Investigation of increased listeriosis revealed two fishery production plants with persistent Listeria contamination in Finland in 2010.

PubMed

Nakari, U-M; Rantala, L; Pihlajasaari, A; Toikkanen, S; Johansson, T; Hellsten, C; Raulo, S M; Kuusi, M; Siitonen, A; Rimhanen-Finne, R

2014-11-01

In 2010, a marked increase in listeriosis incidence was observed in Finland. Listeria monocytogenes PFGE profile 96 was responsible for one-fifth of the reported cases and a cluster of PFGE profile 62 was also detected. Investigations revealed two fishery production plants with persistent Listeria contamination. It appears likely that the plants were at least partly responsible for the increase of listeriosis. Epidemiological investigation revealed that 57% (31/54) of cases with underlying immunosuppressive condition or medication reported eating gravad or cold-smoked fish. Two public notices were issued by THL and Evira informing which groups were most at risk from the effects of listeriosis and should therefore be cautious in consuming certain products. Systematic sampling of foods and adequate epidemiological investigation methods are required to identify the sources of Listeria infections. Continuous control measures at fishery production plants producing risk products are essential.

Decomposition of ultrathin LiF cathode underlayer in organic-based devices evidenced by ToF-SIMS depth profiling

NASA Astrophysics Data System (ADS)

Pakhomov, Georgy L.; Drozdov, Mikhail N.; Travkin, Vlad V.; Bochkarev, Mikhail N.

2017-11-01

In this work we investigate the chemical composition of an archetypal thin-film organic device with the Ag/LiF cathode using the time-of-flight secondary ion mass spectrometry (ToF-SIMS) with depth profiling. The LiF cathode underlayer is partly decomposed because a significant amount of lithium is released into the bulk of the multilayer device. The released lithium diffuses all the way to the substrate, accumulating, as revealed by ToF-SIMS depth profiles, at the interfaces rather than uniformly doping the underlying layers. Particularly, the bottom anode becomes chemically modified.

Ribosome profiling reveals the what, when, where and how of protein synthesis.

PubMed

Brar, Gloria A; Weissman, Jonathan S

2015-11-01

Ribosome profiling, which involves the deep sequencing of ribosome-protected mRNA fragments, is a powerful tool for globally monitoring translation in vivo. The method has facilitated discovery of the regulation of gene expression underlying diverse and complex biological processes, of important aspects of the mechanism of protein synthesis, and even of new proteins, by providing a systematic approach for experimental annotation of coding regions. Here, we introduce the methodology of ribosome profiling and discuss examples in which this approach has been a key factor in guiding biological discovery, including its prominent role in identifying thousands of novel translated short open reading frames and alternative translation products.

Transcriptional blood signatures distinguish pulmonary tuberculosis, pulmonary sarcoidosis, pneumonias and lung cancers.

PubMed

Bloom, Chloe I; Graham, Christine M; Berry, Matthew P R; Rozakeas, Fotini; Redford, Paul S; Wang, Yuanyuan; Xu, Zhaohui; Wilkinson, Katalin A; Wilkinson, Robert J; Kendrick, Yvonne; Devouassoux, Gilles; Ferry, Tristan; Miyara, Makoto; Bouvry, Diane; Valeyre, Dominique; Dominique, Valeyre; Gorochov, Guy; Blankenship, Derek; Saadatian, Mitra; Vanhems, Phillip; Beynon, Huw; Vancheeswaran, Rama; Wickremasinghe, Melissa; Chaussabel, Damien; Banchereau, Jacques; Pascual, Virginia; Ho, Ling-Pei; Lipman, Marc; O'Garra, Anne

2013-01-01

New approaches to define factors underlying the immunopathogenesis of pulmonary diseases including sarcoidosis and tuberculosis are needed to develop new treatments and biomarkers. Comparing the blood transcriptional response of tuberculosis to other similar pulmonary diseases will advance knowledge of disease pathways and help distinguish diseases with similar clinical presentations. To determine the factors underlying the immunopathogenesis of the granulomatous diseases, sarcoidosis and tuberculosis, by comparing the blood transcriptional responses in these and other pulmonary diseases. We compared whole blood genome-wide transcriptional profiles in pulmonary sarcoidosis, pulmonary tuberculosis, to community acquired pneumonia and primary lung cancer and healthy controls, before and after treatment, and in purified leucocyte populations. An Interferon-inducible neutrophil-driven blood transcriptional signature was present in both sarcoidosis and tuberculosis, with a higher abundance and expression in tuberculosis. Heterogeneity of the sarcoidosis signature correlated significantly with disease activity. Transcriptional profiles in pneumonia and lung cancer revealed an over-abundance of inflammatory transcripts. After successful treatment the transcriptional activity in tuberculosis and pneumonia patients was significantly reduced. However the glucocorticoid-responsive sarcoidosis patients showed a significant increase in transcriptional activity. 144-blood transcripts were able to distinguish tuberculosis from other lung diseases and controls. Tuberculosis and sarcoidosis revealed similar blood transcriptional profiles, dominated by interferon-inducible transcripts, while pneumonia and lung cancer showed distinct signatures, dominated by inflammatory genes. There were also significant differences between tuberculosis and sarcoidosis in the degree of their transcriptional activity, the heterogeneity of their profiles and their transcriptional response to treatment.

Effects of Impression Management Efforts on FIROB Profiles

ERIC Educational Resources Information Center

Hinrichsen, James J.; And Others

1975-01-01

Thirty male and 30 female undergraduates were tested in six groups of 10. Each subject completed the FIRO-B under three different instructional sets. The instructional sets were (a) "normal condition", (b) "fake good", and (c) "fake bad". The study revealed that the FIRO-B is susceptible to undetected faking. (Author)

A toxicity signature for species-specific disruption of embryonic vasculogenesis derived from ToxCast in vitro profiling data

EPA Science Inventory

Blood vessel formation is crucial for normal embryo development and is sensitive to disruption by diverse teratogens. Recent studies have begun to reveal the cell signaling networks underlying vasculogenesis and angiogenesis and how these pathways might be perturbed by specific c...

Disclosure of the differences of Mesorhizobium loti under the free-living and symbiotic conditions by comparative proteome analysis without bacteroid isolation.

PubMed

Tatsukami, Yohei; Nambu, Mami; Morisaka, Hironobu; Kuroda, Kouichi; Ueda, Mitsuyoshi

2013-07-31

Rhizobia are symbiotic nitrogen-fixing soil bacteria that show a symbiotic relationship with their host legume. Rhizobia have 2 different physiological conditions: a free-living condition in soil, and a symbiotic nitrogen-fixing condition in the nodule. The lifestyle of rhizobia remains largely unknown, although genome and transcriptome analyses have been carried out. To clarify the lifestyle of bacteria, proteome analysis is necessary because the protein profile directly reflects in vivo reactions of the organisms. In proteome analysis, high separation performance is required to analyze complex biological samples. Therefore, we used a liquid chromatography-tandem mass spectrometry system, equipped with a long monolithic silica capillary column, which is superior to conventional columns. In this study, we compared the protein profile of Mesorhizobium loti MAFF303099 under free-living condition to that of symbiotic conditions by using small amounts of crude extracts. We identified 1,533 and 847 proteins for M. loti under free-living and symbiotic conditions, respectively. Pathway analysis by Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed that many of the enzymes involved in the central carbon metabolic pathway were commonly detected under both conditions. The proteins encoded in the symbiosis island, the transmissible chromosomal region that includes the genes that are highly upregulated under the symbiotic condition, were uniquely detected under the symbiotic condition. The features of the symbiotic condition that have been reported by transcriptome analysis were confirmed at the protein level by proteome analysis. In addition, the genes of the proteins involved in cell surface structure were repressed under the symbiotic nitrogen-fixing condition. Furthermore, farnesyl pyrophosphate (FPP) was found to be biosynthesized only in rhizobia under the symbiotic condition. The obtained protein profile appeared to reflect the difference in phenotypes under the free-living and symbiotic conditions. In addition, KEGG pathway analysis revealed that the cell surface structure of rhizobia was largely different under each condition, and surprisingly, rhizobia might provided FPP to the host as a source of secondary metabolism. M. loti changed its metabolism and cell surface structure in accordance with the surrounding conditions.

Disclosure of the differences of Mesorhizobium loti under the free-living and symbiotic conditions by comparative proteome analysis without bacteroid isolation

PubMed Central

2013-01-01

Background Rhizobia are symbiotic nitrogen-fixing soil bacteria that show a symbiotic relationship with their host legume. Rhizobia have 2 different physiological conditions: a free-living condition in soil, and a symbiotic nitrogen-fixing condition in the nodule. The lifestyle of rhizobia remains largely unknown, although genome and transcriptome analyses have been carried out. To clarify the lifestyle of bacteria, proteome analysis is necessary because the protein profile directly reflects in vivo reactions of the organisms. In proteome analysis, high separation performance is required to analyze complex biological samples. Therefore, we used a liquid chromatography-tandem mass spectrometry system, equipped with a long monolithic silica capillary column, which is superior to conventional columns. In this study, we compared the protein profile of Mesorhizobium loti MAFF303099 under free-living condition to that of symbiotic conditions by using small amounts of crude extracts. Result We identified 1,533 and 847 proteins for M. loti under free-living and symbiotic conditions, respectively. Pathway analysis by Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed that many of the enzymes involved in the central carbon metabolic pathway were commonly detected under both conditions. The proteins encoded in the symbiosis island, the transmissible chromosomal region that includes the genes that are highly upregulated under the symbiotic condition, were uniquely detected under the symbiotic condition. The features of the symbiotic condition that have been reported by transcriptome analysis were confirmed at the protein level by proteome analysis. In addition, the genes of the proteins involved in cell surface structure were repressed under the symbiotic nitrogen-fixing condition. Furthermore, farnesyl pyrophosphate (FPP) was found to be biosynthesized only in rhizobia under the symbiotic condition. Conclusion The obtained protein profile appeared to reflect the difference in phenotypes under the free-living and symbiotic conditions. In addition, KEGG pathway analysis revealed that the cell surface structure of rhizobia was largely different under each condition, and surprisingly, rhizobia might provided FPP to the host as a source of secondary metabolism. M. loti changed its metabolism and cell surface structure in accordance with the surrounding conditions. PMID:23898917

Statistical inference methods for sparse biological time series data.

PubMed

Ndukum, Juliet; Fonseca, Luís L; Santos, Helena; Voit, Eberhard O; Datta, Susmita

2011-04-25

Comparing metabolic profiles under different biological perturbations has become a powerful approach to investigating the functioning of cells. The profiles can be taken as single snapshots of a system, but more information is gained if they are measured longitudinally over time. The results are short time series consisting of relatively sparse data that cannot be analyzed effectively with standard time series techniques, such as autocorrelation and frequency domain methods. In this work, we study longitudinal time series profiles of glucose consumption in the yeast Saccharomyces cerevisiae under different temperatures and preconditioning regimens, which we obtained with methods of in vivo nuclear magnetic resonance (NMR) spectroscopy. For the statistical analysis we first fit several nonlinear mixed effect regression models to the longitudinal profiles and then used an ANOVA likelihood ratio method in order to test for significant differences between the profiles. The proposed methods are capable of distinguishing metabolic time trends resulting from different treatments and associate significance levels to these differences. Among several nonlinear mixed-effects regression models tested, a three-parameter logistic function represents the data with highest accuracy. ANOVA and likelihood ratio tests suggest that there are significant differences between the glucose consumption rate profiles for cells that had been--or had not been--preconditioned by heat during growth. Furthermore, pair-wise t-tests reveal significant differences in the longitudinal profiles for glucose consumption rates between optimal conditions and heat stress, optimal and recovery conditions, and heat stress and recovery conditions (p-values <0.0001). We have developed a nonlinear mixed effects model that is appropriate for the analysis of sparse metabolic and physiological time profiles. The model permits sound statistical inference procedures, based on ANOVA likelihood ratio tests, for testing the significance of differences between short time course data under different biological perturbations.

Approximate Stokes Drift Profiles and their use in Ocean Modelling

NASA Astrophysics Data System (ADS)

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).

High frequency longitudinal profiling reveals hydrologic controls on solute sourcing, transport and processing in a karst river

NASA Astrophysics Data System (ADS)

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.

Metabolite Profiling of Low-P Tolerant and Low-P Sensitive Maize Genotypes under Phosphorus Starvation and Restoration Conditions

PubMed Central

Ganie, Arshid Hussain; Ahmad, Altaf; Pandey, Renu; Aref, Ibrahim M.; Yousuf, Peerzada Yasir; Ahmad, Sayeed; Iqbal, Muhammad

2015-01-01

Background 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. Methodology/Principal Findings 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. Conclusion The new insights generated on the maize metabolome in resposne to P-starvation and restoration would be useful towards improvement of the P-use efficiency in maize. PMID:26090681

Propagating stress-pulses and wiggling transition revealed in string dynamics

NASA Astrophysics Data System (ADS)

Yao, Zhenwei

2018-02-01

Understanding string dynamics yields insights into the intricate dynamic behaviors of various filamentary thin structures in nature and industry covering multiple length scales. In this work, we investigate the planar dynamics of a flexible string where one end is free and the other end is subject to transverse and longitudinal motions. Under transverse harmonic motion, we reveal the propagating pulse structure in the stress profile over the string, and analyze its role in bringing the system into a chaotic state. For a string where one end is under longitudinal uniform acceleration, we identify the wiggling transition, derive the analytical wiggling solution from the string equations, and present the phase diagram.

Drought-responsive protein profiles reveal diverse defense pathways in corn kernels under field drought atress

USDA-ARS?s Scientific Manuscript database

Drought stress is a major factor which contributes to disease susceptibility and yield loss in agricultural crops. To identify drought responsive proteins and explore metabolic pathways involved in maize tolerance to drought stress, two lines (B73 and Lo964) with contrasting drought sensitivity were...

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

PubMed Central

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

Transcriptional Blood Signatures Distinguish Pulmonary Tuberculosis, Pulmonary Sarcoidosis, Pneumonias and Lung Cancers

PubMed Central

Bloom, Chloe I.; Graham, Christine M.; Berry, Matthew P. R.; Rozakeas, Fotini; Redford, Paul S.; Wang, Yuanyuan; Xu, Zhaohui; Wilkinson, Katalin A.; Wilkinson, Robert J.; Kendrick, Yvonne; Devouassoux, Gilles; Ferry, Tristan; Miyara, Makoto; Bouvry, Diane; Dominique, Valeyre; Gorochov, Guy; Blankenship, Derek; Saadatian, Mitra; Vanhems, Phillip; Beynon, Huw; Vancheeswaran, Rama; Wickremasinghe, Melissa; Chaussabel, Damien; Banchereau, Jacques; Pascual, Virginia; Ho, Ling-pei; Lipman, Marc; O’Garra, Anne

2013-01-01

Rationale New approaches to define factors underlying the immunopathogenesis of pulmonary diseases including sarcoidosis and tuberculosis are needed to develop new treatments and biomarkers. Comparing the blood transcriptional response of tuberculosis to other similar pulmonary diseases will advance knowledge of disease pathways and help distinguish diseases with similar clinical presentations. Objectives To determine the factors underlying the immunopathogenesis of the granulomatous diseases, sarcoidosis and tuberculosis, by comparing the blood transcriptional responses in these and other pulmonary diseases. Methods We compared whole blood genome-wide transcriptional profiles in pulmonary sarcoidosis, pulmonary tuberculosis, to community acquired pneumonia and primary lung cancer and healthy controls, before and after treatment, and in purified leucocyte populations. Measurements and Main Results An Interferon-inducible neutrophil-driven blood transcriptional signature was present in both sarcoidosis and tuberculosis, with a higher abundance and expression in tuberculosis. Heterogeneity of the sarcoidosis signature correlated significantly with disease activity. Transcriptional profiles in pneumonia and lung cancer revealed an over-abundance of inflammatory transcripts. After successful treatment the transcriptional activity in tuberculosis and pneumonia patients was significantly reduced. However the glucocorticoid-responsive sarcoidosis patients showed a significant increase in transcriptional activity. 144-blood transcripts were able to distinguish tuberculosis from other lung diseases and controls. Conclusions Tuberculosis and sarcoidosis revealed similar blood transcriptional profiles, dominated by interferon-inducible transcripts, while pneumonia and lung cancer showed distinct signatures, dominated by inflammatory genes. There were also significant differences between tuberculosis and sarcoidosis in the degree of their transcriptional activity, the heterogeneity of their profiles and their transcriptional response to treatment. PMID:23940611

Profiling differential gene expression of corals along a transect of waters adjacent to the Bermuda municipal dump.

PubMed

Morgan, Michael B; Edge, Sara E; Snell, Terry W

2005-01-01

A coral cDNA array containing 32 genes was used to examine the gene expression profiles of coral populations located at four sites that varied with distance from a semi-submerged municipal dump in Castle Harbour, Bermuda (previously identified as a point source of anthropogenic stressors). Genes on the array represent transcripts induced under controlled laboratory conditions to a variety of stressors both natural (temperature, sediment, salinity, darkness) and xenobiotic (heavy metals, pesticides, PAH) in origin. The gene expression profiles produced revealed information about the types of stressors. Consistent with other studies undertaken in Castle Harbour, the coral cDNA array detected responses to heavy metals, sedimentation, as well as oxidative stress.

Molecular events of apical bud formation in white spruce, Picea glauca.

PubMed

El Kayal, Walid; Allen, Carmen C G; Ju, Chelsea J-T; Adams, Eri; King-Jones, Susanne; Zaharia, L Irina; Abrams, Suzanne R; Cooke, Janice E K

2011-03-01

Bud formation is an adaptive trait that temperate forest trees have acquired to facilitate seasonal synchronization. We have characterized transcriptome-level changes that occur during bud formation of white spruce [Picea glauca (Moench) Voss], a primarily determinate species in which preformed stem units contained within the apical bud constitute most of next season's growth. Microarray analysis identified 4460 differentially expressed sequences in shoot tips during short day-induced bud formation. Cluster analysis revealed distinct temporal patterns of expression, and functional classification of genes in these clusters implied molecular processes that coincide with anatomical changes occurring in the developing bud. Comparing expression profiles in developing buds under long day and short day conditions identified possible photoperiod-responsive genes that may not be essential for bud development. Several genes putatively associated with hormone signalling were identified, and hormone quantification revealed distinct profiles for abscisic acid (ABA), cytokinins, auxin and their metabolites that can be related to morphological changes to the bud. Comparison of gene expression profiles during bud formation in different tissues revealed 108 genes that are differentially expressed only in developing buds and show greater transcript abundance in developing buds than other tissues. These findings provide a temporal roadmap of bud formation in white spruce. © 2011 Blackwell Publishing Ltd.

Metabolomic Profiling of Soybeans (Glycine Max L.) Reveals Importance of Sugar and Nitogen Metabolisms under Drought and Heat Stress

USDA-ARS?s Scientific Manuscript database

Soybean, an important legume crop, is continually threatened by abiotic stresses, especially drought and heat stress. At molecular levels, reduced yields due to drought and heat stress can be seen in the alterations of metabolic homeostasis of vegetative tissues. A global metabolomics approach can b...

Responses of soil microbial activity to cadmium pollution and elevated CO2.

PubMed

Chen, Yi Ping; Liu, Qiang; Liu, Yong Jun; Jia, Feng An; He, Xin Hua

2014-03-06

To address the combined effects of cadmium (Cd) and elevated CO2 on soil microbial communities, DGGE (denaturing gradient gel electrophoresis) profiles, respiration, carbon (C) and nitrogen (N) concentrations, loessial soils were exposed to four levels of Cd, i.e., 0 (Cd0), 1.5 (Cd1.5), 3.0 (Cd3.0) and 6.0 (Cd6.0) mg Cd kg(-1) soil, and two levels of CO2, i.e., 360 (aCO2) and 480 (eCO2) ppm. Compared to Cd0, Cd1.5 increased fungal abundance but decreased bacterial abundance under both CO2 levels, whilst Cd3.0 and Cd6.0 decreased both fungal and bacterial abundance. Profiles of DGGE revealed alteration of soil microbial communities under eCO2. Soil respiration decreased with Cd concentrations and was greater under eCO2 than under aCO2. Soil total C and N were greater under higher Cd. These results suggest eCO2 could stimulate, while Cd pollution could restrain microbial reproduction and C decomposition with the restraint effect alleviated by eCO2.

Inertia in the Brazil nut problem.

PubMed

Nahmad-Molinari, Y; Canul-Chay, G; Ruiz-Suárez, J C

2003-10-01

The rise dynamics of a large particle, in a granular bed under vertical vibrations, is experimentally studied with an inductive device designed to track the particle while it climbs through the granulate under different conditions. A model based on energy considerations is presented to explain our experimental data, drawing the important conclusion that it is the inertia of the particle, assisted by Reynolds dilatancy, the driven force behind its ascension mechanism. The ascension reveals a friction profile within the column which remains unchanged for different accelerations.

Genome-wide expression profiling in leaves and roots of date palm (Phoenix dactylifera L.) exposed to salinity.

PubMed

Yaish, Mahmoud W; Patankar, Himanshu V; Assaha, Dekoum V M; Zheng, Yun; Al-Yahyai, Rashid; Sunkar, Ramanjulu

2017-03-22

Date palm, as one of the most important fruit crops in North African and West Asian countries including Oman, is facing serious growth problems due to salinity, arising from persistent use of saline water for irrigation. Although date palm is a relatively salt-tolerant plant species, its adaptive mechanisms to salt stress are largely unknown. In order to get an insight into molecular mechanisms of salt tolerance, RNA was profiled in leaves and roots of date palm seedlings subjected to NaCl for 10 days. Under salt stress, photosynthetic parameters were differentially affected; all gas exchange parameters were decreased but the quantum yield of PSII was unaffected while non-photochemical quenching was increased. Analyses of gene expression profiles revealed 2630 and 4687 genes were differentially expressed in leaves and roots, respectively, under salt stress. Of these, 194 genes were identified as commonly responding in both the tissue sources. Gene ontology (GO) analysis in leaves revealed enrichment of transcripts involved in metabolic pathways including photosynthesis, sucrose and starch metabolism, and oxidative phosphorylation, while in roots genes involved in membrane transport, phenylpropanoid biosynthesis, purine, thiamine, and tryptophan metabolism, and casparian strip development were enriched. Differentially expressed genes (DEGs) common to both tissues included the auxin responsive gene, GH3, a putative potassium transporter 8 and vacuolar membrane proton pump. Leaf and root tissues respond differentially to salinity stress and this study has revealed genes and pathways that are associated with responses to elevated NaCl levels and thus may play important roles in salt tolerance providing a foundation for functional characterization of salt stress-responsive genes in the date palm.

Gel-free/label-free proteomic analysis of root tip of soybean over time under flooding and drought stresses.

PubMed

Wang, Xin; Oh, MyeongWon; Sakata, Katsumi; Komatsu, Setsuko

2016-01-01

Growth in the early stage of soybean is markedly inhibited under flooding and drought stresses. To explore the responsive mechanisms of soybean, temporal protein profiles of root tip under flooding and drought stresses were analyzed using gel-free/label-free proteomic technique. Root tip was analyzed because it was the most sensitive organ against flooding, and it was beneficial to root penetration under drought. UDP glucose: glycoprotein glucosyltransferase was decreased and increased in soybean root under flooding and drought, respectively. Temporal protein profiles indicated that fermentation and protein synthesis/degradation were essential in root tip under flooding and drought, respectively. In silico protein-protein interaction analysis revealed that the inductive and suppressive interactions between S-adenosylmethionine synthetase family protein and B-S glucosidase 44 under flooding and drought, respectively, which are related to carbohydrate metabolism. Furthermore, biotin/lipoyl attachment domain containing protein and Class II aminoacyl tRNA/biotin synthetases superfamily protein were repressed in the root tip during time-course stresses. These results suggest that biotin and biotinylation might be involved in energy management to cope with flooding and drought in early stage of soybean-root tip. Copyright © 2015 Elsevier B.V. All rights reserved.

Nutritional and anti-nutritional composition of velvet bean: an under-utilized food legume in south India.

PubMed

Vadivel, V; Janardhanan, K

2000-07-01

Four accessions of the under-utilized legume, velvet bean (Mucuna pruriens var. utilis (Wall. ex Wight) Bak. ex Burck), collected from three different locations of Western Ghats, South India were analysed for proximate composition, mineral profiles, the protein fractions, amino acid profiles of total seed protein, in vitro protein digestibility and certain anti-nutritional factors to determine their potential as an alternative source to alleviate protein-energy-malnutrition among the people of South India. The major findings of the study were as follows: crude protein ranged from 20.2-29.3%, crude lipid 6.3-7.4%, total dietary fibre 8.7-10.5%, ash 3.3-5.5% and carbohydrates 49.9-61.2%. The energy level of the seed (1562-1597 kJ 100 g-1 DM) was comparable with commonly consumed Indian pulses. Mineral profiles, viz. sodium, potassium, calcium, magnesium, phosphorus, iron, copper, zinc and manganese ranged from 43.1-150.1, 778.1-1846.0, 393.4-717.7, 174.9-387.6, 98.4-592.1, 10.8-15.0, 0.9-2.2, 5.0-10.9, 3.9-4.3 mg 100(-1) seed flour, respectively. The data on seed protein fractions revealed that the globulins constitute the major bulk of the seed protein as in most legumes. Profiles of amino acids of total seed proteins detected in the present study revealed that they contain relatively higher levels of all essential amino acids except threonine, leucine and lysine in black-coloured seed coat accessions and phenylalanine and tyrosine in white-coloured seed coat accession compared with the FAO/WHO (1991) requirement pattern. The in vitro protein digestibility of the legumes under study ranged from 72.4-76.9%. Anti-nutritional substances like total free phenolics, tannins, L-DOPA, trypsin inhibitor activity and phytohaemagglutinating activity also were investigated. The detected anti-nutritional factors probably have little nutritional significance if the beans are properly processed.

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

PubMed Central

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

Increased plasma proline concentrations are associated with sarcopenia in the elderly.

PubMed

Toyoshima, Kenji; Nakamura, Marie; Adachi, Yusuke; Imaizumi, Akira; Hakamada, Tomomi; Abe, Yasuko; Kaneko, Eiji; Takahashi, Soiciro; Shimokado, Kentaro

2017-01-01

Metabolome analyses have shown that plasma amino acid profiles reflect various pathological conditions, such as cancer and diabetes mellitus. It remains unclear, however, whether plasma amino acid profiles change in patients with sarcopenia. This study therefore aimed to investigate whether sarcopenia-specific changes occur in plasma amino acid profiles. A total of 153 community-dwelling and seven institutionalized elderly individuals (56 men, 104 women; mean age, 77.7±7.0 years) were recruited for this cross-sectional analysis. We performed a comprehensive geriatric assessment, which included an evaluation of hand grip strength, gait speed, muscle mass and blood chemistry, including the concentration of 18 amino acids. Twenty-eight of the 160 participants met the criteria for sarcopenia established by the Asian Working Group on Sarcopenia in Older People. Univariate analysis revealed associations between the presence of sarcopenia and a higher plasma concentration of proline and glutamine, lower concentrations of histidine and tryptophan. Multivariable analysis revealed that a higher concentration of proline was the only variable independently associated with sarcopenia. The plasma concentration of proline may be useful for understanding the underlying pathophysiology of sarcopenia.

Insight from uncertainty: bootstrap-derived diffusion metrics differentially predict memory function among older adults.

PubMed

Vorburger, Robert S; Habeck, Christian G; Narkhede, Atul; Guzman, Vanessa A; Manly, Jennifer J; Brickman, Adam M

2016-01-01

Diffusion tensor imaging suffers from an intrinsic low signal-to-noise ratio. Bootstrap algorithms have been introduced to provide a non-parametric method to estimate the uncertainty of the measured diffusion parameters. To quantify the variability of the principal diffusion direction, bootstrap-derived metrics such as the cone of uncertainty have been proposed. However, bootstrap-derived metrics are not independent of the underlying diffusion profile. A higher mean diffusivity causes a smaller signal-to-noise ratio and, thus, increases the measurement uncertainty. Moreover, the goodness of the tensor model, which relies strongly on the complexity of the underlying diffusion profile, influences bootstrap-derived metrics as well. The presented simulations clearly depict the cone of uncertainty as a function of the underlying diffusion profile. Since the relationship of the cone of uncertainty and common diffusion parameters, such as the mean diffusivity and the fractional anisotropy, is not linear, the cone of uncertainty has a different sensitivity. In vivo analysis of the fornix reveals the cone of uncertainty to be a predictor of memory function among older adults. No significant correlation occurs with the common diffusion parameters. The present work not only demonstrates the cone of uncertainty as a function of the actual diffusion profile, but also discloses the cone of uncertainty as a sensitive predictor of memory function. Future studies should incorporate bootstrap-derived metrics to provide more comprehensive analysis.

Behaviorally activated mRNA expression profiles produce signatures of learning and enhanced inhibition in aged rats with preserved memory.

PubMed

Haberman, Rebecca P; Colantuoni, Carlo; Koh, Ming Teng; Gallagher, Michela

2013-01-01

Aging is often associated with cognitive decline, but many elderly individuals maintain a high level of function throughout life. Here we studied outbred rats, which also exhibit individual differences across a spectrum of outcomes that includes both preserved and impaired spatial memory. Previous work in this model identified the CA3 subfield of the hippocampus as a region critically affected by age and integral to differing cognitive outcomes. Earlier microarray profiling revealed distinct gene expression profiles in the CA3 region, under basal conditions, for aged rats with intact memory and those with impairment. Because prominent age-related deficits within the CA3 occur during neural encoding of new information, here we used microarray analysis to gain a broad perspective of the aged CA3 transcriptome under activated conditions. Behaviorally-induced CA3 expression profiles differentiated aged rats with intact memory from those with impaired memory. In the activated profile, we observed substantial numbers of genes (greater than 1000) exhibiting increased expression in aged unimpaired rats relative to aged impaired, including many involved in synaptic plasticity and memory mechanisms. This unimpaired aged profile also overlapped significantly with a learning induced gene profile previously acquired in young adults. Alongside the increased transcripts common to both young learning and aged rats with preserved memory, many transcripts behaviorally-activated in the current study had previously been identified as repressed in the aged unimpaired phenotype in basal expression. A further distinct feature of the activated profile of aged rats with intact memory is the increased expression of an ensemble of genes involved in inhibitory synapse function, which could control the phenotype of neural hyperexcitability found in the CA3 region of aged impaired rats. These data support the conclusion that aged subjects with preserved memory recruit adaptive mechanisms to retain tight control over excitability under both basal and activated conditions.

Organogenic nodule development in hop (Humulus lupulus L.): Transcript and metabolic responses

PubMed Central

Fortes, Ana M; Santos, Filipa; Choi, Young H; Silva, Marta S; Figueiredo, Andreia; Sousa, Lisete; Pessoa, Fernando; Santos, Bartolomeu A; Sebastiana, Mónica; Palme, Klaus; Malhó, Rui; Verpoorte, Rob; Pais, Maria S

2008-01-01

Background Hop (Humulus lupulus L.) is an economically important plant forming organogenic nodules which can be used for genetic transformation and micropropagation. We are interested in the mechanisms underlying reprogramming of cells through stress and hormone treatments. Results An integrated molecular and metabolomic approach was used to investigate global gene expression and metabolic responses during development of hop's organogenic nodules. Transcript profiling using a 3,324-cDNA clone array revealed differential regulation of 133 unigenes, classified into 11 functional categories. Several pathways seem to be determinant in organogenic nodule formation, namely defense and stress response, sugar and lipid metabolism, synthesis of secondary metabolites and hormone signaling. Metabolic profiling using 1H NMR spectroscopy associated to two-dimensional techniques showed the importance of metabolites related to oxidative stress response, lipid and sugar metabolism and secondary metabolism in organogenic nodule formation. Conclusion The expression profile of genes pivotal for energy metabolism, together with metabolites profile, suggested that these morphogenic structures gain energy through a heterotrophic, transport-dependent and sugar-degrading anaerobic metabolism. Polyamines and auxins are likely to be involved in the regulation of expression of many genes related to organogenic nodule formation. These results represent substantial progress toward a better understanding of this complex developmental program and reveal novel information regarding morphogenesis in plants. PMID:18823540

Real-time RT-PCR profiling of transcription factors including 34 MYBs and signaling components in white lupin reveals their P status dependent and organ-specific expression

USDA-ARS?s Scientific Manuscript database

Phosphorus (P) is often a limiting macronutrient because of its low availability in soils. White lupin (Lupinus albus L.) plants are well adapted to growth under P-deficient conditions. White lupin acclimation to P-deficiency includes changes in root architecture and enhanced expression of numerous ...

Metabolomic Analysis of Alfalfa (Medicago sativa L.) Root-Symbiotic Rhizobia Responses under Alkali Stress.

PubMed

Song, Tingting; Xu, Huihui; Sun, Na; Jiang, Liu; Tian, Pu; Yong, Yueyuan; Yang, Weiwei; Cai, Hua; Cui, Guowen

2017-01-01

Alkaline salts (e.g., NaHCO 3 and Na 2 CO 3 ) causes more severe morphological and physiological damage to plants than neutral salts (e.g., NaCl and Na 2 SO 4 ) due to differences in pH. The mechanism by which plants respond to alkali stress is not fully understood, especially in plants having symbotic relationships such as alfalfa ( Medicago sativa L.). Therefore, a study was designed to evaluate the metabolic response of the root-nodule symbiosis in alfalfa under alkali stress using comparative metabolomics. Rhizobium-nodulized (RI group) and non-nodulized (NI group) alfalfa roots were treated with 200 mmol/L NaHCO 3 and, roots samples were analyzed for malondialdehydyde (MDA), proline, glutathione (GSH), superoxide dismutase (SOD), and peroxidase (POD) content. Additionally, metabolite profiling was conducted using gas chromatography combined with time-of-flight mass spectrometry (GC/TOF-MS). Phenotypically, the RI alfalfa exhibited a greater resistance to alkali stress than the NI plants examined. Physiological analysis and metabolic profiling revealed that RI plants accumulated more antioxidants (SOD, POD, GSH), osmolytes (sugar, glycols, proline), organic acids (succinic acid, fumaric acid, and alpha-ketoglutaric acid), and metabolites that are involved in nitrogen fixation. Our pairwise metabolomics comparisons revealed that RI alfalfa plants exhibited a distinct metabolic profile associated with alkali putative tolerance relative to NI alfalfa plants. Data provide new information about the relationship between non-nodulized, rhizobium-nodulized alfalfa and alkali resistance.

Metabolomic Analysis of Alfalfa (Medicago sativa L.) Root-Symbiotic Rhizobia Responses under Alkali Stress

PubMed Central

Song, Tingting; Xu, Huihui; Sun, Na; Jiang, Liu; Tian, Pu; Yong, Yueyuan; Yang, Weiwei; Cai, Hua; Cui, Guowen

2017-01-01

Alkaline salts (e.g., NaHCO3 and Na2CO3) causes more severe morphological and physiological damage to plants than neutral salts (e.g., NaCl and Na2SO4) due to differences in pH. The mechanism by which plants respond to alkali stress is not fully understood, especially in plants having symbotic relationships such as alfalfa (Medicago sativa L.). Therefore, a study was designed to evaluate the metabolic response of the root-nodule symbiosis in alfalfa under alkali stress using comparative metabolomics. Rhizobium-nodulized (RI group) and non-nodulized (NI group) alfalfa roots were treated with 200 mmol/L NaHCO3 and, roots samples were analyzed for malondialdehydyde (MDA), proline, glutathione (GSH), superoxide dismutase (SOD), and peroxidase (POD) content. Additionally, metabolite profiling was conducted using gas chromatography combined with time-of-flight mass spectrometry (GC/TOF-MS). Phenotypically, the RI alfalfa exhibited a greater resistance to alkali stress than the NI plants examined. Physiological analysis and metabolic profiling revealed that RI plants accumulated more antioxidants (SOD, POD, GSH), osmolytes (sugar, glycols, proline), organic acids (succinic acid, fumaric acid, and alpha-ketoglutaric acid), and metabolites that are involved in nitrogen fixation. Our pairwise metabolomics comparisons revealed that RI alfalfa plants exhibited a distinct metabolic profile associated with alkali putative tolerance relative to NI alfalfa plants. Data provide new information about the relationship between non-nodulized, rhizobium-nodulized alfalfa and alkali resistance. PMID:28744296

Gene-expression profiles of epithelial cells treated with EMD in vitro: analysis using complementary DNA arrays.

PubMed

Kapferer, I; Schmidt, S; Gstir, R; Durstberger, G; Huber, L A; Vietor, I

2011-02-01

During surgical periodontal treatment, EMD is topically applied in order to facilitate regeneration of the periodontal ligament, acellular cementum and alveolar bone. Suppresion of epithelial down-growth is essential for successful periodontal regeneration; however, the underlying mechanisms of how EMD influences epithelial wound healing are poorly understood. In the present study, the effects of EMD on gene-expression profiling in an epithelial cell line (HSC-2) model were investigated. Gene-expression modifications, determined using a comparative genome-wide expression-profiling strategy, were independently validated by quantitative real-time RT-PCR. Additionally, cell cycle, cell growth and in vitro wound-healing assays were conducted. A set of 43 EMD-regulated genes was defined, which may be responsible for the reduced epithelial down-growth upon EMD application. Gene ontology analysis revealed genes that could be attributed to pathways of locomotion, developmental processes and associated processes such as regulation of cell size and cell growth. Additionally, eight regulated genes have previously been reported to take part in the process of epithelial-to-mesenchymal transition. Several independent experimental assays revealed significant inhibition of cell migration, growth and cell cycle by EMD. The set of EMD-regulated genes identified in this study offers the opportunity to clarify mechanisms underlying the effects of EMD on epithelial cells. Reduced epithelial repopulation of the dental root upon periodontal surgery may be the consequence of reduced migration and cell growth, as well as epithelial-to-mesenchymal transition. © 2010 John Wiley & Sons A/S.

Integrative genomic and proteomic profiling of human neuroblastoma SH-SY5Y cells reveals signatures of endosulfan exposure.

PubMed

Gandhi, Deepa; Tarale, Prashant; Naoghare, Pravin K; Bafana, Amit; Kannan, Krishnamurthi; Sivanesan, Saravanadevi

2016-01-01

Endosulfan, an organochlorine pesticide, is known to induce multiple disorders/abnormalities including neuro-degenerative disorders in many animal species. However, the molecular mechanism of endosulfan induced neuronal alterations is still not well understood. In the present study, the effect of sub-lethal concentration of endosulfan (3 μM) on human neuroblastoma cells (SH-SY5Y) was investigated using genomic and proteomic approaches. Microarray and 2D-PAGE followed by MALDI-TOF-MS analysis revealed differential expression of 831 transcripts and 16 proteins in exposed cells. A gene ontology enrichment analysis revealed that the differentially expressed genes and proteins were involved in variety of cellular events such as neuronal developmental pathway, immune response, cell differentiation, apoptosis, transmission of nerve impulse, axonogenesis, etc. The present study attempted to explore the possible molecular mechanism of endosulfan induced neuronal alterations in SH-SY5Y cells using an integrated genomic and proteomic approach. Based on the gene and protein profile possible mechanisms underlying endosulfan neurotoxicity were predicted. Copyright © 2015 Elsevier B.V. All rights reserved.

High resolution electrolyte for thinning InP by anodic dissolution and its applications to EC-V profiling, defect revealing and surface passivation

NASA Technical Reports Server (NTRS)

Faur, Maria; Faur, Mircea; Weinberg, Irving; Goradia, Manju; Vargas, Carlos

1991-01-01

An extensive experimental study was conducted using various electrolytes in an effort to find an appropriate electrolyte for anodic dissolution of InP. From the analysis of electrochemical characteristics in the dark and under different illumination levels, x ray photoelectron spectroscopy and SEM/Nomarski inspection of the surfaces, it was determined that the anodic dissolution of InP front surface layers by FAP electrolyte is a very good choice for rendering smooth surfaces, free of oxides and contaminants and with good electrical characteristics. The FAP electrolyte, based on HF, CH3COOH, and H2O2 appears to be inherently superior to previously reported electrolytes for performing accurate EC-V profiling of InP at current densities of up to 0.3 mA/sq cm. It can also be used for accurate electrochemical revealing of either precipitates or dislocation density with application to EPD mapping as a function of depth, and for defect revealing of multilayer InP structures at any depth and/or at the interfaces.

Aureolib — A Proteome Signature Library: Towards an Understanding of Staphylococcus aureus Pathophysiology

PubMed Central

Pané-Farré, Jan; Kusch, Harald; Wolf, Carmen; Reiß, Swantje; Binh, Le Thi Nguyen; Albrecht, Dirk; Riedel, Katharina; Hecker, Michael; Engelmann, Susanne

2013-01-01

Gel-based proteomics is a powerful approach to study the physiology of Staphylococcus aureus under various growth restricting conditions. We analyzed 679 protein spots from a reference 2-dimensional gel of cytosolic proteins of S. aureus COL by mass spectrometry resulting in 521 different proteins. 4,692 time dependent protein synthesis profiles were generated by exposing S. aureus to nine infection-related stress and starvation stimuli (H2O2, diamide, paraquat, NO, fermentation, nitrate respiration, heat shock, puromycin, mupirocin). These expression profiles are stored in an online resource called Aureolib (http://www.aureolib.de). Moreover, information on target genes of 75 regulators and regulatory elements were included in the database. Cross-comparisons of this extensive data collection of protein synthesis profiles using the tools implemented in Aureolib lead to the identification of stress and starvation specific marker proteins. Altogether, 226 protein synthesis profiles showed induction ratios of 2.5-fold or higher under at least one of the tested conditions with 157 protein synthesis profiles specifically induced in response to a single stimulus. The respective proteins might serve as marker proteins for the corresponding stimulus. By contrast, proteins whose synthesis was increased or repressed in response to more than four stimuli are rather exceptional. The only protein that was induced by six stimuli is the universal stress protein SACOL1759. Most strikingly, cluster analyses of synthesis profiles of proteins differentially synthesized under at least one condition revealed only in rare cases a grouping that correlated with known regulon structures. The most prominent examples are the GapR, Rex, and CtsR regulon. In contrast, protein synthesis profiles of proteins belonging to the CodY and σB regulon are widely distributed. In summary, Aureolib is by far the most comprehensive protein expression database for S. aureus and provides an essential tool to decipher more complex adaptation processes in S. aureus during host pathogen interaction. PMID:23967085

Proteome and metabolome profiling of cytokinin action in Arabidopsis identifying both distinct and similar responses to cytokinin down- and up-regulation.

