknown neurochemicals in select brain regions that distinguish susceptible and resistant individuals in two rodent models of acute social defeat. In the first experiment, male mice were first phenotyped as resistant or susceptible. Then, mice were subjected to acute social defeat, and tissues were immediately collected from the ventromedial prefrontal cortex (vmPFC, basolateral/central amygdala (BLA/CeA, nucleus accumbens (NAc, and dorsal hippocampus (dHPC. Ultra-high performance liquid chromatography coupled with high resolution mass spectrometry (UPLC-HRMS was used for the detection of water-soluble neurochemicals. In the second experiment, male Syrian hamsters were paired in daily agonistic encounters for 2 weeks, during which they formed stable dominant-subordinate relationships. Then, 24 h after the last dominance encounter, animals were exposed to acute social defeat stress. Immediately after social defeat, tissue was collected from the vmPFC, BLA/CeA, NAc, and dHPC for analysis using UPLC-HRMS. Although no single biomarker characterized stress-related phenotypes in both species, commonalities were found. For instance, in both model systems, animals resistant to social defeat stress also show increased concentration of molecules to protect against oxidative stress in the NAc and vmPFC. Additionally, in both mice and hamsters, unidentified spectral features were preliminarily annotated as potential targets for future experiments. Overall, these findings

Ananke: temporal clustering reveals ecological dynamics of microbial communities

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Michael W. Hall

2017-09-01

Full Text Available Taxonomic markers such as the 16S ribosomal RNA gene are widely used in microbial community analysis. A common first step in marker-gene analysis is grouping genes into clusters to reduce data sets to a more manageable size and potentially mitigate the effects of sequencing error. Instead of clustering based on sequence identity, marker-gene data sets collected over time can be clustered based on temporal correlation to reveal ecologically meaningful associations. We present Ananke, a free and open-source algorithm and software package that complements existing sequence-identity-based clustering approaches by clustering marker-gene data based on time-series profiles and provides interactive visualization of clusters, including highlighting of internal OTU inconsistencies. Ananke is able to cluster distinct temporal patterns from simulations of multiple ecological patterns, such as periodic seasonal dynamics and organism appearances/disappearances. We apply our algorithm to two longitudinal marker gene data sets: faecal communities from the human gut of an individual sampled over one year, and communities from a freshwater lake sampled over eleven years. Within the gut, the segregation of the bacterial community around a food-poisoning event was immediately clear. In the freshwater lake, we found that high sequence identity between marker genes does not guarantee similar temporal dynamics, and Ananke time-series clusters revealed patterns obscured by clustering based on sequence identity or taxonomy. Ananke is free and open-source software available at https://github.com/beiko-lab/ananke.

LOGISTIC FUNCTION PROFILE FIT: A least-squares program for fitting interface profiles to an extended logistic function

International Nuclear Information System (INIS)

Kirchhoff, William H.

2012-01-01

The extended logistic function provides a physically reasonable description of interfaces such as depth profiles or line scans of surface topological or compositional features. It describes these interfaces with the minimum number of parameters, namely, position, width, and asymmetry. Logistic Function Profile Fit (LFPF) is a robust, least-squares fitting program in which the nonlinear extended logistic function is linearized by a Taylor series expansion (equivalent to a Newton–Raphson approach) with no apparent introduction of bias in the analysis. The program provides reliable confidence limits for the parameters when systematic errors are minimal and provides a display of the residuals from the fit for the detection of systematic errors. The program will aid researchers in applying ASTM E1636-10, “Standard practice for analytically describing sputter-depth-profile and linescan-profile data by an extended logistic function,” and may also prove useful in applying ISO 18516: 2006, “Surface chemical analysis—Auger electron spectroscopy and x-ray photoelectron spectroscopy—determination of lateral resolution.” Examples are given of LFPF fits to a secondary ion mass spectrometry depth profile, an Auger surface line scan, and synthetic data generated to exhibit known systematic errors for examining the significance of such errors to the extrapolation of partial profiles.

Validation of a combined autosomal/Y-chromosomal STR approach for analyzing typical biological stains in sexual-assault cases.

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Purps, Josephine; Geppert, Maria; Nagy, Marion; Roewer, Lutz

2015-11-01

DNA testing is an established part of the investigation and prosecution of sexual assault. The primary purpose of DNA evidence is to identify a suspect and/or to demonstrate sexual contact. However, due to highly uneven proportions of female and male DNA in typical stains, routine autosomal analysis often fails to detect the DNA of the assailant. To evaluate the forensic efficiency of the combined application of autosomal and Y-chromosomal short tandem repeat (STR) markers, we present a large retrospective casework study of probative evidence collected in sexual-assault cases. We investigated up to 39 STR markers by testing combinations of the 16-locus NGMSElect kit with both the 23-locus PowerPlex Y23 and the 17-locus Yfiler kit. Using this dual approach we analyzed DNA extracts from 2077 biological stains collected in 287 cases over 30 months. To assess the outcome of the combined approach in comparison to stand-alone autosomal analysis we evaluated informative DNA profiles. Our investigation revealed that Y-STR analysis added up to 21% additional, highly informative (complete, single-source) profiles to the set of reportable autosomal STR profiles for typical stains collected in sexual-assault cases. Detection of multiple male contributors was approximately three times more likely with Y-chromosomal profiling than with autosomal STR profiling. In summary, 1/10 cases would have remained inconclusive (and could have been dismissed) if Y-STR analysis had been omitted from DNA profiling in sexual-assault cases. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Temporal gene expression profiling reveals CEBPD as a candidate regulator of brain disease in prosaposin deficient mice

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Ran Huimin

2008-08-01

Full Text Available Abstract Background Prosaposin encodes, in tandem, four small acidic activator proteins (saposins with specificities for glycosphingolipid (GSL hydrolases in lysosomes. Extensive GSL storage occurs in various central nervous system regions in mammalian prosaposin deficiencies. Results Our hypomorphic prosaposin deficient mouse, PS-NA, exhibited 45% WT levels of brain saposins and showed neuropathology that included neuronal GSL storage and Purkinje cell loss. Impairment of neuronal function was observed as early as 6 wks as demonstrated by the narrow bridges tests. Temporal transcriptome microarray analyses of brain tissues were conducted with mRNA from three prosaposin deficient mouse models: PS-NA, prosaposin null (PS-/- and a V394L/V394L glucocerebrosidase mutation combined with PS-NA (4L/PS-NA. Gene expression alterations in cerebrum and cerebellum were detectable at birth preceding the neuronal deficits. Differentially expressed genes encompassed a broad spectrum of cellular functions. The number of down-regulated genes was constant, but up-regulated gene numbers increased with age. CCAAT/enhancer-binding protein delta (CEBPD was the only up-regulated transcription factor in these two brain regions of all three models. Network analyses revealed that CEBPD has functional relationships with genes in transcription, pro-inflammation, cell death, binding, myelin and transport. Conclusion These results show that: 1 Regionally specific gene expression abnormalities precede the brain histological and neuronal function changes, 2 Temporal gene expression profiles provide insights into the molecular mechanism during the GSL storage disease course, and 3 CEBPD is a candidate regulator of brain disease in prosaposin deficiency to participate in modulating disease acceleration or progression.

Phenylpropanoid profiling reveals a class of hydroxycinnamoyl glucaric acid conjugates in Isatis tinctoria leaves.