PubMed

Černý, Martin; Kuklová, Alena; Hoehenwarter, Wolfgang; Fragner, Lena; Novák, Ondrej; Rotková, Gabriela; Jedelsky, Petr L; Žáková, Katerina; Šmehilová, Mária; Strnad, Miroslav; Weckwerth, Wolfram; Brzobohaty, Bretislav

2013-11-01

In plants, numerous developmental processes are controlled by cytokinin (CK) levels and their ratios to levels of other hormones. While molecular mechanisms underlying the regulatory roles of CKs have been intensely researched, proteomic and metabolomic responses to CK deficiency are unknown. Transgenic Arabidopsis seedlings carrying inducible barley cytokinin oxidase/dehydrogenase (CaMV35S>GR>HvCKX2) and agrobacterial isopentenyl transferase (CaMV35S>GR>ipt) constructs were profiled to elucidate proteome- and metabolome-wide responses to down- and up-regulation of CK levels, respectively. Proteome profiling identified >1100 proteins, 155 of which responded to HvCKX2 and/or ipt activation, mostly involved in growth, development, and/or hormone and light signalling. The metabolome profiling covered 79 metabolites, 33 of which responded to HvCKX2 and/or ipt activation, mostly amino acids, carbohydrates, and organic acids. Comparison of the data sets obtained from activated CaMV35S>GR>HvCKX2 and CaMV35S>GR>ipt plants revealed unexpectedly extensive overlaps. Integration of the proteomic and metabolomic data sets revealed: (i) novel components of molecular circuits involved in CK action (e.g. ribosomal proteins); (ii) previously unrecognized links to redox regulation and stress hormone signalling networks; and (iii) CK content markers. The striking overlaps in profiles observed in CK-deficient and CK-overproducing seedlings might explain surprising previously reported similarities between plants with down- and up-regulated CK levels.

Colloidal Aggregate Structure under Shear by USANS

NASA Astrophysics Data System (ADS)

Chatterjee, Tirtha; van Dyk, Antony K.; Ginzburg, Valeriy V.; Nakatani, Alan I.

2015-03-01

Paints are complex formulations of polymeric binders, inorganic pigments, dispersants, surfactants, colorants, rheology modifiers, and other additives. A commercially successful paint exhibits a desired viscosity profile over a wide shear rate range from 10-5 s-1 for settling to >104 s-1 for rolling, and spray applications. Understanding paint formulation structure is critical as it governs the paint viscosity profile. However, probing paint formulation structure under shear is a challenging task due to the formulation complexity containing structures with different hierarchical length scales and their alterations under the influence of an external flow field. In this work mesoscale structures of paint formulations under shear are investigated using Ultra Small-Angle Neutron Scattering (rheo-USANS). Contrast match conditions were utilized to independently probe the structure of latex binder particle aggregates and the TiO2 pigment particle aggregates. Rheo-USANS data revealed that the aggregates are fractal in nature and their self-similarity dimensions and correlations lengths depend on the chemistry of the binder particles, the type of rheology modifier present and the shear stress imposed upon the formulation. These results can be explained in the framework of diffusion and reaction limited transient aggregates structure evolution under simple shear.

MinePath: Mining for Phenotype Differential Sub-paths in Molecular Pathways

PubMed Central

Koumakis, Lefteris; Kartsaki, Evgenia; Chatzimina, Maria; Zervakis, Michalis; Vassou, Despoina; Marias, Kostas; Moustakis, Vassilis; Potamias, George

2016-01-01

Pathway analysis methodologies couple traditional gene expression analysis with knowledge encoded in established molecular pathway networks, offering a promising approach towards the biological interpretation of phenotype differentiating genes. Early pathway analysis methodologies, named as gene set analysis (GSA), view pathways just as plain lists of genes without taking into account either the underlying pathway network topology or the involved gene regulatory relations. These approaches, even if they achieve computational efficiency and simplicity, consider pathways that involve the same genes as equivalent in terms of their gene enrichment characteristics. Most recent pathway analysis approaches take into account the underlying gene regulatory relations by examining their consistency with gene expression profiles and computing a score for each profile. Even with this approach, assessing and scoring single-relations limits the ability to reveal key gene regulation mechanisms hidden in longer pathway sub-paths. We introduce MinePath, a pathway analysis methodology that addresses and overcomes the aforementioned problems. MinePath facilitates the decomposition of pathways into their constituent sub-paths. Decomposition leads to the transformation of single-relations to complex regulation sub-paths. Regulation sub-paths are then matched with gene expression sample profiles in order to evaluate their functional status and to assess phenotype differential power. Assessment of differential power supports the identification of the most discriminant profiles. In addition, MinePath assess the significance of the pathways as a whole, ranking them by their p-values. Comparison results with state-of-the-art pathway analysis systems are indicative for the soundness and reliability of the MinePath approach. In contrast with many pathway analysis tools, MinePath is a web-based system (www.minepath.org) offering dynamic and rich pathway visualization functionality, with the unique characteristic to color regulatory relations between genes and reveal their phenotype inclination. This unique characteristic makes MinePath a valuable tool for in silico molecular biology experimentation as it serves the biomedical researchers’ exploratory needs to reveal and interpret the regulatory mechanisms that underlie and putatively govern the expression of target phenotypes. PMID:27832067

MinePath: Mining for Phenotype Differential Sub-paths in Molecular Pathways.

PubMed

Koumakis, Lefteris; Kanterakis, Alexandros; Kartsaki, Evgenia; Chatzimina, Maria; Zervakis, Michalis; Tsiknakis, Manolis; Vassou, Despoina; Kafetzopoulos, Dimitris; Marias, Kostas; Moustakis, Vassilis; Potamias, George

2016-11-01

Pathway analysis methodologies couple traditional gene expression analysis with knowledge encoded in established molecular pathway networks, offering a promising approach towards the biological interpretation of phenotype differentiating genes. Early pathway analysis methodologies, named as gene set analysis (GSA), view pathways just as plain lists of genes without taking into account either the underlying pathway network topology or the involved gene regulatory relations. These approaches, even if they achieve computational efficiency and simplicity, consider pathways that involve the same genes as equivalent in terms of their gene enrichment characteristics. Most recent pathway analysis approaches take into account the underlying gene regulatory relations by examining their consistency with gene expression profiles and computing a score for each profile. Even with this approach, assessing and scoring single-relations limits the ability to reveal key gene regulation mechanisms hidden in longer pathway sub-paths. We introduce MinePath, a pathway analysis methodology that addresses and overcomes the aforementioned problems. MinePath facilitates the decomposition of pathways into their constituent sub-paths. Decomposition leads to the transformation of single-relations to complex regulation sub-paths. Regulation sub-paths are then matched with gene expression sample profiles in order to evaluate their functional status and to assess phenotype differential power. Assessment of differential power supports the identification of the most discriminant profiles. In addition, MinePath assess the significance of the pathways as a whole, ranking them by their p-values. Comparison results with state-of-the-art pathway analysis systems are indicative for the soundness and reliability of the MinePath approach. In contrast with many pathway analysis tools, MinePath is a web-based system (www.minepath.org) offering dynamic and rich pathway visualization functionality, with the unique characteristic to color regulatory relations between genes and reveal their phenotype inclination. This unique characteristic makes MinePath a valuable tool for in silico molecular biology experimentation as it serves the biomedical researchers' exploratory needs to reveal and interpret the regulatory mechanisms that underlie and putatively govern the expression of target phenotypes.

Loading Mode and Environment Effects on Surface Profile Characteristics of Martensite Plates in Cu-Based SMAs

NASA Astrophysics Data System (ADS)

Suru, Marius-Gabriel; Paraschiv, Adrian-Liviu; Lohan, Nicoleta Monica; Pricop, Bogdan; Ozkal, Burak; Bujoreanu, Leandru-Gheorghe

2014-07-01

The present work reports the influence of the loading mode provided during training under constant stress, in bending, applied to lamellar specimens of Cu-Zn-Al shape memory alloys (SMAs). During training, the specimens were bent by a load fastened at their free end, while being martensitic at room temperature and they lifted the load by one-way effect (1WE), during heating up to austenitic field. On cooling to martensite field, the lower concave surface of bent specimens was compressed, and during heating it was elongated, being subjected to a series of tension-compression cycles, during heating-cooling, respectively. Conversely, the upper convex surface of bent specimens was elongated during cooling and compressed during heating, being subjected to compression-tension cycles. Furthermore, 2WE-trained actuators were tested by means of a hydraulic installation where, this time heating-cooling cycles were performed in oil conditions. Considering that the lower concave surface of the specimens was kept in compressed state, while the upper convex surface was kept in elongated state, the study reveals the influence of the two loading modes and environments on the width of martensite plates of the specimens trained under various numbers of cycles. In this purpose, Cu-Zn-Al specimens, trained under 100-300-500 cycles, were prepared and analyzed by atomic force microscopy (AFM) as well as optical and scanning electron microscopy (OM and SEM, respectively). The analysis also included AFM micrographs corroborated with statistical evaluations in order to reveal the effects of loading mode (tension or compression) in different environmental conditions of the specimens, on the surface profile characteristics of martensite plates, revealed by electropolishing.

Spatial Heterodyne Imager for Mesospheric Radicals on STPSat-1

DTIC Science & Technology

2010-10-22

mesospheric OH density profiles. It also measured the Rayleigh scattered background from the clear atmosphere and solar scattering from polar mesospheric... Microwave Limb Sounder OH data shows good agreement between 60 and 90 km altitude for several latitudes and seasons. We also find good agreement of the... background signals observed by SHIMMER and MAHRSI under similar lighting conditions revealed that MAHRSI radiances are systematically smaller than

Hypothalamus proteomics from mouse models with obesity and anorexia reveals therapeutic targets of appetite regulation

PubMed Central

Manousopoulou, A; Koutmani, Y; Karaliota, S; Woelk, C H; Manolakos, E S; Karalis, K; Garbis, S D

2016-01-01

Objective: This study examined the proteomic profile of the hypothalamus in mice exposed to a high-fat diet (HFD) or with the anorexia of acute illness. This comparison could provide insight on the effects of these two opposite states of energy balance on appetite regulation. Methods: Four to six-week-old male C56BL/6J mice were fed a normal (control 1 group; n=7) or a HFD (HFD group; n=10) for 8 weeks. The control 2 (n=7) and lipopolysaccharide (LPS) groups (n=10) were fed a normal diet for 8 weeks before receiving an injection of saline and LPS, respectively. Hypothalamic regions were analysed using a quantitative proteomics method based on a combination of techniques including iTRAQ stable isotope labeling, orthogonal two-dimensional liquid chromatography hyphenated with nanospray ionization and high-resolution mass spectrometry. Key proteins were validated with quantitative PCR. Results: Quantitative proteomics of the hypothalamous regions profiled a total of 9249 protein groups (q<0.05). Of these, 7718 protein groups were profiled with a minimum of two unique peptides for each. Hierachical clustering of the differentiated proteome revealed distinct proteomic signatures for the hypothalamus under the HFD and LPS nutritional conditions. Literature research with in silico bioinformatics interpretation of the differentiated proteome identified key biological relevant proteins and implicated pathways. Furthermore, the study identified potential pharmacologic targets. In the LPS groups, the anorexigen pro-opiomelanocortin was downregulated. In mice with obesity, nuclear factor-κB, glycine receptor subunit alpha-4 (GlyR) and neuropeptide Y levels were elevated, whereas serotonin receptor 1B levels decreased. Conclusions: High-precision quantitative proteomics revealed that under acute systemic inflammation in the hypothalamus as a response to LPS, homeostatic mechanisms mediating loss of appetite take effect. Conversely, under chronic inflammation in the hypothalamus as a response to HFD, mechanisms mediating a sustained ‘perpetual cycle' of appetite enhancement were observed. The GlyR protein may constitute a novel treatment target for the reduction of central orexigenic signals in obesity. PMID:27110685

Hypothalamus proteomics from mouse models with obesity and anorexia reveals therapeutic targets of appetite regulation.

PubMed

Manousopoulou, A; Koutmani, Y; Karaliota, S; Woelk, C H; Manolakos, E S; Karalis, K; Garbis, S D

2016-04-25

This study examined the proteomic profile of the hypothalamus in mice exposed to a high-fat diet (HFD) or with the anorexia of acute illness. This comparison could provide insight on the effects of these two opposite states of energy balance on appetite regulation. Four to six-week-old male C56BL/6J mice were fed a normal (control 1 group; n=7) or a HFD (HFD group; n=10) for 8 weeks. The control 2 (n=7) and lipopolysaccharide (LPS) groups (n=10) were fed a normal diet for 8 weeks before receiving an injection of saline and LPS, respectively. Hypothalamic regions were analysed using a quantitative proteomics method based on a combination of techniques including iTRAQ stable isotope labeling, orthogonal two-dimensional liquid chromatography hyphenated with nanospray ionization and high-resolution mass spectrometry. Key proteins were validated with quantitative PCR. Quantitative proteomics of the hypothalamous regions profiled a total of 9249 protein groups (q<0.05). Of these, 7718 protein groups were profiled with a minimum of two unique peptides for each. Hierachical clustering of the differentiated proteome revealed distinct proteomic signatures for the hypothalamus under the HFD and LPS nutritional conditions. Literature research with in silico bioinformatics interpretation of the differentiated proteome identified key biological relevant proteins and implicated pathways. Furthermore, the study identified potential pharmacologic targets. In the LPS groups, the anorexigen pro-opiomelanocortin was downregulated. In mice with obesity, nuclear factor-κB, glycine receptor subunit alpha-4 (GlyR) and neuropeptide Y levels were elevated, whereas serotonin receptor 1B levels decreased. High-precision quantitative proteomics revealed that under acute systemic inflammation in the hypothalamus as a response to LPS, homeostatic mechanisms mediating loss of appetite take effect. Conversely, under chronic inflammation in the hypothalamus as a response to HFD, mechanisms mediating a sustained 'perpetual cycle' of appetite enhancement were observed. The GlyR protein may constitute a novel treatment target for the reduction of central orexigenic signals in obesity.

Sex hormones adjust "sex-specific" reactive and diurnal cortisol profiles.

PubMed

Juster, Robert-Paul; Raymond, Catherine; Desrochers, Alexandra Bisson; Bourdon, Olivier; Durand, Nadia; Wan, Nathalie; Pruessner, Jens C; Lupien, Sonia J

2016-01-01

Sex differences in stress hormone functions are presumed to depend on sex hormones. And yet, surprisingly few psychoneuroendocrine studies actually assess within-sex variations of testosterone, estradiol, and progesterone when investigating sex-specific activities of the hypothalamic-pituitary-adrenal axis. In this methodological study of 204 healthy adults (60 men), we assessed whether cortisol profiles would differ between the sexes when unadjusted or adjusted for basal sex hormones among both sexes. Reactive cortisol was sampled using 6 saliva samples measured every 10-min as part of the Trier Social Stress Test that generally activates cortisol among men more than women. Diurnal cortisol was sampled over two days at (1) awakening, (2) 30-min thereafter, (3) 1400 h, (4) 1600 h, and (5) bedtime. Sex hormones were collected at baseline before the psychosocial stressor and on two occasions during diurnal cortisol assessment. Repeated-measures analysis of covariance controlled for key covariates in analyses unadjusted or adjusted for sex hormones. Results revealed that men had higher reactive cortisol than women in unadjusted analysis, but this sex difference was attenuated when adjusting for sex hormones. While diurnal cortisol showed no sex differences in unadjusted models, adjusting for sex hormones revealed that women have higher morning cortisol. Correlations using area under the curve formulae revealed intriguing sex-specific associations with progesterone in men and testosterone in women that we propose have implications for social and affective neuroscience. In summary, our results reveal that adjusting for sex hormones alters "sex-specific" reactive and diurnal cortisol profiles. Copyright © 2015 Elsevier Ltd. All rights reserved.

Increased plasma proline concentrations are associated with sarcopenia in the elderly

PubMed Central

Adachi, Yusuke; Imaizumi, Akira; Hakamada, Tomomi; Abe, Yasuko; Kaneko, Eiji; Takahashi, Soiciro; Shimokado, Kentaro

2017-01-01

Background and purpose Metabolome analyses have shown that plasma amino acid profiles reflect various pathological conditions, such as cancer and diabetes mellitus. It remains unclear, however, whether plasma amino acid profiles change in patients with sarcopenia. This study therefore aimed to investigate whether sarcopenia-specific changes occur in plasma amino acid profiles. Methods A total of 153 community-dwelling and seven institutionalized elderly individuals (56 men, 104 women; mean age, 77.7±7.0 years) were recruited for this cross-sectional analysis. We performed a comprehensive geriatric assessment, which included an evaluation of hand grip strength, gait speed, muscle mass and blood chemistry, including the concentration of 18 amino acids. Results Twenty-eight of the 160 participants met the criteria for sarcopenia established by the Asian Working Group on Sarcopenia in Older People. Univariate analysis revealed associations between the presence of sarcopenia and a higher plasma concentration of proline and glutamine, lower concentrations of histidine and tryptophan. Multivariable analysis revealed that a higher concentration of proline was the only variable independently associated with sarcopenia. Conclusions The plasma concentration of proline may be useful for understanding the underlying pathophysiology of sarcopenia. PMID:28934309

From Intensity Profile to Surface Normal: Photometric Stereo for Unknown Light Sources and Isotropic Reflectances.

PubMed

Lu, Feng; Matsushita, Yasuyuki; Sato, Imari; Okabe, Takahiro; Sato, Yoichi

2015-10-01

We propose an uncalibrated photometric stereo method that works with general and unknown isotropic reflectances. Our method uses a pixel intensity profile, which is a sequence of radiance intensities recorded at a pixel under unknown varying directional illumination. We show that for general isotropic materials and uniformly distributed light directions, the geodesic distance between intensity profiles is linearly related to the angular difference of their corresponding surface normals, and that the intensity distribution of the intensity profile reveals reflectance properties. Based on these observations, we develop two methods for surface normal estimation; one for a general setting that uses only the recorded intensity profiles, the other for the case where a BRDF database is available while the exact BRDF of the target scene is still unknown. Quantitative and qualitative evaluations are conducted using both synthetic and real-world scenes, which show the state-of-the-art accuracy of smaller than 10 degree without using reference data and 5 degree with reference data for all 100 materials in MERL database.

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

PubMed Central

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

Ethnic Identity Development and Acculturation: A Longitudinal Analysis of Mexican-Heritage Youth in the Southwest United States

PubMed Central

Matsunaga, Masaki; Hecht, Michael L.; Elek, Elvira; Ndiaye, Khadidiatou

2010-01-01

Utilizing part of the survey data collected for a National Institute on Drug Abuse (NIDA)–funded project from 29 public elementary schools in Phoenix, Arizona (N = 1,600), this study explored the underlying structure of Mexican-heritage youths’ ethnic identity and cultural/linguistic orientation. Latent profile and transition analyses identified four distinct orientation profiles endorsed by the early adolescents and their developmental trends across four time points. Most Mexican and Mexican American adolescents endorsed bicultural profiles with developmental trends characterized by widespread stasis and transitions toward greater ethnic identity exploration. Multinominal logistic regression analyses revealed associations between profile endorsement and adolescents’ gender, socioeconomic status, parents’ birthplace, and visits outside the United States. These findings are discussed in regard to previous findings on acculturation and ethnic identity development. Individuals’ adaptation to the immediate local environment is noted as a possible cause of prevalent biculturalism. Limitations and future directions for the research on ethnic identity development and acculturation are also discussed. PMID:20740051

Mild and Short-Term Caloric Restriction Prevents Obesity-Induced Cardiomyopathy in Young Zucker Rats without Changing in Metabolites and Fatty Acids Cardiac Profile

PubMed Central

Ruiz-Hurtado, Gema; García-Prieto, Concha F.; Pulido-Olmo, Helena; Velasco-Martín, Juan P.; Villa-Valverde, Palmira; Fernández-Valle, María E.; Boscá, Lisardo; Fernández-Velasco, María; Regadera, Javier; Somoza, Beatriz; Fernández-Alfonso, María S.

2017-01-01

Caloric restriction (CR) ameliorates cardiac dysfunction associated with obesity. However, most of the studies have been performed under severe CR (30–65% caloric intake decrease) for several months or even years in aged animals. Here, we investigated whether mild (20% food intake reduction) and short-term (2-weeks) CR prevented the obese cardiomyopathy phenotype and improved the metabolic profile of young (14 weeks of age) genetically obese Zucker fa/fa rats. Heart weight (HW) and HW/tibia length ratio was significantly lower in fa/fa rats after 2 weeks of CR than in counterparts fed ad libitum. Invasive pressure measurements showed that systolic blood pressure, maximal rate of positive left ventricle (LV) pressure, LV systolic pressure and LV end-diastolic pressure were all significantly higher in obese fa/fa rats than in lean counterparts, which were prevented by CR. Magnetic resonance imaging revealed that the increase in LV end-systolic volume, stroke volume and LV wall thickness observed in fa/fa rats was significantly lower in animals on CR diet. Histological analysis also revealed that CR blocked the significant increase in cardiomyocyte diameter in obese fa/fa rats. High resolution magic angle spinning magnetic resonance spectroscopy analysis of the LV revealed a global decrease in metabolites such as taurine, creatine and phosphocreatine, glutamate, glutamine and glutathione, in obese fa/fa rats, whereas lactate concentration was increased. By contrast, fatty acid concentrations in LV tissue were significantly elevated in obese fa/fa rats. CR failed to restore the LV metabolomic profile of obese fa/fa rats. In conclusion, mild and short-term CR prevented an obesity-induced cardiomyopathy phenotype in young obese fa/fa rats independently of the cardiac metabolic profile. PMID:28203206

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

Wang, Jing; Ma, Zihao; Carr, Steven A.

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).more » 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. Molecular & Cellular Proteomics 16: 10.1074/mcp.M116.060301, 121–134, 2017.« less

Metabolomic profiling of beer reveals effect of temperature on non-volatile small molecules during short-term storage.

PubMed

Heuberger, Adam L; Broeckling, Corey D; Lewis, Matthew R; Salazar, Lauren; Bouckaert, Peter; Prenni, Jessica E

2012-12-01

The effect of temperature on non-volatile compounds in beer has not been well characterised during storage. Here, a metabolomics approach was applied to characterise the effect of storage temperature on non-volatile metabolite variation after 16weeks of storage, using fresh beer as a control. The metabolite profile of room temperature stored (RT) and cold temperature stored (CT) beer differed significantly from fresh, with the most substantial variation observed between RT and fresh beer. Metabolites that changed during storage included prenylated flavonoids, purines, and peptides, and all showed reduced quantitative variation under the CT storage conditions. Corresponding sensory panel observations indicated significant beer oxidation after 12 and 16weeks of storage, with higher values reported for RT samples. These data support that temperature affected beer oxidation during short-term storage, and reveal 5-methylthioadenosine (5-MTA) as a candidate non-volatile metabolite marker for beer oxidation and staling. Copyright © 2012 Elsevier Ltd. All rights reserved.

Metabolomic Profiling of Soybeans (Glycine max L.) Reveals the Importance of Sugar and Nitrogen Metabolism under Drought and Heat Stress

PubMed Central

Das, Aayudh; Rushton, Paul J.; Rohila, Jai S.

2017-01-01

Soybean is an important crop that is continually threatened by abiotic stresses, especially drought and heat stress. At molecular levels, reduced yields due to drought and heat stress can be seen as a result of alterations in metabolic homeostasis of vegetative tissues. At present an incomplete understanding of abiotic stress-associated metabolism and identification of associated metabolites remains a major gap in soybean stress research. A study with a goal to profile leaf metabolites under control conditions (28/24 °C), drought [28/24 °C, 10% volumetric water content (VWC)], and heat stress (43/35 °C) was conducted in a controlled environment. Analyses of non-targeted metabolomic data showed that in response to drought and heat stress, key metabolites (carbohydrates, amino acids, lipids, cofactors, nucleotides, peptides and secondary metabolites) were differentially accumulated in soybean leaves. The metabolites for various cellular processes, such as glycolysis, the tricarboxylic acid (TCA) cycle, the pentose phosphate pathway, and starch biosynthesis, that regulate carbohydrate metabolism, amino acid metabolism, peptide metabolism, and purine and pyrimidine biosynthesis, were found to be affected by drought as well as heat stress. Computationally based regulatory networks predicted additional compounds that address the possibility of other metabolites and metabolic pathways that could also be important for soybean under drought and heat stress conditions. Metabolomic profiling demonstrated that in soybeans, keeping up with sugar and nitrogen metabolism is of prime significance, along with phytochemical metabolism under drought and heat stress conditions. PMID:28587097

Decoding the regulatory landscape of melanoma reveals TEADS as regulators of the invasive cell state

PubMed Central

Verfaillie, Annelien; Imrichova, Hana; Atak, Zeynep Kalender; Dewaele, Michael; Rambow, Florian; Hulselmans, Gert; Christiaens, Valerie; Svetlichnyy, Dmitry; Luciani, Flavie; Van den Mooter, Laura; Claerhout, Sofie; Fiers, Mark; Journe, Fabrice; Ghanem, Ghanem-Elias; Herrmann, Carl; Halder, Georg; Marine, Jean-Christophe; Aerts, Stein

2015-01-01

Transcriptional reprogramming of proliferative melanoma cells into a phenotypically distinct invasive cell subpopulation is a critical event at the origin of metastatic spreading. Here we generate transcriptome, open chromatin and histone modification maps of melanoma cultures; and integrate this data with existing transcriptome and DNA methylation profiles from tumour biopsies to gain insight into the mechanisms underlying this key reprogramming event. This shows thousands of genomic regulatory regions underlying the proliferative and invasive states, identifying SOX10/MITF and AP-1/TEAD as regulators, respectively. Knockdown of TEADs shows a previously unrecognized role in the invasive gene network and establishes a causative link between these transcription factors, cell invasion and sensitivity to MAPK inhibitors. Using regulatory landscapes and in silico analysis, we show that transcriptional reprogramming underlies the distinct cellular states present in melanoma. Furthermore, it reveals an essential role for the TEADs, linking it to clinically relevant mechanisms such as invasion and resistance. PMID:25865119

Gel performance in rheology and profile control under low-frequency vibration: coupling application of physical and chemical EOR techniques.

PubMed

Zheng, Li Ming; Pu, Chun Sheng; Liu, Jing; Ma, Bo; Khan, Nasir

2017-01-01

Flowing gel plugging and low-frequency vibration oil extraction technology have been widely applied in low-permeability formation. High probability of overlapping in action spheres of two technologies might lead to poor operating efficiency during gel injection. Study on flowing gel rheological properties under low-frequency vibration was essential, which was carried out indoor with viscosity measurement. Potential dynamic mechanisms were analyzed for the rheological variation. Under low-frequency vibration, gel rheological properties were found to be obviously influenced, with vibration delaying gel cross-linking in induction period, causing a two-stage gel viscosity change in acceleration period, and decreasing gel strength in stable period. Surface of gel system under vibration presented different fluctuating phenomenon from initial harmonic vibrating to heterogeneous fluctuating (droplet separation might appear) to final harmonic vibrating again. Dynamic displacement in unconsolidated sand pack revealed that low-frequency vibration during gel injection might be a measure to achieve deep profile control, with the gel injection depth increased by 65.8 % compared with the vibration-free sample. At last, suggestions for field test were given in the paper to achieve lower injection friction and better gel plugging efficiency.

Profiling the transcriptome of Gracilaria changii (Rhodophyta) in response to light deprivation.

PubMed

Ho, Chai-Ling; Teoh, Seddon; Teo, Swee-Sen; Rahim, Raha Abdul; Phang, Siew-Moi

2009-01-01

Light regulates photosynthesis, growth and reproduction, yield and properties of phycocolloids, and starch contents in seaweeds. Despite its importance as an environmental cue that regulates many developmental, physiological, and biochemical processes, the network of genes involved during light deprivation are obscure. In this study, we profiled the transcriptome of Gracilaria changii at two different irradiance levels using a cDNA microarray containing more than 3,000 cDNA probes. Microarray analysis revealed that 93 and 105 genes were up- and down-regulated more than 3-fold under light deprivation, respectively. However, only 50% of the transcripts have significant matches to the nonredundant peptide sequences in the database. The transcripts that accumulated under light deprivation include vanadium chloroperoxidase, thioredoxin, ferredoxin component, and reduced nicotinamide adenine dinucleotide dehydrogenase. Among the genes that were down-regulated under light deprivation were genes encoding light harvesting protein, light harvesting complex I, phycobilisome 7.8 kDa linker polypeptide, low molecular weight early light-inducible protein, and vanadium bromoperoxidase. Our findings also provided important clues to the functions of many unknown sequences that could not be annotated using sequence comparison.

Unsteady features of the flow on a bump in transonic environment

NASA Astrophysics Data System (ADS)

Budovsky, A. D.; Sidorenko, A. A.; Polivanov, P. A.; Vishnyakov, O. I.; Maslov, A. A.

2016-10-01

The study deals with experimental investigation of unsteady features of separated flow on a profiled bump in transonic environment. The experiments were conducted in T-325 wind tunnel of ITAM for the following flow conditions: P0 = 1 bar, T0 = 291 K. The base flow around the model was studied by schlieren visualization, steady and unsteady wall pressure measurements and PIV. The experimentally data obtained using PIV are analyzed by Proper Orthogonal Decomposition (POD) technique to investigate the underlying unsteady flow organization, as revealed by the POD eigenmodes. The data obtained show that flow pulsations revealed upstream and downstream of shock wave are correlated and interconnected.

Bacterial microbiota profile in gills of modified atmosphere-packaged oysters stored at 4 °C.

PubMed

Chen, Huibin; Wang, Meiying; Lin, Xiangzhi; Shi, Caihua; Liu, Zhiyu

2017-02-01

As filter-feeding bivalves, oysters can accumulate microorganisms into their gills, causing spoilage and potential safety issues. This study aims to investigate the changes in the gill microbiota of oysters packed under air and modified atmospheres (MAs, 50% CO 2 : 50% N 2 , 70% CO 2 : 30% O 2 , and 50% CO 2 : 50% O 2 ) during storage at 4 °C. The diversity of bacterial microbiota in oyster gills was profiled through polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) analysis on the 16S rRNA gene V3 region to describe the variation during the entire storage period. The DGGE profile revealed high bacterial diversity in the air- and MA-packaged oyster gills, and the spoilage bacterial microbiota varied in the MA-packaged oyster gills. Results indicated that CO 2 :O 2 (70%:30%) was suitable for oyster MA packaging and that high bacterial loads in oyster gills need to be considered during storage. In addition, Lactobacillus and Lactococcus species were found to grow dominantly in fresh oyster gills under MA packaging, which supports the potential application of MA packaging for oyster storage. Copyright © 2016 Elsevier Ltd. All rights reserved.

Progression Rate Associated Peripheral Blood Biomarkers of Parkinson's Disease.

PubMed

Fan, Yanxia; Xiao, Shuping

2018-06-23

Parkinson disease (PD) is one of the most frequent neurodegenerative disorders. The aim of this study was to identify blood biomarkers capable to discriminate PD patients with different progression rates. Differentially expressed genes (DEGs) were acquired by comparing the expression profiles of PD patients with rapid and slow progression rates, using an expression dataset from Gene Expression Omnibus (GEO) under accession code of GSE80599. Altered biological processes and pathways were revealed by functional annotation. Potential biomarkers of PD were identified by protein-protein interaction (PPI) network analysis. Critical transcription factors (TFs) and miRNAs regulating DEGs were predicted by TF analysis and miRNA analysis. A total of 225 DEGs were identified between PD patients with rapid and slow progression profiles. These genes were significantly enriched in biological processes and pathways related to fatty acid metabolism. Among these DEGs, ZFAND4, SRMS, UBL4B, PVALB, DIRAS1, PDP2, LRCH1, and MYL4 were potential progression rate associated biomarkers of PD. Additionally, these DEGs may be regulated by miRNAs of the miR-30 family and TFs STAT1 and GRHL3. Our results may contribute to our understanding of the molecular mechanisms underlying different PD progression profiles.

Impact of ambient and supplemental ultraviolet-B stress on kidney bean plants: an insight into oxidative stress management.

PubMed

Singh, Suruchi; Sarkar, Abhijit; Agrawal, S B; Agrawal, Madhoolika

2014-11-01

In the present study, the response of kidney bean (Phaseolus vulgaris L. cv. Pusa Komal) plants was evaluated under three different levels of ultraviolet-B (UV-B), i.e., excluded UV-B (eUV-B), ambient UV-B (aUV-B; 5.8 kJ m(-2) day(-1)), and supplemental UV-B (sUV-B; 280-315 nm; ambient + 7.2 kJ m(-2) day(-1)), under near-natural conditions. eUV-B treatment clearly demonstrated that both aUV-B and sUV-B are capable of causing significant changes in the plant's growth, metabolism, economic yield, genome template stability, total protein, and antioxidative enzyme profiles. The experimental findings showed maximum plant height at eUV-B, but biomass accumulation was minimum. Significant reductions in quantum yield (Fv/Fm) were observed under both aUV-B and sUV-B, as compared to eUV-B. UV-B-absorbing flavonoids increased under higher UV-B exposures with consequent increments in phenylalanine ammonia lyase (PAL) activities. The final yield was significantly higher in plants grown under eUV-B, compared to those under aUV-B and sUV-B. Total protein profile through sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and analysis of isoenzymes, like superoxide dismutase (SOD), peroxidase (POX), catalase (CAT), ascorbate peroxidase (APX), guaiacol peroxidase (GPX), and glutathione reductase (GR), through native PAGE revealed major changes in the leaf proteome under aUV-B and sUV-B, depicting induction of some major stress-related proteins. The random amplified polymorphic DNA (RAPD) profile of genomic DNA also indicated a significant reduction of genome template stability under UV-B exposure. Thus, it can be inferred that more energy is diverted for inducing protection mechanisms rather than utilizing it for growth under high UV-B level.

The Rice B-Box Zinc Finger Gene Family: Genomic Identification, Characterization, Expression Profiling and Diurnal Analysis

PubMed Central

Huang, Jianyan; Zhao, Xiaobo; Weng, Xiaoyu; Wang, Lei; Xie, Weibo

2012-01-01

Background The B-box (BBX) -containing proteins are a class of zinc finger proteins that contain one or two B-box domains and play important roles in plant growth and development. The Arabidopsis BBX gene family has recently been re-identified and renamed. However, there has not been a genome-wide survey of the rice BBX (OsBBX) gene family until now. Methodology/Principal Findings In this study, we identified 30 rice BBX genes through a comprehensive bioinformatics analysis. Each gene was assigned a uniform nomenclature. We described the chromosome localizations, gene structures, protein domains, phylogenetic relationship, whole life-cycle expression profile and diurnal expression patterns of the OsBBX family members. Based on the phylogeny and domain constitution, the OsBBX gene family was classified into five subfamilies. The gene duplication analysis revealed that only chromosomal segmental duplication contributed to the expansion of the OsBBX gene family. The expression profile of the OsBBX genes was analyzed by Affymetrix GeneChip microarrays throughout the entire life-cycle of rice cultivar Zhenshan 97 (ZS97). In addition, microarray analysis was performed to obtain the expression patterns of these genes under light/dark conditions and after three phytohormone treatments. This analysis revealed that the expression patterns of the OsBBX genes could be classified into eight groups. Eight genes were regulated under the light/dark treatments, and eleven genes showed differential expression under at least one phytohormone treatment. Moreover, we verified the diurnal expression of the OsBBX genes using the data obtained from the Diurnal Project and qPCR analysis, and the results indicated that many of these genes had a diurnal expression pattern. Conclusions/Significance The combination of the genome-wide identification and the expression and diurnal analysis of the OsBBX gene family should facilitate additional functional studies of the OsBBX genes. PMID:23118960

A model of female labor supply in Italy using cohort data.

PubMed

Colombino, U; De Stavola, B

1985-01-01

This paper develops a behavioral model of Italy's female labor supply using cohort data from 1959 to 1981. Both time-series trends and cross-section patterns by age groups of female participation rates in Italy show rather flat profiles. Using an approximate procedure to obtain an estimate of the relevant wage that is the mean of the wages distribution across the whole female population in a given cohort, results show that the flat time-series profile is presumbly produced by economic incentives effects that counterbalance each other. Interaction terms reveal that cross-section profiles by age group do not reflect steady-state dynamics; aging and the presence of children under 6 are less disincentive to younger cohorts. As is typical of most developed countries, this process implies for Italian female participation the emergence of the bimodal cross-section profile by age groups. In the last 20 years, participation rates for all women decreased slightly during the 1st 10 years and then increased, reaching in 1981 a higher level than in 1961. The dependent variable used in the estimation equation is the ratio between particpant (employed and unemployed) women belonging to a cohort; and the total number of women belonging to a cohort in a given year. Results show that as a cohort increases, the negative effects of age and of children are reduced. The results reveal some main points about rather flat participation rate profiles: 1) a very powerful female wage effect, 2) an equally powerful male wage negative effect, and 3) significant interactions,with a positive sign, between cohort and age and between cohort and children. Moreover, younger cohorts, other things being equal, participate more than older cohorts. This is attributable to the fact that the presence of children under 6 and the aging process are less of a disincentive for them than for older cohorts. Overall, the structure of lifetime participation is changing; younger cohorts participation rates, corresponding to child rearing age groups, are higher than older cohorts', and the decreasing effect of age suggests that a reentering phenomenon (after child rearing ages) could be emerging.

Computational gene expression profiling under salt stress reveals patterns of co-expression

PubMed Central

Sanchita; Sharma, Ashok

2016-01-01

Plants respond differently to environmental conditions. Among various abiotic stresses, salt stress is a condition where excess salt in soil causes inhibition of plant growth. To understand the response of plants to the stress conditions, identification of the responsible genes is required. Clustering is a data mining technique used to group the genes with similar expression. The genes of a cluster show similar expression and function. We applied clustering algorithms on gene expression data of Solanum tuberosum showing differential expression in Capsicum annuum under salt stress. The clusters, which were common in multiple algorithms were taken further for analysis. Principal component analysis (PCA) further validated the findings of other cluster algorithms by visualizing their clusters in three-dimensional space. Functional annotation results revealed that most of the genes were involved in stress related responses. Our findings suggest that these algorithms may be helpful in the prediction of the function of co-expressed genes. PMID:26981411

Profiles of Recovery from Mood and Anxiety Disorders: A Person-Centered Exploration of People's Engagement in Self-Management

PubMed Central

Coulombe, Simon; Radziszewski, Stephanie; Meunier, Sophie; Provencher, Hélène; Hudon, Catherine; Roberge, Pasquale; Provencher, Martin D.; Houle, Janie

2016-01-01

Context: A shift toward person-centered care has been occurring in services provided to people with mood and anxiety disorders. Recovery is recognized as encompassing personal aspects in addition to clinical ones. Guidelines now recommend supporting people's engagement in self-management as a complementary recovery avenue. Yet the literature lacks evidence on how individualized combinations of self-management strategies used by people relate to their clinical and personal recovery indicators. Objectives: The aims of this study were to identify profiles underlying mental health recovery, describe the characteristics of participants corresponding to each profile, and examine the associations of profiles with criterion variables. Method: 149 people recovering from anxiety, depressive, or bipolar disorders completed questionnaires on self-management, clinical recovery (symptom severity), personal recovery (positive mental health), and criterion variables (personal goal appraisal, social participation, self-care abilities, coping). Results: Latent profile analysis (LPA) revealed three profiles. The Floundering profile included participants who rarely used self-management strategies and had moderately severe symptoms and the lowest positive mental health. The Flourishing profile was characterized by frequent use of self-empowerment strategies, the least severe symptoms, and the highest positive mental health. Participants in the Struggling profile engaged actively in several self-management strategies focused on symptom reduction and healthy lifestyle. They concomitantly reported high symptom severity and moderately high positive mental health. The study revealed that Floundering was associated with higher probabilities of being a man, being single, and having a low income. People in the Flourishing profile had the most favorable scores on criterion variables, supporting the profiles' construct validity. Discussion: The mixed portrait of Struggling participants on recovery indicators suggests the relationship between health engagement and recovery is more intricate than anticipated. Practitioners should strive for a holistic understanding of their clients' self-management strategies and recovery indicators to provide support personalized to their profile. While people presenting risk factors would benefit from person-centered support, societal efforts are needed in the long term to reduce global health inequalities. The integration of constructs from diverse fields (patient-centered care, chronic illness, positive psychology) and the use of person-oriented analysis yielded new insights into people's engagement in their health and well-being. PMID:27199819

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

PubMed

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.

Common patterns and disease-related signatures in tuberculosis and sarcoidosis.

PubMed

Maertzdorf, Jeroen; Weiner, January; Mollenkopf, Hans-Joachim; Bauer, Torsten; Prasse, Antje; Müller-Quernheim, Joachim; Kaufmann, Stefan H E

2012-05-15

In light of the marked global health impact of tuberculosis (TB), strong focus has been on identifying biosignatures. Gene expression profiles in blood cells identified so far are indicative of a persistent activation of the immune system and chronic inflammatory pathology in active TB. Definition of a biosignature with unique specificity for TB demands that identified profiles can differentiate diseases with similar pathology, like sarcoidosis (SARC). Here, we present a detailed comparison between pulmonary TB and SARC, including whole-blood gene expression profiling, microRNA expression, and multiplex serum analytes. Our analysis reveals that previously disclosed gene expression signatures in TB show highly similar patterns in SARC, with a common up-regulation of proinflammatory pathways and IFN signaling and close similarity to TB-related signatures. microRNA expression also presented a highly similar pattern in both diseases, whereas cytokines in the serum of TB patients revealed a slightly elevated proinflammatory pattern compared with SARC and controls. Our results indicate several differences in expression between the two diseases, with increased metabolic activity and significantly higher antimicrobial defense responses in TB. However, matrix metallopeptidase 14 was identified as the most distinctive marker of SARC. Described communalities as well as unique signatures in blood profiles of two distinct inflammatory pulmonary diseases not only have considerable implications for the design of TB biosignatures and future diagnosis, but they also provide insights into biological processes underlying chronic inflammatory disease entities of different etiology.

Metabolomic Profiling of Plasma from Melioidosis Patients Using UHPLC-QTOF MS Reveals Novel Biomarkers for Diagnosis.

PubMed

Lau, Susanna K P; Lee, Kim-Chung; Lo, George C S; Ding, Vanessa S Y; Chow, Wang-Ngai; Ke, Tony Y H; Curreem, Shirly O T; To, Kelvin K W; Ho, Deborah T Y; Sridhar, Siddharth; Wong, Sally C Y; Chan, Jasper F W; Hung, Ivan F N; Sze, Kong-Hung; Lam, Ching-Wan; Yuen, Kwok-Yung; Woo, Patrick C Y

2016-02-27

To identify potential biomarkers for improving diagnosis of melioidosis, we compared plasma metabolome profiles of melioidosis patients compared to patients with other bacteremia and controls without active infection, using ultra-high-performance liquid chromatography-electrospray ionization-quadruple time-of-flight mass spectrometry. Principal component analysis (PCA) showed that the metabolomic profiles of melioidosis patients are distinguishable from bacteremia patients and controls. Using multivariate and univariate analysis, 12 significant metabolites from four lipid classes, acylcarnitine (n = 6), lysophosphatidylethanolamine (LysoPE) (n = 3), sphingomyelins (SM) (n = 2) and phosphatidylcholine (PC) (n = 1), with significantly higher levels in melioidosis patients than bacteremia patients and controls, were identified. Ten of the 12 metabolites showed area-under-receiver operating characteristic curve (AUC) >0.80 when compared both between melioidosis and bacteremia patients, and between melioidosis patients and controls. SM(d18:2/16:0) possessed the largest AUC when compared, both between melioidosis and bacteremia patients (AUC 0.998, sensitivity 100% and specificity 91.7%), and between melioidosis patients and controls (AUC 1.000, sensitivity 96.7% and specificity 100%). Our results indicate that metabolome profiling might serve as a promising approach for diagnosis of melioidosis using patient plasma, with SM(d18:2/16:0) representing a potential biomarker. Since the 12 metabolites were related to various pathways for energy and lipid metabolism, further studies may reveal their possible role in the pathogenesis and host response in melioidosis.

Metabolomic Profiling of Plasma from Melioidosis Patients Using UHPLC-QTOF MS Reveals Novel Biomarkers for Diagnosis

PubMed Central

Lau, Susanna K. P.; Lee, Kim-Chung; Lo, George C. S.; Ding, Vanessa S. Y.; Chow, Wang-Ngai; Ke, Tony Y. H.; Curreem, Shirly O. T.; To, Kelvin K. W.; Ho, Deborah T. Y.; Sridhar, Siddharth; Wong, Sally C. Y.; Chan, Jasper F. W.; Hung, Ivan F. N.; Sze, Kong-Hung; Lam, Ching-Wan; Yuen, Kwok-Yung; Woo, Patrick C. Y.

2016-01-01

To identify potential biomarkers for improving diagnosis of melioidosis, we compared plasma metabolome profiles of melioidosis patients compared to patients with other bacteremia and controls without active infection, using ultra-high-performance liquid chromatography-electrospray ionization-quadruple time-of-flight mass spectrometry. Principal component analysis (PCA) showed that the metabolomic profiles of melioidosis patients are distinguishable from bacteremia patients and controls. Using multivariate and univariate analysis, 12 significant metabolites from four lipid classes, acylcarnitine (n = 6), lysophosphatidylethanolamine (LysoPE) (n = 3), sphingomyelins (SM) (n = 2) and phosphatidylcholine (PC) (n = 1), with significantly higher levels in melioidosis patients than bacteremia patients and controls, were identified. Ten of the 12 metabolites showed area-under-receiver operating characteristic curve (AUC) >0.80 when compared both between melioidosis and bacteremia patients, and between melioidosis patients and controls. SM(d18:2/16:0) possessed the largest AUC when compared, both between melioidosis and bacteremia patients (AUC 0.998, sensitivity 100% and specificity 91.7%), and between melioidosis patients and controls (AUC 1.000, sensitivity 96.7% and specificity 100%). Our results indicate that metabolome profiling might serve as a promising approach for diagnosis of melioidosis using patient plasma, with SM(d18:2/16:0) representing a potential biomarker. Since the 12 metabolites were related to various pathways for energy and lipid metabolism, further studies may reveal their possible role in the pathogenesis and host response in melioidosis. PMID:26927094

Do cultural conditions induce differential protein expression: Profiling of extracellular proteome of Aspergillus terreus CM20.

PubMed

M, Saritha; Singh, Surender; Tiwari, Rameshwar; Goel, Renu; Nain, Lata

2016-11-01

The present study reports the diversity in extracellular proteins expressed by the filamentous fungus, Aspergillus terreus CM20 with respect to differential hydrolytic enzyme production profiles in submerged fermentation (SmF) and solid-state fermentation (SSF) conditions, and analysis of the extracellular proteome. The SSF method was superior in terms of increase in enzyme activities resulting in 1.5-3 fold enhancement as compared to SmF, which was explained by the difference in growth pattern of the fungus under the two culture conditions. As revealed by zymography, multiple isoforms of endo-β-glucanase, β-glucosidase and xylanase were expressed in SSF, but not in SmF. Extracellular proteome profiling of A. terreus CM20 under SSF condition using liquid chromatography coupled tandem mass spectrometry (LC-MS/MS) identified 63 proteins. Functional classification revealed the hydrolytic system to be composed of glycoside hydrolases (56%), proteases (16%), oxidases and dehydrogenases (6%), decarboxylases (3%), esterases (3%) and other proteins (16%). Twenty families of glycoside hydrolases (GH) (1, 3, 5, 7, 10, 11, 12, 15, 16, 28, 30, 32, 35, 43, 54, 62, 67, 72, 74 and 125), and one family each of auxiliary activities (AA7) and carbohydrate esterase (CE1) were detected, unveiling the vast diversity of synergistically acting biomass-cleaving enzymes expressed by the fungus. Saccharification of alkali-pretreated paddy straw with A. terreus CM20 proteins released high amounts of glucose (439.63±1.50mg/gds), xylose (121.04±1.25mg/gds) and arabinose (56.13±0.56mg/gds), thereby confirming the potential of the enzyme cocktail in bringing about considerable conversion of lignocellulosic polysaccharides to sugar monomers. Copyright © 2016 Elsevier GmbH. All rights reserved.

Probing the magnetic profile of diluted magnetic semiconductors using polarized neutron reflectivity.

PubMed

Luo, X; Tseng, L T; Lee, W T; Tan, T T; Bao, N N; Liu, R; Ding, J; Li, S; Lauter, V; Yi, J B

2017-07-24

Room temperature ferromagnetism has been observed in the Cu doped ZnO films deposited under an oxygen partial pressure of 10 -3 and 10 -5 torr on Pt (200 nm)/Ti (45 nm)/Si (001) substrates using pulsed laser deposition. Due to the deposition at relatively high temperature (873 K), Cu and Ti atoms diffuse to the surface and interface, which significantly affects the magnetic properties. Depth sensitive polarized neutron reflectometry method provides the details of the composition and magnetization profiles and shows that an accumulation of Cu on the surface leads to an increase in the magnetization near the surface. Our results reveal that the presence of the copper at Zn sites induces ferromagnetism at room temperature, confirming intrinsic ferromagnetism.

NMR-based metabolomics reveals the metabolite profiles of Vibrio parahaemolyticus under ferric iron stimulation.

PubMed

Zhou, Jun; Lu, Chenyang; Zhang, Dijun; Ma, Chennv; Su, Xiurong

2017-08-01

Vibrio parahaemolyticus is a halophilic bacterium endemic to coastal areas, and its pathogenicity has caused widespread seafood poisoning. In our previous research, the protein expression of V. parahaemolyticus in Fe 3+ medium was determined using isobaric tags for relative and absolute quantitation (iTRAQ). Here, nuclear magnetic resonance (NMR) was used to detect changes in the V. parahaemolyticus metabolome. NMR spectra were obtained using methanol-water extracts of intracellular metabolites from V. parahaemolyticus under various culture conditions, and 62 metabolites were identified, including serine, arginine, alanine, ornithine, tryptophan, glutamine, malate, NAD + , NADP + , oxypurinol, xanthosine, dCTP, uracil, thymine, hypoxanthine, and betaine. Among these, 21 metabolites were up-regulated after the stimulation of the cells by ferric iron, and 9 metabolites were down-regulated. These metabolites are involved in amino acid and protein synthesis, energy metabolism, DNA and RNA synthesis and osmolality. Based on these results, we conclude that Fe 3+ influences the metabolite profiles of V. parahaemolyticus.

Cognitive Profiles on the Severe Impairment Battery Are Similar in Alzheimer Disease and Down Syndrome With Dementia.

PubMed

Dick, Malcolm B; Doran, Eric; Phelan, Michael; Lott, Ira T

2016-01-01

Previous research has revealed similarities in the neuropathology, clinical presentation, and risk factors between persons with Alzheimer disease from the general population (GP-AD) and those with Down syndrome (DS-AD). Less is known, however, about the extent of similarities and differences in the cognitive profiles of these 2 populations. Fifty-one moderate to severely demented GP-AD and 59 DS-AD individuals participated in this study which compared the cognitive profiles of these 2 populations on the Severe Impairment Battery (SIB), controlling for sex as well as level of functional ability using a modified version of the Bristol Activities of Daily Living Scale. Overall, the neuropsychological profiles of the higher-functioning individuals within the DS-AD and advanced GP-AD groups, as represented by mean difference scores on the SIB as a whole and across the 9 separate cognitive domains, were very similar to one another after adjusting for sex and functional impairment. To our knowledge, this is the first study to directly compare the cognitive profiles of these 2 populations on the SIB. Findings suggest that the underlying dementia in GP-AD and DS-AD may have corresponding and parallel effects on cognition.

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

PubMed Central

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

Global transcriptional profiling of a cold-tolerant rice variety under moderate cold stress reveals different cold stress response mechanisms.

PubMed

Zhao, Junliang; Zhang, Shaohong; Yang, Tifeng; Zeng, Zichong; Huang, Zhanghui; Liu, Qing; Wang, Xiaofei; Leach, Jan; Leung, Hei; Liu, Bin

2015-07-01

Gene expression profiling under severe cold stress (4°C) has been conducted in plants including rice. However, rice seedlings are frequently exposed to milder cold stresses under natural environments. To understand the responses of rice to milder cold stress, a moderately low temperature (8°C) was used for cold treatment prior to genome-wide profiling of gene expression in a cold-tolerant japonica variety, Lijiangxintuanheigu (LTH). A total of 5557 differentially expressed genes (DEGs) were found at four time points during moderate cold stress. Both the DEGs and differentially expressed transcription factor genes were clustered into two groups based on their expression, suggesting a two-phase response to cold stress and a determinative role of transcription factors in the regulation of stress response. The induction of OsDREB2A under cold stress is reported for the first time in this study. Among the anti-oxidant enzyme genes, glutathione peroxidase (GPX) and glutathione S-transferase (GST) were upregulated, suggesting that the glutathione system may serve as the main reactive oxygen species (ROS) scavenger in LTH. Changes in expression of genes in signal transduction pathways for auxin, abscisic acid (ABA) and salicylic acid (SA) imply their involvement in cold stress responses. The induction of ABA response genes and detection of enriched cis-elements in DEGs suggest that ABA signaling pathway plays a dominant role in the cold stress response. Our results suggest that rice responses to cold stress vary with the specific temperature imposed and the rice genotype. © 2014 Scandinavian Plant Physiology Society.

Label-free quantitative proteomics to investigate strawberry fruit proteome changes under controlled atmosphere and low temperature storage.

PubMed

Li, Li; Luo, Zisheng; Huang, Xinhong; Zhang, Lu; Zhao, Pengyu; Ma, Hongyuan; Li, Xihong; Ban, Zhaojun; Liu, Xia

2015-04-29

To elucidate the mechanisms contributing to fruit responses to senescence and stressful environmental stimuli under low temperature (LT) and controlled atmosphere (CA) storage, a label-free quantitative proteomic investigation was conducted in strawberry (Fragaria ananassa, Duch. cv. 'Akihime'). Postharvest physiological quality traits including firmness, total soluble solids, total acidity, ascorbic acid and volatile production were characterized following storage under different conditions. The observed post-storage protein expression profiles may be associated with delayed senescence features in strawberry. A total of 454 proteins were identified in differentially treated strawberry fruits. Quantitative analysis, using normalized spectral counts, revealed 73 proteins common to all treatments, which formed three clusters in a hierarchical clustering analysis. The proteins spanned a range of functions in various metabolic pathways and networks involved in carbohydrate and energy metabolism, volatile biosynthesis, phenylpropanoid activity, stress response and protein synthesis, degradation and folding. After CA and LT storage, 16 (13) and 11 (17) proteins, respectively, were significantly increased (decreased) in abundance, while expression profile of 12 proteins was significantly changed by both CA and LT. To summarize, the differential variability of abundance in strawberry proteome, working in a cooperative manner, provided an overview of the biological processes that occurred during CA and LT storage. Controlled atmosphere storage at an optimal temperature is regarded to be an effective postharvest technology to delay fruit senescence and maintain fruit quality during shelf life. Nonetheless, little information on fruit proteomic changes under controlled atmosphere and/or low temperature storage is available. The significance of this paper is that it is the first study employing a label-free approach in the investigation of strawberry fruit response to controlled atmosphere and cold storage. Changes in postharvest physiological quality traits including volatile production, firmness, ascorbic acid, soluble solids and total acidity were also characterized. Significant biological changes associated with senescence were revealed and differentially abundant proteins under various storage conditions were identified. Proteomic profiles were linked to physiological aspects of strawberry fruit senescence in order to provide new insights into possible regulation mechanisms. Findings from this study not only provide proteomic information on fruit regulation, but also pave the way for further quantitative studies at the transcriptomic and metabolomic levels. Copyright © 2015 Elsevier B.V. All rights reserved.

Multivariate Analysis of the Cotton Seed Ionome Reveals a Shared Genetic Architecture

PubMed Central

Pauli, Duke; Ziegler, Greg; Ren, Min; Jenks, Matthew A.; Hunsaker, Douglas J.; Zhang, Min; Baxter, Ivan; Gore, Michael A.

2018-01-01

To mitigate the effects of heat and drought stress, a better understanding of the genetic control of physiological responses to these environmental conditions is needed. To this end, we evaluated an upland cotton (Gossypium hirsutum L.) mapping population under water-limited and well-watered conditions in a hot, arid environment. The elemental concentrations (ionome) of seed samples from the population were profiled in addition to those of soil samples taken from throughout the field site to better model environmental variation. The elements profiled in seeds exhibited moderate to high heritabilities, as well as strong phenotypic and genotypic correlations between elements that were not altered by the imposed irrigation regimes. Quantitative trait loci (QTL) mapping results from a Bayesian classification method identified multiple genomic regions where QTL for individual elements colocalized, suggesting that genetic control of the ionome is highly interrelated. To more fully explore this genetic architecture, multivariate QTL mapping was implemented among groups of biochemically related elements. This analysis revealed both additional and pleiotropic QTL responsible for coordinated control of phenotypic variation for elemental accumulation. Machine learning algorithms that utilized only ionomic data predicted the irrigation regime under which genotypes were evaluated with very high accuracy. Taken together, these results demonstrate the extent to which the seed ionome is genetically interrelated and predictive of plant physiological responses to adverse environmental conditions. PMID:29437829

In silico analysis of stomach lineage specific gene set expression pattern in gastric cancer.

PubMed

Pandi, Narayanan Sathiya; Suganya, Sivagurunathan; Rajendran, Suriliyandi

2013-10-04

Stomach lineage specific gene products act as a protective barrier in the normal stomach and their expression maintains the normal physiological processes, cellular integrity and morphology of the gastric wall. However, the regulation of stomach lineage specific genes in gastric cancer (GC) is far less clear. In the present study, we sought to investigate the role and regulation of stomach lineage specific gene set (SLSGS) in GC. SLSGS was identified by comparing the mRNA expression profiles of normal stomach tissue with other organ tissue. The obtained SLSGS was found to be under expressed in gastric tumors. Functional annotation analysis revealed that the SLSGS was enriched for digestive function and gastric epithelial maintenance. Employing a single sample prediction method across GC mRNA expression profiles identified the under expression of SLSGS in proliferative type and invasive type gastric tumors compared to the metabolic type gastric tumors. Integrative pathway activation prediction analysis revealed a close association between estrogen-α signaling and SLSGS expression pattern in GC. Elevated expression of SLSGS in GC is associated with an overall increase in the survival of GC patients. In conclusion, our results highlight that estrogen mediated regulation of SLSGS in gastric tumor is a molecular predictor of metabolic type GC and prognostic factor in GC. Copyright © 2013 Elsevier Inc. All rights reserved.

Gene expression profiling of single cells on large-scale oligonucleotide arrays

PubMed Central

Hartmann, Claudia H.; Klein, Christoph A.

2006-01-01

Over the last decade, important insights into the regulation of cellular responses to various stimuli were gained by global gene expression analyses of cell populations. More recently, specific cell functions and underlying regulatory networks of rare cells isolated from their natural environment moved to the center of attention. However, low cell numbers still hinder gene expression profiling of rare ex vivo material in biomedical research. Therefore, we developed a robust method for gene expression profiling of single cells on high-density oligonucleotide arrays with excellent coverage of low abundance transcripts. The protocol was extensively tested with freshly isolated single cells of very low mRNA content including single epithelial, mature and immature dendritic cells and hematopoietic stem cells. Quantitative PCR confirmed that the PCR-based global amplification method did not change the relative ratios of transcript abundance and unsupervised hierarchical cluster analysis revealed that the histogenetic origin of an individual cell is correctly reflected by the gene expression profile. Moreover, the gene expression data from dendritic cells demonstrate that cellular differentiation and pathway activation can be monitored in individual cells. PMID:17071717

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

PubMed

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.

Science Teaching Orientations and Technology-Enhanced Tools for Student Learning

NASA Astrophysics Data System (ADS)

Campbell, Todd; Longhurst, Max; Duffy, Aaron M.; Wolf, Paul G.; Shelton, Brett E.

2013-10-01

This qualitative study examines teacher orientations and technology-enhanced tools for student learning within a science literacy framework. Data for this study came from a group of 10 eighth grade science teachers. Each of these teachers was a participant in a professional development (PD) project focused on reformed and technology-enhanced science instruction shaped by national standards documents. The research is focused on identifying teacher orientations and use of technology-enhanced tools prior to or unaffected by PD. The primary data sources for this study are drawn from learning journals and classroom observations. Qualitative methods were used to analyze learning journals, while descriptive statistics were used from classroom observations to further explore and triangulate the emergent qualitative findings. Two teacher orientation teacher profiles were developed to reveal the emergent teacher orientation dimensions and technology-enhanced tool categories found: "more traditional teacher orientation profile" and "toward a reformed-based teacher orientation profile." Both profiles were founded on "knowledge of" beliefs about the goals and purposes for science education, while neither profile revealed sophisticated beliefs about the nature of science. The "traditional" profile revealed more teacher-centered beliefs about science teaching and learning, and the "towards reformed-based" profile revealed student-centered beliefs. Finally, only technology-enhanced tools supportive of collaborative construction of science knowledge were found connected to the "towards reformed-based" profile. This research is concluded with a proposed "reformed-based teacher orientation profile" as a future target for science teaching and learning with technology-enhanced tools in a science literacy framework.

Comparative metagenomic and metatranscriptomic analyses of microbial communities in acid mine drainage.

PubMed

Chen, Lin-xing; Hu, Min; Huang, Li-nan; Hua, Zheng-shuang; Kuang, Jia-liang; Li, Sheng-jin; Shu, Wen-sheng

2015-07-01

The microbial communities in acid mine drainage have been extensively studied to reveal their roles in acid generation and adaption to this environment. Lacking, however, are integrated community- and organism-wide comparative gene transcriptional analyses that could reveal the response and adaptation mechanisms of these extraordinary microorganisms to different environmental conditions. In this study, comparative metagenomics and metatranscriptomics were performed on microbial assemblages collected from four geochemically distinct acid mine drainage (AMD) sites. Taxonomic analysis uncovered unexpectedly high microbial biodiversity of these extremely acidophilic communities, and the abundant taxa of Acidithiobacillus, Leptospirillum and Acidiphilium exhibited high transcriptional activities. Community-wide comparative analyses clearly showed that the AMD microorganisms adapted to the different environmental conditions via regulating the expression of genes involved in multiple in situ functional activities, including low-pH adaptation, carbon, nitrogen and phosphate assimilation, energy generation, environmental stress resistance, and other functions. Organism-wide comparative analyses of the active taxa revealed environment-dependent gene transcriptional profiles, especially the distinct strategies used by Acidithiobacillus ferrivorans and Leptospirillum ferrodiazotrophum in nutrients assimilation and energy generation for survival under different conditions. Overall, these findings demonstrate that the gene transcriptional profiles of AMD microorganisms are closely related to the site physiochemical characteristics, providing clues into the microbial response and adaptation mechanisms in the oligotrophic, extremely acidic environments.

Identification of differentially expressed genes in cucumber (Cucumis sativus L.) root under waterlogging stress by digital gene expression profile.

PubMed

Qi, Xiao-Hua; Xu, Xue-Wen; Lin, Xiao-Jian; Zhang, Wen-Jie; Chen, Xue-Hao

2012-03-01

High-throughput tag-sequencing (Tag-seq) analysis based on the Solexa Genome Analyzer platform was applied to analyze the gene expression profiling of cucumber plant at 5 time points over a 24h period of waterlogging treatment. Approximately 5.8 million total clean sequence tags per library were obtained with 143013 distinct clean tag sequences. Approximately 23.69%-29.61% of the distinct clean tags were mapped unambiguously to the unigene database, and 53.78%-60.66% of the distinct clean tags were mapped to the cucumber genome database. Analysis of the differentially expressed genes revealed that most of the genes were down-regulated in the waterlogging stages, and the differentially expressed genes mainly linked to carbon metabolism, photosynthesis, reactive oxygen species generation/scavenging, and hormone synthesis/signaling. Finally, quantitative real-time polymerase chain reaction using nine genes independently verified the tag-mapped results. This present study reveals the comprehensive mechanisms of waterlogging-responsive transcription in cucumber. Copyright © 2011 Elsevier Inc. All rights reserved.

Serum miRNAs Signature Plays an Important Role in Keloid Disease.

PubMed

Luan, Y; Liu, Y; Liu, C; Lin, Q; He, F; Dong, X; Xiao, Z

2016-01-01

The molecular mechanism underlying the pathogenesis of keloid is largely unknown. MicroRNA (miRNA) is a class of small regulatory RNA that has emerged as a group of posttranscriptional gene repressors, participating in diverse pathophysiological processes of skin diseases. We investigated the expression profiles of miRNAs in the sera of patients to decipher the complicated factors involved in the development of keloid disease. MiRNA expression profiling in the sera from 9 keloid patients and 7 normal controls were characterized using a miRNA microarray containing established human mature and precursor miRNA sequences. Quantitative real-time PCR was performed to confirm the expression of miRNAs. The putative targets of differentially expressed miRNAs were functionally annotated by bioinformatics. MiRNA microarray analysis identified 37 differentially expressed miRNAs (17 upregulated and 20 downregulated) in keloid patients, compared to the healthy controls. Functional annotations revealed that the targets of those differentially expressed miRNAs were enriched in signaling pathways essential for scar formation and wound healing. The expression profiling of miRNAs is altered in the keloid, providing a clue for the molecular mechanisms underlying its initiation and progression. MiRNAs may partly contribute to the etiology of keloids by affecting the critical signaling pathways relevant to keloid pathogenesis.

Increased antioxidant activity and changes in phenolic profile of Kalanchoe pinnata (Lamarck) Persoon (Crassulaceae) specimens grown under supplemental blue light.

PubMed

Nascimento, Luana B S; Leal-Costa, Marcos V; Coutinho, Marcela A S; Moreira, Nattacha dos S; Lage, Celso L S; Barbi, Nancy dos S; Costa, Sônia S; Tavares, Eliana S

2013-01-01

Antioxidant compounds protect plants against oxidative stress caused by environmental conditions. Different light qualities, such as UV-A radiation and blue light, have shown positive effects on the production of phenols in plants. Kalanchoe pinnata (Lamarck) Persoon (Crassulaceae) is used for treating wounds and inflammations. Some of these beneficial effects are attributed to the antioxidant activity of plant components. We investigated the effects of blue light and UV-A radiation supplementation on the total phenol content, antioxidant activity and chromatographic profile of aqueous extracts from leaves of K. pinnata. Monoclonal plants were grown under white light, white plus blue light and white plus UV-A radiation. Supplemental blue light improved the antioxidant activity and changed the phenolic profile of the extracts. Analysis by HPLC of supplemental blue-light plant extracts revealed a higher proportion of the major flavonoid quercetin 3-O-α-L-arabinopyranosyl (1→2) α-L-rhamnopyranoside, as well as the presence of a wide variety of other phenolic substances. These findings may explain the higher antioxidant activity observed for this extract. Blue light is proposed as a supplemental light source in the cultivation of K. pinnata, to improve its antioxidant activity. © 2012 Wiley Periodicals, Inc. Photochemistry and Photobiology © 2012 The American Society of Photobiology.

An Integrated Multi-Omics Study Revealed Metabolic Alterations Underlying the Effects of Coffee Consumption

PubMed Central

Takahashi, Shoko; Saito, Kenji; Jia, Huijuan; Kato, Hisanori

2014-01-01

Many epidemiological studies have indicated that coffee consumption may reduce the risks of developing obesity and diabetes, but the underlying mechanisms of these effects are poorly understood. Our previous study revealed the changes on gene expression profiles in the livers of C57BL/6J mice fed a high-fat diet containing three types of coffee (caffeinated, decaffeinated and green unroasted coffee), using DNA microarrays. The results revealed remarkable alterations in lipid metabolism-related molecules which may be involved in the anti-obesity effects of coffee. We conducted the present study to further elucidate the metabolic alterations underlying the effects of coffee consumption through comprehensive proteomic and metabolomic analyses. Proteomics revealed an up-regulation of isocitrate dehydrogenase (a key enzyme in the TCA cycle) and its related proteins, suggesting increased energy generation. The metabolomics showed an up-regulation of metabolites involved in the urea cycle, with which the transcriptome data were highly consistent, indicating accelerated energy expenditure. The TCA cycle and the urea cycle are likely be accelerated in a concerted manner, since they are directly connected by mutually providing each other's intermediates. The up-regulation of these pathways might result in a metabolic shift causing increased ATP turnover, which is related to the alterations of lipid metabolism. This mechanism may play an important part in the suppressive effects of coffee consumption on obesity, inflammation, and hepatosteatosis. This study newly revealed global metabolic alterations induced by coffee intake, providing significant insights into the association between coffee intake and the prevention of type 2 diabetes, utilizing the benefits of multi-omics analyses. PMID:24618914

Comprehensive Genomic Profiling of Esthesioneuroblastoma Reveals Additional Treatment Options.

PubMed

Gay, Laurie M; Kim, Sungeun; Fedorchak, Kyle; Kundranda, Madappa; Odia, Yazmin; Nangia, Chaitali; Battiste, James; Colon-Otero, Gerardo; Powell, Steven; Russell, Jeffery; Elvin, Julia A; Vergilio, Jo-Anne; Suh, James; Ali, Siraj M; Stephens, Philip J; Miller, Vincent A; Ross, Jeffrey S

2017-07-01

Esthesioneuroblastoma (ENB), also known as olfactory neuroblastoma, is a rare malignant neoplasm of the olfactory mucosa. Despite surgical resection combined with radiotherapy and adjuvant chemotherapy, ENB often relapses with rapid progression. Current multimodality, nontargeted therapy for relapsed ENB is of limited clinical benefit. We queried whether comprehensive genomic profiling (CGP) of relapsed or refractory ENB can uncover genomic alterations (GA) that could identify potential targeted therapies for these patients. CGP was performed on formalin-fixed, paraffin-embedded sections from 41 consecutive clinical cases of ENBs using a hybrid-capture, adaptor ligation based next-generation sequencing assay to a mean coverage depth of 593X. The results were analyzed for base substitutions, insertions and deletions, select rearrangements, and copy number changes (amplifications and homozygous deletions). Clinically relevant GA (CRGA) were defined as GA linked to drugs on the market or under evaluation in clinical trials. A total of 28 ENBs harbored GA, with a mean of 1.5 GA per sample. Approximately half of the ENBs (21, 51%) featured at least one CRGA, with an average of 1 CRGA per sample. The most commonly altered gene was TP53 (17%), with GA in PIK3CA , NF1 , CDKN2A , and CDKN2C occurring in 7% of samples. We report comprehensive genomic profiles for 41 ENB tumors. CGP revealed potential new therapeutic targets, including targetable GA in the mTOR, CDK and growth factor signaling pathways, highlighting the clinical value of genomic profiling in ENB. Comprehensive genomic profiling of 41 relapsed or refractory ENBs reveals recurrent alterations or classes of mutation, including amplification of tyrosine kinases encoded on chromosome 5q and mutations affecting genes in the mTOR/PI3K pathway. Approximately half of the ENBs (21, 51%) featured at least one clinically relevant genomic alteration (CRGA), with an average of 1 CRGA per sample. The most commonly altered gene was TP53 (17%), and alterations in PIK3CA , NF1 , CDKN2A , or CDKN2C were identified in 7% of samples. Responses to treatment with the kinase inhibitors sunitinib, everolimus, and pazopanib are presented in conjunction with tumor genomics. © AlphaMed Press 2017.

Studies of the Influence of Beam Profile and Cooling Conditions on the Laser Deposition of a Directionally-Solidified Superalloy.

PubMed

Yang, Shuo; Du, Dong; Chang, Baohua

2018-02-04

In the laser deposition of single crystal and directionally-solidified superalloys, it is desired to form laser deposits with high volume fractions of columnar grains by suppressing the columnar-to-equiaxed transition efficiently. In this paper, the influence of beam profile (circular and square shapes) and cooling conditions (natural cooling and forced cooling) on the geometric morphology and microstructure of deposits were experimentally studied in the laser deposition of a directionally-solidified superalloy, IC10, and the mechanisms of influence were revealed through a numerical simulation of the thermal processes during laser deposition. The results show that wider and thinner deposits were obtained with the square laser beam than those with the circular laser beam, regardless of whether natural or forced cooling conditions was used. The heights and contact angles of deposits were notably increased due to the reduced substrate temperatures by the application of forced cooling for both laser beam profiles. Under natural cooling conditions, columnar grains formed epitaxially at both the center and the edges of the deposits with the square laser beam, but only at the center of the deposits with the circular laser beam; under forced cooling conditions, columnar grains formed at both the center and the edges of deposits regardless of the laser beam profile. The high ratios of thermal gradient and solidification velocity in the height direction of the deposits were favorable to forming deposits with higher volume fractions of columnar grains.

Studies of the Influence of Beam Profile and Cooling Conditions on the Laser Deposition of a Directionally-Solidified Superalloy

PubMed Central

Yang, Shuo; Du, Dong

2018-01-01

In the laser deposition of single crystal and directionally-solidified superalloys, it is desired to form laser deposits with high volume fractions of columnar grains by suppressing the columnar-to-equiaxed transition efficiently. In this paper, the influence of beam profile (circular and square shapes) and cooling conditions (natural cooling and forced cooling) on the geometric morphology and microstructure of deposits were experimentally studied in the laser deposition of a directionally-solidified superalloy, IC10, and the mechanisms of influence were revealed through a numerical simulation of the thermal processes during laser deposition. The results show that wider and thinner deposits were obtained with the square laser beam than those with the circular laser beam, regardless of whether natural or forced cooling conditions was used. The heights and contact angles of deposits were notably increased due to the reduced substrate temperatures by the application of forced cooling for both laser beam profiles. Under natural cooling conditions, columnar grains formed epitaxially at both the center and the edges of the deposits with the square laser beam, but only at the center of the deposits with the circular laser beam; under forced cooling conditions, columnar grains formed at both the center and the edges of deposits regardless of the laser beam profile. The high ratios of thermal gradient and solidification velocity in the height direction of the deposits were favorable to forming deposits with higher volume fractions of columnar grains. PMID:29401715

Isoprene emission by poplar is not important for the feeding behaviour of poplar leaf beetles.

PubMed

Müller, Anna; Kaling, Moritz; Faubert, Patrick; Gort, Gerrit; Smid, Hans M; Van Loon, Joop J A; Dicke, Marcel; Kanawati, Basem; Schmitt-Kopplin, Philippe; Polle, Andrea; Schnitzler, Jörg-Peter; Rosenkranz, Maaria

2015-06-30

Chrysomela populi (poplar leaf beetle) is a common herbivore in poplar plantations whose infestation causes major economic losses. Because plant volatiles act as infochemicals, we tested whether isoprene, the main volatile organic compound (VOC) produced by poplars (Populus x canescens), affects the performance of C. populi employing isoprene emitting (IE) and transgenic isoprene non-emitting (NE) plants. Our hypothesis was that isoprene is sensed and affects beetle orientation or that the lack of isoprene affects plant VOC profiles and metabolome with consequences for C. populi feeding. Electroantennographic analysis revealed that C. populi can detect higher terpenes, but not isoprene. In accordance to the inability to detect isoprene, C. populi showed no clear preference for IE or NE poplar genotypes in the choice experiments, however, the beetles consumed a little bit less leaf mass and laid fewer eggs on NE poplar trees in field experiments. Slight differences in the profiles of volatile terpenoids between IE and NE genotypes were detected by gas chromatography - mass spectrometry. Non-targeted metabolomics analysis by Fourier Transform Ion Cyclotron Resonance Mass Spectrometer revealed genotype-, time- and herbivore feeding-dependent metabolic changes both in the infested and adjacent undamaged leaves under field conditions. We show for the first time that C. populi is unable to sense isoprene. The detected minor differences in insect feeding in choice experiments and field bioassays may be related to the revealed changes in leaf volatile emission and metabolite composition between the IE and NE poplars. Overall our results indicate that lacking isoprene emission is of minor importance for C. populi herbivory under natural conditions, and that the lack of isoprene is not expected to change the economic losses in poplar plantations caused by C. populi infestation.

De novo Transcriptome Analysis of Miscanthus lutarioriparius Identifies Candidate Genes in Rhizome Development

PubMed Central

Hu, Ruibo; Yu, Changjiang; Wang, Xiaoyu; Jia, Chunlin; Pei, Shengqiang; He, Kang; He, Guo; Kong, Yingzhen; Zhou, Gongke

2017-01-01

HIGHLIGHT De novo transcriptome profiling of five tissues reveals candidate genes putatively involved in rhizome development in M. lutarioriparius. Miscanthus lutarioriparius is a promising lignocellulosic feedstock for second-generation bioethanol production. However, the genomic resource for this species is relatively limited thus hampers our understanding of the molecular mechanisms underlying many important biological processes. In this study, we performed the first de novo transcriptome analysis of five tissues (leaf, stem, root, lateral bud and rhizome bud) of M. lutarioriparius with an emphasis to identify putative genes involved in rhizome development. Approximately 66 gigabase (GB) paired-end clean reads were obtained and assembled into 169,064 unigenes with an average length of 759 bp. Among these unigenes, 103,899 (61.5%) were annotated in seven public protein databases. Differential gene expression profiling analysis revealed that 4,609, 3,188, 1,679, 1,218, and 1,077 genes were predominantly expressed in root, leaf, stem, lateral bud, and rhizome bud, respectively. Their expression patterns were further classified into 12 distinct clusters. Pathway enrichment analysis revealed that genes predominantly expressed in rhizome bud were mainly involved in primary metabolism and hormone signaling and transduction pathways. Noteworthy, 19 transcription factors (TFs) and 16 hormone signaling pathway-related genes were identified to be predominantly expressed in rhizome bud compared with the other tissues, suggesting putative roles in rhizome formation and development. In addition, a predictive regulatory network was constructed between four TFs and six auxin and abscisic acid (ABA) -related genes. Furthermore, the expression of 24 rhizome-specific genes was further validated by quantitative real-time RT-PCR (qRT-PCR) analysis. Taken together, this study provide a global portrait of gene expression across five different tissues and reveal preliminary insights into rhizome growth and development. The data presented will contribute to our understanding of the molecular mechanisms underlying rhizome development in M. lutarioriparius and remarkably enrich the genomic resources of Miscanthus. PMID:28446913

Transcriptional profiling of the pea shoot apical meristem reveals processes underlying its function and maintenance

PubMed Central

Wong, Chui E; Bhalla, Prem L; Ottenhof, Harald; Singh, Mohan B

2008-01-01

Background Despite the importance of the shoot apical meristem (SAM) in plant development and organ formation, our understanding of the molecular mechanisms controlling its function is limited. Genomic tools have the potential to unravel the molecular mysteries of the SAM, and legume systems are increasingly being used in plant-development studies owing to their unique characteristics such as nitrogen fixation, secondary metabolism, and pod development. Garden pea (Pisum sativum) is a well-established classic model species for genetics studies that has been used since the Mendel era. In addition, the availability of a plethora of developmental mutants makes pea an ideal crop legume for genomics studies. This study aims to utilise genomics tools in isolating genes that play potential roles in the regulation of SAM activity. Results In order to identify genes that are differentially expressed in the SAM, we generated 2735 ESTs from three cDNA libraries derived from freshly micro-dissected SAMs from 10-day-old garden peas (Pisum sativum cv Torsdag). Custom-designed oligonucleotide arrays were used to compare the transcriptional profiles of pea SAMs and non-meristematic tissues. A total of 184 and 175 transcripts were significantly up- or down-regulated in the pea SAM, respectively. As expected, close to 61% of the transcripts down-regulated in the SAM were found in the public database, whereas sequences from the same source only comprised 12% of the genes that were expressed at higher levels in the SAM. This highlights the under-representation of transcripts from the meristematic tissues in the current public pea protein database, and demonstrates the utility of our SAM EST collection as an essential genetic resource for revealing further information on the regulation of this developmental process. In addition to unknowns, many of the up-regulated transcripts are known to encode products associated with cell division and proliferation, epigenetic regulation, auxin-mediated responses and microRNA regulation. Conclusion The presented data provide a picture of the transcriptional profile of the pea SAM, and reveal possible roles of differentially expressed transcripts in meristem function and maintenance. PMID:18590528

Fundamental Patterns Underlying Neurotoxicity Revealed by DNA Microarray Expression Profiling

DTIC Science & Technology

2004-09-01

treated SH - SY5Y cells also resulted in an up-regulation of CHOP, albeit with a much later, more prolonged time course (Conn et al., 2002). Similarly... neuroblastoma and PC-12 cell lines , 6-OHDA has been shown to increase the levels of ubiquitin-conjugated proteins (Dawson and Mandir, 2002). Here, Sqstml...screened to determine changes in gene expression caused by MPP+, the active metabolite of MPTP, and 6-OHDA in a mouse CNS dopaminergic cell line

Search for auroral belt E-parallel fields with high-velocity barium ion injections

NASA Technical Reports Server (NTRS)

Heppner, J. P.; Ledley, B. G.; Miller, M. L.; Marionni, P. A.; Pongratz, M. B.

1989-01-01

In April 1984, four high-velocity shaped-charge Ba(+) injections were conducted from two sounding rockets at 770-975 km over northern Alaska under conditions of active auroral and magnetic disturbance. Spatial ionization (brightness) profiles of high-velocity Ba(+) clouds from photometric scans following each release were found to be consistent with the 28-sec theoretical time constant for Ba photoionization determined by Carlsten (1975). These observations therefore revealed no evidence of anomalous fast ionization predicted by the Alfven critical velocity hypothesis.

Diverse Molecular Targets for Chalcones with Varied Bioactivities

PubMed Central

Zhou, Bo; Xing, Chengguo

2015-01-01

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

Using Bio-Optics to Reveal Phytoplankton Physiology from a Wirewalker Autonomous Platform

NASA Technical Reports Server (NTRS)

Omand, M. M.; Cetinic, I.; Lucas, A. J.

2017-01-01

Rapid, wave-powered profiling of bio-optical properties from an autonomous Wirewalker platform provides useful insights into phytoplankton physiology, including the patterns of diel growth, phytoplankton mortality, nonphotochemical quenching of chlorophyll a fluorescence, and natural (sun-induced) fluorescence of mixed communities. Methods are proposed to quantify each of these processes. Such autonomous measurements of phytoplankton physiological rates and responses open up new possibilities for studying phytoplankton in situ, over longer periods, and under a broader range of environmental conditions.

Transcriptome complexity in cardiac development and diseases--an expanding universe between genome and phenome.

PubMed

Gao, Chen; Wang, Yibin

2014-01-01

With the advancement of transcriptome profiling by micro-arrays and high-throughput RNA-sequencing, transcriptome complexity and its dynamics are revealed at different levels in cardiovascular development and diseases. In this review, we will highlight the recent progress in our knowledge of cardiovascular transcriptome complexity contributed by RNA splicing, RNA editing and noncoding RNAs. The emerging importance of many of these previously under-explored aspects of gene regulation in cardiovascular development and pathology will be discussed.

Biomarkers are used to predict quantitative metabolite concentration profiles in human red blood cells

DOE PAGES

Yurkovich, James T.; Yang, Laurence; Palsson, Bernhard O.; ...

2017-03-06

Deep-coverage metabolomic profiling has revealed a well-defined development of metabolic decay in human red blood cells (RBCs) under cold storage conditions. A set of extracellular biomarkers has been recently identified that reliably defines the qualitative state of the metabolic network throughout this metabolic decay process. Here, we extend the utility of these biomarkers by using them to quantitatively predict the concentrations of other metabolites in the red blood cell. We are able to accurately predict the concentration profile of 84 of the 91 (92%) measured metabolites ( p < 0.05) in RBC metabolism using only measurements of these five biomarkers.more » The median of prediction errors (symmetric mean absolute percent error) across all metabolites was 13%. Furthermore, the ability to predict numerous metabolite concentrations from a simple set of biomarkers offers the potential for the development of a powerful workflow that could be used to evaluate the metabolic state of a biological system using a minimal set of measurements.« less

High-throughput STR analysis for DNA database using direct PCR.

PubMed

Sim, Jeong Eun; Park, Su Jeong; Lee, Han Chul; Kim, Se-Yong; Kim, Jong Yeol; Lee, Seung Hwan

2013-07-01

Since the Korean criminal DNA database was launched in 2010, we have focused on establishing an automated DNA database profiling system that analyzes short tandem repeat loci in a high-throughput and cost-effective manner. We established a DNA database profiling system without DNA purification using a direct PCR buffer system. The quality of direct PCR procedures was compared with that of conventional PCR system under their respective optimized conditions. The results revealed not only perfect concordance but also an excellent PCR success rate, good electropherogram quality, and an optimal intra/inter-loci peak height ratio. In particular, the proportion of DNA extraction required due to direct PCR failure could be minimized to <3%. In conclusion, the newly developed direct PCR system can be adopted for automated DNA database profiling systems to replace or supplement conventional PCR system in a time- and cost-saving manner. © 2013 American Academy of Forensic Sciences Published 2013. This article is a U.S. Government work and is in the public domain in the U.S.A.

Multiplexed Thiol Reactivity Profiling for Target Discovery of Electrophilic Natural Products.

PubMed

Tian, Caiping; Sun, Rui; Liu, Keke; Fu, Ling; Liu, Xiaoyu; Zhou, Wanqi; Yang, Yong; Yang, Jing

2017-11-16

Electrophilic groups, such as Michael acceptors, expoxides, are common motifs in natural products (NPs). Electrophilic NPs can act through covalent modification of cysteinyl thiols on functional proteins, and exhibit potent cytotoxicity and anti-inflammatory/cancer activities. Here we describe a new chemoproteomic strategy, termed multiplexed thiol reactivity profiling (MTRP), and its use in target discovery of electrophilic NPs. We demonstrate the utility of MTRP by identifying cellular targets of gambogic acid, an electrophilic NP that is currently under evaluation in clinical trials as anticancer agent. Moreover, MTRP enables simultaneous comparison of seven structurally diversified α,β-unsaturated γ-lactones, which provides insights into the relative proteomic reactivity and target preference of diverse structural scaffolds coupled to a common electrophilic motif and reveals various potential druggable targets with liganded cysteines. We anticipate that this new method for thiol reactivity profiling in a multiplexed manner will find broad application in redox biology and drug discovery. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

PubMed

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.