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Nguyen, Thi-Kieu-Oanh; Jamali, Arash; Grand, Eric; Morreel, Kris; Marcelo, Paulo; Gontier, Eric; Dauwe, Rebecca

2017-12-01

The brassicaceous herb, Isatis tinctoria, is an ancient medicinal plant whose rosette leaf extracts have anti-inflammatory and anti-allergic activity. Brassicaceae are known to accumulate a variety of phenylpropanoids in their rosette leaves acting as antioxidants and a UV-B shield, and these compounds often have pharmacological potential. Nevertheless, knowledge about the phenylpropanoid content of I. tinctoria leaves remains limited to the characterization of a number of flavonoids. In this research, we profiled the methanol extracts of I. tinctoria fresh leaf extracts by liquid chromatography - mass spectrometry (LC-MS) and focused on the phenylpropanoid derivatives. We report the structural characterization of 99 compounds including 18 flavonoids, 21 mono- or oligolignols, 2 benzenoids, and a wide spectrum of 58 hydroxycinnamic acid esters. Besides the sinapate esters of malate, glucose and gentiobiose, which are typical of brassicaceous plants, these conjugates comprised a large variety of glucaric acid esters that have not previously been reported in plants. Feeding with 13 C 6 -glucaric acid showed that glucaric acid is an acyl acceptor of an as yet unknown acyltransferase activity in I. tinctoria rosette leaves. The large amount of hydroxycinnamic acid derivatives changes radically our view of the woad metabolite profile and potentially contributes to the pharmacological activity of I. tinctoria leaf extracts. Copyright © 2017 Elsevier Ltd. All rights reserved.

Diagnosis of adenylosuccinate lyase deficiency by metabolomic profiling in plasma reveals a phenotypic spectrum

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Taraka R. Donti

2016-09-01

Full Text Available Adenylosuccinate lyase (ADSL deficiency is a rare autosomal recessive neurometabolic disorder that presents with a broad-spectrum of neurological and physiological symptoms. The ADSL gene produces an enzyme with binary molecular roles in de novo purine synthesis and purine nucleotide recycling. The biochemical phenotype of ADSL deficiency, accumulation of SAICAr and succinyladenosine (S-Ado in biofluids of affected individuals, serves as the traditional target for diagnosis with targeted quantitative urine purine analysis employed as the predominate method of detection. In this study, we report the diagnosis of ADSL deficiency using an alternative method, untargeted metabolomic profiling, an analytical scheme capable of generating semi-quantitative z-score values for over 1000 unique compounds in a single analysis of a specimen. Using this method to analyze plasma, we diagnosed ADSL deficiency in four patients and confirmed these findings with targeted quantitative biochemical analysis and molecular genetic testing. ADSL deficiency is part of a large a group of neurometabolic disorders, with a wide range of severity and sharing a broad differential diagnosis. This phenotypic similarity among these many inborn errors of metabolism (IEMs has classically stood as a hurdle in their initial diagnosis and subsequent treatment. The findings presented here demonstrate the clinical utility of metabolomic profiling in the diagnosis of ADSL deficiency and highlights the potential of this technology in the diagnostic evaluation of individuals with neurologic phenotypes.

A fully digital approach to replicate peri-implant soft tissue contours and emergence profile in the esthetic zone.

Science.gov (United States)

Monaco, Carlo; Evangelisti, Edoardo; Scotti, Roberto; Mignani, Giuseppe; Zucchelli, Giovanni

2016-12-01

This short communication reports on a novel digital technique designated - the "Fully Digital Technique (FDT)" - to take the impression of the peri-implant soft tissue and emergence profile with an intraoral scanner, digitally capturing both the three dimensional position of the implant platform and the coronal and gingival parts of the provisional retained restoration. A first intraoral digital impression, which generated a standard triangulation language file (STL1), was taken using a standardized implant scanbody to detect the position of the implant. A second digital impression (STL2) with the provisional retained restoration in situ was performed in two steps: the first part of the scan captured all details of the vestibular and palatal sides of the provisional retained restoration and the adjacent teeth. The provisional retained restoration was then unscrewed, and the subgingival part of the restoration was scanned directly out of the mouth to determine its subgingival shape. STL1 and STL2 were imported into imaging software and superimposed using the "best fit" algorithm to achieve a new merged file (STL3) with the 3D implant position, the peri-implant mucosa, and emergence profile. The merged file was used to design the CAD/CAM customized abutment and to realize a stereolithographic model by 3D printing. The STL superimposition of digital impressions of the implant position and the provisional retained restoration constitute a novel technique to obtain a single STL file with the implant position and its peri-implant mucosal architecture. FDT is a rapid digital approach for achieving all information of the peri-implant soft tissue and emergence profile directly from the provisional retained restoration. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

In vivo Host-Pathogen Interaction as Revealed by Global Proteomic Profiling of Zebrafish Larvae

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Francisco Díaz-Pascual

2017-07-01

Full Text Available The outcome of a host-pathogen interaction is determined by the conditions of the host, the pathogen, and the environment. Although numerous proteomic studies of in vitro-grown microbial pathogens have been performed, in vivo proteomic approaches are still rare. In addition, increasing evidence supports that in vitro studies inadequately reflect in vivo conditions. Choosing the proper host is essential to detect the expression of proteins from the pathogen in vivo. Numerous studies have demonstrated the suitability of zebrafish (Danio rerio embryos as a model to in vivo studies of Pseudomonas aeruginosa infection. In most zebrafish-pathogen studies, infection is achieved by microinjection of bacteria into the larvae. However, few reports using static immersion of bacterial pathogens have been published. In this study we infected 3 days post-fertilization (DPF zebrafish larvae with P. aeruginosa PAO1 by immersion and injection and tracked the in vivo immune response by the zebrafish. Additionally, by using non-isotopic (Q-exactive metaproteomics we simultaneously evaluated the proteomic response of the pathogen (P. aeruginosa PAO1 and the host (zebrafish. We found some zebrafish metabolic pathways, such as hypoxia response via HIF activation pathway, were exclusively enriched in the larvae exposed by static immersion. In contrast, we found that inflammation mediated by chemokine and cytokine signaling pathways was exclusively enriched in the larvae exposed by injection, while the integrin signaling pathway and angiogenesis were solely enriched in the larvae exposed by immersion. We also found important virulence factors from P. aeruginosa that were enriched only after exposure by injection, such as the Type-III secretion system and flagella-associated proteins. On the other hand, P. aeruginosa proteins involved in processes like biofilm formation, and cellular responses to antibiotic and starvation were enriched exclusively after exposure by

Burnout, work engagement and workaholism among highly educated employees: Profiles, antecedents and outcomes

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Hely Innanen

2014-06-01

Full Text Available The present study examined the longitudinal profiles of burnout, engagement and workaholism among highly educated employees. First, the latent profile modeling indicated two latent classes: Engaged and Exhausted-Workaholic. Second, the results revealed that employees with the Engaged profile experienced high levels of energy and dedication, whereas employees with the Exhausted-Workaholic profile experienced exhaustion, cynicism and workaholism. Social pessimism in the transition from high education to work predicted poor subjective well-being at work. Further, workaholism decreased during the career among members of the Exhausted-Workaholic profile suggesting positive direction during career. Finally, Engaged employees experienced detachment and relaxation, life satisfaction and rewards.

Biochemical association of metabolic profile and microbiome in chronic pressure ulcer wounds.

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Mary Cloud B Ammons

Full Text Available Chronic, non-healing wounds contribute significantly to the suffering of patients with co-morbidities in the clinical population with mild to severely compromised immune systems. Normal wound healing proceeds through a well-described process. However, in chronic wounds this process seems to become dysregulated at the transition between resolution of inflammation and re-epithelialization. Bioburden in the form of colonizing bacteria is a major contributor to the delayed headlining in chronic wounds such as pressure ulcers. However how the microbiome influences the wound metabolic landscape is unknown. Here, we have used a Systems Biology approach to determine the biochemical associations between the taxonomic and metabolomic profiles of wounds colonized by bacteria. Pressure ulcer biopsies were harvested from primary chronic wounds and bisected into top and bottom sections prior to analysis of microbiome by pyrosequencing and analysis of metabolome using 1H nuclear magnetic resonance (NMR spectroscopy. Bacterial taxonomy revealed that wounds were colonized predominantly by three main phyla, but differed significantly at the genus level. While taxonomic profiles demonstrated significant variability between wounds, metabolic profiles shared significant similarity based on the depth of the wound biopsy. Biochemical association between taxonomy and metabolic landscape indicated significant wound-to-wound similarity in metabolite enrichment sets and metabolic pathway impacts, especially with regard to amino acid metabolism. To our knowledge, this is the first demonstration of a statistically robust correlation between bacterial colonization and metabolic landscape within the chronic wound environment.

Self-Protection Profiles of Worth and Academic Goals in University Students

Science.gov (United States)

Ferradás, María del Mar; Freire, Carlos; Núñez, José Carlos

2017-01-01

This work analyzes the possible existence of self-protection profiles based on a combination of self-handicapping (behavioral and claimed) strategies and defensive pessimism in university students. Similarly, the relationship between these profiles and academic goals (learning, performance-approach, performance-avoidance, and work-avoidance) is…

¹H NMR-based metabolic profiling of human rectal cancer tissue

Science.gov (United States)

2013-01-01

Background Rectal cancer is one of the most prevalent tumor types. Understanding the metabolic profile of rectal cancer is important for developing therapeutic approaches and molecular diagnosis. Methods Here, we report a metabonomics profiling of tissue samples on a large cohort of human rectal cancer subjects (n = 127) and normal controls (n = 43) using 1H nuclear magnetic resonance (1H NMR) based metabonomics assay, which is a highly sensitive and non-destructive method for the biomarker identification in biological systems. Principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) and orthogonal projection to latent structure with discriminant analysis (OPLS-DA) were applied to analyze the 1H-NMR profiling data to identify the distinguishing metabolites of rectal cancer. Results Excellent separation was obtained and distinguishing metabolites were observed among the different stages of rectal cancer tissues (stage I = 35; stage II = 37; stage III = 37 and stage IV = 18) and normal controls. A total of 38 differential metabolites were identified, 16 of which were closely correlated with the stage of rectal cancer. The up-regulation of 10 metabolites, including lactate, threonine, acetate, glutathione, uracil, succinate, serine, formate, lysine and tyrosine, were detected in the cancer tissues. On the other hand, 6 metabolites, including myo-inositol, taurine, phosphocreatine, creatine, betaine and dimethylglycine were decreased in cancer tissues. These modified metabolites revealed disturbance of energy, amino acids, ketone body and choline metabolism, which may be correlated with the progression of human rectal cancer. Conclusion Our findings firstly identify the distinguishing metabolites in different stages of rectal cancer tissues, indicating possibility of the attribution of metabolites disturbance to the progression of rectal cancer. The altered metabolites may be as potential biomarkers, which would

Transcriptome Comparative Profiling of Barley eibi1 Mutant Reveals Pleiotropic Effects of HvABCG31 Gene on Cuticle Biogenesis and Stress Responsive Pathways

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Eviatar Nevo

2013-10-01

Full Text Available Wild barley eibi1 mutant with HvABCG31 gene mutation has low capacity to retain leaf water, a phenotype associated with reduced cutin deposition and a thin cuticle. To better understand how such a mutant plant survives, we performed a genome-wide gene expression analysis. The leaf transcriptomes between the near-isogenic lines eibi1 and the wild type were compared using the 22-k Barley1 Affymetrix microarray. We found that the pleiotropic effect of the single gene HvABCG31 mutation was linked to the co-regulation of metabolic processes and stress-related system. The cuticle development involved cytochrome P450 family members and fatty acid metabolism pathways were significantly up-regulated by the HvABCG31 mutation, which might be anticipated to reduce the levels of cutin monomers or wax and display conspicuous cuticle defects. The candidate genes for responses to stress were induced by eibi1 mutant through activating the jasmonate pathway. The down-regulation of co-expressed enzyme genes responsible for DNA methylation and histone deacetylation also suggested that HvABCG31 mutation may affect the epigenetic regulation for barley development. Comparison of transcriptomic profiling of barley under biotic and abiotic stresses revealed that the functions of HvABCG31 gene to high-water loss rate might be different from other osmotic stresses of gene mutations in barley. The transcriptional profiling of the HvABCG31 mutation provided candidate genes for further investigation of the physiological and developmental changes caused by the mutant.

Phylogeny of haemosporidian blood parasites revealed by a multi-gene approach.

Science.gov (United States)

Borner, Janus; Pick, Christian; Thiede, Jenny; Kolawole, Olatunji Matthew; Kingsley, Manchang Tanyi; Schulze, Jana; Cottontail, Veronika M; Wellinghausen, Nele; Schmidt-Chanasit, Jonas; Bruchhaus, Iris; Burmester, Thorsten

2016-01-01

The apicomplexan order Haemosporida is a clade of unicellular blood parasites that infect a variety of reptilian, avian and mammalian hosts. Among them are the agents of human malaria, parasites of the genus Plasmodium, which pose a major threat to human health. Illuminating the evolutionary history of Haemosporida may help us in understanding their enormous biological diversity, as well as tracing the multiple host switches and associated acquisitions of novel life-history traits. However, the deep-level phylogenetic relationships among major haemosporidian clades have remained enigmatic because the datasets employed in phylogenetic analyses were severely limited in either gene coverage or taxon sampling. Using a PCR-based approach that employs a novel set of primers, we sequenced fragments of 21 nuclear genes from seven haemosporidian parasites of the genera Leucocytozoon, Haemoproteus, Parahaemoproteus, Polychromophilus and Plasmodium. After addition of genomic data from 25 apicomplexan species, the unreduced alignment comprised 20,580 bp from 32 species. Phylogenetic analyses were performed based on nucleotide, codon and amino acid data employing Bayesian inference, maximum likelihood and maximum parsimony. All analyses resulted in highly congruent topologies. We found consistent support for a basal position of Leucocytozoon within Haemosporida. In contrast to all previous studies, we recovered a sister group relationship between the genera Polychromophilus and Plasmodium. Within Plasmodium, the sauropsid and mammal-infecting lineages were recovered as sister clades. Support for these relationships was high in nearly all trees, revealing a novel phylogeny of Haemosporida, which is robust to the choice of the outgroup and the method of tree inference. Copyright © 2015 Elsevier Inc. All rights reserved.