A transcriptional profile of the decidua in preeclampsia

PubMed Central

LØSET, Mari; MUNDAL, Siv B.; JOHNSON, Matthew P.; FENSTAD, Mona H.; FREED, Katherine A.; LIAN, Ingrid A.; EIDE, Irina P.; BJØRGE, Line; BLANGERO, John; MOSES, Eric K.; AUSTGULEN, Rigmor

2010-01-01

OBJECTIVE To obtain insight into possible mechanisms underlying preeclampsia using genome-wide transcriptional profiling in decidua basalis. STUDY DESIGN Genome-wide transcriptional profiling was performed on decidua basalis tissue from preeclamptic (n = 37) and normal pregnancies (n = 58). Differentially expressed genes were identified and merged into canonical pathways and networks. RESULTS Of the 26,504 expressed transcripts detected, 455 were differentially expressed (P <0.05, FDR P <0.1). Both novel (ARL5B, SLITRK4) and previously reported preeclampsia-associated genes (PLA2G7, HMOX1) were identified. Pathway analysis revealed that ‘tryptophan metabolism’, ‘endoplasmic reticulum stress’, ‘linoleic acid metabolism’, ‘notch signaling’, ‘fatty acid metabolism’, ‘arachidonic acid metabolism’ and ‘NRF2-mediated oxidative stress response’ were overrepresented canonical pathways. CONCLUSION In the present study single genes, canonical pathways and gene-gene networks that are likely to play an important role in the pathogenesis of preeclampsia, have been identified. Future functional studies are needed to accomplish a greater understanding of the mechanisms involved. PMID:20934677

Biomarkers are used to predict quantitative metabolite concentration profiles in human red blood cells

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

Yurkovich, James T.; Yang, Laurence; Palsson, Bernhard O.

Deep-coverage metabolomic profiling has revealed a well-defined development of metabolic decay in human red blood cells (RBCs) under cold storage conditions. A set of extracellular biomarkers has been recently identified that reliably defines the qualitative state of the metabolic network throughout this metabolic decay process. Here, we extend the utility of these biomarkers by using them to quantitatively predict the concentrations of other metabolites in the red blood cell. We are able to accurately predict the concentration profile of 84 of the 91 (92%) measured metabolites ( p < 0.05) in RBC metabolism using only measurements of these five biomarkers.more » The median of prediction errors (symmetric mean absolute percent error) across all metabolites was 13%. Furthermore, the ability to predict numerous metabolite concentrations from a simple set of biomarkers offers the potential for the development of a powerful workflow that could be used to evaluate the metabolic state of a biological system using a minimal set of measurements.« less

A chronological expression profile of gene activity during embryonic mouse brain development.

PubMed

Goggolidou, P; Soneji, S; Powles-Glover, N; Williams, D; Sethi, S; Baban, D; Simon, M M; Ragoussis, I; Norris, D P

2013-12-01

The brain is a functionally complex organ, the patterning and development of which are key to adult health. To help elucidate the genetic networks underlying mammalian brain patterning, we conducted detailed transcriptional profiling during embryonic development of the mouse brain. A total of 2,400 genes were identified as showing differential expression between three developmental stages. Analysis of the data identified nine gene clusters to demonstrate analogous expression profiles. A significant group of novel genes of as yet undiscovered biological function were detected as being potentially relevant to brain development and function, in addition to genes that have previously identified roles in the brain. Furthermore, analysis for genes that display asymmetric expression between the left and right brain hemispheres during development revealed 35 genes as putatively asymmetric from a combined data set. Our data constitute a valuable new resource for neuroscience and neurodevelopment, exposing possible functional associations between genes, including novel loci, and encouraging their further investigation in human neurological and behavioural disorders.

Metagenomic Analysis Revealing Antibiotic Resistance Genes (ARGs) and Their Genetic Compartments in the Tibetan Environment.

PubMed

Chen, Baowei; Yuan, Ke; Chen, Xin; Yang, Ying; Zhang, Tong; Wang, Yawei; Luan, Tiangang; Zou, Shichun; Li, Xiangdong

2016-07-05

Comprehensive profiles of antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs) in a minimally impacted environment are essential to understanding the evolution and dissemination of modern antibiotic resistance. Chemical analyses of the samples collected from Tibet demonstrated that the region under investigation was almost devoid of anthropogenic antibiotics. The soils, animal wastes, and sediments were different from each other in terms of bacterial community structures, and in the typical profiles of ARGs and MGEs. Diverse ARGs that encoded resistance to common antibiotics (e.g., beta-lactams, fluoroquinolones, etc.) were found mainly via an efflux mechanism completely distinct from modern antibiotic resistome. In addition, a very small fraction of ARGs in the Tibetan environment were carried by MGEs, indicating the low potential of these ARGs to be transferred among bacteria. In comparison to the ARG profiles in relatively pristine Tibet, contemporary ARGs and MGEs in human-impacted environments have evolved substantially since the broad use of anthropogenic antibiotics.

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

PubMed Central

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

Global Profiling and Molecular Characterization of Alternative Splicing Events Misregulated in Lung Cancer ▿ †

PubMed Central

Misquitta-Ali, Christine M.; Cheng, Edith; O'Hanlon, Dave; Liu, Ni; McGlade, C. Jane; Tsao, Ming Sound; Blencowe, Benjamin J.

2011-01-01

Alternative splicing (AS) is a widespread mechanism underlying the generation of proteomic and regulatory complexity. However, which of the myriad of human AS events play important roles in disease is largely unknown. To identify frequently occurring AS events in lung cancer, we used AS microarray profiling and reverse transcription-PCR (RT-PCR) assays to survey patient-matched normal and adenocarcinoma tumor tissues from the lungs of 29 individuals diagnosed with non-small cell lung cancer (NSCLC). Of 5,183 profiled alternative exons, four displayed tumor-associated changes in the majority of the patients. These events affected transcripts from the VEGFA, MACF1, APP, and NUMB genes. Similar AS changes were detected in NUMB and APP transcripts in primary breast and colon tumors. Tumor-associated increases in NUMB exon 9 inclusion correlated with reduced levels of NUMB protein expression and activation of the Notch signaling pathway, an event that has been linked to tumorigenesis. Moreover, short hairpin RNA (shRNA) knockdown of NUMB followed by isoform-specific rescue revealed that expression of the exon 9-skipped (nontumor) isoform represses Notch target gene activation whereas expression of the exon 9-included (tumor) isoform lacks this activity and is capable of promoting cell proliferation. The results thus reveal widespread AS changes in NSCLC that impact cell signaling in a manner that likely contributes to tumorigenesis. PMID:21041478

Global profiling and molecular characterization of alternative splicing events misregulated in lung cancer.

PubMed

Misquitta-Ali, Christine M; Cheng, Edith; O'Hanlon, Dave; Liu, Ni; McGlade, C Jane; Tsao, Ming Sound; Blencowe, Benjamin J

2011-01-01

Alternative splicing (AS) is a widespread mechanism underlying the generation of proteomic and regulatory complexity. However, which of the myriad of human AS events play important roles in disease is largely unknown. To identify frequently occurring AS events in lung cancer, we used AS microarray profiling and reverse transcription-PCR (RT-PCR) assays to survey patient-matched normal and adenocarcinoma tumor tissues from the lungs of 29 individuals diagnosed with non-small cell lung cancer (NSCLC). Of 5,183 profiled alternative exons, four displayed tumor-associated changes in the majority of the patients. These events affected transcripts from the VEGFA, MACF1, APP, and NUMB genes. Similar AS changes were detected in NUMB and APP transcripts in primary breast and colon tumors. Tumor-associated increases in NUMB exon 9 inclusion correlated with reduced levels of NUMB protein expression and activation of the Notch signaling pathway, an event that has been linked to tumorigenesis. Moreover, short hairpin RNA (shRNA) knockdown of NUMB followed by isoform-specific rescue revealed that expression of the exon 9-skipped (nontumor) isoform represses Notch target gene activation whereas expression of the exon 9-included (tumor) isoform lacks this activity and is capable of promoting cell proliferation. The results thus reveal widespread AS changes in NSCLC that impact cell signaling in a manner that likely contributes to tumorigenesis.

Genetic diversity among and within cultured cyanobionts of diverse species of Azolla.

PubMed

Sood, A; Prasanna, R; Prasanna, B M; Singh, P K

2008-01-01

The cyanobionts isolated from 10 Azolla accessions belonging to 6 species (Azolla mexicana, A. microphylla, A. rubra, A. caroliniana, A. filiculoides, A. pinnata) were cultured under laboratory conditions and analyzed on the basis of whole cell protein profiles and molecular marker dataset generated using repeat sequence primers (STRR(mod) and HipTG). The biochemical and molecular marker profiles of the cyanobionts were compared with those of the free-living cyanobacteria and symbiotic Nostoc strains from Anthoceros sp., Cycas sp. and Gunnera monoika. Cluster analysis revealed the genetic diversity among the selected strains, and identified 3 distinct clusters. Group 1 included cyanobionts from all the 10 accessions of Azolla, group 2 comprised all the symbiotic Nostoc strains, while group 3 included the free-living cyanobacteria belonging to the genera Nostoc and Anabaena. The interrelationships among the Azolla cyanobionts were further revealed by principal component analysis. Cyanobionts from A. caroliniana-A. microphylla grouped together while cyanobionts associated with A. mexicana-A. filiculoides along with A. pinnata formed another group. A. rubra cyanobionts had intermediate relationship with both the subgroups. This is the first study analyzing the diversity existing among the cultured cyanobionts of diverse Azolla species through the use of biochemical and molecular profiles and also the genetic distinctness of these free-living cyanobionts as compared to cyanobacterial strains of the genera Anabaena and Nostoc.

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

PubMed Central

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

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

PubMed

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 Latent Profile Analysis of Aggression and Victimization Across Relationship Types Among Veterans Who Use Substances.

PubMed

Anderson, RaeAnn E; Bonar, Erin E; Walton, Maureen A; Goldstick, Jason E; Rauch, Sheila A M; Epstein-Ngo, Quyen M; Chermack, Stephen T

2017-07-01

This study examined patterns of violence victimization and aggression in both intimate partner and nonpartner relationships among U.S. military veterans using latent profile analysis to identify subtypes of violence involvement. Participants were 839 substance use treatment-seeking veterans (93% male) from a large Veterans Affairs Medical Center who completed screening measures for a randomized controlled trial. Past-year violence involvement, including both intimate partner violence (IPV) and nonpartner violence (NPV), was common in the sample, although NPV occurred at somewhat higher rates. When we included either IPV or NPV aggression or victimization, more than 40% reported involvement with physical violence, 30% with violence involving injury, and 86% with psychological aggression. Latent profile analysis including both aggression and victimization in partner and nonpartner relationships indicated a four-profile solution: no/low violence (NLV; n = 377), predominantly IPV (n = 219), predominantly NPV (n = 134), and high general violence (HGV; n = 109). Multinomial logistic regression analyses revealed that, compared with the NLV group, the remaining three groups differed in age, cocaine use, posttraumatic stress disorder (PTSD) symptoms, and legal involvement. Legal issues appeared to differentiate the profiles most, with the predominantly NPV and HGV profiles reporting more instances of driving under the influence and the HGV profile reporting legal problems related to aggression. IPV and NPV are fairly common among veterans seeking substance use treatment. The clinical characteristics of violence profiles indicate that cocaine use, PTSD symptoms, and legal involvement are treatment needs that vary with violence profile and may be useful for clinical decision making.

Genome-wide analysis of soybean HD-Zip gene family and expression profiling under salinity and drought treatments.

PubMed

Chen, Xue; Chen, Zhu; Zhao, Hualin; Zhao, Yang; Cheng, Beijiu; Xiang, Yan

2014-01-01

Homeodomain-leucine zipper (HD-Zip) proteins, a group of homeobox transcription factors, participate in various aspects of normal plant growth and developmental processes as well as environmental responses. To date, no overall analysis or expression profiling of the HD-Zip gene family in soybean (Glycine max) has been reported. An investigation of the soybean genome revealed 88 putative HD-Zip genes. These genes were classified into four subfamilies, I to IV, based on phylogenetic analysis. In each subfamily, the constituent parts of gene structure and motif were relatively conserved. A total of 87 out of 88 genes were distributed unequally on 20 chromosomes with 36 segmental duplication events, indicating that segmental duplication is important for the expansion of the HD-Zip family. Analysis of the Ka/Ks ratios showed that the duplicated genes of the HD-Zip family basically underwent purifying selection with restrictive functional divergence after the duplication events. Analysis of expression profiles showed that 80 genes differentially expressed across 14 tissues, and 59 HD-Zip genes are differentially expressed under salinity and drought stress, with 20 paralogous pairs showing nearly identical expression patterns and three paralogous pairs diversifying significantly under drought stress. Quantitative real-time RT-PCR (qRT-PCR) analysis of six paralogous pairs of 12 selected soybean HD-Zip genes under both drought and salinity stress confirmed their stress-inducible expression patterns. This study presents a thorough overview of the soybean HD-Zip gene family and provides a new perspective on the evolution of this gene family. The results indicate that HD-Zip family genes may be involved in many plant responses to stress conditions. Additionally, this study provides a solid foundation for uncovering the biological roles of HD-Zip genes in soybean growth and development.

Self-organization of mesoscopic silver wires by electrochemical deposition.

PubMed

Zhong, Sheng; Koch, Thomas; Walheim, Stefan; Rösner, Harald; Nold, Eberhard; Kobler, Aaron; Scherer, Torsten; Wang, Di; Kübel, Christian; Wang, Mu; Hahn, Horst; Schimmel, Thomas

2014-01-01

Long, straight mesoscale silver wires have been fabricated from AgNO3 electrolyte via electrodeposition without the help of templates, additives, and surfactants. Although the wire growth speed is very fast due to growth under non-equilibrium conditions, the wire morphology is regular and uniform in diameter. Structural studies reveal that the wires are single-crystalline, with the [112] direction as the growth direction. A possible growth mechanism is suggested. Auger depth profile measurements show that the wires are stable against oxidation under ambient conditions. This unique system provides a convenient way for the study of self-organization in electrochemical environments as well as for the fabrication of highly-ordered, single-crystalline metal nanowires.

Boron depth profiles and residual damage following rapid thermal annealing of low-temperature BSi molecular ion implantation in silicon

NASA Astrophysics Data System (ADS)

Liang, J. H.; Wang, S. C.

2007-08-01

The influence of substrate temperature on both the implantation and post-annealing characteristics of molecular-ion-implanted 5 × 1014 cm-2 77 keV BSi in silicon was investigated in terms of boron depth profiles and damage microstructures. The substrate temperatures under investigation consisted of room temperature (RT) and liquid nitrogen temperature (LT). Post-annealing treatments were performed using rapid thermal annealing (RTA) at 1050 °C for 25 s. Boron depth profiles and damage microstructures in both the as-implanted and as-annealed specimens were determined using secondary ion mass spectrometry (SIMS) and transmission electron microscopy (TEM), respectively. The as-implanted results revealed that, compared to the RT specimen, the LT specimen yields a shallower boron depth profile with a reduced tail into the bulk. An amorphous layer containing a smooth amorphous-to-crystalline (a/c) interface is evident in the LT specimen while just the opposite is true in the as-implanted RT one. The as-annealed results illustrated that the extension of the boron depth profile into the bulk via transient-enhanced diffusion (TED) in the LT specimen is less than it is in the RT one. Only residual defects are visible in the LT specimen while two clear bands of dislocation loops appear in the RT one.

In silico analysis of stomach lineage specific gene set expression pattern in gastric cancer

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

Pandi, Narayanan Sathiya, E-mail: sathiyapandi@gmail.com; Suganya, Sivagurunathan; Rajendran, Suriliyandi

Highlights: •Identified stomach lineage specific gene set (SLSGS) was found to be under expressed in gastric tumors. •Elevated expression of SLSGS in gastric tumor is a molecular predictor of metabolic type gastric cancer. •In silico pathway scanning identified estrogen-α signaling is a putative regulator of SLSGS in gastric cancer. •Elevated expression of SLSGS in GC is associated with an overall increase in the survival of GC patients. -- Abstract: Stomach lineage specific gene products act as a protective barrier in the normal stomach and their expression maintains the normal physiological processes, cellular integrity and morphology of the gastric wall. However,more » the regulation of stomach lineage specific genes in gastric cancer (GC) is far less clear. In the present study, we sought to investigate the role and regulation of stomach lineage specific gene set (SLSGS) in GC. SLSGS was identified by comparing the mRNA expression profiles of normal stomach tissue with other organ tissue. The obtained SLSGS was found to be under expressed in gastric tumors. Functional annotation analysis revealed that the SLSGS was enriched for digestive function and gastric epithelial maintenance. Employing a single sample prediction method across GC mRNA expression profiles identified the under expression of SLSGS in proliferative type and invasive type gastric tumors compared to the metabolic type gastric tumors. Integrative pathway activation prediction analysis revealed a close association between estrogen-α signaling and SLSGS expression pattern in GC. Elevated expression of SLSGS in GC is associated with an overall increase in the survival of GC patients. In conclusion, our results highlight that estrogen mediated regulation of SLSGS in gastric tumor is a molecular predictor of metabolic type GC and prognostic factor in GC.« less

Bacterial profiling of White Plague Disease across corals and oceans indicates a conserved and distinct disease microbiome

PubMed Central

Roder, Cornelia; Arif, Chatchanit; Daniels, Camille; Weil, Ernesto; Voolstra, Christian R

2014-01-01

Coral diseases are characterized by microbial community shifts in coral mucus and tissue, but causes and consequences of these changes are vaguely understood due to the complexity and dynamics of coral-associated bacteria. We used 16S rRNA gene microarrays to assay differences in bacterial assemblages of healthy and diseased colonies displaying White Plague Disease (WPD) signs from two closely related Caribbean coral species, Orbicella faveolata and Orbicella franksi. Analysis of differentially abundant operational taxonomic units (OTUs) revealed strong differences between healthy and diseased specimens, but not between coral species. A subsequent comparison to data from two Indo-Pacific coral species (Pavona duerdeni and Porites lutea) revealed distinct microbial community patterns associated with ocean basin, coral species and health state. Coral species were clearly separated by site, but also, the relatedness of the underlying bacterial community structures resembled the phylogenetic relationship of the coral hosts. In diseased samples, bacterial richness increased and putatively opportunistic bacteria were consistently more abundant highlighting the role of opportunistic conditions in structuring microbial community patterns during disease. Our comparative analysis shows that it is possible to derive conserved bacterial footprints of diseased coral holobionts that might help in identifying key bacterial species related to the underlying etiopathology. Furthermore, our data demonstrate that similar-appearing disease phenotypes produce microbial community patterns that are consistent over coral species and oceans, irrespective of the putative underlying pathogen. Consequently, profiling coral diseases by microbial community structure over multiple coral species might allow the development of a comparative disease framework that can inform on cause and relatedness of coral diseases. PMID:24350609

Biochemical and transcriptomic analyses reveal different metabolite biosynthesis profiles among three color and developmental stages in 'Anji Baicha' (Camellia sinensis).

PubMed

Li, Chun-Fang; Xu, Yan-Xia; Ma, Jian-Qiang; Jin, Ji-Qiang; Huang, Dan-Juan; Yao, Ming-Zhe; Ma, Chun-Lei; Chen, Liang

2016-09-08

The new shoots of the albino tea cultivar 'Anji Baicha' are yellow or white at low temperatures and turn green as the environmental temperatures increase during the early spring. 'Anji Baicha' metabolite profiles exhibit considerable variability over three color and developmental stages, especially regarding the carotenoid, chlorophyll, and theanine concentrations. Previous studies focused on physiological characteristics, gene expression differences, and variations in metabolite abundances in albino tea plant leaves at specific growth stages. However, the molecular mechanisms regulating metabolite biosynthesis in various color and developmental stages in albino tea leaves have not been fully characterized. We used RNA-sequencing to analyze 'Anji Baicha' leaves at the yellow-green, albescent, and re-greening stages. The leaf transcriptomes differed considerably among the three stages. Functional classifications based on Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed that differentially expressed unigenes were mainly related to metabolic pathways, biosynthesis of secondary metabolites, phenylpropanoid biosynthesis, and carbon fixation in photosynthetic organisms. Chemical analyses revealed higher β-carotene and theanine levels, but lower chlorophyll a levels, in the albescent stage than in the green stage. Furthermore, unigenes involved in carotenoid, chlorophyll, and theanine biosyntheses were identified, and the expression patterns of the differentially expressed unigenes in these biosynthesis pathways were characterized. Through co-expression analyses, we identified the key genes in these pathways. These genes may be responsible for the metabolite biosynthesis differences among the different leaf color and developmental stages of 'Anji Baicha' tea plants. Our study presents the results of transcriptomic and biochemical analyses of 'Anji Baicha' tea plants at various stages. The distinct transcriptome profiles for each color and developmental stage enabled us to identify changes to biosynthesis pathways and revealed the contributions of such variations to the albino phenotype of tea plants. Furthermore, comparisons of the transcriptomes and related metabolites helped clarify the molecular regulatory mechanisms underlying the secondary metabolic pathways in different stages.

Emergent Self-Organized Criticality in Gene Expression Dynamics: Temporal Development of Global Phase Transition Revealed in a Cancer Cell Line

PubMed Central

Tsuchiya, Masa; Giuliani, Alessandro; Hashimoto, Midori; Erenpreisa, Jekaterina; Yoshikawa, Kenichi

2015-01-01

Background The underlying mechanism of dynamic control of the genome-wide expression is a fundamental issue in bioscience. We addressed it in terms of phase transition by a systemic approach based on both density analysis and characteristics of temporal fluctuation for the time-course mRNA expression in differentiating MCF-7 breast cancer cells. Methodology In a recent work, we suggested criticality as an essential aspect of dynamic control of genome-wide gene expression. Criticality was evident by a unimodal-bimodal transition through flattened unimodal expression profile. The flatness on the transition suggests the existence of a critical transition at which up- and down-regulated expression is balanced. Mean field (averaging) behavior of mRNAs based on the temporal expression changes reveals a sandpile type of transition in the flattened profile. Furthermore, around the transition, a self-similar unimodal-bimodal transition of the whole expression occurs in the density profile of an ensemble of mRNA expression. These singular and scaling behaviors identify the transition as the expression phase transition driven by self-organized criticality (SOC). Principal Findings Emergent properties of SOC through a mean field approach are revealed: i) SOC, as a form of genomic phase transition, consolidates distinct critical states of expression, ii) Coupling of coherent stochastic oscillations between critical states on different time-scales gives rise to SOC, and iii) Specific gene clusters (barcode genes) ranging in size from kbp to Mbp reveal similar SOC to genome-wide mRNA expression and ON-OFF synchronization to critical states. This suggests that the cooperative gene regulation of topological genome sub-units is mediated by the coherent phase transitions of megadomain-scaled conformations between compact and swollen chromatin states. Conclusion and Significance In summary, our study provides not only a systemic method to demonstrate SOC in whole-genome expression, but also introduces novel, physically grounded concepts for a breakthrough in the study of biological regulation. PMID:26067993

Laser-ablation electrospray ionization mass spectrometry with ion mobility separation reveals metabolites in the symbiotic interactions of soybean roots and rhizobia.

PubMed

Stopka, Sylwia A; Agtuca, Beverly J; Koppenaal, David W; Paša-Tolić, Ljiljana; Stacey, Gary; Vertes, Akos; Anderton, Christopher R

2017-07-01

Technologies enabling in situ metabolic profiling of living plant systems are invaluable for understanding physiological processes and could be used for rapid phenotypic screening (e.g., to produce plants with superior biological nitrogen-fixing ability). The symbiotic interaction between legumes and nitrogen-fixing soil bacteria results in a specialized plant organ (i.e., root nodule) where the exchange of nutrients between host and endosymbiont occurs. Laser-ablation electrospray ionization mass spectrometry (LAESI-MS) is a method that can be performed under ambient conditions requiring minimal sample preparation. Here, we employed LAESI-MS to explore the well characterized symbiosis between soybean (Glycine max L. Merr.) and its compatible symbiont, Bradyrhizobium japonicum. The utilization of ion mobility separation (IMS) improved the molecular coverage, selectivity, and identification of the detected biomolecules. Specifically, incorporation of IMS resulted in an increase of 153 differentially abundant spectral features in the nodule samples. The data presented demonstrate the advantages of using LAESI-IMS-MS for the rapid analysis of intact root nodules, uninfected root segments, and free-living rhizobia. Untargeted pathway analysis revealed several metabolic processes within the nodule (e.g., zeatin, riboflavin, and purine synthesis). Compounds specific to the uninfected root and bacteria were also detected. Lastly, we performed depth profiling of intact nodules to reveal the location of metabolites to the cortex and inside the infected region, and lateral profiling of sectioned nodules confirmed these molecular distributions. Our results established the feasibility of LAESI-IMS-MS for the analysis and spatial mapping of plant tissues, with its specific demonstration to improve our understanding of the soybean-rhizobial symbiosis. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

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

PubMed

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.

Laser-ablation electrospray ionization mass spectrometry with ion mobility separation reveals metabolites in the symbiotic interactions of soybean roots and rhizobia

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

Stopka, Sylwia A.; Agtuca, Beverly J.; Koppenaal, David W.

Technologies enabling in situ metabolic profiling of living plant systems are invaluable for understanding physiological processes and could be used for rapid phenotypic screening (e.g., to produce plants with superior biological nitrogen fixing ability). The symbiotic interaction between legumes and nitrogen-fixing soil bacteria results in a specialized plant organ (i.e., root nodule), where the exchange of nutrients between host and endosymbiont occurs. Laser ablation electrospray ionization mass spectrometry (LAESI-MS) is a method that can be performed under ambient conditions requiring minimal sample preparation. Here, we employed LAESI-MS to explore the well-characterized symbiosis between soybean (Glycine max L. Merr.) and itsmore » compatible symbiont, Bradyrhizobium japonicum. The utilization of ion mobility separation (IMS) improved the molecular coverage, selectivity, and identification of the detected biomolecules. Specifically, incorporation of IMS resulted in an increase of 153 detected metabolites in the nodule samples. The data presented demonstrates the advantages of using LAESI-IMS-MS for the rapid analysis of intact root nodules, uninfected root segments, and free-living rhizobia. Untargeted pathway analysis revealed several metabolic processes within the nodule (e.g., zeatin, riboflavin, and purine synthesis). Compounds specific to the uninfected root and bacteria were also detected. Lastly, we performed depth-profiling of intact nodules to reveal the location of metabolites to the cortex and inside the infected region, and lateral profiling of sectioned nodules confirmed these molecular distributions. Our results established the feasibility of LAESI-IMS-MS for the analysis and spatial mapping of plant tissues, with its specific demonstration to improve our understanding of the soybean-rhizobial symbiosis.« less

Bacteria-to-Archaea ratio depending on soil depth and agrogenic impact

NASA Astrophysics Data System (ADS)

Semenov, Mikhail; Manucharova, Natalia; Kuzyakov, Yakov

2014-05-01

Archaeal communities and their potential roles in the soil ecosystem are affected by a number of soil proprerties and environmental factors. Competitive interactions between Archaea and Bacteria play a particular role in spread and abundance of these two domains. Therefore, the goal of the study was to evaluate the Bacteria-to-Archaea ratio in different soils. The research was carried out at field and natural ecosystems of European part of Russia. Samples were collected within the soil profiles (3-6 horizons) of chernozem and kastanozem with distinctly different agrogenic impact. In situ hybridization with fluorescently labeled rRNA-targeted oligonucleotide probes (FISH) was used to determine the abundance of metabolically active cells of Archaea and Bacteria. The Cmic, Corg, C/N, DNA content and growth characteristics have been analyzed as well. Determination of number of metabolically active cells in chernozem under arable land and forest revealed that abundance of Archaea in topsoil under forest was higher more than 2 times comparing with arable land, but leveled off in the deeper horizons. Plowing of Chernozem decreased amount of archaeal and bacterial active cells simultaneously, however, Bacteria were more resistant to agrogenic impact than Archaea. Determination of the taxonomic composition within Bacteria domain showed a significant decrease in the abundance of phylogenetic groups Firmicutes and Actinobacteria in the topsoil under arable land comparing to the forest, which is the main reason for the declining of the total amount of prokaryotic cells. In kastanozem significant change in the number of metabolically active cells due to plowing was detected only within 40 cm soil layer, and this effect disappeared in lower horizons. The number of Archaea was higher in the upper horizons of arable as compared to virgin soil. Conversely, the number of Bacteria in the upper layers of the soil after plowing kastanozem decreased. Relationship between soil organic carbon content and the amount of soil metabolically active Bacteria and Archaea cells revealed that distribution of both Bacteria and Archaea throughout the soil profile was governed by organic matter content. Thus, the organic matter content seemed to be the main factor of declining Bacteria-to- Archaea ratio down the profile (from 7.1 to 4.2 for virgin soil and from 5 to 3.9 for arable soil). In conclusion, Archaea out-compete Bacteria under conditions of reduced energy supply.

A flatter gallium profile for high-efficiency Cu(In,Ga)(Se,S)2 solar cell and improved robustness against sulfur-gradient variation

NASA Astrophysics Data System (ADS)

Huang, Chien-Yao; Lee, Wen-Chin; Lin, Albert

2016-09-01

Co-optimization of the gallium and sulfur profiles in penternary Cu(In,Ga)(Se,S)2 thin film solar cell and its impacts on device performance and variability are investigated in this work. An absorber formation method to modulate the gallium profiling under low sulfur-incorporation is disclosed, which solves the problem of Ga-segregation in selenization. Flatter Ga-profiles, which lack of experimental investigations to date, are explored and an optimal Ga-profile achieving 17.1% conversion efficiency on a 30 cm × 30 cm sub-module without anti-reflection coating is presented. Flatter Ga-profile gives rise to the higher Voc × Jsc by improved bandgap matching to solar spectrum, which is hard to be achieved by the case of Ga-accumulation. However, voltage-induced carrier collection loss is found, as evident from the measured voltage-dependent photocurrent characteristics based on a small-signal circuit model. The simulation results reveal that the loss is attributed to the synergistic effect of the detrimental gallium and sulfur gradients, which can deteriorate the carrier collection especially in quasi-neutral region (QNR). Furthermore, the underlying physics is presented, and it provides a clear physical picture to the empirical trends of device performance, I-V characteristics, and voltage-dependent photocurrent, which cannot be explained by the standard solar circuit model. The parameter "FGa" and front sulfur-gradient are found to play critical roles on the trade-off between space charge region (SCR) recombination and QNR carrier collection. The co-optimized gallium and sulfur gradients are investigated, and the corresponding process modification for further efficiency-enhancement is proposed. In addition, the performance impact of sulfur-gradient variation is studied, and a gallium design for suppressing the sulfur-induced variability is proposed. Device performances of varied Ga-profiles with front sulfur-gradients are simulated based on a compact device model. Finally, an exploratory path toward 20% high-efficiency Ga-profile with robustness against sulfur-induced performance variability is presented.

Overexpressing of OsAMT1-3, a High Affinity Ammonium Transporter Gene, Modifies Rice Growth and Carbon-Nitrogen Metabolic Status

PubMed Central

Bao, Aili; Liang, Zhijun; Zhao, Zhuqing; Cai, Hongmei

2015-01-01

AMT1-3 encodes the high affinity NH4+ transporter in rice roots and is predominantly expressed under nitrogen starvation. In order to evaluate the effect of AMT1-3 gene on rice growth, nitrogen absorption and metabolism, we generated AMT1-3-overexpressing plants and analyzed the growth phenotype, yield, carbon and nitrogen metabolic status, and gene expression profiles. Although AMT1-3 mRNA accumulated in transgenic plants, these plants displayed significant decreases in growth when compared to the wild-type plants. The nitrogen uptake assay using a 15N tracer revealed poor nitrogen uptake ability in AMT1-3-overexpressing plants. We found significant decreases in AMT1-3-overexpressing plant leaf carbon and nitrogen content accompanied with a higher leaf C/N ratio. Significant changes in soluble proteins and carbohydrates were also observed in AMT1-3-overexpressing plants. In addition, metabolite profile analysis demonstrated significant changes in individual sugars, organic acids and free amino acids. Gene expression analysis revealed distinct expression patterns of genes that participate in carbon and nitrogen metabolism. Additionally, the correlation between the metabolites and gene expression patterns was consistent in AMT1-3-overexpressing plants under both low and high nitrogen growth conditions. Therefore, we hypothesized that the carbon and nitrogen metabolic imbalance caused by AMT1-3 overexpressing attributed to the poor growth and yield of transgenic plants. PMID:25915023

Quantitative PCR Profiling of Escherichia coli in Livestock Feces Reveals Increased Population Resilience Relative to Culturable Counts under Temperature Extremes.

PubMed

Oliver, David M; Bird, Clare; Burd, Emmy; Wyman, Michael

2016-09-06

The relationship between culturable counts (CFU) and quantitative PCR (qPCR) cell equivalent counts of Escherichia coli in dairy feces exposed to different environmental conditions and temperature extremes was investigated. Fecal samples were collected in summer and winter from dairy cowpats held under two treatments: field-exposed versus polytunnel-protected. A significant correlation in quantified E. coli was recorded between the qPCR and culture-based methods (r = 0.82). Evaluation of the persistence profiles of E. coli over time revealed no significant difference in the E. coli numbers determined as either CFU or gene copies during the summer for the field-exposed cowpats, whereas significantly higher counts were observed by qPCR for the polytunnel-protected cowpats, which were exposed to higher ambient temperatures. In winter, the qPCR returned significantly higher counts of E. coli for the field-exposed cowpats, thus representing a reversal of the findings from the summer sampling campaign. Results from this study suggest that with increasing time post-defecation and with the onset of challenging environmental conditions, such as extremes in temperature, culture-based counts begin to underestimate the true resilience of viable E. coli populations in livestock feces. This is important not only in the long term as the Earth changes in response to climate-change drivers but also in the short term during spells of extremely cold or hot weather.

Sulfur alleviates arsenic toxicity by reducing its accumulation and modulating proteome, amino acids and thiol metabolism in rice leaves

NASA Astrophysics Data System (ADS)

Dixit, Garima; Singh, Amit Pal; Kumar, Amit; Dwivedi, Sanjay; Deeba, Farah; Kumar, Smita; Suman, Shankar; Adhikari, Bijan; Shukla, Yogeshwar; Trivedi, Prabodh Kumar; Pandey, Vivek; Tripathi, Rudra Deo

2015-11-01

Arsenic (As) contamination of water is a global concern and rice consumption is the biggest dietary exposure to human posing carcinogenic risks, predominantly in Asia. Sulfur (S) is involved in di-sulfide linkage in many proteins and plays crucial role in As detoxification. Present study explores role of variable S supply on rice leaf proteome, its inclination towards amino acids (AA) profile and non protein thiols under arsenite exposure. Analysis of 282 detected proteins on 2-DE gel revealed 113 differentially expressed proteins, out of which 80 were identified by MALDI-TOF-TOF. The identified proteins were mostly involved in glycolysis, TCA cycle, AA biosynthesis, photosynthesis, protein metabolism, stress and energy metabolism. Among these, glycolytic enzymes play a major role in AA biosynthesis that leads to change in AAs profiling. Proteins of glycolytic pathway, photosynthesis and energy metabolism were also validated by western blot analysis. Conclusively S supplementation reduced the As accumulation in shoot positively skewed thiol metabolism and glycolysis towards AA accumulation under AsIII stress.

Understanding the molecular basis of plant growth promotional effect of Pseudomonas fluorescens on rice through protein profiling.

PubMed

Kandasamy, Saveetha; Loganathan, Karthiba; Muthuraj, Raveendran; Duraisamy, Saravanakumar; Seetharaman, Suresh; Thiruvengadam, Raguchander; Ponnusamy, Balasubramanian; Ramasamy, Samiyappan

2009-12-24

Plant Growth Promoting Rhizobacteria (PGPR), Pseudomonas fluorescens strain KH-1 was found to exhibit plant growth promotional activity in rice under both in-vitro and in-vivo conditions. But the mechanism underlying such promotional activity of P. fluorescens is not yet understood clearly. In this study, efforts were made to elucidate the molecular responses of rice plants to P. fluorescens treatment through protein profiling. Two-dimensional polyacrylamide gel electrophoresis strategy was adopted to identify the PGPR responsive proteins and the differentially expressed proteins were analyzed by mass spectrometry. Priming of P. fluorescens, 23 different proteins found to be differentially expressed in rice leaf sheaths and MS analysis revealed the differential expression of some important proteins namely putative p23 co-chaperone, Thioredoxin h- rice, Ribulose-bisphosphate carboxylase large chain precursor, Nucleotide diPhosphate kinase, Proteosome sub unit protein and putative glutathione S-transferase protein. Functional analyses of the differential proteins were reported to be directly or indirectly involved in growth promotion in plants. Thus, this study confirms the primary role of PGPR strain KH-1 in rice plant growth promotion.

Cellular Fatty Acid Composition, Soluble-Protein Profile, and Antimicrobial Resistance Pattern of Eubacterium lentum

PubMed Central

Mosca, Adriana; Summanen, Paula; Finegold, Sydney M.; De Michele, Giampiero; Miragliotta, Giuseppe

1998-01-01

Phenotypic heterogeneity among isolates of Eubacterium lentum has been recognized for many years. To better delineate their taxonomic relatedness, 29 clinical isolates of E. lentum were examined for soluble-protein content, cellular fatty acid profile, and antimicrobial resistance pattern in order to ascertain whether differences in these characteristics could be correlated with differences in biochemical activities. Among 29 isolates we could identify 6 that were different from all the others. These strains were coccobacilli with translucent colonies; they were catalase and H2S negative, not fluorescent under UV light, and susceptible to beta-lactam drugs; growth was not stimulated by arginine; and fatty acid analysis revealed the presence of straight-chain fatty acids. The remainder of the strains, including the type species, were pleomorphic bacilli with speckled colonies and were catalase and H2S positive; all but two were fluorescent under UV light; they were resistant to beta-lactam antibiotics; growth was greatly stimulated by arginine; and they demonstrated saturated branched-chain fatty acids. Our data suggest that E. lentum can be further differentiated into different types. PMID:9508307

Integrative functional genomics of salt acclimatization in the model legume Lotus japonicus.

PubMed

Sanchez, Diego H; Lippold, Felix; Redestig, Henning; Hannah, Matthew A; Erban, Alexander; Krämer, Ute; Kopka, Joachim; Udvardi, Michael K

2008-03-01

The model legume Lotus japonicus was subjected to non-lethal long-term salinity and profiled at the ionomic, transcriptomic and metabolomic levels. Two experimental designs with various stress doses were tested: a gradual step acclimatization and an initial acclimatization approach. Ionomic profiling by inductively coupled plasma/atomic emission spectrometry (ICP-AES) revealed salt stress-induced reductions in potassium, phosphorus, sulphur, zinc and molybdenum. Microarray profiling using the Lotus Genechip allowed the identification of 912 probesets that were differentially expressed under the acclimatization regimes. Gas chromatography/mass spectrometry-based metabolite profiling identified 147 differentially accumulated soluble metabolites, indicating a change in metabolic phenotype upon salt acclimatization. Metabolic changes were characterized by a general increase in the steady-state levels of many amino acids, sugars and polyols, with a concurrent decrease in most organic acids. Transcript and metabolite changes exhibited a stress dose-dependent response within the range of NaCl concentrations used, although threshold and plateau behaviours were also observed. The combined observations suggest a successive and increasingly global requirement for the reprogramming of gene expression and metabolic pathways to maintain ionic and osmotic homeostasis. A simple qualitative model is proposed to explain the systems behaviour of plants during salt acclimatization.

Discovery of a Potent BTK Inhibitor with a Novel Binding Mode by Using Parallel Selections with a DNA-Encoded Chemical Library.

PubMed

Cuozzo, John W; Centrella, Paolo A; Gikunju, Diana; Habeshian, Sevan; Hupp, Christopher D; Keefe, Anthony D; Sigel, Eric A; Soutter, Holly H; Thomson, Heather A; Zhang, Ying; Clark, Matthew A

2017-05-04

We have identified and characterized novel potent inhibitors of Bruton's tyrosine kinase (BTK) from a single DNA-encoded library of over 110 million compounds by using multiple parallel selection conditions, including variation in target concentration and addition of known binders to provide competition information. Distinct binding profiles were observed by comparing enrichments of library building block combinations under these conditions; one enriched only at high concentrations of BTK and was competitive with ATP, and another enriched at both high and low concentrations of BTK and was not competitive with ATP. A compound representing the latter profile showed low nanomolar potency in biochemical and cellular BTK assays. Results from kinetic mechanism of action studies were consistent with the selection profiles. Analysis of the co-crystal structure of the most potent compound demonstrated a novel binding mode that revealed a new pocket in BTK. Our results demonstrate that profile-based selection strategies using DNA-encoded libraries form the basis of a new methodology to rapidly identify small molecule inhibitors with novel binding modes to clinically relevant targets. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effects of age, sex, and genotype on high-sensitivity metabolomic profiles in the fruit fly, Drosophila melanogaster

PubMed Central

Hoffman, Jessica M; Soltow, Quinlyn A; Li, Shuzhao; Sidik, Alfire; Jones, Dean P; Promislow, Daniel E L

2014-01-01

Researchers have used whole-genome sequencing and gene expression profiling to identify genes associated with age, in the hope of understanding the underlying mechanisms of senescence. But there is a substantial gap from variation in gene sequences and expression levels to variation in age or life expectancy. In an attempt to bridge this gap, here we describe the effects of age, sex, genotype, and their interactions on high-sensitivity metabolomic profiles in the fruit fly, Drosophila melanogaster. Among the 6800 features analyzed, we found that over one-quarter of all metabolites were significantly associated with age, sex, genotype, or their interactions, and multivariate analysis shows that individual metabolomic profiles are highly predictive of these traits. Using a metabolomic equivalent of gene set enrichment analysis, we identified numerous metabolic pathways that were enriched among metabolites associated with age, sex, and genotype, including pathways involving sugar and glycerophospholipid metabolism, neurotransmitters, amino acids, and the carnitine shuttle. Our results suggest that high-sensitivity metabolomic studies have excellent potential not only to reveal mechanisms that lead to senescence, but also to help us understand differences in patterns of aging among genotypes and between males and females. PMID:24636523

RASopathies are associated with a distinct personality profile.

PubMed

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.

Analysis of global gene expression in Brachypodium distachyon reveals extensive network plasticity in response to abiotic stress.