Comprehensive transcriptional profiling of NaCl-stressed Arabidopsis roots reveals novel classes of responsive genes

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Deyholos Michael K

2006-10-01

Full Text Available Abstract Background Roots are an attractive system for genomic and post-genomic studies of NaCl responses, due to their primary importance to agriculture, and because of their relative structural and biochemical simplicity. Excellent genomic resources have been established for the study of Arabidopsis roots, however, a comprehensive microarray analysis of the root transcriptome following NaCl exposure is required to further understand plant responses to abiotic stress and facilitate future, systems-based analyses of the underlying regulatory networks. Results We used microarrays of 70-mer oligonucleotide probes representing 23,686 Arabidopsis genes to identify root transcripts that changed in relative abundance following 6 h, 24 h, or 48 h of hydroponic exposure to 150 mM NaCl. Enrichment analysis identified groups of structurally or functionally related genes whose members were statistically over-represented among up- or down-regulated transcripts. Our results are consistent with generally observed stress response themes, and highlight potentially important roles for underappreciated gene families, including: several groups of transporters (e.g. MATE, LeOPT1-like; signalling molecules (e.g. PERK kinases, MLO-like receptors, carbohydrate active enzymes (e.g. XTH18, transcription factors (e.g. members of ZIM, WRKY, NAC, and other proteins (e.g. 4CL-like, COMT-like, LOB-Class 1. We verified the NaCl-inducible expression of selected transcription factors and other genes by qRT-PCR. Conclusion Micorarray profiling of NaCl-treated Arabidopsis roots revealed dynamic changes in transcript abundance for at least 20% of the genome, including hundreds of transcription factors, kinases/phosphatases, hormone-related genes, and effectors of homeostasis, all of which highlight the complexity of this stress response. Our identification of these transcriptional responses, and groups of evolutionarily related genes with either similar or divergent

A Systematic Protein Refolding Screen Method using the DGR Approach Reveals that Time and Secondary TSA are Essential Variables.

Science.gov (United States)

Wang, Yuanze; van Oosterwijk, Niels; Ali, Ameena M; Adawy, Alaa; Anindya, Atsarina L; Dömling, Alexander S S; Groves, Matthew R

2017-08-24

Refolding of proteins derived from inclusion bodies is very promising as it can provide a reliable source of target proteins of high purity. However, inclusion body-based protein production is often limited by the lack of techniques for the detection of correctly refolded protein. Thus, the selection of the refolding conditions is mostly achieved using trial and error approaches and is thus a time-consuming process. In this study, we use the latest developments in the differential scanning fluorimetry guided refolding approach as an analytical method to detect correctly refolded protein. We describe a systematic buffer screen that contains a 96-well primary pH-refolding screen in conjunction with a secondary additive screen. Our research demonstrates that this approach could be applied for determining refolding conditions for several proteins. In addition, it revealed which "helper" molecules, such as arginine and additives are essential. Four different proteins: HA-RBD, MDM2, IL-17A and PD-L1 were used to validate our refolding approach. Our systematic protocol evaluates the impact of the "helper" molecules, the pH, buffer system and time on the protein refolding process in a high-throughput fashion. Finally, we demonstrate that refolding time and a secondary thermal shift assay buffer screen are critical factors for improving refolding efficiency.

Transcriptomic profiling-based mutant screen reveals three new transcription factors mediating menadione resistance in Neurospora crassa.

Science.gov (United States)

Zhu, Jufen; Yu, Xinxu; Xie, Baogui; Gu, Xiaokui; Zhang, Zhenying; Li, Shaojie

2013-06-01

To gain insight into the regulatory mechanisms of oxidative stress responses in filamentous fungi, the genome-wide transcriptional response of Neurospora crassa to menadione was analysed by digital gene expression (DGE) profiling, which identified 779 upregulated genes and 576 downregulated genes. Knockout mutants affecting 130 highly-upregulated genes were tested for menadione sensitivity, which revealed that loss of the transcription factor siderophore regulation (SRE) (a transcriptional repressor for siderophore biosynthesis), catatase-3, cytochrome c peroxidase or superoxide dismutase 1 copper chaperone causes hypersensitivity to menadione. Deletion of sre dramatically increased transcription of the siderophore biosynthesis gene ono and the siderophore iron transporter gene sit during menadione stress, suggesting that SRE is required for repression of iron uptake under oxidative stress conditions. Contrary to its phenotype, the sre deletion mutant showed higher transcriptional levels of genes encoding reactive oxygen species (ROS) scavengers than wild type during menadione stress, which implies that the mutant suffers a higher level of oxidative stress than wild type. Uncontrolled iron uptake in the sre mutant might exacerbate cellular oxidative stress. This is the first report of a negative regulator of iron assimilation participating in the fungal oxidative stress response. In addition to SRE, eight other transcription factor genes were also menadione-responsive but their single gene knockout mutants showed wild-type menadione sensitivity. Two of them, named as mit-2 (menadione induced transcription factor-2) and mit-4 (menadione induced transcription factor-4), were selected for double mutant analysis. The double mutant was hypersensitive to menadione. Similarly, the double mutation of mit-2 and sre also had additive effects on menadione sensitivity, suggesting multiple transcription factors mediate oxidative stress resistance in an additive manner

Mission-profile-based stress analysis of bond-wires in SiC power modules

DEFF Research Database (Denmark)

Bahman, Amir Sajjad; Iannuzzo, Francesco; Blaabjerg, Frede

2016-01-01

This paper proposes a novel mission-profile-based reliability analysis approach for stress on bond wires in Silicon Carbide (SiC) MOSFET power modules using statistics and thermo-mechanical FEM analysis. In the proposed approach, both the operational and environmental thermal stresses are taken...... into account. The approach uses a two-dimension statistical analysis of the operating conditions in a real one-year mission profile sampled at time frames 5 minutes long. For every statistical bin corresponding to a given operating condition, the junction temperature evolution is estimated by a thermal network...... and the mechanical stress on bond wires is consequently extracted by finite-element simulations. In the final step, the considered mission profile is translated in a stress sequence to be used for Rainflow counting calculation and lifetime estimation....

A measure of family eating habits: initial psychometric properties using the profile pattern approach (PPA).

Science.gov (United States)

Klempel, Natalie; Kim, Se-Kang; Wilson, Monique; Annunziato, Rachel A

2013-01-01

Although it seems likely that family characteristics and eating habits are a major factor in the development of eating behaviors, there are no self-report measures that examine how individuals view their family's eating habits. Seventy-one women ages 18-22 were recruited from a private university in a large northeastern city and asked to complete a short questionnaire packet consisting of demographic questions, the newly developed Family Eating Habits Questionnaire (FEHQ) and the Eating Inventory (EI). Internal consistency and test-retest reliability of the FEHQ was established. Significant associations were found between the FEHQ and the EI, indicating convergent validity for the FEHQ. Further validation was conducted using a novel statistical technique, the profile pattern approach (PPA). The results of the present study are limited by the restricted sample characteristic of a university setting. However, our findings show that the family eating habits' measure appears psychometrically sound. A future aim will be to continue validating this instrument in other samples, particularly to determine its predictive value. Copyright © 2012 Elsevier Ltd. All rights reserved.

Effects of Ramadan Fasting on Lipid Profile: A Narrative Review

OpenAIRE

Mohsen Mazidi; Peyman Rezaie; Ehsan Karimi; Mohsen Nematy

2014-01-01

Ramadan Fasting during the month of Ramadan is a religious obligation, practiced by millions of people around the world. Ramadan fasting is essentially a fundamental change in lifestyle for one lunar month. This type of fasting may have significant effects on lipid profile. Although there is no scientific consensus about the effects of fasting on cardiovascular risks such as changes in lipid profile, some studies have revealed the positive effects of Ramadan fasting (and similar religious fas...

Anti-cancer agents in Saudi Arabian herbals revealed by automated high-content imaging

KAUST Repository

Hajjar, Dina

2017-06-13

Natural products have been used for medical applications since ancient times. Commonly, natural products are structurally complex chemical compounds that efficiently interact with their biological targets, making them useful drug candidates in cancer therapy. Here, we used cell-based phenotypic profiling and image-based high-content screening to study the mode of action and potential cellular targets of plants historically used in Saudi Arabia\\'s traditional medicine. We compared the cytological profiles of fractions taken from Juniperus phoenicea (Arar), Anastatica hierochuntica (Kaff Maryam), and Citrullus colocynthis (Hanzal) with a set of reference compounds with established modes of action. Cluster analyses of the cytological profiles of the tested compounds suggested that these plants contain possible topoisomerase inhibitors that could be effective in cancer treatment. Using histone H2AX phosphorylation as a marker for DNA damage, we discovered that some of the compounds induced double-strand DNA breaks. Furthermore, chemical analysis of the active fraction isolated from Juniperus phoenicea revealed possible anti-cancer compounds. Our results demonstrate the usefulness of cell-based phenotypic screening of natural products to reveal their biological activities.

Antimicrobial susceptibility profiles and prevalence of ESBLS among ...

African Journals Online (AJOL)

Genetic relatedness of the MDR isolates was apparently influenced by the resistance profiles, hotel type and clinical characteristics. Conclusion: This study revealed that apparently healthy people working in the hospitality industry carry MDR E. coli that could potentially be transmitted to the general public. Infections by such ...

A linear programming approach for estimating the structure of a sparse linear genetic network from transcript profiling data

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Chandra Nagasuma R

2009-02-01

Full Text Available Abstract Background A genetic network can be represented as a directed graph in which a node corresponds to a gene and a directed edge specifies the direction of influence of one gene on another. The reconstruction of such networks from transcript profiling data remains an important yet challenging endeavor. A transcript profile specifies the abundances of many genes in a biological sample of interest. Prevailing strategies for learning the structure of a genetic network from high-dimensional transcript profiling data assume sparsity and linearity. Many methods consider relatively small directed graphs, inferring graphs with up to a few hundred nodes. This work examines large undirected graphs representations of genetic networks, graphs with many thousands of nodes where an undirected edge between two nodes does not indicate the direction of influence, and the problem of estimating the structure of such a sparse linear genetic network (SLGN from transcript profiling data. Results The structure learning task is cast as a sparse linear regression problem which is then posed as a LASSO (l1-constrained fitting problem and solved finally by formulating a Linear Program (LP. A bound on the Generalization Error of this approach is given in terms of the Leave-One-Out Error. The accuracy and utility of LP-SLGNs is assessed quantitatively and qualitatively using simulated and real data. The Dialogue for Reverse Engineering Assessments and Methods (DREAM initiative provides gold standard data sets and evaluation metrics that enable and facilitate the comparison of algorithms for deducing the structure of networks. The structures of LP-SLGNs estimated from the INSILICO1, INSILICO2 and INSILICO3 simulated DREAM2 data sets are comparable to those proposed by the first and/or second ranked teams in the DREAM2 competition. The structures of LP-SLGNs estimated from two published Saccharomyces cerevisae cell cycle transcript profiling data sets capture known

Depth profile measurement with lenslet images of the plenoptic camera

Science.gov (United States)

Yang, Peng; Wang, Zhaomin; Zhang, Wei; Zhao, Hongying; Qu, Weijuan; Zhao, Haimeng; Asundi, Anand; Yan, Lei

2018-03-01

An approach for carrying out depth profile measurement of an object with the plenoptic camera is proposed. A single plenoptic image consists of multiple lenslet images. To begin with, these images are processed directly with a refocusing technique to obtain the depth map, which does not need to align and decode the plenoptic image. Then, a linear depth calibration is applied based on the optical structure of the plenoptic camera for depth profile reconstruction. One significant improvement of the proposed method concerns the resolution of the depth map. Unlike the traditional method, our resolution is not limited by the number of microlenses inside the camera, and the depth map can be globally optimized. We validated the method with experiments on depth map reconstruction, depth calibration, and depth profile measurement, with the results indicating that the proposed approach is both efficient and accurate.

Metabolic signatures of extreme longevity in northern Italian centenarians reveal a complex remodeling of lipids, amino acids, and gut microbiota metabolism.

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Sebastiano Collino

Full Text Available The aging phenotype in humans has been thoroughly studied but a detailed metabolic profiling capable of shading light on the underpinning biological processes of longevity is still missing. Here using a combined metabonomics approach compromising holistic (1H-NMR profiling and targeted MS approaches, we report for the first time the metabolic phenotype of longevity in a well characterized human aging cohort compromising mostly female centenarians, elderly, and young individuals. With increasing age, targeted MS profiling of blood serum displayed a marked decrease in tryptophan concentration, while an unique alteration of specific glycerophospholipids and sphingolipids are seen in the longevity phenotype. We hypothesized that the overall lipidome changes specific to longevity putatively reflect centenarians' unique capacity to adapt/respond to the accumulating oxidative and chronic inflammatory conditions characteristic of their extreme aging phenotype. Our data in centenarians support promotion of cellular detoxification mechanisms through specific modulation of the arachidonic acid metabolic cascade as we underpinned increased concentration of 8,9-EpETrE, suggesting enhanced cytochrome P450 (CYP enzyme activity. Such effective mechanism might result in the activation of an anti-oxidative response, as displayed by decreased circulating levels of 9-HODE and 9-oxoODE, markers of lipid peroxidation and oxidative products of linoleic acid. Lastly, we also revealed that the longevity process deeply affects the structure and composition of the human gut microbiota as shown by the increased extrection of phenylacetylglutamine (PAG and p-cresol sulfate (PCS in urine of centenarians. Together, our novel approach in this representative Italian longevity cohort support the hypothesis that a complex remodeling of lipid, amino acid metabolism, and of gut microbiota functionality are key regulatory processes marking exceptional longevity in humans.

Demand side management using profile steering

NARCIS (Netherlands)

Gerards, Marco Egbertus Theodorus; Toersche, Hermen; Hoogsteen, Gerwin; van der Klauw, Thijs; Hurink, Johann L.; Smit, Gerardus Johannes Maria

2015-01-01

Many Demand Side Management (DSM) approaches use energy prices as steering signals. This paper shows that such steering signals may result in power quality problems and high losses. As an alternative, this paper proposes to use desired (e.g., flat) power profiles as steering signals and presents an

A methodological approach to assessing alveolar ridge preservation procedures in humans: soft tissue profile.

Science.gov (United States)

Vanhoutte, Vanessa; Rompen, Eric; Lecloux, Geoffrey; Rues, Stefan; Schmitter, Marc; Lambert, France

2014-03-01

The aesthetic results of implant restoration in the anterior maxilla are particularly related to the soft tissue profile. Although socket preservation techniques appear to reduce bone remodelling after tooth extraction, there is still few investigations assessing the external soft tissue profile after such procedures. The goal of this study was to describe an accurate technique to evaluate soft tissue contour changes after performing socket preservation procedures. The secondary objective was to apply the newly developed measuring method to a specific socket preservation using a "saddled" connective tissue graft combined with the insertion of slowly resorbable biomaterials into the socket. A total of 14 patients needing tooth replacement in the aesthetic region were included to receive a socket preservation procedure using a connective tissue graft. Impressions were taken before the tooth extraction (baseline) and at 2, 4, and 12 weeks after the procedure. The corresponding plaster casts were scanned, and the evolution of the soft tissue profile in relation to the baseline situation was assessed using imaging software. The measuring technique allowed assessing the soft tissue profiles accurately at different levels of the alveolar process. The insertion of a saddled connective tissue appeared to compensate for the horizontal and vertical bone remodelling after a socket preservation procedure in most regions of the alveolar crest. After 12 weeks, the only significant change was located in the more cervical and central region of the alveolar process and reached a median drop of 0.62 mm from baseline. Within the limitations of this study, we found that a saddled connective tissue graft combined with a socket preservation procedure could almost completely counteract the bone remodelling in terms of the external soft tissue profile. The minor changes found in the cervical region might disappear with the emergence profile of the prosthodontic components. The described

Contextual Risk Profiles and Trajectories of Adolescent Dating Violence Perpetration.