PubMed

Priest, Henry D; Fox, Samuel E; Rowley, Erik R; Murray, Jessica R; Michael, Todd P; Mockler, Todd C

2014-01-01

Brachypodium distachyon is a close relative of many important cereal crops. Abiotic stress tolerance has a significant impact on productivity of agriculturally important food and feedstock crops. Analysis of the transcriptome of Brachypodium after chilling, high-salinity, drought, and heat stresses revealed diverse differential expression of many transcripts. Weighted Gene Co-Expression Network Analysis revealed 22 distinct gene modules with specific profiles of expression under each stress. Promoter analysis implicated short DNA sequences directly upstream of module members in the regulation of 21 of 22 modules. Functional analysis of module members revealed enrichment in functional terms for 10 of 22 network modules. Analysis of condition-specific correlations between differentially expressed gene pairs revealed extensive plasticity in the expression relationships of gene pairs. Photosynthesis, cell cycle, and cell wall expression modules were down-regulated by all abiotic stresses. Modules which were up-regulated by each abiotic stress fell into diverse and unique gene ontology GO categories. This study provides genomics resources and improves our understanding of abiotic stress responses of Brachypodium.

Effect of starter cultures and packaging methods on amino acid profile and eating quality characteristics of pork ham.

PubMed

Gogoi, Protiva; Borpuzari, R N; Borpuzari, T; Hazarika, R A; Bora, J R

2015-08-01

Wet cured pork hams were inoculated with a mixed starter cultures comprising of Lactobacillus acidophilus and Micrococcus varians M483 at the dose level of 106 cfu/g and the un inoculated hams served as controls. The amino acid profile of hams of the treated and the control groups stored at 4oC under MAP and VP and evaluated on 60th day of storage revealed that treated hams liberated higher concentration of free amino acids except for proline and methionine which were found in higher concentration (P < 0.01) in the MAP control samples. The MAP control samples liberated glutamic acid (85.65 ± 1.40 ppm), cystine (21.56 ± 1.14 ppm) and tyrosine (16.63 ± 1.94 ppm) whereas, the treated samples did not release these amino acids. The VP control samples too liberated cystine (6.98 ± 1.36 ppm) and arginine (42.70 ± 2.78 ppm) but the treated ham of the VP did not liberate these amino acids. The VP hams had higher concentration (P < 0.01) of free proline, glycine, alanine, valine, methionine, isoleucine, phenylalanine, lysine and histidine than the MAP samples. Colour analysis of ham using CIE Lab colour system revealed that the treated samples had significantly higher concentrations of L*, a* and b* components. The L* and a* values were higher in the MAP than under VP systems while the b* values were higher in the VP samples than the MAP samples. Neither the bacterial cultures nor the packaging system influenced the textural property of ham. Starter cultures inoculated hams were rated superior (P < 0.05) in terms of their sensory properties. Hams packaged under MAP were rated superior (P < 0.05) than those packaged under VP in terms of appearance, colour, taste, tenderness, flavour, juiciness and overall acceptability.

Distinct biological subtypes and patterns of genome evolution in lymphoma revealed by circulating tumor DNA.

PubMed

Scherer, Florian; Kurtz, David M; Newman, Aaron M; Stehr, Henning; Craig, Alexander F M; Esfahani, Mohammad Shahrokh; Lovejoy, Alexander F; Chabon, Jacob J; Klass, Daniel M; Liu, Chih Long; Zhou, Li; Glover, Cynthia; Visser, Brendan C; Poultsides, George A; Advani, Ranjana H; Maeda, Lauren S; Gupta, Neel K; Levy, Ronald; Ohgami, Robert S; Kunder, Christian A; Diehn, Maximilian; Alizadeh, Ash A

2016-11-09

Patients with diffuse large B cell lymphoma (DLBCL) exhibit marked diversity in tumor behavior and outcomes, yet the identification of poor-risk groups remains challenging. In addition, the biology underlying these differences is incompletely understood. We hypothesized that characterization of mutational heterogeneity and genomic evolution using circulating tumor DNA (ctDNA) profiling could reveal molecular determinants of adverse outcomes. To address this hypothesis, we applied cancer personalized profiling by deep sequencing (CAPP-Seq) analysis to tumor biopsies and cell-free DNA samples from 92 lymphoma patients and 24 healthy subjects. At diagnosis, the amount of ctDNA was found to strongly correlate with clinical indices and was independently predictive of patient outcomes. We demonstrate that ctDNA genotyping can classify transcriptionally defined tumor subtypes, including DLBCL cell of origin, directly from plasma. By simultaneously tracking multiple somatic mutations in ctDNA, our approach outperformed immunoglobulin sequencing and radiographic imaging for the detection of minimal residual disease and facilitated noninvasive identification of emergent resistance mutations to targeted therapies. In addition, we identified distinct patterns of clonal evolution distinguishing indolent follicular lymphomas from those that transformed into DLBCL, allowing for potential noninvasive prediction of histological transformation. Collectively, our results demonstrate that ctDNA analysis reveals biological factors that underlie lymphoma clinical outcomes and could facilitate individualized therapy. Copyright © 2016, American Association for the Advancement of Science.

Canonical discrimination of the effect of a new broiler production facility on soil chemical profiles as related to current management practices.

PubMed

Sheffield, Cynthia L; Crippen, Tawni L; Byrd, J Allen; Beier, Ross C; Yeater, Kathleen

2015-01-01

The effect dirt-floored broiler houses have on the underlying native soil, and the potential for contamination of the ground water by leaching under the foundation, is an understudied area. This study examines alterations in fifteen quantitative soil parameters (Ca, Cu, electrical conductivity, Fe, K, Mg, Mn, Na, NO3, organic matter, P, pH, S, soil moisture and Zn) in the underlayment of a newly constructed dirt-floored broiler house over the first two years of production (Native through Flock 11). The experiment was conducted near NW Robertson County, Texas, where the native soil is a fine, smectitic thermic Udertic Paleustalfs and the slopes range from zero to three percent. Multiple samples were collected from under each of three water and three feed lines the length of the house, in a longitudinal study during February 2008 through August 2010. To better define the relationship between the soil parameters and sampling times, a canonical discriminant analysis approach was used. The soil profiles assembled into five distinctive clusters corresponding to time and management practices. Results of this work revealed that the majority of parameters increased over time. The management practices of partial and total house clean-outs markedly altered soil profiles the house underlayment, thus reducing the risk of infiltration into the ground water near the farm. This is important as most broiler farms consist of several houses within a small area, so the cumulative ecological impact could be substantial if not properly managed.

Canonical Discrimination of the Effect of a New Broiler Production Facility on Soil Chemical Profiles as Related to Current Management Practices

PubMed Central

Sheffield, Cynthia L.; Crippen, Tawni L.; Byrd, J. Allen; Beier, Ross C.; Yeater, Kathleen

2015-01-01

The effect dirt-floored broiler houses have on the underlying native soil, and the potential for contamination of the ground water by leaching under the foundation, is an understudied area. This study examines alterations in fifteen quantitative soil parameters (Ca, Cu, electrical conductivity, Fe, K, Mg, Mn, Na, NO3, organic matter, P, pH, S, soil moisture and Zn) in the underlayment of a newly constructed dirt-floored broiler house over the first two years of production (Native through Flock 11). The experiment was conducted near NW Robertson County, Texas, where the native soil is a fine, smectitic thermic Udertic Paleustalfs and the slopes range from zero to three percent. Multiple samples were collected from under each of three water and three feed lines the length of the house, in a longitudinal study during February 2008 through August 2010. To better define the relationship between the soil parameters and sampling times, a canonical discriminant analysis approach was used. The soil profiles assembled into five distinctive clusters corresponding to time and management practices. Results of this work revealed that the majority of parameters increased over time. The management practices of partial and total house clean-outs markedly altered soil profiles the house underlayment, thus reducing the risk of infiltration into the ground water near the farm. This is important as most broiler farms consist of several houses within a small area, so the cumulative ecological impact could be substantial if not properly managed. PMID:26029909

Fecal Microbiota and Metabolome in a Mouse Model of Spontaneous Chronic Colitis: Relevance to Human Inflammatory Bowel Disease.

PubMed

Robinson, Ainsley M; Gondalia, Shakuntla V; Karpe, Avinash V; Eri, Rajaraman; Beale, David J; Morrison, Paul D; Palombo, Enzo A; Nurgali, Kulmira

2016-12-01

Dysbiosis of the gut microbiota may be involved in the pathogenesis of inflammatory bowel disease (IBD). However, the mechanisms underlying the role of the intestinal microbiome and metabolome in IBD onset and its alteration during active treatment and recovery remain unknown. Animal models of chronic intestinal inflammation with similar microbial and metabolomic profiles would enable investigation of these mechanisms and development of more effective treatments. Recently, the Winnie mouse model of colitis closely representing the clinical symptoms and characteristics of human IBD has been developed. In this study, we have analyzed fecal microbial and metabolomic profiles in Winnie mice and discussed their relevance to human IBD. The 16S rRNA gene was sequenced from fecal DNA of Winnie and C57BL/6 mice to define operational taxonomic units at ≥97% similarity threshold. Metabolomic profiling of the same fecal samples was performed by gas chromatography-mass spectrometry. Composition of the dominant microbiota was disturbed, and prominent differences were evident at all levels of the intestinal microbiome in fecal samples from Winnie mice, similar to observations in patients with IBD. Metabolomic profiling revealed that chronic colitis in Winnie mice upregulated production of metabolites and altered several metabolic pathways, mostly affecting amino acid synthesis and breakdown of monosaccharides to short chain fatty acids. Significant dysbiosis in the Winnie mouse gut replicates many changes observed in patients with IBD. These results provide justification for the suitability of this model to investigate mechanisms underlying the role of intestinal microbiota and metabolome in the pathophysiology of IBD.

Behavioral profiles in frontal lobe epilepsy: Autobiographic memory versus mood impairment.

PubMed

Rayner, Genevieve; Jackson, Graeme D; Wilson, Sarah J

2015-02-01

Autobiographic memory encompasses the encoding and retrieval of episodes, people, and places encountered in everyday life. It can be impaired in both epilepsy and frontal lobe damage. Here, we performed an initial investigation of how autobiographic memory is impacted by chronic frontal lobe epilepsy (FLE) together with its underlying pathology. We prospectively studied a series of nine consecutive patients with medically refractory FLE, relative to 24 matched healthy controls. Seven of the nine patients had frontal lobe structural abnormalities. Episodic and semantic autobiographic memory functioning was profiled, and factors associated with impaired autobiographic memory were identified among epileptologic, neuroimaging, neuropsychiatric, and cognitive variables including auditory-verbal and visual memory, and the executive function of cognitive control. Results showed that the FLE group experienced significantly higher rates of autobiographic memory and mood disturbance (p < 0.001), with detailed assessment of individual patients revealing two profiles of impairment, primarily characterized by cognitive or mood disturbance. Five of the patients (56%) exhibited significant episodic autobiographic memory deficits, whereas in three of these, knowledge of semantic autobiographic facts was preserved. Four of them also had reduced cognitive control. Mood disorder was largely unrelated to poor autobiographic memory. In contrast, the four cases with preserved autobiographic memory were notable for their past or current depressive symptoms. These findings provide preliminary data that frontal lobe seizure activity with its underlying pathology may selectively disrupt large-scale cognitive or affective networks, giving rise to different neurobehavioral profiles that may be used to inform clinical management. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

Transcriptome Profiling of the Abdominal Skin of Larimichthys crocea in Light Stress

NASA Astrophysics Data System (ADS)

Han, Zhaofang; Lv, Changhuan; Xiao, Shijun; Ye, Kun; Zhang, Dongling; Tsai, Huai Jen; Wang, Zhiyong

2018-04-01

Large yellow croaker ( Larimichthys crocea), one of the most important marine fish species in China, can change its abdominal skin color when it is shifted from light to dark or from dark to light, providing us an opportunity of investigating the molecular responding mechanism of teleost in light stress. The gene expression profile of fish under light stress is rarely documented. In this research, the transcriptome profiles of the abdominal skin of L. crocea exposed to light or dark for 0 h, 0.5 h and 2 h were produced by next-generation sequencing (NGS). The cluster results demonstrated that stress period, rather than light intensity ( e.g., light or dark), is the major influencing factor. Differently expressed genes (DEGs) were identified between 0 h and 0.5 h groups, between 0 h and 2 h groups, between 0.5 h light and 0.5 h dark, and between 2 h light and 2 h dark, respectively. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation revealed that the genes relating to immunity, energy metabolism, and cytoskeletal protein binding were significantly enriched. The detailed analysis of transcriptome profiles also revealed regular gene expression trends, indicating that the elaborate gene regulation networks underlined the molecular responses of the fish to light stress. This transcriptome analysis suggested that systematic and complicated regulatory cascades were functionally activated in response to external stress, and coloration change caused by light stress was mainly attributed to the change in the density of chromatophores for L. crocea. This study also provided valuable information for skin coloration or light stress research on other marine fish species.

Transcriptome-wide identification and expression profiles of the WRKY transcription factor family in Broomcorn millet (Panicum miliaceum L.).

PubMed

Yue, Hong; Wang, Meng; Liu, Siyan; Du, Xianghong; Song, Weining; Nie, Xiaojun

2016-05-10

WRKY genes, as the most pivotal transcription factors in plants, play the indispensable roles in regulating various physiological processes, including plant growth and development as well as in response to stresses. Broomcorn millet is one of the most important crops in drought areas worldwide. However, the WRKY gene family in broomcorn millet remains unknown. A total of 32 PmWRKY genes were identified in this study using computational prediction method. Structural analysis found that PmWRKY proteins contained a highly conserved motif WRKYGQK and two common variant motifs, namely WRKYGKK and WRKYGEK. Phylogenetic analysis of PmWRKYs together with the homologous genes from the representative species could classify them into three groups, with the number of 1, 15, and 16, respectively. Finally, the transcriptional profiles of these 32 PmWRKY genes in various tissues or under different abiotic stresses were systematically investigated using qRT-PCR analysis. Results showed that the expression level of 22 PmWRKY genes varied significantly under one or more abiotic stress treatments, which could be defined as abiotic stress-responsive genes. This was the first study to identify the organization and transcriptional profiles of PmWRKY genes, which not only facilitates the functional analysis of the PmWRKY genes, and also lays the foundation to reveal the molecular mechanism of stress tolerance in this important crop.

High-Throughput Sequencing Reveals Principles of Adeno-Associated Virus Serotype 2 Integration

PubMed Central

Janovitz, Tyler; Klein, Isaac A.; Oliveira, Thiago; Mukherjee, Piali; Nussenzweig, Michel C.; Sadelain, Michel

2013-01-01

Viral integrations are important in human biology, yet genome-wide integration profiles have not been determined for many viruses. Adeno-associated virus (AAV) infects most of the human population and is a prevalent gene therapy vector. AAV integrates into the human genome with preference for a single locus, termed AAVS1. However, the genome-wide integration of AAV has not been defined, and the principles underlying this recombination remain unclear. Using a novel high-throughput approach, integrant capture sequencing, nearly 12 million AAV junctions were recovered from a human cell line, providing five orders of magnitude more data than were previously available. Forty-five percent of integrations occurred near AAVS1, and several thousand novel integration hotspots were identified computationally. Most of these occurred in genes, with dozens of hotspots targeting known oncogenes. Viral replication protein binding sites (RBS) and transcriptional activity were major factors favoring integration. In a first for eukaryotic viruses, the data reveal a unique asymmetric integration profile with distinctive directional orientation of viral genomes. These studies provide a new understanding of AAV integration biology through the use of unbiased high-throughput data acquisition and bioinformatics. PMID:23720718

Improved CO sub 2 enhanced oil recovery -- Mobility control by in-situ chemical precipitation

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

Ameri, S.; Aminian, K.; Wasson, J.A.

1991-06-01

The overall objective of this study has been to evaluate the feasibility of chemical precipitation to improve CO{sub 2} sweep efficiency and mobility control. The laboratory experiments have indicated that carbonate precipitation can alter the permeability of the core samples under reservoir conditions. Furthermore, the relative permeability measurements have revealed that precipitation reduces the gas permeability in favor of liquid permeability. This indicates that precipitation is occurring preferentially in the larger pores. Additional experimental work with a series of connected cores have indicated that the permeability profile can be successfully modified. However, Ph control plays a critical role in propagationmore » of the chemical precipitation reaction. A numerical reservoir model has been utilized to evaluate the effects of permeability heterogeneity and permeability modification on the CO{sub 2} sweep efficiency. The computer simulation results indicate that the permeability profile modification can significantly enhance CO{sub 2} vertical and horizontal sweep efficiencies. The scoping studies with the model have further revealed that only a fraction of high permeability zones need to be altered to achieve sweep efficiency enhancement. 64 refs., 30 figs., 16 tabs.« less

Proteomics reveals the effects of sustained weight loss on the human plasma proteome.

PubMed

Geyer, Philipp E; Wewer Albrechtsen, Nicolai J; Tyanova, Stefka; Grassl, Niklas; Iepsen, Eva W; Lundgren, Julie; Madsbad, Sten; Holst, Jens J; Torekov, Signe S; Mann, Matthias

2016-12-22

Sustained weight loss is a preferred intervention in a wide range of metabolic conditions, but the effects on an individual's health state remain ill-defined. Here, we investigate the plasma proteomes of a cohort of 43 obese individuals that had undergone 8 weeks of 12% body weight loss followed by a year of weight maintenance. Using mass spectrometry-based plasma proteome profiling, we measured 1,294 plasma proteomes. Longitudinal monitoring of the cohort revealed individual-specific protein levels with wide-ranging effects of losing weight on the plasma proteome reflected in 93 significantly affected proteins. The adipocyte-secreted SERPINF1 and apolipoprotein APOF1 were most significantly regulated with fold changes of -16% and +37%, respectively (P < 10 -13 ), and the entire apolipoprotein family showed characteristic differential regulation. Clinical laboratory parameters are reflected in the plasma proteome, and eight plasma proteins correlated better with insulin resistance than the known marker adiponectin. Nearly all study participants benefited from weight loss regarding a ten-protein inflammation panel defined from the proteomics data. We conclude that plasma proteome profiling broadly evaluates and monitors intervention in metabolic diseases. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

Characterising the latent structure and organisation of self-reported thoughts, feelings and behaviours in adolescents and young adults

PubMed Central

Neufeld, Sharon; Jones, Peter B.; Fonagy, Peter; Bullmore, Edward T.; Dolan, Raymond J.; Moutoussis, Michael; Toseeb, Umar; Goodyer, Ian M.

2017-01-01

Little is known about the underlying relationships between self-reported mental health items measuring both positive and negative emotional and behavioural symptoms at the population level in young people. Improved measurement of the full range of mental well-being and mental illness may aid in understanding the aetiological substrates underlying the development of both mental wellness as well as specific psychiatric diagnoses. A general population sample aged 14 to 24 years completed self-report questionnaires on anxiety, depression, psychotic-like symptoms, obsessionality and well-being. Exploratory and confirmatory factor models for categorical data and latent profile analyses were used to evaluate the structure of both mental wellness and illness items. First order, second order and bifactor structures were evaluated on 118 self-reported items obtained from 2228 participants. A bifactor solution was the best fitting latent variable model with one general latent factor termed ‘distress’ and five ‘distress independent’ specific factors defined as self-confidence, antisocial behaviour, worry, aberrant thinking, and mood. Next, six distinct subgroups were derived from a person-centred latent profile analysis of the factor scores. Finally, concurrent validity was assessed using information on hazardous behaviours (alcohol use, substance misuse, self-harm) and treatment for mental ill health: both discriminated between the latent traits and latent profile subgroups. The findings suggest a complex, multidimensional mental health structure in the youth population rather than the previously assumed first or second order factor structure. Additionally, the analysis revealed a low hazardous behaviour/low mental illness risk subgroup not previously described. Population sub-groups show greater validity over single variable factors in revealing mental illness risks. In conclusion, our findings indicate that the structure of self reported mental health is multidimensional in nature and uniquely finds improved prediction to mental illness risk within person-centred subgroups derived from the multidimensional latent traits. PMID:28403164

Characterising the latent structure and organisation of self-reported thoughts, feelings and behaviours in adolescents and young adults.

PubMed

St Clair, Michelle C; Neufeld, Sharon; Jones, Peter B; Fonagy, Peter; Bullmore, Edward T; Dolan, Raymond J; Moutoussis, Michael; Toseeb, Umar; Goodyer, Ian M

2017-01-01

Little is known about the underlying relationships between self-reported mental health items measuring both positive and negative emotional and behavioural symptoms at the population level in young people. Improved measurement of the full range of mental well-being and mental illness may aid in understanding the aetiological substrates underlying the development of both mental wellness as well as specific psychiatric diagnoses. A general population sample aged 14 to 24 years completed self-report questionnaires on anxiety, depression, psychotic-like symptoms, obsessionality and well-being. Exploratory and confirmatory factor models for categorical data and latent profile analyses were used to evaluate the structure of both mental wellness and illness items. First order, second order and bifactor structures were evaluated on 118 self-reported items obtained from 2228 participants. A bifactor solution was the best fitting latent variable model with one general latent factor termed 'distress' and five 'distress independent' specific factors defined as self-confidence, antisocial behaviour, worry, aberrant thinking, and mood. Next, six distinct subgroups were derived from a person-centred latent profile analysis of the factor scores. Finally, concurrent validity was assessed using information on hazardous behaviours (alcohol use, substance misuse, self-harm) and treatment for mental ill health: both discriminated between the latent traits and latent profile subgroups. The findings suggest a complex, multidimensional mental health structure in the youth population rather than the previously assumed first or second order factor structure. Additionally, the analysis revealed a low hazardous behaviour/low mental illness risk subgroup not previously described. Population sub-groups show greater validity over single variable factors in revealing mental illness risks. In conclusion, our findings indicate that the structure of self reported mental health is multidimensional in nature and uniquely finds improved prediction to mental illness risk within person-centred subgroups derived from the multidimensional latent traits.

Metabolic and transcriptomic signatures of rice floral organs reveal sugar starvation as a factor in reproductive failure under heat and drought stress.

PubMed

Li, Xia; Lawas, Lovely M F; Malo, Richard; Glaubitz, Ulrike; Erban, Alexander; Mauleon, Ramil; Heuer, Sigrid; Zuther, Ellen; Kopka, Joachim; Hincha, Dirk K; Jagadish, Krishna S V

2015-10-01

Heat and drought stress are projected to become major challenges to sustain rice (Oryza sativa L.) yields with global climate change. Both stresses lead to yield losses when they coincide with flowering. A significant knowledge gap exists in the mechanistic understanding of the responses of rice floral organs that determine reproductive success under stress. Our work connects the metabolomic and transcriptomic changes in anthers, pistils before pollination and pollinated pistils in a heat-tolerant (N22) and a heat-sensitive (Moroberekan) cultivar. Systematic analysis of the floral organs revealed contrasts in metabolic profiles across anthers and pistils. Constitutive metabolic markers were identified that can define reproductive success in rice under stress. Six out of nine candidate metabolites identified by intersection analysis of stressed anthers were differentially accumulated in N22 compared with Moroberekan under non-stress conditions. Sugar metabolism was identified to be the crucial metabolic and transcriptional component that differentiated floral organ tolerance or susceptibility to stress. While susceptible Moroberekan specifically showed high expression of the Carbon Starved Anthers (CSA) gene under combined heat and drought, tolerant N22 responded with high expression of genes encoding a sugar transporter (MST8) and a cell wall invertase (INV4) as markers of high sink strength. © 2015 John Wiley & Sons Ltd.

Hey hey hey hey, it was the DNA

NASA Astrophysics Data System (ADS)

Williams, Martin A. K.

2016-05-01

The investigation of the emergence of spatial patterning in the density profiles of the individual elements of multicomponent systems was perhaps first popularised in a biophysical context by Turing’s work on embryogenesis in 1952. How molecular-scale properties transpire to produce patterns at larger scales continues to fascinate today. Now a model DNA-nanotube system, whose assemblies have been reported recently by Glaser et al (2016 New J. Phys. 18 055001), promises to reveal insights by allowing the mechanical properties of the underlying macromolecular entities to be controlled independently of their chemical nature.

Fast Faraday fading of long range satellite signals.

NASA Technical Reports Server (NTRS)

Heron, M. L.

1972-01-01

20 MHz radio signals have been received during the day from satellite Beacon-B when it was below the optical horizon by using a bank of narrow filters to improve the signal to noise ratio. The Faraday fading rate becomes constant, under these conditions, at a level determined by the plasma frequency just below the F-layer peak. Variations in the Faraday fading rate reveal fluctuations in the electron density near the peak, while the rate of attaining the constant level depends on the shape of the electron density profile.

Alterations in the lenticular protein profile in experimental selenite-induced cataractogenesis and prevention by ellagic acid.

PubMed

Sakthivel, Muniyan; Geraldine, Pitchairaj; Thomas, Philip A

2011-08-01

Accumulating evidence suggests that oxidative stress underlies age-related formation of cataract, and that antioxidants retard cataractogenesis. This study aimed to evaluate whether ellagic acid, a natural polyphenol with antioxidant properties, prevents alterations in the lenticular protein profile in an experimental model of selenite cataract. Alterations in lenticular protein were determined by two-dimensional electrophoresis (2DE) and image analysis. Eluted αA-crystallin spots were analyzed by mass spectrometry. Western blot analysis was also performed to confirm the differential expression of certain crystallins and cytoskeletal proteins. In cataractous lenses, 2DE and image analysis revealed approximately 45 and 60 prominent spots in soluble and insoluble protein fractions respectively. Analysis of the pI and molecular weight of protein spots revealed differences in the expression of crystallin proteins in soluble and insoluble fractions. Western blot analysis confirmed changes in the expression of αA- and βB1- crystallins in both soluble and insoluble protein fractions, while mass spectrometry confirmed the degradation of αA-crystallin in selenite cataractous lenses. Western blot analysis also confirmed the occurrence of altered expression of certain cytoskeletal proteins in insoluble fractions. However, the lenticular protein profile in lenses from selenite-challenged, ellagic acid-treated rats was essentially similar to that noted in lenses from normal rats. The present study confirms the importance of structural and cytoskeletal proteins in the maintenance of lenticular transparency; the results also suggest that ellagic acid prevents lenticular protein alterations induced by selenite in an experimental setting.

Genome-wide identification and expression profile analysis of the NAC transcription factor family during abiotic and biotic stress in woodland strawberry

PubMed Central

Qi, Yanxiang; Liu, Xiaomei; Pu, Jinji

2018-01-01

The NAC transcription factors involved plant development and response to various stress stimuli. However, little information is available concerning the NAC family in the woodland strawberry. Herein, 37 NAC genes were identified from the woodland strawberry genome and were classified into 13 groups based on phylogenetic analysis. And further analyses of gene structure and conserved motifs showed closer relationship of them in every subgroup. Quantitative real-time PCR evaluation different tissues revealed distinct spatial expression profiles of the FvNAC genes. The comprehensive expression of FvNAC genes revealed under abiotic stress (cold, heat, drought, salt), signal molecule treatments (H2O2, ABA, melatonin, rapamycin), biotic stress (Colletotrichum gloeosporioides and Ralstonia solanacearum). Expression profiles derived from quantitative real-time PCR suggested that 5 FvNAC genes responded dramatically to the various abiotic and biotic stresses, indicating their contribution to abiotic and biotic stresses resistance in woodland strawberry. Interestingly, FvNAC genes showed greater extent responded to the cold treatment than other abiotic stress, and H2O2 exhibited a greater response than ABA, melatonin, and rapamycin. For biotic stresses, 3 FvNAC genes were up-regulated during infection with C. gloeosporioides, while 6 FvNAC genes were down-regulated during infection with R. solanacearum. In conclusion, this study identified candidate FvNAC genes to be used for the genetic improvement of abiotic and biotic stress tolerance in woodland strawberry. PMID:29897926

Principal component analysis for the comparison of metabolic profiles from human rectal cancer biopsies and colorectal xenografts using high-resolution magic angle spinning 1H magnetic resonance spectroscopy

PubMed Central

Seierstad, Therese; Røe, Kathrine; Sitter, Beathe; Halgunset, Jostein; Flatmark, Kjersti; Ree, Anne H; Olsen, Dag Rune; Gribbestad, Ingrid S; Bathen, Tone F

2008-01-01

Background This study was conducted in order to elucidate metabolic differences between human rectal cancer biopsies and colorectal HT29, HCT116 and SW620 xenografts by using high-resolution magnetic angle spinning (MAS) magnetic resonance spectroscopy (MRS) and for determination of the most appropriate human rectal xenograft model for preclinical MR spectroscopy studies. A further aim was to investigate metabolic changes following irradiation of HT29 xenografts. Methods HR MAS MRS of tissue samples from xenografts and rectal biopsies were obtained with a Bruker Avance DRX600 spectrometer and analyzed using principal component analysis (PCA) and partial least square (PLS) regression analysis. Results and conclusion HR MAS MRS enabled assignment of 27 metabolites. Score plots from PCA of spin-echo and single-pulse spectra revealed separate clusters of the different xenografts and rectal biopsies, reflecting underlying differences in metabolite composition. The loading profile indicated that clustering was mainly based on differences in relative amounts of lipids, lactate and choline-containing compounds, with HT29 exhibiting the metabolic profile most similar to human rectal cancers tissue. Due to high necrotic fractions in the HT29 xenografts, radiation-induced changes were not detected when comparing spectra from untreated and irradiated HT29 xenografts. However, PLS calibration relating spectral data to the necrotic fraction revealed a significant correlation, indicating that necrotic fraction can be assessed from the MR spectra. PMID:18439252

Single cell gene expression profiling in Alzheimer's disease.

PubMed

Ginsberg, Stephen D; Che, Shaoli; Counts, Scott E; Mufson, Elliott J

2006-07-01

Development and implementation of microarray techniques to quantify expression levels of dozens to hundreds to thousands of transcripts simultaneously within select tissue samples from normal control subjects and neurodegenerative diseased brains has enabled scientists to create molecular fingerprints of vulnerable neuronal populations in Alzheimer's disease (AD) and related disorders. A goal is to sample gene expression from homogeneous cell types within a defined region without potential contamination by expression profiles of adjacent neuronal subpopulations and nonneuronal cells. The precise resolution afforded by single cell and population cell RNA analysis in combination with microarrays and real-time quantitative polymerase chain reaction (qPCR)-based analyses allows for relative gene expression level comparisons across cell types under different experimental conditions and disease progression. The ability to analyze single cells is an important distinction from global and regional assessments of mRNA expression and can be applied to optimally prepared tissues from animal models of neurodegeneration as well as postmortem human brain tissues. Gene expression analysis in postmortem AD brain regions including the hippocampal formation and neocortex reveals selectively vulnerable cell types share putative pathogenetic alterations in common classes of transcripts, for example, markers of glutamatergic neurotransmission, synaptic-related markers, protein phosphatases and kinases, and neurotrophins/neurotrophin receptors. Expression profiles of vulnerable regions and neurons may reveal important clues toward the understanding of the molecular pathogenesis of various neurological diseases and aid in identifying rational targets toward pharmacotherapeutic interventions for progressive, late-onset neurodegenerative disorders such as mild cognitive impairment (MCI) and AD.

Identification of basic/helix-loop-helix transcription factors reveals candidate genes involved in anthocyanin biosynthesis from the strawberry white-flesh mutant.

PubMed

Zhao, Fengli; Li, Gang; Hu, Panpan; Zhao, Xia; Li, Liangjie; Wei, Wei; Feng, Jiayue; Zhou, Houcheng

2018-02-09

As the second largest transcription factor family in plant, the basic helix-loop-helix (bHLH) transcription factor family, characterized by the conserved bHLH domain, plays a central regulatory role in many biological process. However, the bHLH transcription factor family of strawberry has not been systematically identified, especially for the anthocyanin biosynthesis. Here, we identified a total of 113 bHLH transcription factors and described their chromosomal distribution and bioinformatics for the diploid woodland strawberry Fragaria vesca. In addition, transcription profiles of 113 orthologous bHLH genes from various tissues were analyzed for the cultivar 'Benihoppe', its white-flesh mutant 'Xiaobai', and the 'Snow Princess' from their fruit development to the ripening, as well as those under either the ABA or Eth treatment. Both the RT-PCR and qRT-PCR results show that seven selected FabHLH genes (FabHLH17, FabHLH25, FabHLH27, FabHLH29, FabHLH40, FabHLH80, FabHLH98) are responsive to the fruit anthocyanin biosynthesis and hormone signaling according to transcript profiles where three color modes are observed for strawberry's fruit skin and flesh. Further, prediction for the protein interaction network reveals that four bHLHs (FabHLH25, FabHLH29, FabHLH80, FabHLH98) are involved in the fruit anthocyanin biosynthesis and hormone signaling transduction. These bioinformatics and expression profiles provide a good basis for a further investigation of strawberry bHLH genes.

The glacimarine sediment budget of the Nares Strait-Petermann Fjord area since the Last Glacial Maximum

NASA Astrophysics Data System (ADS)

Jakobsson, M.; Hogan, K.; Mayer, L. A.; Mix, A. C.; Nielsen, T.; Kamla, E.; Stranne, C.; Eriksson, B.; Jerram, K.

2016-12-01

During the Petermann 2015 Expedition of the Swedish icebreaker Oden more than 6500 line-km of high-resolution chirp sub-bottom profiles (2-7 kHz) were acquired in Petermann Fjord and Nares Strait in the area immediately outside of the fjord. The sub-bottom profiles reveal a highly-variable distribution of post-glacial sediment that appears to be largely controlled by the rugged relief of the underlying bedrock. Sediment thicknesses are between 0-60 m above bedrock and comprise predominantly acoustically-stratified, homogeneous to transparent acoustic facies. In Petermann Fjord itself unlithified sediment cover typically comprises two units: an underlying acoustically-transparent unit overlain by an acoustically-stratified unit. Both of these units are conformable over scoured and fairly flat bedrock terrain; small basins are present only locally. Outside of the fjord are a few local sedimentary basins containing up to 40 m of stratified basin-fill deposits, and several areas of stacked mass-flow deposits. Glacial lineations both in the fjord and Nares Strait are formed in an acoustically-homogenous unit that underlies stratified and transparent units. In addition to the sub-bottom profiles, approximately 780 line-km of 2D seismic reflection profiles were acquired using an airgun (210 cu in.) and a 300-m long streamer. These profiles have allowed us to map full unlithified sediment thicknesses down to basement in the area. Here we present the results of this mapping and we calculate the volumes of a prominent grounding-zone wedge at the mouth of Petermann Fjord, and smaller GZWs in Kennedy Channel. These features demarcate former still-stand positions of grounded ice retreating through this system, both towards the present-day grounding line of Petermann Glacier and southwards through Nares Strait. Post-glacial sediment volumes are also calculated and the sedimentary processes responsible for their distribution examined. These data, when combined with chronological information, will provide sediment fluxes through the Petermann system and help us to identify how the system has responded to a past global warming event, namely the last deglaciation. This is particularly important in light of the recent thinning and acceleration of NW Greenland's marine-terminating outlet glaciers at present.

Untargeted mass spectrometry-based metabolomic profiling of pleural effusions: fatty acids as novel cancer biomarkers for malignant pleural effusions.

PubMed

Lam, Ching-Wan; Law, Chun-Yiu

2014-09-05

Untargeted mass spectrometry-based metabolomic profiling is a powerful analytical method used for broad-spectrum identification and quantification of metabolites in biofluids in human health and disease states. In this study, we exploit metabolomic profiling for cancer biomarker discovery for diagnosis of malignant pleural effusions. We envisage the result will be clinically useful since currently there are no cancer biomarkers that are accurate enough for the diagnosis of malignant pleural effusions. Metabolomes of 32 malignant pleural effusions from lung cancer patients and 18 benign effusions from patients with pulmonary tuberculosis were analyzed using reversed-phase liquid chromatography tandem mass spectrometry (LC-MS/MS) using AB SCIEX TripleTOF 5600. MS spectra were analyzed using XCMS, PeakView, and LipidView. Metabolome-Wide Association Study (MWAS) was performed by Receiver Operating Characteristic Curve Explorer and Tester (ROCCET). Insignificant markers were filtered out using a metabolome-wide significance level (MWSL) with p-value < 2 × 10(-5) for t test. Only compounds in Human Metabolome Database (HMDB) will be used as cancer biomarkers. ROCCET analysis of ESI positive and negative MS spectra revealed free fatty acid (FFA) 18:1 (oleic acid) had the largest area-under-ROC of 0.96 (95% CI = 0.87-1.00) in malignant pleural effusions. Using a ratio of FFA 18:1-to-ceramide (d18:1/16:0), the area-under-ROC was further increased to 0.99 (95% CI = 0.91-1.00) with sensitivity 93.8% and specificity 100.0%. Using untargeted metabolomic profiling, the diagnostic cancer biomarker with the largest area-under-ROC can be determined objectively. This lipogenic phenotype could be explained by overexpression of fatty acid synthase (FASN) in cancer cells. The diagnostic performance of FFA 18:1-to-ceramide (d18:1/16:0) ratio supports its use for diagnosis of malignant pleural effusions.

Metabolite profiling and transcript analysis reveal specificities in the response of a berry derived cell culture to abiotic stresses

PubMed Central

Ayenew, Biruk; Degu, Asfaw; Manela, Neta; Perl, Avichai; Shamir, Michal O.; Fait, Aaron

2015-01-01

As climate changes, there is a need to understand the expected effects on viticulture. In nature, stresses exist in a combined manner, hampering the elucidation of the effect of individual cues on grape berry metabolism. Cell suspension culture originated from pea-size Gamy Red grape berry was used to harness metabolic response to high light (HL; 2500 μmol m-2s-1), high temperature (HT; 40°C) and their combination in comparison to 25°C and 100 μmol m-2s-1 under controlled condition. When LC–MS and GC–MS based metabolite profiling was implemented and integrated with targeted RT-qPCR transcript analysis specific responses were observed to the different cues. HL enhanced polyphenol metabolism while HT and its combination with HL induced amino acid and organic acid metabolism with additional effect on polyphenols. The trend of increment in TCA cycle genes like ATCs, ACo1, and IDH in the combined treatment might support the observed increment in organic acids, GABA shunt, and their derivatives. The apparent phenylalanine reduction with polyphenol increment under HL suggests enhanced fueling of the precursor toward the downstream phenylpropanoid pathway. In the polyphenol metabolism, a differential pattern of expression of flavonoid 3′,5′ hydroxylase and flavonoid 3′ hydroxylase was observed under high light (HL) and combined cues which were accompanied by characteristic metabolite profiles. HT decreased glycosylated cyanidin and peonidin forms while the combined cues increased acetylated and coumarylated peonidin forms. Transcription factors regulating anthocyanin metabolism and their methylation, MYB, OMT, UFGT, and DFR, were expressed differentially among the treatments, overall in agreement with the metabolite profiles. Taken together these data provide insights into the coordination of central and secondary metabolism in relation to multiple abiotic stresses. PMID:26442042

Exercise motivation and nonspecific back pain: A comparison of patients and nonpatients.

PubMed

Kleinert, Jens; Ott, Ida; Mierswa, Tobias; Levenig, Claudia G; Wenge, Kerstin; Hasenbring, Monika; Kellmann, Michael

2017-08-01

Motivation is a key variable to consider during exercise or exercise therapy of individuals with back pain. Based on organismic integration theory, this study aims to improve the understanding of exercise motivation in patients and nonpatients by evaluating the relationships between typical motivational profiles and personal characteristics, therapy parameters and pain related variables. One hundred nine women and 145 men with back pain (mean age 33.3 years; 31.9% currently under the care of a physician) involved in some kind of exercise for current nonspecific back pain voluntarily participated in this study. An adapted version of the Behavioral Regulation in Sport Questionnaire was used to measure exercise motivation. Furthermore, data on pain, disability status, level of sport activity, body concept, and the type of treatment or exercise were gathered. Autonomous forms of regulation were most prevalent among subjects. Of 4 motivational profiles found, 2 showed a positive pattern (29.1% highly motivated individuals, 21.7% autonomously convinced individuals), and 2 showed a more negative pattern (19.7% controlled convinced individuals, 29.5% less motivated individuals). Relationships between profiles and age, body concept, involvement in sport competition, and type of exercise were found. The different motivational profiles respectively reveal specific practical relevance. In particular, the controlled convinced pattern is supposed to be more maladaptive than all other profiles. The insights provided by this study supports the development of motivation-oriented treatments based on the assessment of individuals' motivational profiles. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Analysis of hepatic transcript profile and plasma lipid profile in early lactating dairy cows fed grape seed and grape marc meal extract.

PubMed

Gessner, Denise K; Winkler, Anne; Koch, Christian; Dusel, Georg; Liebisch, Gerhard; Ringseis, Robert; Eder, Klaus

2017-03-23

It was recently reported that dairy cows fed a polyphenol-rich grape seed and grape marc meal extract (GSGME) during the transition period had an increased milk yield, but the underlying reasons remained unclear. As polyphenols exert a broad spectrum of metabolic effects, we hypothesized that feeding of GSGME influences metabolic pathways in the liver which could account for the positive effects of GSGME in dairy cows. In order to identify these pathways, we performed genome-wide transcript profiling in the liver and lipid profiling in plasma of dairy cows fed GSGME during the transition period at 1 week postpartum. Transcriptomic analysis of the liver revealed 207 differentially expressed transcripts, from which 156 were up- and 51 were down-regulated, between cows fed GSGME and control cows. Gene set enrichment analysis of the 155 up-regulated mRNAs showed that the most enriched gene ontology (GO) biological process terms were dealing with cell cycle regulation and the most enriched Kyoto Encyclopedia of Genes and Genomes pathways were p53 signaling and cell cycle. Functional analysis of the 43 down-regulated mRNAs revealed that a great part of these genes are involved in endoplasmic reticulum (ER) stress-induced unfolded protein response (UPR) and inflammatory processes. Accordingly, protein folding, response to unfolded protein, unfolded protein binding, chemokine activity and heat shock protein binding were identified as one of the most enriched GO biological process and molecular function terms assigned to the down-regulated genes. In line with the transcriptomics data the plasma concentrations of the acute phase proteins serum amyloid A (SAA) and haptoglobin were reduced in cows fed GSGME compared to control cows. Lipidomic analysis of plasma revealed no differences in the concentrations of individual species of major and minor lipid classes between cows fed GSGME and control cows. Analysis of hepatic transcript profile in cows fed GSGME during the transition period at 1 week postpartum indicates that polyphenol-rich feed components are able to inhibit ER stress-induced UPR and inflammatory processes, both of which are considered to contribute to liver-associated diseases and to impair milk performance in dairy cows, in the liver of dairy cows during early lactation.

Brief report: Academic amotivation in light of the dark side of identity formation.