Science.gov (United States)

Reyes, H Luz McNaughton; Foshee, Vangie A; Markiewitz, Nathan; Chen, May S; Ennett, Susan T

2018-04-09

Social ecological and developmental system perspectives suggest that interactions among factors within and across multiple contexts (e.g., neighborhood, peer, family) must be considered in explaining dating violence perpetration. Yet, to date, most extant research on dating violence has focused on individual, rather than contextual predictors, and used variable-centered approaches that fail to capture the configurations of factors that may jointly explain involvement in dating violence. The current study used a person-centered approach, latent profile analysis, to identify key configurations (or profiles) of contextual risk and protective factors for dating violence perpetration across the neighborhood, school, friend and family contexts. We then examine the longitudinal associations between these contextual risk profiles, assessed during middle school, and trajectories of psychological and physical dating violence perpetration across grades 8 through 12. Five contextual risk profiles were identified: school, neighborhood, and family risk; school and family risk; school and friend risk; school and neighborhood risk; and low risk. The highest levels of psychological and physical perpetration across grades 8 through 12 were among adolescents in the profile characterized by high levels of school, neighborhood, and family risk. Results suggest that early interventions to reduce violence exposure and increase social regulation across multiple social contexts may be effective in reducing dating violence perpetration across adolescence.

Relationships between physical education students' motivational profiles, enjoyment, state anxiety, and self-reported physical activity.

Science.gov (United States)

Yli-Piipari, Sami; Watt, Anthony; Jaakkola, Timo; Liukkonen, Jarmo; Nurmi, Jari-Erik

2009-01-01

The purpose of this study was to analyze motivational profiles based on the self-determination theory (Deci and Ryan, 2000) and how these profiles are related to physical education students' enjoyment, state anxiety, and physical activity. The participants, 429 sixth grade students (girls = 216; boys = 213) completed SMS, Sport Enjoyment Scale, PESAS, and Physical Activity Scale. Cluster analyses identified two motivational profiles: 1) the "High motivation profile", in which the students had high intrinsic and extrinsic motivation, and low levels of amotivation, and 2) the "Low motivation profile", in which the students had low intrinsic and extrinsic motivation, and low levels of amotivation. The students in the first cluster enjoyed physical education more and were physically more active. The results revealed that students may be motivated towards physical education lessons both intrinsically and extrinsically, and still experience enjoyment in physical education. Key pointsTWO MOTIVATIONAL PROFILES WERE REVEALED: 1) the "High motivation profile", in which the students had high intrinsic and extrinsic motivation, and low levels of amotivation, and 2) the "Low motivation profile", in which the students had low intrinsic and extrinsic motivation, and low levels of amotivation.The students in the first profile enjoyed physical education more and were physically more active than the students in the second profile.Moreover, the representatives of the "High motivation profile "experienced greater anxiety toward physical education than the representatives of the "Low motivation profile"These findings raised an interesting question whether students engaging in physical education benefit more from the presence of both self-determined and non-self-determined forms of motivation, or are the benefits higher if students are primarily self-determined?

Revealing the functions of the transketolase enzyme isoforms in Rhodopseudomonas palustris using a systems biology approach.

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Chia-Wei Hu

Full Text Available BACKGROUND: Rhodopseudomonas palustris (R. palustris is a purple non-sulfur anoxygenic phototrophic bacterium that belongs to the class of proteobacteria. It is capable of absorbing atmospheric carbon dioxide and converting it to biomass via the process of photosynthesis and the Calvin-Benson-Bassham (CBB cycle. Transketolase is a key enzyme involved in the CBB cycle. Here, we reveal the functions of transketolase isoforms I and II in R. palustris using a systems biology approach. METHODOLOGY/PRINCIPAL FINDINGS: By measuring growth ability, we found that transketolase could enhance the autotrophic growth and biomass production of R. palustris. Microarray and real-time quantitative PCR revealed that transketolase isoforms I and II were involved in different carbon metabolic pathways. In addition, immunogold staining demonstrated that the two transketolase isoforms had different spatial localizations: transketolase I was primarily associated with the intracytoplasmic membrane (ICM but transketolase II was mostly distributed in the cytoplasm. Comparative proteomic analysis and network construction of transketolase over-expression and negative control (NC strains revealed that protein folding, transcriptional regulation, amino acid transport and CBB cycle-associated carbon metabolism were enriched in the transketolase I over-expressed strain. In contrast, ATP synthesis, carbohydrate transport, glycolysis-associated carbon metabolism and CBB cycle-associated carbon metabolism were enriched in the transketolase II over-expressed strain. Furthermore, ATP synthesis assays showed a significant increase in ATP synthesis in the transketolase II over-expressed strain. A PEPCK activity assay showed that PEPCK activity was higher in transketolase over-expressed strains than in the negative control strain. CONCLUSIONS/SIGNIFICANCE: Taken together, our results indicate that the two isoforms of transketolase in R. palustris could affect photoautotrophic growth

Metaphorical profile of distress in English media discourse

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Verbytska Anna

2017-12-01

Full Text Available The current research is directed towards the transition of distress studies in the English speaking culture from the prototype towards the conceptual metaphor approach. It enables the enlightenment of mental images, which underlie distress language usage in modern mass communication. The analysis involves identification of conceptual distress metaphors and metonymies within the image-schematic structure. The study includes a cognitive semantic analysis of linguistic units of the distress lexicon retrieved from the GloWbE, BNC, COCA, English newspapers and media platforms. Figurative language reveals conventional beliefs about distress represented in English media discourse, such as strong associations of emotion with darkness and coldness. Metaphorical mappings contain views about the reasons for distress experience which lie in the loss of balance or inner equilibrium, loss of control, and convictions about the reaction characterizing a person as being weak and brittle. The findings of data analysis are summed up in a metaphorical profile of distress (MPD which discloses the behavioural patterns (communicative behaviour, adequacy/inadequacy of behaviour, ability to socialize and physical effects including health issues.

Plasma Free Amino Acid Profiling of Five Types of Cancer Patients and Its Application for Early Detection

Science.gov (United States)

Miyagi, Yohei; Higashiyama, Masahiko; Gochi, Akira; Akaike, Makoto; Ishikawa, Takashi; Miura, Takeshi; Saruki, Nobuhiro; Bando, Etsuro; Kimura, Hideki; Imamura, Fumio; Moriyama, Masatoshi; Ikeda, Ichiro; Chiba, Akihiko; Oshita, Fumihiro; Imaizumi, Akira; Yamamoto, Hiroshi; Miyano, Hiroshi; Horimoto, Katsuhisa; Tochikubo, Osamu; Mitsushima, Toru; Yamakado, Minoru; Okamoto, Naoyuki

2011-01-01

Background Recently, rapid advances have been made in metabolomics-based, easy-to-use early cancer detection methods using blood samples. Among metabolites, profiling of plasma free amino acids (PFAAs) is a promising approach because PFAAs link all organ systems and have important roles in metabolism. Furthermore, PFAA profiles are known to be influenced by specific diseases, including cancers. Therefore, the purpose of the present study was to determine the characteristics of the PFAA profiles in cancer patients and the possibility of using this information for early detection. Methods and Findings Plasma samples were collected from approximately 200 patients from multiple institutes, each diagnosed with one of the following five types of cancer: lung, gastric, colorectal, breast, or prostate cancer. Patients were compared to gender- and age- matched controls also used in this study. The PFAA levels were measured using high-performance liquid chromatography (HPLC)–electrospray ionization (ESI)–mass spectrometry (MS). Univariate analysis revealed significant differences in the PFAA profiles between the controls and the patients with any of the five types of cancer listed above, even those with asymptomatic early-stage disease. Furthermore, multivariate analysis clearly discriminated the cancer patients from the controls in terms of the area under the receiver-operator characteristics curve (AUC of ROC >0.75 for each cancer), regardless of cancer stage. Because this study was designed as case-control study, further investigations, including model construction and validation using cohorts with larger sample sizes, are necessary to determine the usefulness of PFAA profiling. Conclusions These findings suggest that PFAA profiling has great potential for improving cancer screening and diagnosis and understanding disease pathogenesis. PFAA profiles can also be used to determine various disease diagnoses from a single blood sample, which involves a relatively simple

Plasma free amino acid profiling of five types of cancer patients and its application for early detection.