PubMed

Cannard, Christine; Lannegrand-Willems, Lyda; Safont-Mottay, Claire; Zimmermann, Grégoire

2016-02-01

The study intended to determine motivational profiles of first-year undergraduates and aimed their characterization in terms of identity processes. First, a cluster analysis revealed five motivational profiles: combined (i.e., high quantity of motivation, low amotivation); intrinsic (i.e., high intrinsic, low introjected and external regulation, low amotivation); "demotivated" (i.e., very low quantity of motivation and amotivation); extrinsic (i.e., high extrinsic and identified regulation and low intrinsic and amotivation); and "amotivated" (i.e., low intrinsic and identified, very high amotivation). Second, using Lebart's (2000) methodology, the most characteristic identity processes were listed for each motivational cluster. Demotivated and amotivated profiles were refined in terms of adaptive and maladaptive forms of exploration. Notably, exploration in breadth and in depth were underrepresented in demotivated students compared to the total sample; commitment and ruminative exploration were under and overrepresented respectively in amotivated students. Educational and clinical implications are proposed and future research is suggested. Copyright © 2015 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

The relation between rumination and temporal features of emotion intensity.

PubMed

Résibois, Maxime; Kalokerinos, Elise K; Verleysen, Gregory; Kuppens, Peter; Van Mechelen, Iven; Fossati, Philippe; Verduyn, Philippe

2018-03-01

Intensity profiles of emotional experience over time have been found to differ primarily in explosiveness (i.e. whether the profile has a steep vs. a gentle start) and accumulation (i.e. whether intensity increases over time vs. goes back to baseline). However, the determinants of these temporal features remain poorly understood. In two studies, we examined whether emotion regulation strategies are predictive of the degree of explosiveness and accumulation of negative emotional episodes. Participants were asked to draw profiles reflecting changes in the intensity of emotions elicited either by negative social feedback in the lab (Study 1) or by negative events in daily life (Study 2). In addition, trait (Study 1 & 2), and state (Study 2) usage of a set of emotion regulation strategies was assessed. Multilevel analyses revealed that trait rumination (especially the brooding component) was positively associated with emotion accumulation (Study 1 & 2). State rumination was also positively associated with emotion accumulation and, to a lesser extent, with emotion explosiveness (Study 2). These results provide support for emotion regulation theories, which hypothesise that rumination is a central mechanism underlying the maintenance of negative emotions.

Salt stress-induced changes in antioxidative defense system and proteome profiles of salt-tolerant and sensitive Frankia strains.

PubMed

Srivastava, Amrita; Singh, Anumeha; Singh, Satya S; Mishra, Arun K

2017-04-16

An appreciation of comparative microbial survival is most easily done while evaluating their adaptive strategies during stress. In the present experiment, antioxidative and whole cell proteome variations based on spectrophotometric analysis and SDS-PAGE and 2-dimensional gel electrophoresis have been analysed among salt-tolerant and salt-sensitive Frankia strains. This is the first report of proteomic basis underlying salt tolerance in these newly isolated Frankia strains from Hippophae salicifolia D. Don. Salt-tolerant strain HsIi10 shows higher increment in the contents of superoxide dismutase, catalase and ascorbate peroxidase as compared to salt-sensitive strain HsIi8. Differential 2-DGE profile has revealed differential profiles for salt-tolerant and salt-sensitive strains. Proteomic confirmation of salt tolerance in the strains with inbuilt efficiency of thriving in nitrogen-deficient locales is a definite advantage for these microbes. This would be equally beneficial for improvement of soil nitrogen status. Efficient protein regulation in HsIi10 suggests further exploration for its potential use as biofertilizer in saline soils.

Effects of sunlight exclusion on the profiles of monoterpene biosynthesis and accumulation in grape exocarp and mesocarp.

PubMed

Zhang, Erpeng; Chai, Fengmei; Zhang, Haohao; Li, Shaohua; Liang, Zhenchang; Fan, Peige

2017-12-15

Terpenes are important aroma compounds in table Muscat grape and wine, and their content in the berry can be affected by sunlight. The effects of sunlight exclusion on monoterpene profiles and relevant gene expression profiles in the exocarp and mesocarp of table Muscat grape 'Jingxiangyu' at different development stages were thoroughly surveyed by bagging pre-veraison clusters in special opaque boxes. The responses of monoterpenes to sunlight treatments varied in three types, representatively linalool, ocimene and geraniol. Linalool was the most sensitive compound to sunlight, whose biosynthesis was severely inhibited by sunlight exclusion and then was elevated by re-exposure. Ocimene and glycosylated geraniol showed a certain suppressive and stimulative responses to sunlight exclusion respectively. Further transcription analysis revealed that VvPNLinNer1, VvCSbOci, VvGT7 and VvGT14 genes were mainly responsible for monoterpene accumulation and sensitivity to sunlight. VvDXS2 and VvDXR genes were partially related to the differential accumulation of total terpenes under different sunlight treatments. Copyright © 2017 Elsevier Ltd. All rights reserved.

Analysis of temporal transcription expression profiles reveal links between protein function and developmental stages of Drosophila melanogaster.

PubMed

Wan, Cen; Lees, Jonathan G; Minneci, Federico; Orengo, Christine A; Jones, David T

2017-10-01

Accurate gene or protein function prediction is a key challenge in the post-genome era. Most current methods perform well on molecular function prediction, but struggle to provide useful annotations relating to biological process functions due to the limited power of sequence-based features in that functional domain. In this work, we systematically evaluate the predictive power of temporal transcription expression profiles for protein function prediction in Drosophila melanogaster. Our results show significantly better performance on predicting protein function when transcription expression profile-based features are integrated with sequence-derived features, compared with the sequence-derived features alone. We also observe that the combination of expression-based and sequence-based features leads to further improvement of accuracy on predicting all three domains of gene function. Based on the optimal feature combinations, we then propose a novel multi-classifier-based function prediction method for Drosophila melanogaster proteins, FFPred-fly+. Interpreting our machine learning models also allows us to identify some of the underlying links between biological processes and developmental stages of Drosophila melanogaster.

Joint small-angle X-ray and neutron scattering data analysis of asymmetric lipid vesicles

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

Eicher, Barbara; Heberle, Frederick A.; Marquardt, Drew T.

2017-02-28

Low- and high-resolution models describing the internal transbilayer structure of asymmetric lipid vesicles have been developed. These models can be used for the joint analysis of small-angle neutron and X-ray scattering data. The models describe the underlying scattering length density/electron density profiles either in terms of slabs or through the so-called scattering density profile, previously applied to symmetric lipid vesicles. Both models yield structural details of asymmetric membranes, such as the individual area per lipid, and the hydrocarbon thickness of the inner and outer bilayer leaflets. The scattering density profile model, however, comes at a cost of increased computational effortmore » but results in greater structural resolution, showing a slightly lower packing of lipids in the outer bilayer leaflet of ~120 nm diameter palmitoyloleoyl phosphatidylcholine (POPC) vesicles, compared to the inner leaflet. Here, analysis of asymmetric dipalmitoyl phosphatidylcholine/POPC vesicles did not reveal evidence of transbilayer coupling between the inner and outer leaflets at 323 K, i.e.above the melting transition temperature of the two lipids.« less

Classification and prediction of toxicity of chemicals using an automated phenotypic profiling of Caenorhabditis elegans.

PubMed

Gao, Shan; Chen, Weiyang; Zeng, Yingxin; Jing, Haiming; Zhang, Nan; Flavel, Matthew; Jois, Markandeya; Han, Jing-Dong J; Xian, Bo; Li, Guojun

2018-04-18

Traditional toxicological studies have relied heavily on various animal models to understand the effect of various compounds in a biological context. Considering the great cost, complexity and time involved in experiments using higher order organisms. Researchers have been exploring alternative models that avoid these disadvantages. One example of such a model is the nematode Caenorhabditis elegans. There are some advantages of C. elegans, such as small size, short life cycle, well defined genome, ease of maintenance and efficient reproduction. As these benefits allow large scale studies to be initiated with relative ease, the problem of how to efficiently capture, organize and analyze the resulting large volumes of data must be addressed. We have developed a new method for quantitative screening of chemicals using C. elegans. 33 features were identified for each chemical treatment. The compounds with different toxicities were shown to alter the phenotypes of C. elegans in distinct and detectable patterns. We found that phenotypic profiling revealed conserved functions to classify and predict the toxicity of different chemicals. Our results demonstrate the power of phenotypic profiling in C. elegans under different chemical environments.

Global gas chromatography/time-of-flight mass spectrometry (GC/TOFMS)-based metabonomic profiling of lyophilized human feces.

PubMed

Phua, Lee Cheng; Koh, Poh Koon; Cheah, Peh Yean; Ho, Han Kiat; Chan, Eric Chun Yong

2013-10-15

Gas chromatography mass spectrometry (GC/MS)-based fecal metabonomics represents a powerful systems biology approach for elucidating metabolic biomarkers of lower gastrointestinal tract (GIT) diseases. Unlike metabolic profiling of fecal water, the profiling of complete fecal material remains under-explored. Here, a gas chromatography/time-of-flight mass spectrometry (GC/TOFMS) method was developed and validated for the global metabonomic profiling of human feces. Fecal and fecal water metabotypes were also profiled and compared. Additionally, the unclear influence of blood in stool on the fecal metabotype was investigated unprecedentedly. Eighty milligram of lyophilized feces was ultrasonicated with 1mL of methanol:water (8:2) for 30min, followed by centrifugation, drying of supernatant, oximation and trimethylsilylation for 45min. Lyophilized feces demonstrated a more comprehensive metabolic coverage than fecal water, based on the number of chromatographic peaks. Principal component analysis (PCA) indicated occult blood (1mgHb/g feces) exerted a negligible effect on the fecal metabotype. Conversely, a unique metabotype related to feces spiked with gross blood (100mgHb/g feces) was revealed (PCA, R(2)X=0.837, Q(2)=0.794), confirming the potential confounding effect of gross GIT bleeding on the fecal metabotype. This pertinent finding highlights the importance of prudent interpretation of fecal metabonomic data, particularly in GIT diseases where bleeding is prevalent. Copyright © 2013 Elsevier B.V. All rights reserved.

Profiling Instructional Effectiveness to Reveal Its Relationship to Learning

ERIC Educational Resources Information Center

Kalender, Ilker

2014-01-01

The purpose of the present study is to define instructional profiles and investigate the relationship between these profiles and learning indicators such as end-of-semester grades and self-reported amount of learning. Instructional profiles were obtained using a segmentation method. Student ratings were used as indicators of instructional…

The marine atmospheric boundary layer under strong wind conditions: Organized turbulence structure and flux estimates by airborne measurements

NASA Astrophysics Data System (ADS)

Brilouet, Pierre-Etienne; Durand, Pierre; Canut, Guylaine

2017-02-01

During winter, cold air outbreaks take place in the northwestern Mediterranean sea. They are characterized by local strong winds (Mistral and Tramontane) which transport cold and dry continental air across a warmer sea. In such conditions, high values of surface sensible and latent heat flux are observed, which favor deep oceanic convection. The HyMeX/ASICS-MED field campaign was devoted to the study of these processes. Airborne measurements, gathered in the Gulf of Lion during the winter of 2013, allowed for the exploration of the mean and turbulent structure of the marine atmospheric boundary layer (MABL). A spectral analysis based on an analytical model was conducted on 181 straight and level runs. Profiles of characteristic length scales and sharpness parameter of the vertical wind spectrum revealed larger eddies along the mean wind direction associated with an organization of the turbulence field into longitudinal rolls. These were highlighted by boundary layer cloud bands on high-resolution satellite images. A one-dimensional description of the vertical exchanges is then a tricky issue. Since the knowledge of the flux profile throughout the entire MABL is essential for the estimation of air-sea exchanges, a correction of eddy covariance turbulent fluxes was developed taking into account the systematic and random errors due to sampling and data processing. This allowed the improvement of surface fluxes estimates, computed from the extrapolation of the stacked levels. A comparison between those surface fluxes and bulk fluxes computed at a moored buoy revealed considerable differences, mainly regarding the latent heat flux under strong wind conditions.

Circular RNAs play an important role in late-stage gastric cancer: Circular RNA expression profiles and bioinformatics analyses.

PubMed

Fang, Yantian; Ma, Minzhe; Wang, Jiangli; Liu, Xiaowen; Wang, Yanong

2017-06-01

Gastric cancer is one of the most common tumors of the digestive system. Here, analysis of the expression profiles of circular RNAs in advanced gastric adenocarcinoma and adjacent normal mucosa tissues revealed differential expression of 306 circular RNAs, among which 273 were predicted to exert regulatory effects on target microRNAs. The downstream pathway networks of circular RNA-microRNA were mapped and the node genes were identified. In particular, we found that the expression of hsa_circ_0058246 was elevated in tumor specimens of patients with poor clinical outcomes. Our collective findings indicate that circular RNAs play a critical role in gastric cancer tumorigenesis. Data from this study provide a new perspective on the molecular pathways underlying metastasis and recurrence of gastric cancer and highlight potential therapeutic targets that may contribute to more effective diagnosis and treatment of the disease.

Iterative local Gaussian clustering for expressed genes identification linked to malignancy of human colorectal carcinoma

PubMed Central

Wasito, Ito; Hashim, Siti Zaiton M; Sukmaningrum, Sri

2007-01-01

Gene expression profiling plays an important role in the identification of biological and clinical properties of human solid tumors such as colorectal carcinoma. Profiling is required to reveal underlying molecular features for diagnostic and therapeutic purposes. A non-parametric density-estimation-based approach called iterative local Gaussian clustering (ILGC), was used to identify clusters of expressed genes. We used experimental data from a previous study by Muro and others consisting of 1,536 genes in 100 colorectal cancer and 11 normal tissues. In this dataset, the ILGC finds three clusters, two large and one small gene clusters, similar to their results which used Gaussian mixture clustering. The correlation of each cluster of genes and clinical properties of malignancy of human colorectal cancer was analysed for the existence of tumor or normal, the existence of distant metastasis and the existence of lymph node metastasis. PMID:18305825

Iterative local Gaussian clustering for expressed genes identification linked to malignancy of human colorectal carcinoma.

PubMed

Wasito, Ito; Hashim, Siti Zaiton M; Sukmaningrum, Sri

2007-12-30

Gene expression profiling plays an important role in the identification of biological and clinical properties of human solid tumors such as colorectal carcinoma. Profiling is required to reveal underlying molecular features for diagnostic and therapeutic purposes. A non-parametric density-estimation-based approach called iterative local Gaussian clustering (ILGC), was used to identify clusters of expressed genes. We used experimental data from a previous study by Muro and others consisting of 1,536 genes in 100 colorectal cancer and 11 normal tissues. In this dataset, the ILGC finds three clusters, two large and one small gene clusters, similar to their results which used Gaussian mixture clustering. The correlation of each cluster of genes and clinical properties of malignancy of human colorectal cancer was analysed for the existence of tumor or normal, the existence of distant metastasis and the existence of lymph node metastasis.

Metabolomic analysis of avocado fruits by GC-APCI-TOF MS: effects of ripening degrees and fruit varieties.

PubMed

Hurtado-Fernández, E; Pacchiarotta, T; Mayboroda, O A; Fernández-Gutiérrez, A; Carrasco-Pancorbo, A

2015-01-01

In order to investigate avocado fruit ripening, nontargeted GC-APCI-TOF MS metabolic profiling analyses were carried out. Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were used to explore the metabolic profiles from fruit samples of 13 varieties at two different ripening degrees. Mannoheptulose; pentadecylfuran; aspartic, malic, stearic, citric and pantothenic acids; mannitol; and β-sitosterol were some of the metabolites found as more influential for the PLS-DA model. The similarities among genetically related samples (putative mutants of "Hass") and their metabolic differences from the rest of the varieties under study have also been evaluated. The achieved results reveal new insights into avocado fruit composition and metabolite changes, demonstrating therefore the value of metabolomics as a functional genomics tool in characterizing the mechanism of fruit ripening development, a key developmental stage in most economically important fruit crops.

Genome-wide transcriptional profiling of human glioblastoma cells in response to ITE treatment.

PubMed

Kang, Bo; Zhou, Yanwen; Zheng, Min; Wang, Ying-Jie

2015-09-01

A ligand-activated transcription factor aryl hydrocarbon receptor (AhR) is recently revealed to play a key role in embryogenesis and tumorigenesis (Feng et al. [1], Safe et al. [2]) and 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) (Song et al. [3]) is an endogenous AhR ligand that possesses anti-tumor activity. In order to gain insights into how ITE acts via the AhR in embryogenesis and tumorigenesis, we analyzed the genome-wide transcriptional profiles of the following three groups of cells: the human glioblastoma U87 parental cells, U87 tumor sphere cells treated with vehicle (DMSO) and U87 tumor sphere cells treated with ITE. Here, we provide the details of the sample gathering strategy and show the quality controls and the analyses associated with our gene array data deposited into the Gene Expression Omnibus (GEO) under the accession code of GSE67986.

Effects of achievement contexts on the meaning structure of emotion words.

PubMed

Gentsch, Kornelia; Loderer, Kristina; Soriano, Cristina; Fontaine, Johnny R J; Eid, Michael; Pekrun, Reinhard; Scherer, Klaus R

2018-03-01

Little is known about the impact of context on the meaning of emotion words. In the present study, we used a semantic profiling instrument (GRID) to investigate features representing five emotion components (appraisal, bodily reaction, expression, action tendencies, and feeling) of 11 emotion words in situational contexts involving success or failure. We compared these to the data from an earlier study in which participants evaluated the typicality of features out of context. Profile analyses identified features for which typicality changed as a function of context for all emotion words, except contentment, with appraisal features being most frequently affected. Those context effects occurred for both hypothesised basic and non-basic emotion words. Moreover, both data sets revealed a four-dimensional structure. The four dimensions were largely similar (valence, power, arousal, and novelty). The results suggest that context may not change the underlying dimensionality but affects facets of the meaning of emotion words.

Evaluation of acoustic Doppler velocimetry (ADV) performance under various probe configurations

NASA Astrophysics Data System (ADS)

Liu, Da; Valyrakis, Manousos

2017-04-01

Acoustic Doppler velocimetry (ADV) is widely used as one of the most versatile and robust flow diagnostics tools for both laboratory and field studies across a range of research and applied themes spanning engineering eco-hydraulics and geomorphology. A range of specific ADV probes with varying specifications, are readily available for use by professionals and researchers. However, in practice using certain ADV equipment under certain default configurations can easily result in obtaining flow diagnostics that are non-representative of the real flow conditions. This appears to be true for most probes but even more those with which higher temporal resolution can be achieved - which many times is desired for assessing turbulence levels, amongst others. A preliminary examination revealed that there is a varying level of dependency on a number of the probes' configuration parameters, which even though detailed in the user manual, a definite guide for the user is lacking. Subsequently users of this equipment may end up underutilizing or using it in a manner that returns inaccurate results. There are little, if any, resources in obtaining a better understanding on how to use the probe effectively. To this goal a series of laboratory experiments are conducted, under the same open channel flow conditions, using a profiler (ADCP VectrinoII from Nortek®) aiming to cover the full range of probe configuration combinations that can be used in practice. For each experiment, single or multiple point measurements are taken to reconstruct velocity and turbulence intensity profiles. These are conducted at the same location (mid-channel) under the same flow conditions (referring to steady uniform flow and fully developed turbulence) for all probe configurations. In particular, the effect of tested parameters (including Range length, Range to fist cell, Sampling rate, Ping algorithm, Transmit pulse size and Cell size) on the sensitivity and accuracy of the obtained results is assessed. The signal to noise ratio (SNR) and the correlation of the measurement are used in evaluating the data quality, while a qualitative comparison of the resulting profiles for flow diagnostics is enabled using reference profiles obtained via a VectrinoI ADV (from Nortek®) and MicroADV (from Sontek®) respectively under the exactly same flow condition at the same location. These observations are important to identify its best configuration for a given probe towards improving the data quality and accuracy.

Psychiatric reactions to continuous traumatic stress: A Latent Profile Analysis of two Israeli samples.

PubMed

Itzhaky, Liat; Gelkopf, Mark; Levin, Yafit; Stein, Jacob Y; Solomon, Zahava

2017-10-01

Many individuals worldwide are exposed to continuous traumatic stress (CTS). However, the psychiatric sequela of CTS and the relevance of posttraumatic stress disorder (PTSD) diagnostic criteria in this situation have yet to be determined. Filling this gap, the present study assessed psychiatric reactions to CTS and the relationship between such reactions and functional impairment among two representative samples of adults exposed to ongoing shelling over 6 (n=387) and 9 years (n=468). Assessment included PTSD symptomatology (i.e., intrusion, avoidance, hyperarousal), anxiety, somatization, and depression. Profile categorization aimed to underscore variations in symptom clustering and severity, and determine whether or not a profile is dominated by PTSD symptoms. Latent Profile analyses (LPA) of sample I revealed four distinct symptoms profiles: (1) 'symptomatically resilient'; (2) 'symptomatically low-moderate'; (3) 'symptomatically moderate-high'; and (4) 'symptomatically overall high'. LPA of sample II revealed three distinct symptoms profiles: (1) 'symptomatically resilient'; (2) 'symptomatically low-moderate'; (3) "symptomatically moderate-high". Moreover, profile variation was implicated in dysfunction. Consistent with studies focusing on single trauma exposure, the findings revealed that the most prevalent profile was the symptomatically resilient, indicating that most people exposed to CTS seem to evince a scarce number of psychiatric symptoms. Moreover, reactions to CTS proved broader than the existing PTSD symptomatology. Examining symptom dominance and severity in relation to impairment and dysfunction, and clinical considerations are discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Metabolomics and transcriptomics profiles reveal the dysregulation of the tricarboxylic acid cycle and related mechanisms in prostate cancer.

PubMed

Shao, Yaping; Ye, Guozhu; Ren, Shancheng; Piao, Hai-Long; Zhao, Xinjie; Lu, Xin; Wang, Fubo; Ma, Wang; Li, Jia; Yin, Peiyuan; Xia, Tian; Xu, Chuanliang; Yu, Jane J; Sun, Yinghao; Xu, Guowang

2018-07-15

Genetic alterations drive metabolic reprograming to meet increased biosynthetic precursor and energy demands for cancer cell proliferation and survival in unfavorable environments. A systematic study of gene-metabolite regulatory networks and metabolic dysregulation should reveal the molecular mechanisms underlying prostate cancer (PCa) pathogenesis. Herein, we performed gas chromatography-mass spectrometry (GC-MS)-based metabolomics and RNA-seq analyses in prostate tumors and matched adjacent normal tissues (ANTs) to elucidate the molecular alterations and potential underlying regulatory mechanisms in PCa. Significant accumulation of metabolic intermediates and enrichment of genes in the tricarboxylic acid (TCA) cycle were observed in tumor tissues, indicating TCA cycle hyperactivation in PCa tissues. In addition, the levels of fumarate and malate were highly correlated with the Gleason score, tumor stage and expression of genes encoding related enzymes and were significantly related to the expression of genes involved in branched chain amino acid degradation. Using an integrated omics approach, we further revealed the potential anaplerotic routes from pyruvate, glutamine catabolism and branched chain amino acid (BCAA) degradation contributing to replenishing metabolites for TCA cycle. Integrated omics techniques enable the performance of network-based analyses to gain a comprehensive and in-depth understanding of PCa pathophysiology and may facilitate the development of new and effective therapeutic strategies. © 2018 UICC.

Physiological and Proteomics Analyses Reveal Low-Phosphorus Stress Affected the Regulation of Photosynthesis in Soybean.

PubMed

Chu, Shanshan; Li, Hongyan; Zhang, Xiangqian; Yu, Kaiye; Chao, Maoni; Han, Suoyi; Zhang, Dan

2018-06-06

Previous studies have revealed a significant genetic relationship between phosphorus (P)-efficiency and photosynthesis-related traits in soybean. In this study, we used proteome profiling in combination with expression analysis, biochemical investigations, and leaf ultrastructural analysis to identify the underlying physiological and molecular responses. The expression analysis and ultrastructural analysis showed that the photosynthesis key genes were decreased at transcript levels and the leaf mesophyll and chloroplast were severely damaged after low-P stress. Approximately 55 protein spots showed changes under low-P condition by mass spectrometry, of which 17 were involved in various photosynthetic processes. Further analysis revealed the depression of photosynthesis caused by low-P stress mainly involves the regulation of leaf structure, adenosine triphosphate (ATP) synthesis, absorption and transportation of CO₂, photosynthetic electron transport, production of assimilatory power, and levels of enzymes related to the Calvin cycle. In summary, our findings indicated that the existence of a stringent relationship between P supply and the genomic control of photosynthesis in soybean. As an important strategy to protect soybean photosynthesis, P could maintain the stability of cell structure, up-regulate the enzymes’ activities, recover the process of photosystem II (PSII), and induce the expression of low-P responsive genes and proteins.

Transcriptional profiling of Medicago truncatula under salt stress identified a novel CBF transcription factor MtCBF4 that plays an important role in abiotic stress responses

PubMed Central

2011-01-01

Background Salt stress hinders the growth of plants and reduces crop production worldwide. However, different plant species might possess different adaptive mechanisms to mitigate salt stress. We conducted a detailed pathway analysis of transcriptional dynamics in the roots of Medicago truncatula seedlings under salt stress and selected a transcription factor gene, MtCBF4, for experimental validation. Results A microarray experiment was conducted using root samples collected 6, 24, and 48 h after application of 180 mM NaCl. Analysis of 11 statistically significant expression profiles revealed different behaviors between primary and secondary metabolism pathways in response to external stress. Secondary metabolism that helps to maintain osmotic balance was induced. One of the highly induced transcription factor genes was successfully cloned, and was named MtCBF4. Phylogenetic analysis revealed that MtCBF4, which belongs to the AP2-EREBP transcription factor family, is a novel member of the CBF transcription factor in M. truncatula. MtCBF4 is shown to be a nuclear-localized protein. Expression of MtCBF4 in M. truncatula was induced by most of the abiotic stresses, including salt, drought, cold, and abscisic acid, suggesting crosstalk between these abiotic stresses. Transgenic Arabidopsis over-expressing MtCBF4 enhanced tolerance to drought and salt stress, and activated expression of downstream genes that contain DRE elements. Over-expression of MtCBF4 in M. truncatula also enhanced salt tolerance and induced expression level of corresponding downstream genes. Conclusion Comprehensive transcriptomic analysis revealed complex mechanisms exist in plants in response to salt stress. The novel transcription factor gene MtCBF4 identified here played an important role in response to abiotic stresses, indicating that it might be a good candidate gene for genetic improvement to produce stress-tolerant plants. PMID:21718548

Antimicrobial breakpoint estimation accounting for variability in pharmacokinetics.

PubMed

Bi, Goue Denis Gohore; Li, Jun; Nekka, Fahima

2009-06-26

Pharmacokinetic and pharmacodynamic (PK/PD) indices are increasingly being used in the microbiological field to assess the efficacy of a dosing regimen. In contrast to methods using MIC, PK/PD-based methods reflect in vivo conditions and are more predictive of efficacy. Unfortunately, they entail the use of one PK-derived value such as AUC or Cmax and may thus lead to biased efficiency information when the variability is large. The aim of the present work was to evaluate the efficacy of a treatment by adjusting classical breakpoint estimation methods to the situation of variable PK profiles. We propose a logical generalisation of the usual AUC methods by introducing the concept of "efficiency" for a PK profile, which involves the efficacy function as a weight. We formulated these methods for both classes of concentration- and time-dependent antibiotics. Using drug models and in silico approaches, we provide a theoretical basis for characterizing the efficiency of a PK profile under in vivo conditions. We also used the particular case of variable drug intake to assess the effect of the variable PK profiles generated and to analyse the implications for breakpoint estimation. Compared to traditional methods, our weighted AUC approach gives a more powerful PK/PD link and reveals, through examples, interesting issues about the uniqueness of therapeutic outcome indices and antibiotic resistance problems.

Cytokine profile of food-allergic post-liver transplant children is identified by high levels of IL-5 and low IL-10 secretion from patients' peripheral blood mononuclear cells.

PubMed

Nahum, Amit; Brener, Avivit; Granot, Ettie

2015-11-01

Severe allergic reaction to food following liver transplantation is a well-known phenomenon. However, the mechanisms underlying this phenomenon are not yet elucidated. This study aimed to reveal the nature of the immune response in post-transplanted allergic patients and compare them to non-allergic transplanted as well as allergic and non-allergic control subjects, with focus on cytokine milieu. Post-liver transplant patients with and without allergic reactions as well as food-allergic but otherwise healthy and healthy non-allergic control patients were recruited. We reviewed patient records and routine laboratory tests and assayed subjects' PBMCs, studying cytokine secretion profile in response to different stimuli. Post-transplant patients with food allergy showed a unique cytokine profile in response to various stimuli, with extremely elevated IL-5, low IL-10 secretion, and somewhat higher IFN-γ. T regulatory cell number was not significantly different among the groups of patients and controls. Immune response of food-allergic post-liver transplant patients is identified by a unique cytokine profile when compared to allergic but otherwise healthy individuals. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Global Analysis of Gene Expression Profiles in Physic Nut (Jatropha curcas L.) Seedlings Exposed to Salt Stress

PubMed Central

Wu, Pingzhi; Chen, Yaping; Li, Meiru; Jiang, Huawu; Wu, Guojiang

2014-01-01

Background Salt stress interferes with plant growth and production. Plants have evolved a series of molecular and morphological adaptations to cope with this abiotic stress, and overexpression of salt response genes reportedly enhances the productivity of various crops. However, little is known about the salt responsive genes in the energy plant physic nut (Jatropha curcas L.). Thus, excavate salt responsive genes in this plant are informative in uncovering the molecular mechanisms for the salt response in physic nut. Methodology/Principal Findings We applied next-generation Illumina sequencing technology to analyze global gene expression profiles of physic nut plants (roots and leaves) 2 hours, 2 days and 7 days after the onset of salt stress. A total of 1,504 and 1,115 genes were significantly up and down-regulated in roots and leaves, respectively, under salt stress condition. Gene ontology (GO) analysis of physiological process revealed that, in the physic nut, many “biological processes” were affected by salt stress, particular those categories belong to “metabolic process”, such as “primary metabolism process”, “cellular metabolism process” and “macromolecule metabolism process”. The gene expression profiles indicated that the associated genes were responsible for ABA and ethylene signaling, osmotic regulation, the reactive oxygen species scavenging system and the cell structure in physic nut. Conclusions/Significance The major regulated genes detected in this transcriptomic data were related to trehalose synthesis and cell wall structure modification in roots, while related to raffinose synthesis and reactive oxygen scavenger in leaves. The current study shows a comprehensive gene expression profile of physic nut under salt stress. The differential expression genes detected in this study allows the underling the salt responsive mechanism in physic nut with the aim of improving its salt resistance in the future. PMID:24837971

Global analysis of gene expression profiles in physic nut (Jatropha curcas L.) seedlings exposed to salt stress.

PubMed

Zhang, Lin; Zhang, Chao; Wu, Pingzhi; Chen, Yaping; Li, Meiru; Jiang, Huawu; Wu, Guojiang

2014-01-01

Salt stress interferes with plant growth and production. Plants have evolved a series of molecular and morphological adaptations to cope with this abiotic stress, and overexpression of salt response genes reportedly enhances the productivity of various crops. However, little is known about the salt responsive genes in the energy plant physic nut (Jatropha curcas L.). Thus, excavate salt responsive genes in this plant are informative in uncovering the molecular mechanisms for the salt response in physic nut. We applied next-generation Illumina sequencing technology to analyze global gene expression profiles of physic nut plants (roots and leaves) 2 hours, 2 days and 7 days after the onset of salt stress. A total of 1,504 and 1,115 genes were significantly up and down-regulated in roots and leaves, respectively, under salt stress condition. Gene ontology (GO) analysis of physiological process revealed that, in the physic nut, many "biological processes" were affected by salt stress, particular those categories belong to "metabolic process", such as "primary metabolism process", "cellular metabolism process" and "macromolecule metabolism process". The gene expression profiles indicated that the associated genes were responsible for ABA and ethylene signaling, osmotic regulation, the reactive oxygen species scavenging system and the cell structure in physic nut. The major regulated genes detected in this transcriptomic data were related to trehalose synthesis and cell wall structure modification in roots, while related to raffinose synthesis and reactive oxygen scavenger in leaves. The current study shows a comprehensive gene expression profile of physic nut under salt stress. The differential expression genes detected in this study allows the underling the salt responsive mechanism in physic nut with the aim of improving its salt resistance in the future.

Evaluating the Energy Recovery Potential of Nigerian Coals under Non-Isothermal Thermogravimetry

NASA Astrophysics Data System (ADS)

Bevan Nyakuma, Bemgba; Oladokun, Olagoke; Jauro, Aliyu; Damian Nyakuma, Denen

2017-07-01

This study investigated the fuel properties and energy recovery potential of two coal samples from Ihioma (IHM) and Ogboligbo (OGB) environs in Nigeria. The ultimate, proximate, and bomb calorimetric analyses of the coal were examined. Next, the rank classification and potential application of the coals were evaluated according to the ASTM standard D388. Lastly, thermal decomposition behaviour was examined by non-isothermal thermogravimetry (TG) under pyrolysis conditions from 30 - 900 °C. The results indicated IHM and OGB contain high proportions of combustible elements for potential thermal conversion. The higher heating value (HHV) of IHM was 20.37 MJ/kg whereas OGB was 16.33 MJ/kg. TG analysis revealed 55% weight loss for OGB and 76% for IHM. The residual mass was 23% for IHM and 44% for OGB. Based on the temperature profile characteristics (TPCs); Ton , Tmax , and Toff , IHM was more reactive than OGB due to its higher volatile matter (VM). Overall, results revealed the coals are Lignite (Brown) low-rank coals (LRCs) with potential for electric power generation.

Exploring candidate biomarkers for lung and prostate cancers using gene expression and flux variability analysis.

PubMed

Asgari, Yazdan; Khosravi, Pegah; Zabihinpour, Zahra; Habibi, Mahnaz

2018-02-19

Genome-scale metabolic models have provided valuable resources for exploring changes in metabolism under normal and cancer conditions. However, metabolism itself is strongly linked to gene expression, so integration of gene expression data into metabolic models might improve the detection of genes involved in the control of tumor progression. Herein, we considered gene expression data as extra constraints to enhance the predictive powers of metabolic models. We reconstructed genome-scale metabolic models for lung and prostate, under normal and cancer conditions to detect the major genes associated with critical subsystems during tumor development. Furthermore, we utilized gene expression data in combination with an information theory-based approach to reconstruct co-expression networks of the human lung and prostate in both cohorts. Our results revealed 19 genes as candidate biomarkers for lung and prostate cancer cells. This study also revealed that the development of a complementary approach (integration of gene expression and metabolic profiles) could lead to proposing novel biomarkers and suggesting renovated cancer treatment strategies which have not been possible to detect using either of the methods alone.

Alteration of the Alkaloid Profile in Genetically Modified Tobacco Reveals a Role of Methylenetetrahydrofolate Reductase in Nicotine N-Demethylation1[C][W][OA

PubMed Central

Hung, Chiu-Yueh; Fan, Longjiang; Kittur, Farooqahmed S.; Sun, Kehan; Qiu, Jie; Tang, She; Holliday, Bronwyn M.; Xiao, Bingguang; Burkey, Kent O.; Bush, Lowell P.; Conkling, Mark A.; Roje, Sanja; Xie, Jiahua

2013-01-01

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme of the tetrahydrofolate (THF)-mediated one-carbon (C1) metabolic network. This enzyme catalyzes the reduction of 5,10-methylene-THF to 5-methyl-THF. The latter donates its methyl group to homocysteine, forming methionine, which is then used for the synthesis of S-adenosyl-methionine, a universal methyl donor for numerous methylation reactions, to produce primary and secondary metabolites. Here, we demonstrate that manipulating tobacco (Nicotiana tabacum) MTHFR gene (NtMTHFR1) expression dramatically alters the alkaloid profile in transgenic tobacco plants by negatively regulating the expression of a secondary metabolic pathway nicotine N-demethylase gene, CYP82E4. Quantitative real-time polymerase chain reaction and alkaloid analyses revealed that reducing NtMTHFR expression by RNA interference dramatically induced CYP82E4 expression, resulting in higher nicotine-to-nornicotine conversion rates. Conversely, overexpressing NtMTHFR1 suppressed CYP82E4 expression, leading to lower nicotine-to-nornicotine conversion rates. However, the reduced expression of NtMTHFR did not affect the methionine and S-adenosyl-methionine levels in the knockdown lines. Our finding reveals a new regulatory role of NtMTHFR1 in nicotine N-demethylation and suggests that the negative regulation of CYP82E4 expression may serve to recruit methyl groups from nicotine into the C1 pool under C1-deficient conditions. PMID:23221678

Soil profiles' development and differentiation as revealed by their magnetic signal

NASA Astrophysics Data System (ADS)

Jordanova, Neli; Jordanova, Diana

2017-04-01

Soil profiles' development is a major theme in soil science research, as far as it gives basic information on soil genesis and classification. The use of soil magnetic properties as indicators for physical and geochemical conditions during pedogenesis received great attention during the last decade mainly in relation to paleoclimate reconstructions. However, tracking the observed general relationships with respect to degree of soil differentiation would lead to capitalization of this knowledge and its further utilization as pedogenic indicator. Here we present an overview of the observed relationships and depth variations of magnetic characteristics along ten soil profiles of Chernozems, Luvisols and Planosols from Bulgaria. Depending on the general soil group considered, different relationships between depth distribution of the relative amount of superparamagnetic (SP), single domain (SD) and larger pseudo single domain (PSD) to multi domain (MD) ferrimagnetic fractions are revealed. The profiles of the soil group with pronounced accumulation of organic matter in the mineral topsoil (Chernozems and Phaeozems) a systematic shift in the relative maxima of SP- and SD- like concentration proxies is observed with the increase of profile differentiation. In contrast, the group of soils with clay-enriched subsoil horizon (e.g. Luvisols) shows different evolution of the depth distribution of the grain-size proxy parameters. The increase of profile's degradation leads to a decrease in the amount of the SP fraction and a split in its maxima into two depth intervals related to the eluvial and illuvial horizons respectively. Along with this tendency, the maximum of the SD fraction moves to progressively deeper levels of the illuvial horizon. The third soil group of the Planosols is characterized by specific re-distribution of the iron oxides, caused by the oscillating oxidation - reduction fluctuations within the profile. The diagnostic eluvial and illuvial soil horizons are enriched with stable SD magnetite-like fraction, likely originating from ferrihydrite transformations under repeating oxidative - reductive conditions. The major magnetic phase in illuvial horizons is hematite, while in eluvial and C-horizons magnetite dominates. These different trends in the evolution of mineralogy and magnetic grain size fractions along the depth of the various soil groups are useful indicators of the soil chemistry, as well as the dynamics of the main soil forming processes.

Transcriptome profiling reveals the immune response of goose T cells under selenium stimuli.

PubMed

Cao, Nan; Li, Wanyan; Li, Bingxin; Tian, Yunbo; Xu, Danning

2017-12-01

The goose is an economically important poultry species and a principal natural host of avian viruses. This study aimed to determine the effects of selenium on the immune response of geese. Under selenium stimulation, gene expression profiling was investigated using transcriptome sequencing. The selenoproteins were promoted by selenium stimulation, while the heat shock proteins, interleukin and interferons were mainly down-regulated. After comparison, 2228 differentially expressed genes were primarily involved in immune and environmental response, and infectious disease and genetic information processing related pathways were identified. Specifically, the enzymes of the lysosomes which acted as a safeguard in preventing pathogens were mostly up-regulated and six randomly selected differentially expressed genes were validated by quantitative polymerase chain reaction. In addition, the most proportional increased transcription factor family basic helix-loop-helix (bHLH) located in the 5' flank of selenoprotein P-like protein for selenium metabolism was identified by response to the selenium stimulation in this study. These analyses show that selenium can promote immune function by activating selenoproteins, transcript factors and lysosome pathway related genes, while weakening cytokine content genes in geese. © 2017 Japanese Society of Animal Science.

Understanding the molecular basis of plant growth promotional effect of Pseudomonas fluorescens on rice through protein profiling

PubMed Central

2009-01-01

Background Plant Growth Promoting Rhizobacteria (PGPR), Pseudomonas fluorescens strain KH-1 was found to exhibit plant growth promotional activity in rice under both in-vitro and in-vivo conditions. But the mechanism underlying such promotional activity of P. fluorescens is not yet understood clearly. In this study, efforts were made to elucidate the molecular responses of rice plants to P. fluorescens treatment through protein profiling. Two-dimensional polyacrylamide gel electrophoresis strategy was adopted to identify the PGPR responsive proteins and the differentially expressed proteins were analyzed by mass spectrometry. Results Priming of P. fluorescens, 23 different proteins found to be differentially expressed in rice leaf sheaths and MS analysis revealed the differential expression of some important proteins namely putative p23 co-chaperone, Thioredoxin h- rice, Ribulose-bisphosphate carboxylase large chain precursor, Nucleotide diPhosphate kinase, Proteosome sub unit protein and putative glutathione S-transferase protein. Conclusion Functional analyses of the differential proteins were reported to be directly or indirectly involved in growth promotion in plants. Thus, this study confirms the primary role of PGPR strain KH-1 in rice plant growth promotion. PMID:20034395

Evaluation and management of juvenile recurrent parotitis in children from northern Greece

PubMed Central

Papadopoulou-Alataki, E; Chatziavramidis, A; Vampertzi, O; Alataki, S; Konstantinidis, I

2015-01-01

Background: Juvenile Recurrent Parotitis (JRP) is a recurrent parotid inflammation of childhood.  The aim of our study was to investigate the clinical, laboratory and imaging profile of children with JRP as well as to estimate the impact of siadendoscopy as a therapeutic tool in the clinical outcome of JRP. Methods: Twenty-three children with JRP aged 3.5-16 years, were investigated. Twelve of them underwent sialendoscopy: seven aged <8 years under general and five aged >8 years under local anesthesia. Results: The age at onset ranged from 2-15 years while the number of episodes from 2-8 per year. The autoantibody profile was negative in all patients, suggesting no evidence for autoimmune diseases.  Antibody deficiency was found in two children. The imaging studies reveal an overall parotid swelling and intraparotid lymph nodes while microabscesses were present in 31% of the patients. Twelve patients who underwent sialendoscopy had a significant improvement in their clinical outcome; the mean episodes of JRP before sialendoscopy was 3.9/year and reduced to 0.4 at the post-intervention year. Conclusion: Sialendoscopy represents an alternative and promising perspective in the management of JRP. Hippokratia 2015; 19 (4): 356-359. PMID:27688702

Mycosporine-like amino acids (MAAs) profile of a rice-field cyanobacterium Anabaena doliolum as influenced by PAR and UVR.