Directory of Open Access Journals (Sweden)

Yohei Miyagi

Full Text Available BACKGROUND: Recently, rapid advances have been made in metabolomics-based, easy-to-use early cancer detection methods using blood samples. Among metabolites, profiling of plasma free amino acids (PFAAs is a promising approach because PFAAs link all organ systems and have important roles in metabolism. Furthermore, PFAA profiles are known to be influenced by specific diseases, including cancers. Therefore, the purpose of the present study was to determine the characteristics of the PFAA profiles in cancer patients and the possibility of using this information for early detection. METHODS AND FINDINGS: Plasma samples were collected from approximately 200 patients from multiple institutes, each diagnosed with one of the following five types of cancer: lung, gastric, colorectal, breast, or prostate cancer. Patients were compared to gender- and age- matched controls also used in this study. The PFAA levels were measured using high-performance liquid chromatography (HPLC-electrospray ionization (ESI-mass spectrometry (MS. Univariate analysis revealed significant differences in the PFAA profiles between the controls and the patients with any of the five types of cancer listed above, even those with asymptomatic early-stage disease. Furthermore, multivariate analysis clearly discriminated the cancer patients from the controls in terms of the area under the receiver-operator characteristics curve (AUC of ROC >0.75 for each cancer, regardless of cancer stage. Because this study was designed as case-control study, further investigations, including model construction and validation using cohorts with larger sample sizes, are necessary to determine the usefulness of PFAA profiling. CONCLUSIONS: These findings suggest that PFAA profiling has great potential for improving cancer screening and diagnosis and understanding disease pathogenesis. PFAA profiles can also be used to determine various disease diagnoses from a single blood sample, which involves a

Large-scale integration of small molecule-induced genome-wide transcriptional responses, Kinome-wide binding affinities and cell-growth inhibition profiles reveal global trends characterizing systems-level drug action

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Dusica eVidovic

2014-09-01

Full Text Available The Library of Integrated Network-based Cellular Signatures (LINCS project is a large-scale coordinated effort to build a comprehensive systems biology reference resource. The goals of the program include the generation of a very large multidimensional data matrix and informatics and computational tools to integrate, analyze, and make the data readily accessible. LINCS data include genome-wide transcriptional signatures, biochemical protein binding profiles, cellular phenotypic response profiles and various other datasets for a wide range of cell model systems and molecular and genetic perturbations. Here we present a partial survey of this data facilitated by data standards and in particular a robust compound standardization workflow; we integrated several types of LINCS signatures and analyzed the results with a focus on mechanism of action and chemical compounds. We illustrate how kinase targets can be related to disease models and relevant drugs. We identified some fundamental trends that appear to link Kinome binding profiles and transcriptional signatures to chemical information and biochemical binding profiles to transcriptional responses independent of chemical similarity. To fill gaps in the datasets we developed and applied predictive models. The results can be interpreted at the systems level as demonstrated based on a large number of signaling pathways. We can identify clear global relationships, suggesting robustness of cellular responses to chemical perturbation. Overall, the results suggest that chemical similarity is a useful measure at the systems level, which would support phenotypic drug optimization efforts. With this study we demonstrate the potential of such integrated analysis approaches and suggest prioritizing further experiments to fill the gaps in the current data.

Phenotypically anchored transcriptome profiling of developmental exposure to the antimicrobial agent, triclosan, reveals hepatotoxicity in embryonic zebrafish

International Nuclear Information System (INIS)

Haggard, Derik E.; Noyes, Pamela D.; Waters, Katrina M.; Tanguay, Robert L.

2016-01-01

Triclosan (TCS) is an antimicrobial agent commonly found in a variety of personal care products and cosmetics. TCS readily enters the environment through wastewater and is detected in human plasma, urine, and breast milk due to its widespread use. Studies have implicated TCS as a disruptor of thyroid and estrogen signaling; therefore, research examining the developmental effects of TCS is warranted. In this study, we used embryonic zebrafish to investigate the developmental toxicity and potential mechanism of action of TCS. Embryos were exposed to graded concentrations of TCS from 6 to 120 hours post-fertilization (hpf) and the concentration where 80% of the animals had mortality or morbidity at 120 hpf (EC 80 ) was calculated. Transcriptomic profiling was conducted on embryos exposed to the EC 80 (7.37 μM). We identified a total of 922 significant differentially expressed transcripts (FDR adjusted P-value ≤ 0.05; fold change ≥ 2). Pathway and gene ontology enrichment analyses identified biological networks and transcriptional hubs involving normal liver functioning, suggesting TCS may be hepatotoxic in zebrafish. Tissue-specific gene enrichment analysis further supported the role of the liver as a target organ for TCS toxicity. We also examined the in vitro bioactivity profile of TCS reported by the ToxCast screening program. TCS had a diverse bioactivity profile and was a hit in 217 of the 385 assay endpoints we identified. We observed similarities in gene expression and hepatic steatosis assays; however, hit data for TCS were more concordant with the hypothesized CAR/PXR activity of TCS from rodent and human in vitro studies. - Highlights: • Triclosan is a common antimicrobial agent with widespread human exposure. • Exposure to the triclosan EC 80 causes robust gene expression changes in zebrafish. • The liver may be a target organ of triclosan toxicity in embryonic zebrafish. • Triclosan disrupts normal liver functioning and development in

Phenotypically anchored transcriptome profiling of developmental exposure to the antimicrobial agent, triclosan, reveals hepatotoxicity in embryonic zebrafish

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Haggard, Derik E. [Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR (United States); Noyes, Pamela D. [Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR (United States); Office of Science Coordination and Policy (OSCP), Office of Chemical Safety and Pollution Prevention, U.S. Environmental Protection Agency, Washington, DC (United States); Waters, Katrina M. [Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA (United States); Tanguay, Robert L., E-mail: Robert.Tanguay@oregonstate.edu [Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR (United States)

2016-10-01

Triclosan (TCS) is an antimicrobial agent commonly found in a variety of personal care products and cosmetics. TCS readily enters the environment through wastewater and is detected in human plasma, urine, and breast milk due to its widespread use. Studies have implicated TCS as a disruptor of thyroid and estrogen signaling; therefore, research examining the developmental effects of TCS is warranted. In this study, we used embryonic zebrafish to investigate the developmental toxicity and potential mechanism of action of TCS. Embryos were exposed to graded concentrations of TCS from 6 to 120 hours post-fertilization (hpf) and the concentration where 80% of the animals had mortality or morbidity at 120 hpf (EC{sub 80}) was calculated. Transcriptomic profiling was conducted on embryos exposed to the EC{sub 80} (7.37 μM). We identified a total of 922 significant differentially expressed transcripts (FDR adjusted P-value ≤ 0.05; fold change ≥ 2). Pathway and gene ontology enrichment analyses identified biological networks and transcriptional hubs involving normal liver functioning, suggesting TCS may be hepatotoxic in zebrafish. Tissue-specific gene enrichment analysis further supported the role of the liver as a target organ for TCS toxicity. We also examined the in vitro bioactivity profile of TCS reported by the ToxCast screening program. TCS had a diverse bioactivity profile and was a hit in 217 of the 385 assay endpoints we identified. We observed similarities in gene expression and hepatic steatosis assays; however, hit data for TCS were more concordant with the hypothesized CAR/PXR activity of TCS from rodent and human in vitro studies. - Highlights: • Triclosan is a common antimicrobial agent with widespread human exposure. • Exposure to the triclosan EC{sub 80} causes robust gene expression changes in zebrafish. • The liver may be a target organ of triclosan toxicity in embryonic zebrafish. • Triclosan disrupts normal liver functioning and

Nonparametric estimates of drift and diffusion profiles via Fokker-Planck algebra.