PubMed

Singh, Shailendra P; Sinha, Rajeshwar P; Klisch, Manfred; Häder, Donat-P

2008-12-01

The mycosporine-like amino acid (MAA) profile of a rice-field cyanobacterium, Anabaena doliolum, was studied under PAR and PAR + UVR conditions. The high-performance liquid chromatographic analysis of water-soluble compounds reveals the biosynthesis of three MAAs, mycosporine-glycine (lambda (max) = 310 nm), porphyra-334 (lambda (max) = 334 nm) and shinorine (lambda (max) = 334 nm), with retention times of 4.1, 3.5 and 2.3 min, respectively. This is the first report for the occurrence of mycosporine-glycine and porphyra-334 in addition to shinorine in Anabaena strains studied so far. The results indicate that mycosporine-glycine (monosubstituted) acts as a precursor for the biosynthesis of the bisubstituted MAAs shinorine and porphyra-334. Mycosporine-glycine was under constitutive control while porphyra-334 and shinorine were induced by UV-B radiation, indicating the involvement of UV-regulated enzymes in the biotransformation of MAAs. It seems that A. doliolum is able to protect its cell machinery from UVR by synthesizing a complex set of MAAs and thus is able to survive successfully during the summer in its natural brightly lit habitats.

Transcriptome profiling of sleeping, waking, and sleep deprived adult heterozygous Aldh1L1 - eGFP-L10a mice.

PubMed

Bellesi, Michele; de Vivo, Luisa; Tononi, Giulio; Cirelli, Chiara

2015-12-01

Transcriptomic studies revealed that hundreds of mRNAs show differential expression in the brains of sleeping relative to awake rats, mice, flies, and sparrows. Although these results have offered clues regarding the molecular consequences of sleep and sleep loss, their functional significance thus far has been limited. This is probably because the previous studies pooled transcripts from all brain cells, including neurons and glia. In Bellesi et al. 2015 [1], we used the translating ribosome affinity purification technology (TRAP) and microarray analysis to obtain a genome-wide mRNA profiling of astrocytes as a function of sleep and wake. We used bacterial artificial chromosome (BAC) transgenic mice expressing eGFP tagged ribosomal protein L10a under the promoter of the Aldh1L1 gene, a highly expressed astrocytic gene. Using this approach, we could extract only the astrocytic mRNAs, and only those already committed to be translated into proteins (L10a is part of the translational machinery). Here, we report a detailed description of the protocol used in the study [1]. Array data have been submitted to NCBI GEO under accession number (GSE69079).

Effect of oxygen concentration in ZDP containing oils on surface composition and wear

NASA Technical Reports Server (NTRS)

Brainard, W. A.; Ferrante, J.

1983-01-01

A pin-on-disk wear study was performed with the lubricants dibutyl sebacate (DBS) and mineral oil (MO) with and without 1 weight percent zinc-dialkyl-dithiophospatee (ZDP) as an additive. The pin was annealed pure iron and the disk was M-2 tool steel. The selected load and speed guaranteed boundary lubrication. The ambient atmospheric oxygen concentration in an oxygen-nitrogen mixture was varied from 0 percent to 20 percent in order to examine its relationship to ZDP effectiveness. Auger electron spectroscopy combined with argon ion bombardment (depth profiling) was used to determine surface elemental composition on the pin when tested in DBS with and without ZDP. The ambient atmosphere was found to cause large variations in wear rate and surface composition. With MO, ZDP reduced wear under all conditions, but had little advantage over oxides formed at 20 percent oxygen atmosphere. With DBS, ZDP reduced wear at 0 percent oxygen, but gave varied results at other oxygen concentrations. Depth profiling revealed sulfuide formation at 0 percent oxygen and probably sulfates at 20 percent oxygen. The results are significant because varied oxygen concentrations can occur under actual lubricating conditions in practical machinery.

Targeting Unique Metabolic Properties of Breast Tumor Initiating Cells

PubMed Central

Feng, Weiguo; Gentles, Andrew; Nair, Ramesh V.; Huang, Min; Lin, Yuan; Lee, Cleo Y.; Cai, Shang; Scheeren, Ferenc A.; Kuo, Angera H.; Diehn, Maximilian

2014-01-01

Normal stem cells from a variety of tissues display unique metabolic properties compared to their more differentiated progeny. However, relatively little is known about heterogeneity of metabolic properties cancer stem cells, also called tumor initiating cells (TICs). In this study we show that, analogous to some normal stem cells, breast TICs have distinct metabolic properties compared to non-tumorigenic cancer cells (NTCs). Transcriptome profiling using RNA-Seq revealed TICs under-express genes involved in mitochondrial biology and mitochondrial oxidative phosphorylation and metabolic analyses revealed TICs preferentially perform glycolysis over oxidative phosphorylation compared to NTCs. Mechanistic analyses demonstrated that decreased expression and activity of pyruvate dehydrogenase (Pdh), a key regulator of oxidative phosphorylation, play a critical role in promoting the pro-glycolytic phenotype of TICs. Metabolic reprogramming via forced activation of Pdh preferentially eliminates TICs both in vitro and in vivo. Our findings reveal unique metabolic properties of TICs and demonstrate that metabolic reprogramming represents a promising strategy for targeting these cells. PMID:24497069

Spatial Phosphoprotein Profiling Reveals a Compartmentalized Extracellular Signal-regulated Kinase Switch Governing Neurite Growth and Retraction

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

Wang, Yingchun; Yang, Feng; Fu, Yi

Abstract - Brain development and spinal cord regeneration require neurite sprouting and growth cone navigation in response to extension and collapsing factors present in the extracellular environment. These external guidance cues control neurite growth cone extension and retraction processes through intracellular protein phosphorylation of numerous cytoskeletal, adhesion, and polarity complex signaling proteins. However, the complex kinase/substrate signaling networks that mediate neuritogenesis have not been investigated. Here, we compare the neurite phosphoproteome under growth and retraction conditions using neurite purification methodology combined with mass spectrometry. More than 4000 non-redundant phosphorylation sites from 1883 proteins have been annotated and mapped to signalingmore » pathways that control kinase/phosphatase networks, cytoskeleton remodeling, and axon/dendrite specification. Comprehensive informatics and functional studies revealed a compartmentalized ERK activation/deactivation cytoskeletal switch that governs neurite growth and retraction, respectively. Our findings provide the first system-wide analysis of the phosphoprotein signaling networks that enable neurite growth and retraction and reveal an important molecular switch that governs neuritogenesis.« less

Hypothalamic transcriptomes of 99 mouse strains reveal trans eQTL hotspots, splicing QTLs and novel non-coding genes

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

Hasin-Brumshtein, Yehudit; Khan, Arshad H.; Hormozdiari, Farhad

2016-09-13

Previous studies had shown that the integration of genome wide expression profiles, in metabolic tissues, with genetic and phenotypic variance, provided valuable insight into the underlying molecular mechanisms. We used RNA-Seq to characterize hypothalamic transcriptome in 99 inbred strains of mice from the Hybrid Mouse Diversity Panel (HMDP), a reference resource population for cardiovascular and metabolic traits. We report numerous novel transcripts supported by proteomic analyses, as well as novel non coding RNAs. High resolution genetic mapping of transcript levels in HMDP, reveals bothlocalandtransexpression Quantitative Trait Loci (eQTLs) demonstrating 2transeQTL 'hotspots' associated with expression of hundreds of genes. We alsomore » report thousands of alternative splicing events regulated by genetic variants. Finally, comparison with about 150 metabolic and cardiovascular traits revealed many highly significant associations. Our data provide a rich resource for understanding the many physiologic functions mediated by the hypothalamus and their genetic regulation.« less

Salicylic acid and nitric oxide alleviate high temperature induced oxidative damage in Lablab purpureus L plants by regulating bio-physical processes and DNA methylation.

PubMed

Rai, Krishna Kumar; Rai, Nagendra; Rai, Shashi Pandey

2018-07-01

Salicylic acid (SA) and sodium nitroprusside (SNP, NO donor) modulates plant growth and development processes and recent findings have also revealed their involvement in the regulation of epigenetic factors under stress condition. In the present study, some of these factors were comparatively studied in hyacinth bean plants subjected to high temperature (HT) environment (40-42 °C) with and without exogenous application of SA and SNP under field condition. Exogenous application of SA and SNP substantially modulated the growth and biophysical process of hyacinth bean plants under HT environment. Exogenous application of SA and SNP also remarkably regulated the activities of antioxidant enzymes, modulated mRNA level of certain enzymes, improves plant water relation, enhance photosynthesis and thereby increasing plant defence under HT. Coupled restriction enzyme digestion-random amplification (CRED-RA) technique revealed that many methylation changes were "dose dependent" and HT significantly increased DNA damages as evidenced by both increase and decrease in bands profiles, methylation and de-methylation pattern. Thus, the result of the present study clearly shows that exogenous SA and SNP regulates DNA methylation pattern, modulates stress-responsive genes and can impart transient HT tolerance by synchronizing growth and physiological acclimatization of plants, thus narrowing the gaps between physio-biochemical and molecular events in addressing HT tolerance. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Protective effects of Arctium lappa L. root extracts (AREs) on high fat diet induced quail atherosclerosis.

PubMed

Wang, Zhi; Li, Ping; Wang, Chenjing; Jiang, Qixiao; Zhang, Lei; Cao, Yu; Zhong, Weizhen; Wang, Chunbo

2016-01-08

This study was designed to evaluate the protective effects of Arctium lappa L. root extracts (AREs) from different extraction methods (aqueous, ethanol, chloroform and flavone) on atherosclerosis. Quails (Coturnix coturnix) were subjected to high fat diet, with or without one of the four different AREs or positive control simvastatin. Blood samples were collected before treatment, after 4.5 weeks or ten weeks to assess lipid profile (Levels of total cholesterol (TC), Triacylglycerol (TG), low-density lipoprotein (LDL) and high-density lipoprotein (HDL)). After ten weeks, the serum levels of nitric oxide (NO) as well as antioxidant and pro-oxidative status (Levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), nicotinamide adenine dinucleotide phosphate (NADPH) and glutathione peroxidase (GSH-Px)) were measured. Furthermore, aortas were collected after ten weeks treatment, aorta lipid contents (TC, TG and LDL) were assessed, and histology was used to confirm atherosclerotic changes. The results indicated that high fat diet significantly deteriorated lipid profile and antioxidant status in quail serum, while all the extracts significantly reverted the changes similar to simvastatin. Aorta lipid profile assessment revealed similar results. Histology on aortas from quails treated for ten weeks confirmed atherosclerotic changes in high fat diet group, while the extracts significantly alleviated the atherosclerotic changes similar to simvastatin. Among the different extracts, flavones fraction exerted best protective effects. Our data suggest that the protective effects of AREs were medicated via hypolipidemic and anti-oxidant effects. Underlying molecular mechanisms are under investigation.

Modulatory Effects of Modafinil on Neural Circuits Regulating Emotion and Cognition

PubMed Central

Rasetti, Roberta; Mattay, Venkata S; Stankevich, Beth; Skjei, Kelsey; Blasi, Giuseppe; Sambataro, Fabio; Arrillaga-Romany, Isabel C; Goldberg, Terry E; Callicott, Joseph H; Apud, José A; Weinberger, Daniel R

2010-01-01

Modafinil differs from other arousal-enhancing agents in chemical structure, neurochemical profile, and behavioral effects. Most functional neuroimaging studies to date examined the effect of modafinil only on information processing underlying executive cognition, but cognitive enhancers in general have been shown to have pronounced effects on emotional behavior, too. We examined the effect of modafinil on neural circuits underlying affective processing and cognitive functions. Healthy volunteers were enrolled in this double-blinded placebo-controlled trial (100 mg/day for 7 days). They underwent BOLD fMRI while performing an emotion information-processing task that activates the amygdala and two prefrontally dependent cognitive tasks—a working memory (WM) task and a variable attentional control (VAC) task. A clinical assessment that included measurement of blood pressure, heart rate, the Hamilton anxiety scale, and the profile of mood state (POMS) questionnaire was also performed on each test day. BOLD fMRI revealed significantly decreased amygdala reactivity to fearful stimuli on modafinil compared with the placebo condition. During executive cognition tasks, a WM task and a VAC task, modafinil reduced BOLD signal in the prefrontal cortex and anterior cingulate. Although not statistically significant, there were trends for reduced anxiety, for decreased fatigue-inertia and increased vigor-activity, as well as decreased anger-hostility on modafinil. Modafinil in low doses has a unique physiologic profile compared with stimulant drugs: it enhances the efficiency of prefrontal cortical cognitive information processing, while dampening reactivity to threatening stimuli in the amygdala, a brain region implicated in anxiety. PMID:20555311

Penetration of filamentary structures in the x-point region of spherical tokamaks

NASA Astrophysics Data System (ADS)

Baver, D. A.; Myra, J. R.; Scotti, F.; Zweben, S. J.; Militello, F.; Walkden, N.

2017-10-01

ArbiTER is a flexible eigenvalue code designed for plasma physics applications. It is used here to gain insight into the spatial dependence of filamentary structures in the scrape-off layer of spherical tokamaks. In particular, observations on MAST reveal the presence of a quiescent x-point region. Observations in NSTX similarly reveal a reduction in divertor fluctuations near the separatrix and a loss of midplane correlation. We will report on the penetration of filamentary structures into the vicinity of the x-point, as well as growth rate trends, for a variety of profiles and toroidal mode numbers. This will determine whether linear properties of these structures can explain experimental observations. Work supported by the U.S. Department of Energy Office of Science, Office of Fusion Energy Sciences, under Award Number DE-FG02-02ER54678.

Genome-Wide Analysis of Soybean HD-Zip Gene Family and Expression Profiling under Salinity and Drought Treatments

PubMed Central

Chen, Xue; Chen, Zhu; Zhao, Hualin; Zhao, Yang; Cheng, Beijiu; Xiang, Yan

2014-01-01

Background Homeodomain-leucine zipper (HD-Zip) proteins, a group of homeobox transcription factors, participate in various aspects of normal plant growth and developmental processes as well as environmental responses. To date, no overall analysis or expression profiling of the HD-Zip gene family in soybean (Glycine max) has been reported. Methods and Findings An investigation of the soybean genome revealed 88 putative HD-Zip genes. These genes were classified into four subfamilies, I to IV, based on phylogenetic analysis. In each subfamily, the constituent parts of gene structure and motif were relatively conserved. A total of 87 out of 88 genes were distributed unequally on 20 chromosomes with 36 segmental duplication events, indicating that segmental duplication is important for the expansion of the HD-Zip family. Analysis of the Ka/Ks ratios showed that the duplicated genes of the HD-Zip family basically underwent purifying selection with restrictive functional divergence after the duplication events. Analysis of expression profiles showed that 80 genes differentially expressed across 14 tissues, and 59 HD-Zip genes are differentially expressed under salinity and drought stress, with 20 paralogous pairs showing nearly identical expression patterns and three paralogous pairs diversifying significantly under drought stress. Quantitative real-time RT-PCR (qRT-PCR) analysis of six paralogous pairs of 12 selected soybean HD-Zip genes under both drought and salinity stress confirmed their stress-inducible expression patterns. Conclusions This study presents a thorough overview of the soybean HD-Zip gene family and provides a new perspective on the evolution of this gene family. The results indicate that HD-Zip family genes may be involved in many plant responses to stress conditions. Additionally, this study provides a solid foundation for uncovering the biological roles of HD-Zip genes in soybean growth and development. PMID:24498296

A new tool for laboratory studies on volatilization: extension of applicability of the photovolatility chamber.

PubMed

Wolters, André; Kromer, Thomas; Linnemann, Volker; Schäffer, Andreas; Vereecken, Harry

2003-04-01

Volatilization from soil and plant surfaces after application is an important source of pesticide residues to the atmosphere. The laboratory photovolatility chamber allows the simultaneous measurement of volatilization and photodegradation of 14C-labeled pesticides under controlled climatic conditions. Both continuous air sampling, which quantifies volatile organic compounds and 14CO2 separately, and the detection of surface-located residues allow for a mass balance of radioactivity. The setup of the photovolatility chamber was optimized, and additional sensors were installed to characterize the influence of soil moisture, soil temperature, and evaporation on volatilization. The modified flow profile in the glass dome of the chamber arising from the use of a high-performance metal bellows pump was measured. Diminished air velocity near the soil surface and a wind velocity of 0.2 m/s in 3 cm height allowed the requirements of the German guideline on assessing pesticide volatilization for registration purposes to be fulfilled. Determination of soil moisture profiles of the upper soil layer illustrated that defined water content in the soil up to a depth of 4 cm could be achieved by water saturation of air. Cumulative volatilization of [phenyl-UL-14C]parathion-methyl ranged from 2.4% under dry conditions to 32.9% under moist conditions and revealed the clear dependence of volatilization on the water content in the top layer.

Preparation and characterization of silica xerogels as carriers for drugs.

PubMed

Czarnobaj, K

2008-11-01

The aim of the present study was to utilize the sol-gel method to synthesize different forms of xerogel matrices for drugs and to investigate how the synthesis conditions and solubility of drugs influence the change of the profile of drug release and the structure of the matrices. Silica xerogels doped with drugs were prepared by the sol-gel method from a hydrolyzed tetraethoxysilane (TEOS) solution containing two model compounds: diclofenac diethylamine, (DD)--a water-soluble drug or ibuprofen, (IB)--a water insoluble drug. Two procedures were used for the synthesis of sol-gel derived materials: one-step procedure (the sol-gel reaction was carried out under acidic or basic conditions) and the two-step procedure (first, hydrolysis of TEOS was carried out under acidic conditions, and then condensation of silanol groups was carried out under basic conditions) in order to obtain samples with altered microstructures. In vitro release studies of drugs revealed a similar release profile in two steps: an initial diffusion-controlled release followed by a slower release rate. In all the cases studied, the released amount of DD was higher and the released time was shorter compared with IB for the same type of matrices. The released amount of drugs from two-step prepared xerogels was always lower than that from one-step base-catalyzed xerogels. One-step acid-catalyzed xerogels proved unsuitable as the carriers for the examined drugs.

The Bulging Behavior of Thick-Walled 6063 Aluminum Alloy Tubes Under Double-Sided Pressures

NASA Astrophysics Data System (ADS)

Cui, Xiao-Lei; Wang, Xiao-Song; Yuan, Shi-Jian

2015-05-01

To make further exploration on the deformation behavior of tube under double-sided pressures, the thick-walled 6063 aluminum alloy tubes with an outer diameter of 65 mm and an average thickness of 7.86 mm have been used to be bulged under the combined action of internal and external pressures. In the experiment, two ends of the thick-walled tubes were fixed using the tooth and groove match. Three levels of external pressure (0 MPa, 40 MPa, and 80 MPa), in conjunction with the internal pressure, were applied on the tube outside and inside simultaneously. The effect of external pressure on the bulging behavior of the thick-walled tubes, such as the limiting expansion ratio, the bulging zone profile, and the thickness distribution, has been investigated. It is shown that the limiting expansion ratio, the bulging zone profile, and the thickness distribution in the homogeneous bulging area are all insensitive to the external pressure. However, the external pressure can make the thick-walled tube achieve a thinner wall at the fracture area. It reveals that the external pressure can only improve the fracture limit of the thick-walled 6063 tubes, but it has very little effect on their homogeneous bulging behavior. It might be because the external pressure can only increase the magnitude of the hydrostatic pressure for the tube but has no effect on the Lode parameter.

Atomic force microscopy and nanoindentation investigation of polydimethylsiloxane elastomeric substrate compliancy for various sputtered thin film morphologies.

PubMed

Maji, Debashis; Das, Soumen

2018-03-01

Crack free electrically continuous metal thin films over soft elastomeric substrates play an integral part in realization of modern day flexible bioelectronics and biosensors. Under nonoptimized deposition conditions, delamination, and/or cracking of the top film as well as the underlying soft substrate hinders optimal performance of these devices. Hence it is very important to understand and control not only the various deposition factors like power, time, or deposition pressure but also investigate the various interfacial physics playing a critical role in assuring thin film adhesion and substrate compliancy. In the present study, various nanomechanical information of the underlying substrate, namely, crack profile, average roughness, Young's modulus, and adhesion force were studied for uncracked and cracked polydimethylsiloxane (PDMS) surfaces along with pristine and conventional plasma treated PDMS samples as control. Quantification of the above parameters were done using three-dimensional surface profiler, scanning electron microscopy, nanoindentation, and atomic force microscopy techniques to elucidate the modulus range, average roughness, and adhesion force. Comparative analysis with control revealed remarkable similarity between increased modulus values, increased surface roughness, and reduced adhesion force accounting for reduced substrate compliancy and resulting in film cracking or buckling which are critical for development of various bioflexible devices. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 725-737, 2018. © 2017 Wiley Periodicals, Inc.

Differential transcriptome analysis reveals genes related to cold tolerance in seabuckthorn carpenter moth, Eogystia hippophaecolus

PubMed Central

Hu, Ping; Wang, Tao; Tao, Jing; Zong, Shixiang

2017-01-01

Seabuckthorn carpenter moth, Eogystia hippophaecolus (Lepidoptera: Cossidae), is an important pest of sea buckthorn (Hippophae rhamnoides), which is a shrub that has significant ecological and economic value in China. E. hippophaecolus is highly cold tolerant, but limited studies have been conducted to elucidate the molecular mechanisms underlying its cold resistance. Here we sequenced the E. hippophaecolus transcriptome using RNA-Seq technology and performed de novo assembly from the short paired-end reads. We investigated the larval response to cold stress by comparing gene expression profiles between treatments. We obtained 118,034 unigenes, of which 22,161 were annotated with gene descriptions, conserved domains, gene ontology terms, and metabolic pathways. These resulted in 57 GO terms and 193 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. By comparing transcriptome profiles for differential gene expression, we identified many differentially expressed proteins and genes, including heat shock proteins and cuticular proteins which have previously been reported to be involved in cold resistance of insects. This study provides a global transcriptome analysis and an assessment of differential gene expression in E. hippophaecolus under cold stress. We found seven differential expressed genes in common between developmental stages, which were verified with qPCR. Our findings facilitate future genomic studies aimed at improving our understanding of the molecular mechanisms underlying the response of insects to low temperatures. PMID:29131867

Differential transcriptome analysis reveals genes related to cold tolerance in seabuckthorn carpenter moth, Eogystia hippophaecolus.

PubMed

Cui, Mingming; Hu, Ping; Wang, Tao; Tao, Jing; Zong, Shixiang

2017-01-01

Seabuckthorn carpenter moth, Eogystia hippophaecolus (Lepidoptera: Cossidae), is an important pest of sea buckthorn (Hippophae rhamnoides), which is a shrub that has significant ecological and economic value in China. E. hippophaecolus is highly cold tolerant, but limited studies have been conducted to elucidate the molecular mechanisms underlying its cold resistance. Here we sequenced the E. hippophaecolus transcriptome using RNA-Seq technology and performed de novo assembly from the short paired-end reads. We investigated the larval response to cold stress by comparing gene expression profiles between treatments. We obtained 118,034 unigenes, of which 22,161 were annotated with gene descriptions, conserved domains, gene ontology terms, and metabolic pathways. These resulted in 57 GO terms and 193 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. By comparing transcriptome profiles for differential gene expression, we identified many differentially expressed proteins and genes, including heat shock proteins and cuticular proteins which have previously been reported to be involved in cold resistance of insects. This study provides a global transcriptome analysis and an assessment of differential gene expression in E. hippophaecolus under cold stress. We found seven differential expressed genes in common between developmental stages, which were verified with qPCR. Our findings facilitate future genomic studies aimed at improving our understanding of the molecular mechanisms underlying the response of insects to low temperatures.

Application of frequency- and time-domain electromagnetic surveys to characterize hydrostratigraphy and landfill construction at the Amargosa Desert Research Site, Beatty, Nevada

USGS Publications Warehouse

White, Eric A.; Day-Lewis, Frederick D.; Johnson, Carole D.; Lane, John W.

2016-01-01

In 2014 and 2015, the U.S. Geological Survey (USGS), conducted frequency-domain electromagnetic (FDEM) surveys at the USGS Amargosa Desert Research Site (ADRS), approximately 17 kilometers (km) south of Beatty, Nevada. The FDEM surveys were conducted within and adjacent to a closed low-level radioactive waste disposal site located at the ADRS. FDEM surveys were conducted on a grid of north-south and east-west profiles to assess the locations and boundaries of historically recorded waste-disposal trenches. In 2015, the USGS conducted time-domain (TDEM) soundings along a profile adjacent to the disposal site (landfill) in cooperation with the U.S. Environmental Protection Agency (USEPA), to assess the thickness and characteristics of the underlying deep unsaturated zone, and the hydrostratigraphy of the underlying saturated zone.FDEM survey results indicate the general location and extent of the waste-disposal trenches and reveal potential differences in material properties and the type and concentration of waste in several areas of the landfill. The TDEM surveys provide information on the underlying hydrostratigraphy and characteristics of the unsaturated zone that inform the site conceptual model and support an improved understanding of the hydrostratigraphic framework. Additional work is needed to interpret the TDEM results in the context of the local and regional structural geology.

Contrasting strategies used by lichen microalgae to cope with desiccation-rehydration stress revealed by metabolite profiling and cell wall analysis.

PubMed

Centeno, Danilo C; Hell, Aline F; Braga, Marcia R; Del Campo, Eva M; Casano, Leonardo M

2016-05-01

Most lichens in general, and their phycobionts in particular, are desiccation tolerant, but their mechanisms of desiccation tolerance (DT) remain obscure. The physiological responses and cell wall features of two putatively contrasting lichen-forming microalgae, Trebouxia sp. TR9 (TR9), isolated from Ramalina farinacea (adapted to frequent desiccation-rehydration cycles), and Coccomyxa solorina-saccatae (Csol), obtained from Solorina saccata (growing in usually humid limestone crevices, subjected to seasonal dry periods) was characterized. Microalgal cultures were desiccated under 25%-30% RH and then rehydrated. Under these conditions, RWC and ψw decreased faster and simultaneously during dehydration in Csol, whereas TR9 maintained its ψw until 70% RWC. The metabolic profile indicated that polyols played a key role in DT of both microalgae. However, TR9 constitutively accumulated higher amounts of polyols, whereas Csol induced the polyol synthesis under desiccation-rehydration. Csol also accumulated ascorbic acid, while TR9 synthesized protective raffinose-family oligosaccharides (RFOs) and increased its content of phenolics. Additionally, TR9 exhibited thicker and qualitatively different cell wall and extracellular polymeric layer compared with Csol, indicating higher water retention capability. The findings were consistent with the notion that lichen microalgae would have evolved distinct strategies to cope with desiccation-rehydration stress in correspondence with the water regime of their respective habitats. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

Discovery of X-Ray Emission from the Crab Pulsar at Pulse Minimum

NASA Technical Reports Server (NTRS)

Tennant, Allyn F.; Becker, Werner; Juda, Michael X.; Elsner, Ronald F.; Kolodziejczak, Jeffery J.; Murray, Stephen S.; ODell, Stephen L.; Paerels, Frits; Swartz, Douglas A.; Shibazaki, Noriaki;

Discovery of X-Ray Emission from the Crab Pulsar at Pulse Minimum

NASA Technical Reports Server (NTRS)

Tennant, Allyn F.; Becker, Werner; Juda, Michael; Elsner, Ronald F.; Kolodziejczak, Jeffery J.; Murray, Stephen S.; ODell, Stephen L.; Paerels, Frits; Swartz, Douglas A.

2001-01-01

The Chandra X-Ray Observatory observed the Crab pulsar using the Low-Energy Transmission Grating with the High-Resolution Camera. Time-resolved zeroth-order images reveal that the pulsar emits X-rays at all pulse phases. Analysis of the flux at minimum - most likely non-thermal in origin - places an upper limit (T(sub infinity) < 2.1 MK) on the surface temperature of the underlying neutron star. In addition, analysis of the pulse profile establishes that the error in the Chandra-determined absolute time is quite small, -0.2 +/- 0.1 ms.

Fast deep-tissue multispectral optoacoustic tomography (MSOT) for preclinical imaging of cancer and cardiovascular disease

NASA Astrophysics Data System (ADS)

Taruttis, Adrian; Razansky, Daniel; Ntziachristos, Vasilis

2012-02-01

Optoacoustic imaging has enabled the visualization of optical contrast at high resolutions in deep tissue. Our Multispectral optoacoustic tomography (MSOT) imaging results reveal internal tissue heterogeneity, where the underlying distribution of specific endogenous and exogenous sources of absorption can be resolved in detail. Technical advances in cardiac imaging allow motion-resolved multispectral measurements of the heart, opening the way for studies of cardiovascular disease. We further demonstrate the fast characterization of the pharmacokinetic profiles of lightabsorbing agents. Overall, our MSOT findings indicate new possibilities in high resolution imaging of functional and molecular parameters.

Simulation of non-Newtonian oil-water core annular flow through return bends

NASA Astrophysics Data System (ADS)

Jiang, Fan; Wang, Ke; Skote, Martin; Wong, Teck Neng; Duan, Fei

2018-01-01

The volume of fluid (VOF) model is used together with the continuum surface force (CSF) model to numerically simulate the non-Newtonian oil-water core annular flow across return bends. A comprehensive study is conducted to generate the profiles of pressure, velocity, volume fraction and wall shear stress for different oil properties, flow directions, and bend geometries. It is revealed that the oil core may adhere to the bend wall under certain operating conditions. Through the analysis of the total pressure gradient and fouling angle, suitable bend geometric parameters are identified for avoiding the risk of fouling.

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

PubMed

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.

Genetic profiling of two phenotypically distinct outbred rats derived from a colony of the Zucker fatty rats maintained at Tokyo Medical University

PubMed Central

Nakanishi, Satoshi; Kuramoto, Takashi; Kashiwazaki, Naomi; Yokoi, Norihide

2016-01-01

The Zucker fatty (ZF) rat is an outbred rat and a well-known model of obesity without diabetes, harboring a missense mutation (fatty, abbreviated as fa) in the leptin receptor gene (Lepr). Slc:Zucker (Slc:ZF) outbred rats exhibit obesity while Hos:ZFDM-Leprfa (Hos:ZFDM) outbred rats exhibit obesity and type 2 diabetes. Both outbred rats have been derived from an outbred ZF rat colony maintained at Tokyo Medical University. So far, genetic profiles of these outbred rats remain unknown. Here, we applied a simple genotyping method using Ampdirect reagents and FTA cards (Amp-FTA) in combination with simple sequence length polymorphisms (SSLP) markers to determine genetic profiles of Slc:ZF and Hos:ZFDM rats. Among 27 SSLP marker loci, 24 loci (89%) were fixed for specific allele at each locus in Slc:ZF rats and 26 loci (96%) were fixed in Hos:ZFDM rats, respectively. This indicates the low genetic heterogeneity in both colonies of outbred rats. Nine loci (33%) showed different alleles between the two outbred rats, suggesting considerably different genetic profiles between the two outbred rats in spite of the same origin. Additional analysis using 72 SSLP markers further supported these results and clarified the profiles in detail. This study revealed that genetic profiles of the Slc:ZF and Hos:ZFDM outbred rats are different for about 30% of the SSLP marker loci, which is the underlying basis for the phenotypic difference between the two outbred rats. PMID:27795491

Metabolite profiling and associated gene expression reveal two metabolic shifts during the seed-to-seedling transition in Arabidopsis thaliana.

PubMed

Silva, Anderson Tadeu; Ligterink, Wilco; Hilhorst, Henk W M

2017-11-01

Metabolic and transcriptomic correlation analysis identified two distinctive profiles involved in the metabolic preparation for seed germination and seedling establishment, respectively. Transcripts were identified that may control metabolic fluxes. The transition from a quiescent metabolic state (dry seed) to the active state of a vigorous seedling is crucial in the plant's life cycle. We analysed this complex physiological trait by measuring the changes in primary metabolism that occur during the transition in order to determine which metabolic networks are operational. The transition involves several developmental stages from seed germination to seedling establishment, i.e. between imbibition of the mature dry seed and opening of the cotyledons, the final stage of seedling establishment. We hypothesized that the advancement of growth is associated with certain signature metabolite profiles. Metabolite-metabolite correlation analysis underlined two specific profiles which appear to be involved in the metabolic preparation for seed germination and efficient seedling establishment, respectively. Metabolite profiles were also compared to transcript profiles and although transcriptional changes did not always equate to a proportional metabolic response, in depth correlation analysis identified several transcripts that may directly influence the flux through metabolic pathways during the seed-to-seedling transition. This correlation analysis also pinpointed metabolic pathways which are significant for the seed-to-seedling transition, and metabolite contents that appeared to be controlled directly by transcript abundance. This global view of the transcriptional and metabolic changes during the seed-to-seedling transition in Arabidopsis opens up new perspectives for understanding the complex regulatory mechanism underlying this transition.

(U-Th)/He geochronology of goethite and the origin and evolution of cangas

NASA Astrophysics Data System (ADS)

Monteiro, Hevelyn S.; Vasconcelos, Paulo M.; Farley, Kenneth A.; Spier, Carlos A.; Mello, Claudio L.

2014-04-01

(U-Th)/He geochronology of 147 grains of goethite cements extracted from ferruginous duricrusts (cangas) developed on banded iron-formations from the Quadrilátero Ferrífero region, Minas Gerais, Brazil, records a history of protracted mineral dissolution-reprecipitation that started at ca. 48.1 ± 4.8 Ma and continues intermittently until the Present. A large majority of the samples (more than 30%) are younger than 2 Ma, revealing active mineral dissolution-reprecipitation in the recent past. Within cangas, goethite cements are younger near the surface and become progressively older towards the bottom of the weathering profile, indicating that iron is more effectively cycled in the parts of the weathering profile more strongly affected by biogenic activity. (U-Th)/He geochronology of 14 goethite grains from saprolites in the same profiles yield results ranging from 55.3 ± 5.5 to 25.7 ± 2.6 Ma. For a single weathering profile, goethite cements from cangas are invariably younger than goethite grains from the underlying saprolite, indicating that the duricrust and the saprolite behave as independent and separate systems responding to different environmental controls. Thorium shows conservative behaviour during goethite dissolution-reprecipitation, and it is enriched towards the surface of the weathering profile. Uranium, on the other hand, is preferentially leached from the surface into the saprolite or out of the weathering profile. Recurrent goethite dissolution-reprecipitation lends great textural complexities to cangas, but it is also responsible for its capacity to reheal when physically disrupted. This self-healing property accounts for canga’s role in armoring banded iron-formation landscapes.

Characterization of the cellulose-degrading bacterium NCIMB 10462

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

Dees, C.; Scott, T.C.; Phelps, T.J.

The gram-negative cellulase-producing bacterium NCIMB 10462 has been previously named Pseudomonas fluorescens subsp. or var. cellulose. Because of renewed interest in cellulose-degrading bacteria for use in the bioconversion of cellulose to chemical feed stocks and fuels, we re-examined the characteristics of this microorganism to determine its true metabolic potential. Metabolic and physical characterization of NCIMB 10462 revealed that this is an alkalophilic, non-fermentative, gram-negative, oxidase-positive, motile, cellulose-degrading bacterium. The aerobic substrate utilization profile of this bacterium has few characteristics consistent with a classification of P. fluorescens and a very low probability match with the genus Sphingomonas. However, total lipid analysismore » did not reveal that any sphingolipid bases are produced by this bacterium. NCIMB 10462 grows best aerobically, but also grows well in complex media under reducing conditions. NCIMB 10462 grows slowly under anaerobic conditions on complex media, but growth on cellulosic media occurred only under aerobic conditions. Total fatty acid analysis (MIDI) of NCIMB 10462 failed to group this bacterium with a known pseudomonas species. However, fatty acid analysis of the bacteria when grown at temperatures below 37{degrees}C suggest that the organism is a pseudomonad. Since a predominant characteristic of this bacterium is its ability to degrade cellulose, we suggest that it be called Pseudomonas cellulosa.« less

Regulation of Lipid Metabolism by Dicer Revealed through SILAC Mice

PubMed Central

Huang, Tai-Chung; Saharabuddhe, Nandini A.; Kim, Min-Sik; Getnet, Derese; Yang, Yi; Peterson, Jonathan M.; Ghosh, Bidyut; Chaerkady, Raghothama; Leach, Steven D.; Marchionni, Luigi; Wong, G. William; Pandey, Akhilesh

2012-01-01

Dicer is a ribonuclease whose major role is to generate mature microRNAs although additional functions have been proposed. Deletion of Dicer leads to embryonic lethality in mice. To study the role of Dicer in adults, we generated mice in which administration of tamoxifen induces deletion of Dicer. Surprisingly, disruption of Dicer in adult mice induced lipid accumulation in the small intestine. To dissect the underlying mechanisms, we carried out miRNA, mRNA and proteomic profiling of small intestine. The proteomic analysis was done using mice metabolically labeled with heavy lysine (SILAC mice) for an in vivo readout. We identified 646 proteins of which 80 were upregulated >2-fold and 75 were downregulated. Consistent with the accumulation of lipids, Dicer disruption caused a marked decrease of microsomal triglyceride transfer protein, long-chain fatty acyl-CoA ligase 5, fatty acid binding protein, and very-long-chain fatty acyl-CoA dehydrogenase, among others. We validated these results using multiple reaction monitoring (MRM) experiments by targeting proteotypic peptides. Our data reveal a previously unappreciated role of Dicer in lipid metabolism. These studies demonstrate a systems biology approach by integrating mouse models, metabolic labeling, gene expression profiling and quantitative proteomics can be a powerful tool for understanding complex biological systems. PMID:22313051

Comparison of Leaf Sheath Transcriptome Profiles with Physiological Traits of Bread Wheat Cultivars under Salinity Stress

PubMed Central

Trittermann, Christine; Berger, Bettina; Roy, Stuart J.; Seki, Motoaki; Shinozaki, Kazuo; Tester, Mark

2015-01-01

Salinity stress has significant negative effects on plant biomass production and crop yield. Salinity tolerance is controlled by complex systems of gene expression and ion transport. The relationship between specific features of mild salinity stress adaptation and gene expression was analyzed using four commercial varieties of bread wheat (Triticum aestivum) that have different levels of salinity tolerance. The high-throughput phenotyping system in The Plant Accelerator at the Australian Plant Phenomics Facility revealed variation in shoot relative growth rate and salinity tolerance among the four cultivars. Comparative analysis of gene expression in the leaf sheaths identified genes whose functions are potentially linked to shoot biomass development and salinity tolerance. Early responses to mild salinity stress through changes in gene expression have an influence on the acquisition of stress tolerance and improvement in biomass accumulation during the early “osmotic” phase of salinity stress. In addition, results revealed transcript profiles for the wheat cultivars that were different from those of usual stress-inducible genes, but were related to those of plant growth. These findings suggest that, in the process of breeding, selection of specific traits with various salinity stress-inducible genes in commercial bread wheat has led to adaptation to mild salinity conditions. PMID:26244554

Eya2, a Target Activated by Plzf, Is Critical for PLZF-RARA-Induced Leukemogenesis

PubMed Central

Masuya, Masahiro; Ishii, Satomi; Katayama, Naoyuki

2017-01-01

ABSTRACT PLZF is a transcription factor that confers aberrant self-renewal in leukemogenesis, and the PLZF-RARA fusion gene causes acute promyelocytic leukemia (APL) through differentiation block. However, the molecular mechanisms of aberrant self-renewal underlying PLZF-mediated leukemogenesis are poorly understood. To investigate these mechanisms, comprehensive expression profiling of mouse hematopoietic stem/progenitor cells transduced with Plzf was performed, which revealed the involvement of a key transcriptional coactivator, Eya2, a target molecule shared by Plzf and PLZF-RARA, in the aberrant self-renewal. Indeed, PLZF-RARA as well as Plzf rendered those cells immortalized through upregulation of Eya2. Eya2 also led to immortalization without differentiation block, while depletion of Eya2 suppressed clonogenicity in cells immortalized by PLZF-RARA without influence on differentiation and apoptosis. Interestingly, cancer outlier profile analysis of human samples of acute myeloid leukemia (AML) in The Cancer Genome Atlas (TCGA) revealed a subtype of AML that strongly expressed EYA2. In addition, gene set enrichment analysis of human AML samples, including TCGA data, showed that this subtype of AML was more closely associated with the properties of leukemic stem cells in its gene expression signature than other AMLs. Therefore, EYA2 may be a target for molecular therapy in this subtype of AML, including PLZF-RARA APL. PMID:28416638

Effects of reward and punishment on task performance, mood and autonomic nervous function, and the interaction with personality.

PubMed

Sakuragi, Sokichi; Sugiyama, Yoshiki

2009-06-01

The effects of reward and punishment are different, and there are individual differences in sensitivity to reward and punishment. The purpose of this study was to investigate the effects of reward and punishment on task performance, mood, and autonomic nervous function, along with the interaction with personality. Twenty-one healthy female subjects volunteered for the experiment. The task performance was evaluated by required time and total errors while performing a Wisconsin Card Sorting Test. We assessed their personalities using the Minnesota Multiphasic Personality Inventory (MMPI) questionnaire, and mood states by a profile of mood states. Autonomic nervous function was estimated by a spectral analysis of heart rate variability, baroreflex sensitivity, and blood pressure. Repeated measures analysis of variance (ANOVA) revealed significant interaction of condition x time course on mood and autonomic nervous activity, which would indicate a less stressed state under the rewarding condition, but revealed no significant interaction of condition x time course on the task performance. The interactions with personality were further analyzed by repeated measures ANOVA applying the clinical scales of MMPI as independent variables, and significant interactions of condition x time course x Pt (psychasthenia) on task performance, mood, and blood pressure, were revealed. That is, the high Pt group, whose members tend to be sensitive and prone to worry, showed gradual improvement of task performance under the punishing situation with slight increase in systolic blood pressure, while showed no improvement under the rewarding situation with fatigue sense attenuation. In contrast, the low Pt group, whose members tend to be adaptive and self-confident, showed gradual improvement under the rewarding situation. Therefore, we should carefully choose the strategy of reward or punishment, considering the interaction with personality as well as the context in which it is given.

Profiles of behavioral problems in children who witness domestic violence.

PubMed

Spilsbury, James C; Kahana, Shoshana; Drotar, Dennis; Creeden, Rosemary; Flannery, Daniel J; Friedman, Steve

2008-01-01

Unlike previous investigations of shelter-based samples, our study examined whether profiles of adjustment problems occurred in a community-program-based sample of 175 school-aged children exposed to domestic violence. Cluster analysis revealed three stable profiles/clusters. The largest cluster (69%) consisted of children below clinical thresholds for any internalizing or externalizing problem. Children in the next largest cluster (18%) were characterized as having externalizing problems with or without internalizing problems. The smallest cluster (13%) consisted of children with internalizing problems only. Comparison across demographic and violence characteristics revealed that the profiles differed by child gender, mother's education, child's lifetime exposure to violence, and aspects of the event precipitating contact with the community program. Clinical and future research implications of study findings are discussed.

Personality profile of students entering dentistry, hygiene/therapy and dental nursing at one London dental institute.