Science.gov (United States)

Lund, Steven P; Hubbard, Joseph B; Halter, Michael

2014-11-06

Diffusion processes superimposed upon deterministic motion play a key role in understanding and controlling the transport of matter, energy, momentum, and even information in physics, chemistry, material science, biology, and communications technology. Given functions defining these random and deterministic components, the Fokker-Planck (FP) equation is often used to model these diffusive systems. Many methods exist for estimating the drift and diffusion profiles from one or more identifiable diffusive trajectories; however, when many identical entities diffuse simultaneously, it may not be possible to identify individual trajectories. Here we present a method capable of simultaneously providing nonparametric estimates for both drift and diffusion profiles from evolving density profiles, requiring only the validity of Langevin/FP dynamics. This algebraic FP manipulation provides a flexible and robust framework for estimating stationary drift and diffusion coefficient profiles, is not based on fluctuation theory or solved diffusion equations, and may facilitate predictions for many experimental systems. We illustrate this approach on experimental data obtained from a model lipid bilayer system exhibiting free diffusion and electric field induced drift. The wide range over which this approach provides accurate estimates for drift and diffusion profiles is demonstrated through simulation.

Metabolite Profiling of Low-P Tolerant and Low-P Sensitive Maize Genotypes under Phosphorus Starvation and Restoration Conditions.

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Arshid Hussain Ganie

Full Text Available Maize (Zea mays L. is one of the most widely cultivated crop plants. Unavoidable economic and environmental problems associated with the excessive use of phosphatic fertilizers demands its better management. The solution lies in improving the phosphorus (P use efficiency to sustain productivity even at low P levels. Untargeted metabolomic profiling of contrasting genotypes provides a snap shot of whole metabolome which differs under specific conditions. This information provides an understanding of the mechanisms underlying tolerance to P stress and the approach for increasing P-use-efficiency.A comparative metabolite-profiling approach based on gas chromatography-mass spectrometry (GC/MS was applied to investigate the effect of P starvation and its restoration in low-P sensitive (HM-4 and low-P tolerant (PEHM-2 maize genotypes. A comparison of the metabolite profiles of contrasting genotypes in response to P-deficiency revealed distinct differences among low-P sensitive and tolerant genotypes. Another set of these genotypes were grown under P-restoration condition and sampled at different time intervals (3, 5 and 10 days to investigate if the changes in metabolite profile under P-deficiency was restored. Significant variations in the metabolite pools of these genotypes were observed under P-deficiency which were genotype specific. Out of 180 distinct analytes, 91 were identified. Phosphorus-starvation resulted in accumulation of di- and trisaccharides and metabolites of ammonium metabolism, specifically in leaves, but decreased the levels of phosphate-containing metabolites and organic acids. A sharp increase in the concentrations of glutamine, asparagine, serine and glycine was observed in both shoots and roots under low-P condition.The new insights generated on the maize metabolome in response to P-starvation and restoration would be useful towards improvement of the P-use efficiency in maize.

Will it Ever be Possible to Profile the Terrorist?

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Jonathan A Rae

2012-09-01

Full Text Available 'This paper critiques the claim that terrorists can be profiled – that is to say that terrorists possess distinguishable attributes that can be conceivably identified by an observer. In doing so, the most prominent profiling parameters - racial, gender, age, pathological, psychological and socioeconomic – are investigated. The above approaches are found to have little to no applied value in identifying terrorists from a societal population. The dominant criticisms of these methods emphasise their crude reductionism, an absence of internal and external validity, and their lack of practical application. Current evidence indicates that the profiling of terrorists is a futile venture.'

A Deconvolution Protocol for ChIP-Seq Reveals Analogous Enhancer Structures on the Mouse and Human Ribosomal RNA Genes

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Jean-Clement Mars

2018-01-01

Full Text Available The combination of Chromatin Immunoprecipitation and Massively Parallel Sequencing, or ChIP-Seq, has greatly advanced our genome-wide understanding of chromatin and enhancer structures. However, its resolution at any given genetic locus is limited by several factors. In applying ChIP-Seq to the study of the ribosomal RNA genes, we found that a major limitation to resolution was imposed by the underlying variability in sequence coverage that very often dominates the protein–DNA interaction profiles. Here, we describe a simple numerical deconvolution approach that, in large part, corrects for this variability, and significantly improves both the resolution and quantitation of protein–DNA interaction maps deduced from ChIP-Seq data. This approach has allowed us to determine the in vivo organization of the RNA polymerase I preinitiation complexes that form at the promoters and enhancers of the mouse (Mus musculus and human (Homo sapiens ribosomal RNA genes, and to reveal a phased binding of the HMG-box factor UBF across the rDNA. The data identify and map a “Spacer Promoter” and associated stalled polymerase in the intergenic spacer of the human ribosomal RNA genes, and reveal a very similar enhancer structure to that found in rodents and lower vertebrates.

PCR-based Approaches for the Detection of Clinical Methicillin-resistant Staphylococcus aureus

Science.gov (United States)

Liu, Ying; Zhang, Jiang; Ji, Yinduo

2016-01-01

Staphylococcus aureus is an important pathogen that can cause a variety of infections, including superficial and systematic infections, in humans and animals. The persistent emergence of multidrug resistant S. aureus, particularly methicillin-resistant S. aureus, has caused dramatically economic burden and concerns in the public health due to limited options of treatment of MRSA infections. In order to make a correct choice of treatment for physicians and understand the prevalence of MRSA, it is extremely critical to precisely and timely diagnose the pathogen that induces a specific infection of patients and to reveal the antibiotic resistant profile of the pathogen. In this review, we outlined different PCR-based approaches that have been successfully utilized for the rapid detection of S. aureus, including MRSA and MSSA, directly from various clinical specimens. The sensitivity and specificity of detections were pointed out. Both advantages and disadvantages of listed approaches were discussed. Importantly, an alternative approach is necessary to further confirm the detection results from the molecular diagnostic assays. PMID:27335617

Analysis of BSRT Profiles in the LHC at Injection

CERN Document Server

Fitterer, M; Papadopoulou, S; Papaphilippou, Y; Redaelli, S

2017-01-01

The beam synchrotron radiation telescope (BSRT) at the LHC allows to take profiles of the transverse beam distribution, which can provide useful additional insight in the evolution of the transverse beam distribution. A python class has been developed [1], which allows to read in the BSRT profiles, usually stored in binary format, run different analysis tools and generate plots of the statistical parameters and profiles as well as videos of the the profiles. The detailed analysis will be described in this note. The analysis is based on the data obtained at injection energy (450 GeV) during MD1217 [2] and MD1415 [3] which will be also used as illustrative example. A similar approach is also taken with a MATLAB based analysis described in [4].

Low-molecular weight protein profiling of genetically modified maize using fast liquid chromatography electrospray ionization and time-of-flight mass spectrometry.