PubMed

Belsi, A; Gallagher, J E; Asimakopoulou, K

2011-05-01

King's College London Dental Institute (KCLDI) is the largest school in the UK, training dental professionals: Dentists, Hygienists/Therapists and Dental Nurses. Although previous work has examined dental students, there is a dearth of studies on the personality profile of students of hygiene/therapy and dental nursing. To investigate the personality profile of students studying dentistry, hygiene/therapy and dental nursing at KCLDI, by programme, sex and ethnicity. All entrants into dentistry, hygiene/therapy and dental nursing at KCLDI were invited to participate in the study. A self report questionnaire including the brief version of the Five-Factor Model and personal details was administered to the 218 recruited students in groups and under supervised conditions.   One-way ANOVA on data from 148 questionnaires revealed significant differences; the medical graduate entrants to dentistry appeared to have a more extraverted profile than hygiene/therapy entrants (P<0.04). The graduate entrants to dentistry were more open to experiences than the direct entrants (P<0.03) and the dental nursing trainees (P<0.03). The medical graduate entrants also appeared more open to experiences than the dental nursing trainees; the latter also appeared to have a more sensitive profile compared to the medical entry students (P<0.03). No differences were found between groups in agreeableness and conscientiousness. The findings suggest the presence of personality differences between entrants to dentistry, hygiene/therapy and dental nursing. The implications of these findings are discussed. © 2011 John Wiley & Sons A/S.

Profiles of Identity Exploration and Commitment across Domains

ERIC Educational Resources Information Center

Bartoszuk, Karin; Pittman, Joe F.

2010-01-01

We examined the relationships between family structure, gender and age and profiles of identity exploration and commitment in the ideological (occupation, values, politics, religion, gender roles) and interpersonal identity (dating, friendships, and family) domains among 388 young adults. The general profile revealed low exploration in both…

Transcriptomic and lipidomic profiles of glycerolipids during Arabidopsis flower development.

PubMed

Nakamura, Yuki; Teo, Norman Z W; Shui, Guanghou; Chua, Christine H L; Cheong, Wei-Fun; Parameswaran, Sriram; Koizumi, Ryota; Ohta, Hiroyuki; Wenk, Markus R; Ito, Toshiro

2014-07-01

Flower glycerolipids are the yet-to-be discovered frontier of the lipidome. Although ample evidence suggests important roles for glycerolipids in flower development, stage-specific lipid profiling in tiny Arabidopsis flowers is challenging. Here, we utilized a transgenic system to synchronize flower development in Arabidopsis. The transgenic plant PAP1::AP1-GR ap1-1 cal-5 showed synchronized flower development upon dexamethasone treatment, which enabled massive harvesting of floral samples of homogenous developmental stages for glycerolipid profiling. Glycerolipid profiling revealed a decrease in concentrations of phospholipids involved in signaling during the early development stages, such as phosphatidic acid and phosphatidylinositol, and a marked increase in concentrations of nonphosphorous galactolipids during the late stage. Moreover, in the midstage, phosphatidylinositol 4,5-bisphosphate concentration was increased transiently, which suggests the stimulation of the phosphoinositide metabolism. Accompanying transcriptomic profiling of relevant glycerolipid metabolic genes revealed simultaneous induction of multiple phosphoinositide biosynthetic genes associated with the increased phosphatidylinositol 4,5-bisphosphate concentration, with a high degree of differential expression patterns for genes encoding other glycerolipid-metabolic genes. The phosphatidic acid phosphatase mutant pah1 pah2 showed flower developmental defect, suggesting a role for phosphatidic acid in flower development. Our concurrent profiling of glycerolipids and relevant metabolic gene expression revealed distinct metabolic pathways stimulated at different stages of flower development in Arabidopsis. © 2014 The Authors. New Phytologist © 2014 New Phytologist Trust.

Microwave-assisted chemical pre-treatment of waste sorghum leaves: Process optimization and development of an intelligent model for determination of volatile compound fractions.

PubMed

Rorke, Daneal C S; Suinyuy, Terence N; Gueguim Kana, E B

2017-01-01

This study reports the profiling of volatile compounds generated during microwave-assisted chemical pre-treatment of sorghum leaves. Compounds including acetic acid (0-186.26ng/g SL), furfural (0-240.80ng/g SL), 5-hydroxymethylfurfural (HMF) (0-19.20ng/g SL) and phenol (0-7.76ng/g SL) were detected. The reducing sugar production was optimized. An intelligent model based on Artificial Neural Networks (ANNs) was developed and validated to predict a profile of 21 volatile compounds under novel pre-treatment conditions. This model gave R 2 -values of up to 0.93. Knowledge extraction revealed furfural and phenol exhibited high sensitivity to acid- and alkali concentration and S:L ratio, while phenol showed high sensitivity to microwave duration and intensity. Furthermore, furfural production was majorly dependent on acid concentration and fit a dosage-response relationship model with a 2.5% HCl threshold. Significant non-linearities were observed between pre-treatment conditions and the profile of various compounds. This tool reduces analytical costs through virtual analytical instrumentation, improving process economics. Copyright © 2016 Elsevier Ltd. All rights reserved.

Exploration of dynamic dipole polarizability of impurity doped quantum dots in presence of noise

NASA Astrophysics Data System (ADS)

Ghosh, Anuja; Bera, Aindrila; Saha, Surajit; Arif, Sk. Md.; Ghosh, Manas

2018-02-01

Present study strives to perform a rigorous exploration of dynamic dipole polarizability (DDP) of GaAs quantum dot (QD) containing dopant with special reference to influence of Gaussian white noise. Several physical quantities have been varied over a range to observe the modulations of the DDP profiles. Aforesaid physical quantities include magnetic field, confinement potential, dopant location, dopant potential, noise strength, aluminium concentration (only for Alx Ga1 - x As alloy QD), position-dependent effective mass (PDEM), position-dependent dielectric screening function (PDDSF), anisotropy, hydrostatic pressure (HP) and temperature. The DDP profiles reveal noticeable characteristics governed by the particular physical quantity involved, presence/absence of noise, the manner (additive/multiplicative) noise is applied to the system and the incoming photon frequency. As a general observation we have found that additive noise causing greater deviation of the DDP profile from noise-free state than its multiplicative neighbor. The study highlights viable means of harnessing DDP of doped QD under the governance of noise by appropriate adjustment of several relevant factors. The study merits importance in the light of technological applications of QD-based devices where noise appears as an integral component.

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

PubMed

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

2011-12-01

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

Emission of OH* and CO2* during the high-temperature oxidation of acetone in reflected shock waves

NASA Astrophysics Data System (ADS)

Tereza, A. M.; Smirnov, V. N.; Vlasov, P. A.; Shumova, V. V.; Garmash, A. A.

2018-01-01

Experimental and kinetic modeling study of the ignition of a stoichiometric mixture of acetone with oxygen diluted by argon was carried out behind reflected shock waves within the temperature range of 1350-1810 K for the total mixture concentration [M 50] ~ 10-5 mol/cm3. Emission signals were recorded simultaneously for three different wavelengths: OH* (λ = 308 nm) and {{{CO}}}2* (λ1 = 365 nm; λ2 = 451 nm). It was revealed that the time it takes to reach the maximum of emission of OH* and {{{CO}}}2* is practically the same over the whole temperature range. At the same time, the emission profiles of {{{CO}}}2* after the maximum was attained, recorded at λ2 = 451 nm, differ noticeably from the profiles recorded at λ1 = 365 nm. For numerical modeling of the emission profiles of OH* and {{{CO}}}2* , the corresponding sets of excitation and quenching reactions available in the literature were used. In the course of our numerical simulations we succeeded in good agreement of our own experimental and simulation results on acetone ignition and the results available in the literature for conditions under consideration.

Flow resistance under conditions of intense gravel transport

USGS Publications Warehouse

Pitlick, John

1992-01-01

A study of flow resistance was undertaken in a channelized reach of the North Fork Toutle River, downstream of Mount St. Helens, Washington. Hydraulic and sediment transport data were collected in flows with velocities up to 3 m/s and shear stresses up to 7 times the critical value needed for bed load transport. Details of the flow structure as revealed in vertical velocity profiles indicate that weak bed load transport over a plane gravel bed has little effect on flow resistance. The plane gravel bed persists up to stresses ∼3 times critical, at which point, irregular bed forms appear. Bed forms greatly increase flow resistance and cause velocity profiles to become distorted. The latter arises as an effect of flows becoming depth-limited as bed form amplitude increases. At very high rates of bed load transport, an upper stage plane bed appeared. Velocity profiles measured in these flows match the law of the wall closely, with the equivalent roughness being well represented by ks = 3D84 of the bed load. The effects noted here will be important in very large floods or in rivers that are not free to widen, such as those cut into bedrock.

Surface analysis and depth profiling of corrosion products formed in lead pipes used to supply low alkalinity drinking water.

PubMed

Davidson, C M; Peters, N J; Britton, A; Brady, L; Gardiner, P H E; Lewis, B D

2004-01-01

Modern analytical techniques have been applied to investigate the nature of lead pipe corrosion products formed in pH adjusted, orthophosphate-treated, low alkalinity water, under supply conditions. Depth profiling and surface analysis have been carried out on pipe samples obtained from the water distribution system in Glasgow, Scotland, UK. X-ray diffraction spectrometry identified basic lead carbonate, lead oxide and lead phosphate as the principal components. Scanning electron microscopy/energy-dispersive x-ray spectrometry revealed the crystalline structure within the corrosion product and also showed spatial correlations existed between calcium, iron, lead, oxygen and phosphorus. Elemental profiling, conducted by means of secondary ion mass spectrometry (SIMS) and secondary neutrals mass spectrometry (SNMS) indicated that the corrosion product was not uniform with depth. However, no clear stratification was apparent. Indeed, counts obtained for carbonate, phosphate and oxide were well correlated within the depth range probed by SIMS. SNMS showed relationships existed between carbon, calcium, iron, and phosphorus within the bulk of the scale, as well as at the surface. SIMS imaging confirmed the relationship between calcium and lead and suggested there might also be an association between chloride and phosphorus.

Comparative Lipidomic Profiling of S. cerevisiae and Four Other Hemiascomycetous Yeasts

PubMed Central

Hein, Eva-Maria; Hayen, Heiko

2012-01-01

Glycerophospholipids (GP) are the building blocks of cellular membranes and play essential roles in cell compartmentation, membrane fluidity or apoptosis. In addition, GPs are sources for multifunctional second messengers. Whereas the genome and proteome of the most intensively studied eukaryotic model organism, the baker’s yeast (Saccharomyces cerevisiae), are well characterized, the analysis of its lipid composition is still at the beginning. Moreover, different yeast species can be distinguished on the DNA, RNA and protein level, but it is currently unknown if they can also be differentiated by determination of their GP pattern. Therefore, the GP compositions of five different yeast strains, grown under identical environmental conditions, were elucidated using high performance liquid chromatography coupled to negative electrospray ionization-hybrid linear ion trap-Fourier transform ion cyclotron resonance mass spectrometry in single and multistage mode. Using this approach, relative quantification of more than 100 molecular species belonging to nine GP classes was achieved. The comparative lipidomic profiling of Saccharomyces cerevisiae, Saccharomyces bayanus, Kluyveromyces thermotolerans, Pichia angusta, and Yarrowia lipolytica revealed characteristic GP profiles for each strain. However, genetically related yeast strains show similarities in their GP compositions, e.g., Saccharomyces cerevisiae and Saccharomyces bayanus. PMID:24957378

Hybrid catechin silica nanoparticle influence on Cu(II) toxicity and morphological lesions in primary neuronal cells.

PubMed

Halevas, E; Nday, C M; Salifoglou, A

2016-10-01

Morphological alterations compromising inter-neuronal connectivity may be directly linked to learning-memory deficits in Central Nervous System neurodegenerative processes. Cu(II)-mediated oxidative stress plays a pivotal role in regulating redox reactions generating reactive oxygen species (ROS) and reactive nitrogen species (RNS), known contributors to Alzheimer's disease (AD) pathology. The antioxidant properties of flavonoid catechin have been well-documented in neurodegenerative processes. However, the impact that catechin encapsulation in nanoparticles may have on neuronal survival and morphological lesions has been poorly demonstrated. To investigate potential effects of nano-encapsulated catechin on neuronal survival and morphological aberrations in primary rat hippocampal neurons, poly(ethyleneglycol) (PEG) and cetyltrimethylammonium bromide (CTAB)-modified silica nanoparticles were synthesized. Catechin was loaded on silica nanoparticles in a concentration-dependent fashion, and release studies were carried out. Further physicochemical characterization of the new nano-materials included elemental analysis, particle size, z-potential, FT-IR, Brunauer-Emmett-Teller (BET), thermogravimetric (TGA), and scanning electron microscopy (SEM) analysis in order to optimize material composition linked to the delivery of loaded catechin in the hippocampal cellular milieu. The findings reveal that, under Cu(II)-induced oxidative stress, the loading ability of the PEGylated/CTAB silica nanoparticles was concentration-dependent, based on their catechin release profile. The overall bio-activity profile of the new hybrid nanoparticles a) denoted their enhanced protective activity against oxidative stress and hippocampal cell survival compared to previously reported quercetin, b) revealed that morphological lesions affecting neuronal integrity can be counterbalanced at high copper concentrations, and c) warrants in-depth perusal of molecular events underlying neuronal function and degeneration, collectively linked to preventive nanotechnology in neurodegeneration. Copyright © 2016 Elsevier Inc. All rights reserved.

Pluripotent and Multipotent Stem Cells Display Distinct Hypoxic miRNA Expression Profiles

PubMed Central

Agrawal, Rahul; Dale, Tina P.; Al-Zubaidi, Mohammed A.; Benny Malgulwar, Prit; Forsyth, Nicholas R.; Kulshreshtha, Ritu

2016-01-01

MicroRNAs are reported to have a crucial role in the regulation of self-renewal and differentiation of stem cells. Hypoxia has been identified as a key biophysical element of the stem cell culture milieu however, the link between hypoxia and miRNA expression in stem cells remains poorly understood. We therefore explored miRNA expression in hypoxic human embryonic and mesenchymal stem cells (hESCs and hMSCs). A total of 50 and 76 miRNAs were differentially regulated by hypoxia (2% O2) in hESCs and hMSCs, respectively, with a negligible overlap of only three miRNAs. We found coordinate regulation of precursor and mature miRNAs under hypoxia suggesting their regulation mainly at transcriptional level. Hypoxia response elements were located upstream of 97% of upregulated hypoxia regulated miRNAs (HRMs) suggesting hypoxia-inducible-factor (HIF) driven transcription. HIF binding to the candidate cis-elements of specific miRNAs under hypoxia was confirmed by Chromatin immunoprecipitation coupled with qPCR. Role analysis of a subset of upregulated HRMs identified linkage to reported inhibition of differentiation while a downregulated subset of HRMs had a putative role in the promotion of differentiation. MiRNA-target prediction correlation with published hypoxic hESC and hMSC gene expression profiles revealed HRM target genes enriched in the cytokine:cytokine receptor, HIF signalling and pathways in cancer. Overall, our study reveals, novel and distinct hypoxia-driven miRNA signatures in hESCs and hMSCs with the potential for application in optimised culture and differentiation models for both therapeutic application and improved understanding of stem cell biology. PMID:27783707

Global Genetic Response in a Cancer Cell: Self-Organized Coherent Expression Dynamics

PubMed Central

Tsuchiya, Masa; Hashimoto, Midori; Takenaka, Yoshiko; Motoike, Ikuko N.; Yoshikawa, Kenichi

2014-01-01

Understanding the basic mechanism of the spatio-temporal self-control of genome-wide gene expression engaged with the complex epigenetic molecular assembly is one of major challenges in current biological science. In this study, the genome-wide dynamical profile of gene expression was analyzed for MCF-7 breast cancer cells induced by two distinct ErbB receptor ligands: epidermal growth factor (EGF) and heregulin (HRG), which drive cell proliferation and differentiation, respectively. We focused our attention to elucidate how global genetic responses emerge and to decipher what is an underlying principle for dynamic self-control of genome-wide gene expression. The whole mRNA expression was classified into about a hundred groups according to the root mean square fluctuation (rmsf). These expression groups showed characteristic time-dependent correlations, indicating the existence of collective behaviors on the ensemble of genes with respect to mRNA expression and also to temporal changes in expression. All-or-none responses were observed for HRG and EGF (biphasic statistics) at around 10–20 min. The emergence of time-dependent collective behaviors of expression occurred through bifurcation of a coherent expression state (CES). In the ensemble of mRNA expression, the self-organized CESs reveals distinct characteristic expression domains for biphasic statistics, which exhibits notably the presence of criticality in the expression profile as a route for genomic transition. In time-dependent changes in the expression domains, the dynamics of CES reveals that the temporal development of the characteristic domains is characterized as autonomous bistable switch, which exhibits dynamic criticality (the temporal development of criticality) in the genome-wide coherent expression dynamics. It is expected that elucidation of the biophysical origin for such critical behavior sheds light on the underlying mechanism of the control of whole genome. PMID:24831017

Comprehensive Genomic Analysis and Expression Profiling of the NOX Gene Families under Abiotic Stresses and Hormones in Plants.

PubMed

Chang, Yan-Li; Li, Wen-Yan; Miao, Hai; Yang, Shuai-Qi; Li, Ri; Wang, Xiang; Li, Wen-Qiang; Chen, Kun-Ming

2016-02-23

Plasma membrane NADPH oxidases (NOXs) are key producers of reactive oxygen species under both normal and stress conditions in plants and they form functional subfamilies. Studies of these subfamilies indicated that they show considerable evolutionary selection. We performed a comparative genomic analysis that identified 50 ferric reduction oxidases (FRO) and 77 NOX gene homologs from 20 species representing the eight major plant lineages within the supergroup Plantae: glaucophytes, rhodophytes, chlorophytes, bryophytes, lycophytes, gymnosperms, monocots, and eudicots. Phylogenetic and structural analysis classified these FRO and NOX genes into four well-conserved groups represented as NOX, FRO I, FRO II, and FRO III. Further analysis of NOXs of phylogenetic and exon/intron structures showed that single intron loss and gain had occurred, yielding the diversified gene structures during the evolution of NOXs family genes and which were classified into four conserved subfamilies which are represented as Sub.I, Sub.II, Sub.III, and Sub.IV. Additionally, both available global microarray data analysis and quantitative real-time PCR experiments revealed that the NOX genes in Arabidopsis and rice (Oryza sativa) have different expression patterns in different developmental stages, various abiotic stresses and hormone treatments. Finally, coexpression network analysis of NOX genes in Arabidopsis and rice revealed that NOXs have significantly correlated expression profiles with genes which are involved in plants metabolic and resistance progresses. All these results suggest that NOX family underscores the functional diversity and divergence in plants. This finding will facilitate further studies of the NOX family and provide valuable information for functional validation of this family in plants. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Metabolic profiling of PPARα−/− mice reveals defects in carnitine and amino acid homeostasis that are partially reversed by oral carnitine supplementation

PubMed Central

Makowski, Liza; Noland, Robert C.; Koves, Timothy R.; Xing, Weibing; Ilkayeva, Olga R.; Muehlbauer, Michael J.; Stevens, Robert D.; Muoio, Deborah M.

2009-01-01

Peroxisome proliferator-activated receptor-α (PPARα) is a master transcriptional regulator of β-oxidation and a prominent target of hypolipidemic drugs. To gain deeper insights into the systemic consequences of impaired fat catabolism, we used quantitative, mass spectrometry-based metabolic profiling to investigate the fed-to-fasted transition in PPARα+/+ and PPARα−/− mice. Compared to PPARα+/+ animals, acylcarnitine profiles of PPARα−/− mice revealed 2- to 4-fold accumulation of long-chain species in the plasma, whereas short-chain species were reduced by as much as 69% in plasma, liver, and skeletal muscle. These results reflect a metabolic bottleneck downstream of carnitine palmitoyltransferase-1, a mitochondrial enzyme that catalyzes the first step in β-oxidation. Organic and amino acid profiles of starved PPARα−/− mice suggested compromised citric acid cycle flux, enhanced urea cycle activity, and increased amino acid catabolism. PPARα−/− mice had 40–50% lower plasma and tissue levels of free carnitine, corresponding with diminished hepatic expression of genes involved in carnitine biosynthesis and transport. One week of oral carnitine supplementation conferred partial metabolic recovery in the PPARα−/− mice. In summary, comprehensive metabolic profiling revealed novel biomarkers of defective fat oxidation, while also highlighting the potential value of supplemental carnitine as a therapy and diagnostic tool for metabolic disorders.—Makowski, L., Noland, R. C., Koves, T. R., Xing, W., Ilkayeva, O. R., Muehlbauer, M. J., Stevens, R. D., Muoio, D. M. Metabolic profiling of PPARα−/− mice reveals defects in carnitine and amino acid homeostasis that are partially reversed by oral carnitine supplementation. PMID:18945875

Perinatal Bisphenol A Exposure Induces Chronic Inflammation in Rabbit Offspring via Modulation of Gut Bacteria and Their Metabolites

PubMed Central

Veeramachaneni, D. N. Rao; Walters, William A.; Lozupone, Catherine; Palmer, Jennifer; Hewage, M. K. Kurundu; Bhatnagar, Rohil; Amir, Amnon; Kennett, Mary J.; Knight, Rob

2017-01-01

ABSTRACT Bisphenol A (BPA) accumulates in the maturing gut and liver in utero and is known to alter gut bacterial profiles in offspring. Gut bacterial dysbiosis may contribute to chronic colonic and systemic inflammation. We hypothesized that perinatal BPA exposure-induced intestinal (and liver) inflammation in offspring is due to alterations in the microbiome and colonic metabolome. The 16S rRNA amplicon sequencing analysis revealed differences in beta diversity with a significant reduction in the relative abundances of short-chain fatty acid (SCFA) producers such as Oscillospira and Ruminococcaceae due to BPA exposure. Furthermore, BPA exposure reduced fecal SCFA levels and increased systemic lipopolysaccharide (LPS) levels. BPA exposure-increased intestinal permeability was ameliorated by the addition of SCFA in vitro. Metabolic fingerprints revealed alterations in global metabolism and amino acid metabolism. Thus, our findings indicate that perinatal BPA exposure may cause gut bacterial dysbiosis and altered metabolite profiles, particularly SCFA profiles, leading to chronic colon and liver inflammation. IMPORTANCE Emerging evidence suggests that environmental toxicants may influence inflammation-promoted chronic disease susceptibility during early life. BPA, an environmental endocrine disruptor, can transfer across the placenta and accumulate in fetal gut and liver. However, underlying mechanisms for BPA-induced colonic and liver inflammation are not fully elucidated. In this report, we show how perinatal BPA exposure in rabbits alters gut microbiota and their metabolite profiles, which leads to colonic and liver inflammation as well as to increased gut permeability as measured by elevated serum lipopolysaccharide (LPS) levels in the offspring. Also, perinatal BPA exposure leads to reduced levels of gut bacterial diversity and bacterial metabolites (short-chain fatty acids [SCFA]) and elevated gut permeability—three common early biomarkers of inflammation-promoted chronic diseases. In addition, we showed that SCFA ameliorated BPA-induced intestinal permeability in vitro. Thus, our study results suggest that correcting environmental toxicant-induced bacterial dysbiosis early in life may reduce the risk of chronic diseases later in life. PMID:29034330

Development of nanoemulsion for efficient brain parenteral delivery of cefuroxime: designs, characterizations, and pharmacokinetics

PubMed Central

Harun, Siti Norhawani; Nordin, Syafinaz Amin; Gani, Siti Salwa Abd; Shamsuddin, Ahmad Fuad; Basri, Mahiran; Basri, Hamidon Bin

2018-01-01

Background and aim Drugs that are effective against diseases in the central nervous system and reach the brain via blood must pass through the blood–brain barrier (BBB), a unique interface that protects against potential harmful molecules. This presents a major challenge in neuro-drug delivery. This study attempts to fabricate the cefuroxime-loaded nanoemulsion (CLN) to increase drug penetration into the brain when parenterally administered. Methods The nanoemulsions were formulated using a high-pressure homogenization technique and were characterized for their physicochemical properties. Results The characterizations revealed a particle size of 100.32±0.75 nm, polydispersity index of 0.18±0.01, zeta potential of −46.9±1.39 mV, viscosity of 1.24±0.34 cps, and osmolality of 285.33±0.58 mOsm/kg, indicating that the nanoemulsion has compatibility for parenteral application. CLN was physicochemically stable within 6 months of storage at 4°C, and the transmission electron microscopy revealed that the CLN droplets were almost spherical in shape. The in vitro release of CLN profile followed a sustained release pattern. The pharmacokinetic profile of CLN showed a significantly higher Cmax, area under the curve (AUC)0–t, prolonged half-life, and lower total plasma clearance, indicating that the systemic concentration of cefuroxime was higher in CLN-treated rats as compared to cefuroxime-free treated rats. A similar profile was obtained for the biodistribution of cefuroxime in the brain, in which CLN showed a significantly higher Cmax, AUC0–t, prolonged half-life, and lower clearance as compared to free cefuroxime solution. Conclusion Overall, CLN showed excellent physicochemical properties, fulfilled the requirements for parenteral administration, and presented improved in vivo pharmacokinetic profile, which reflected its practical approach to enhance cefuroxime delivery to the brain. PMID:29731632

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

NASA Astrophysics Data System (ADS)

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

2014-06-01

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

Comparing EPA production and fatty acid profiles of three Phaeodactylum tricornutum strains under western Norwegian climate conditions.

PubMed

Steinrücken, Pia; Prestegard, Siv Kristin; de Vree, Jeroen Hendrik; Storesund, Julia E; Pree, Bernadette; Mjøs, Svein Are; Erga, Svein Rune

2018-03-01

Microalgae could provide a sustainable alternative to fish oil as a source for the omega-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). However, growing microalgae on a large-scale is still more cost-intensive than fish oil production, and outdoor productivities vary greatly with reactor type, geographic location, climate conditions and microalgae species or even strains. The diatom Phaeodactylum tricornutum has been intensively investigated for its potential in large-scale production, due to its robustness and comparatively high growth rates and EPA content. Yet, most research have been performed in southern countries and with a single commercial P . tricornutum strain, while information about productivities at higher latitudes and of local strains is scarce. We examined the potential of the climate conditions in Bergen, western Norway for outdoor cultivation of P . tricornutum in flat panel photobioreactors and cultivated three different strains simultaneously, one commercial strain from Spain (Fito) and two local isolates (M28 and B58), to assess and compare their biomass and EPA productivities, and fatty acid (FA) profiles. The three strains possessed similar biomass productivities (average volumetric productivities of 0.20, 0.18, and 0.21 g L - 1  d - 1 ), that were lower compared to productivities reported from southern latitudes. However, EPA productivities differed between the strains (average volumetric productivities of 9.8, 5.7 and 6.9 mg L - 1  d - 1 ), due to differing EPA contents (average of 4.4, 3.2 and 3.1% of dry weight), and were comparable to results from Italy. The EPA content of strain Fito of 4.4% is higher than earlier reported for P . tricornutum (2.6-3.1%) and was only apparent under outdoor conditions. A principal component analysis (PCA) of the relative FA composition revealed strain-specific profiles. However, including data from laboratory experiments, revealed more significant differences between outdoor and laboratory-grown cultures than between the strains, and higher EPA contents in outdoor grown cultures.

Variations in adolescents' motivational characteristics across gender and physical activity patterns: A latent class analysis approach.

PubMed

Lawler, Margaret; Heary, Caroline; Nixon, Elizabeth

2017-08-17

Neglecting to take account of the underlying context or type of physical activity (PA) that underpins overall involvement has resulted in a limited understanding of adolescents' PA participation. The purpose of the present research was to identify male and female adolescents' leisure time PA patterns and examine whether psychological processes derived from self-determination theory differ as a function of the pattern of PA undertaken. Nine hundred ninety-five students (61.2% females, 38.8% males; M age = 13.72 years, SD = 1.25) from eight secondary schools in Dublin, Ireland completed a physical activity recall 7 day diary and measures of intrinsic motivation, competence, relatedness, autonomy and autonomy support. Based on the diary five binary indicators of physical activity were derived reflecting recommended levels of MVPA on a minimum of 3 days, at least three sessions of non-organized physical activity (e.g. jog), team sport, individual sport, and organized non-sport physical activity (e.g. dance). Latent class analysis was used to identify subgroups of adolescents that engaged in similar patterns of physical activity. Profiles of physical activity participation were subsequently compared on motivational characteristics using Kruskal-Wallis tests. Latent class analysis revealed six distinct classes for girls (Organized Run/Swim & Dance/Gym; Organized Dance; Leisure Active Team Sport; Active Individual Sport; Walk/Run/Outdoor games; Non-Participation) and five for boys (Leisure Active Gym; Leisure Active Individual Sport; Active Team Sport; Active Mixed Type; Non-Participation). Significant differences were found between the classes. Girls characterized by participation in team or individual sport, and boys represented by team sport participation demonstrated significantly higher self-determined motivational characteristics relative to other profiles of physical activity. This research offers a nuanced insight into the underlying type of activities that constitute overall patterns of PA among adolescent boys and girls and further reveals that psychological processes vary dependent on the profile of physical activity undertaken. The findings may be useful for informing interventions aimed at promoting physical activity among young people.

Evolution of N-converting bacteria during the start-up of anaerobic digestion coupled biological nitrogen removal pilot-scale bioreactors treating high-strength animal waste slurry.

PubMed

Anceno, Alfredo J; Rouseau, Pierre; Béline, Fabrice; Shipin, Oleg V; Dabert, Patrick

2009-07-01

Animal wastes have been successfully employed in anaerobic biogas production, viewed as a pragmatic approach to rationalize energy costs in animal farms. Effluents resulting from that process however are still high in nitrogen such that attempts were made to couple biological nitrogen removal (BNR) with anaerobic digestion (AD). The demand for organic substrate in such system is partitioned between the anaerobic metabolism in AD and the heterotrophic denitrification cascade following the autotrophic nitrification in BNR. Investigation of underlying N-converting taxa with respect to process conditions is therefore critical in optimizing N-removal in such treatment system. In this study, a pilot-scale intermittently aerated BNR bioreactor was started up either independently or in series with the AD bioreactor to treat high-strength swine waste slurry. The compositions of NH(3)-oxidizing bacteria (AOB), NO(2)(-)-oxidizing bacteria (NOB) and denitrifiers (nosZ gene) were profiled by polymerase chain reaction-capillary electrophoresis/single strand conformation polymorphism (PCR-CE/SSCP) technique and clone library analysis. Performance data suggested that these two process configurations significantly differ in the modes of biological N-removal. PCR-CE/SSCP based profiling of the underlying nitrifying bacteria also revealed the selection of distinct taxa between process configurations. Under the investigated process conditions, correlation of performance data and composition of underlying nitrifiers suggest that the stand-alone BNR bioreactor tended to favor N-removal via NO(3)(-) whereas the coupled bioreactors could be optimized to achieve the same via a NO(2)(-) shortcut.

Pharmacokinetic profiles contribute to the differences in behavioral pharmacology of 071031B enantiomers as novel serotonin and norepinephrine reuptake inhibitors.

PubMed

Xue, Rui; Li, Ying; He, Xin-Hua; Jin, Zeng-Liang; Fan, Shi-Yong; Zhang, Ting-Ting; Li, Nuo-Min; Yuan, Li; Zheng, Ai-Ping; Zhong, Bo-Hua; Li, Yun-Feng; Zhang, You-Zhi

2017-03-01

Our previous study indicated that a chiral compound 071031B was a novel serotonin and noradrenaline reuptake inhibitor with superior antidepressant activity compared to duloxetine. The present study aimed to investigate chiral pharmacology differences of 071031B enantiomers, S-071031B and R-071031B, and disclose mechanisms underlying the behavioral differences based on target profiles and pharmacokinetic profiles. In vivo behavioral tests indicated that S-071031B was more potent than R-071031B in two depression models (the forced swimming test in mice and rats) and two pain models (the acetic acid-induced writhing and formalin tests in mice). In vitro assays revealed that both S-071031B and R-071031B showed high affinity for human serotonin transporters and norepinephrine transporters with equal potency, and showed consistently equipotent inhibitory effects on serotonin and norepinephrine uptake. Pharmacokinetic studies demonstrated that oral availability and hepatic metabolism, rather than pH stability, intestinal transport, and plasma binding, contributed to enantiomers' behavioral differences. Based on these findings, it is suggested that S-071031B is a more active enantiomer, and the differential pharmacokinetic profiles, but not target affinity, contribute to differences of S-071031B and R-071031B in behavioral pharmacology. Moreover, current PK-PD study may provide positive exploration for chiral antidepressants development.

Potential of in vivo real-time gastric gas profiling: a pilot evaluation of heat-stress and modulating dietary cinnamon effect in an animal model

NASA Astrophysics Data System (ADS)

Ou, Jian Zhen; Cottrell, Jeremy J.; Ha, Nam; Pillai, Naresh; Yao, Chu K.; Berean, Kyle J.; Ward, Stephanie A.; Grando, Danilla; Muir, Jane G.; Harrison, Christopher J.; Wijesiriwardana, Udani; Dunshea, Frank R.; Gibson, Peter R.; Kalantar-Zadeh, Kourosh

2016-09-01

Gastroenterologists are still unable to differentiate between some of the most ordinary disorders of the gut and consequently patients are misdiagnosed. We have developed a swallowable gas sensor capsule for addressing this. The gases of the gut are the by-product of the fermentation processes during digestion, affected by the gut state and can consequently provide the needed information regarding the health of the gut. Here we present the first study on gas sensor capsules for revealing the effect of a medical supplement in an animal (pig) model. We characterise the real-time alterations of gastric-gas in response to environmental heat-stress and dietary cinnamon and use the gas profiles for understanding the bio-physiological changes. Under no heat-stress, feeding increases gastric CO2 concentration, while dietary cinnamon reduces it due to decrease in gastric acid and pepsin secretion. Alternatively, heat-stress leads to hyperventilation in pigs, which reduces CO2 concentration and with the cinnamon treatment, CO2 diminishes even more, resulting in health improvement outcomes. Overall, a good repeatability in gas profiles is also observed. The model demonstrates the strong potential of real-time gas profiler in providing new physiological information that will impact understanding of therapeutics, presenting a highly reliable device for monitoring/diagnostics of gastrointestinal disorders.

Potential of in vivo real-time gastric gas profiling: a pilot evaluation of heat-stress and modulating dietary cinnamon effect in an animal model.

PubMed

Ou, Jian Zhen; Cottrell, Jeremy J; Ha, Nam; Pillai, Naresh; Yao, Chu K; Berean, Kyle J; Ward, Stephanie A; Grando, Danilla; Muir, Jane G; Harrison, Christopher J; Wijesiriwardana, Udani; Dunshea, Frank R; Gibson, Peter R; Kalantar-Zadeh, Kourosh

2016-09-16

Gastroenterologists are still unable to differentiate between some of the most ordinary disorders of the gut and consequently patients are misdiagnosed. We have developed a swallowable gas sensor capsule for addressing this. The gases of the gut are the by-product of the fermentation processes during digestion, affected by the gut state and can consequently provide the needed information regarding the health of the gut. Here we present the first study on gas sensor capsules for revealing the effect of a medical supplement in an animal (pig) model. We characterise the real-time alterations of gastric-gas in response to environmental heat-stress and dietary cinnamon and use the gas profiles for understanding the bio-physiological changes. Under no heat-stress, feeding increases gastric CO2 concentration, while dietary cinnamon reduces it due to decrease in gastric acid and pepsin secretion. Alternatively, heat-stress leads to hyperventilation in pigs, which reduces CO2 concentration and with the cinnamon treatment, CO2 diminishes even more, resulting in health improvement outcomes. Overall, a good repeatability in gas profiles is also observed. The model demonstrates the strong potential of real-time gas profiler in providing new physiological information that will impact understanding of therapeutics, presenting a highly reliable device for monitoring/diagnostics of gastrointestinal disorders.

Understanding developmental and adaptive cues in pine through metabolite profiling and co-expression network analysis

PubMed Central

Cañas, Rafael A.; Canales, Javier; Muñoz-Hernández, Carmen; Granados, Jose M.; Ávila, Concepción; García-Martín, María L.; Cánovas, Francisco M.

2015-01-01

Conifers include long-lived evergreen trees of great economic and ecological importance, including pines and spruces. During their long lives conifers must respond to seasonal environmental changes, adapt to unpredictable environmental stresses, and co-ordinate their adaptive adjustments with internal developmental programmes. To gain insights into these responses, we examined metabolite and transcriptomic profiles of needles from naturally growing 25-year-old maritime pine (Pinus pinaster L. Aiton) trees over a year. The effect of environmental parameters such as temperature and rain on needle development were studied. Our results show that seasonal changes in the metabolite profiles were mainly affected by the needles’ age and acclimation for winter, but changes in transcript profiles were mainly dependent on climatic factors. The relative abundance of most transcripts correlated well with temperature, particularly for genes involved in photosynthesis or winter acclimation. Gene network analysis revealed relationships between 14 co-expressed gene modules and development and adaptation to environmental stimuli. Novel Myb transcription factors were identified as candidate regulators during needle development. Our systems-based analysis provides integrated data of the seasonal regulation of maritime pine growth, opening new perspectives for understanding the complex regulatory mechanisms underlying conifers’ adaptive responses. Taken together, our results suggest that the environment regulates the transcriptome for fine tuning of the metabolome during development. PMID:25873654

Analysis of Chromobacterium sp. natural isolates from different Brazilian ecosystems

PubMed Central

Lima-Bittencourt, Cláudia I; Astolfi-Filho, Spartaco; Chartone-Souza, Edmar; Santos, Fabrício R; Nascimento, Andréa MA

2007-01-01

Background Chromobacterium violaceum is a free-living bacterium able to survive under diverse environmental conditions. In this study we evaluate the genetic and physiological diversity of Chromobacterium sp. isolates from three Brazilian ecosystems: Brazilian Savannah (Cerrado), Atlantic Rain Forest and Amazon Rain Forest. We have analyzed the diversity with molecular approaches (16S rRNA gene sequences and amplified ribosomal DNA restriction analysis) and phenotypic surveys of antibiotic resistance and biochemistry profiles. Results In general, the clusters based on physiological profiles included isolates from two or more geographical locations indicating that they are not restricted to a single ecosystem. The isolates from Brazilian Savannah presented greater physiologic diversity and their biochemical profile was the most variable of all groupings. The isolates recovered from Amazon and Atlantic Rain Forests presented the most similar biochemical characteristics to the Chromobacterium violaceum ATCC 12472 strain. Clusters based on biochemical profiles were congruent with clusters obtained by the 16S rRNA gene tree. According to the phylogenetic analyses, isolates from the Amazon Rain Forest and Savannah displayed a closer relationship to the Chromobacterium violaceum ATCC 12472. Furthermore, 16S rRNA gene tree revealed a good correlation between phylogenetic clustering and geographic origin. Conclusion The physiological analyses clearly demonstrate the high biochemical versatility found in the C. violaceum genome and molecular methods allowed to detect the intra and inter-population diversity of isolates from three Brazilian ecosystems. PMID:17584942

Antimicrobial breakpoint estimation accounting for variability in pharmacokinetics

PubMed Central

Bi, Goue Denis Gohore; Li, Jun; Nekka, Fahima

2009-01-01

Background Pharmacokinetic and pharmacodynamic (PK/PD) indices are increasingly being used in the microbiological field to assess the efficacy of a dosing regimen. In contrast to methods using MIC, PK/PD-based methods reflect in vivo conditions and are more predictive of efficacy. Unfortunately, they entail the use of one PK-derived value such as AUC or Cmax and may thus lead to biased efficiency information when the variability is large. The aim of the present work was to evaluate the efficacy of a treatment by adjusting classical breakpoint estimation methods to the situation of variable PK profiles. Methods and results We propose a logical generalisation of the usual AUC methods by introducing the concept of "efficiency" for a PK profile, which involves the efficacy function as a weight. We formulated these methods for both classes of concentration- and time-dependent antibiotics. Using drug models and in silico approaches, we provide a theoretical basis for characterizing the efficiency of a PK profile under in vivo conditions. We also used the particular case of variable drug intake to assess the effect of the variable PK profiles generated and to analyse the implications for breakpoint estimation. Conclusion Compared to traditional methods, our weighted AUC approach gives a more powerful PK/PD link and reveals, through examples, interesting issues about the uniqueness of therapeutic outcome indices and antibiotic resistance problems. PMID:19558679

Identification of an Effective Early Signaling Signature during Neo-Vasculogenesis In Vivo by Ex Vivo Proteomic Profiling

PubMed Central

Rohban, Rokhsareh; Reinisch, Andreas; Etchart, Nathalie; Schallmoser, Katharina; Hofmann, Nicole A.; Szoke, Krisztina; Brinchmann, Jan E.; Rad, Ehsan Bonyadi; Rohde, Eva; Strunk, Dirk

2013-01-01

Therapeutic neo-vasculogenesis in vivo can be achieved by the co-transplantation of human endothelial colony-forming progenitor cells (ECFCs) with mesenchymal stem/progenitor cells (MSPCs). The underlying mechanism is not completely understood thus hampering the development of novel stem cell therapies. We hypothesized that proteomic profiling could be used to retrieve the in vivo signaling signature during the initial phase of human neo-vasculogenesis. ECFCs and MSPCs were therefore either transplanted alone or co-transplanted subcutaneously into immune deficient mice. Early cell signaling, occurring within the first 24 hours in vivo, was analyzed using antibody microarray proteomic profiling. Vessel formation and persistence were verified in parallel transplants for up to 24 weeks. Proteomic analysis revealed significant alteration of regulatory components including caspases, calcium/calmodulin-dependent protein kinase, DNA protein kinase, human ErbB2 receptor-tyrosine kinase as well as mitogen-activated protein kinases. Caspase-4 was selected from array results as one therapeutic candidate for targeting vascular network formation in vitro as well as modulating therapeutic vasculogenesis in vivo. As a proof-of-principle, caspase-4 and general caspase-blocking led to diminished endothelial network formation in vitro and significantly decreased vasculogenesis in vivo. Proteomic profiling ex vivo thus unraveled a signaling signature which can be used for target selection to modulate neo-vasculogenesis in vivo. PMID:23826172

Integrated Metabolite and Transcript Profiling Identify a Biosynthetic Mechanism for Hispidol in Medicago truncatula Cell Cultures1[C][W][OA

PubMed Central

Farag, Mohamed A.; Deavours, Bettina E.; de Fátima, Ângelo; Naoumkina, Marina; Dixon, Richard A.; Sumner, Lloyd W.

2009-01-01

Metabolic profiling of elicited barrel medic (Medicago truncatula) cell cultures using high-performance liquid chromatography coupled to photodiode and mass spectrometry detection revealed the accumulation of the aurone hispidol (6-hydroxy-2-[(4-hydroxyphenyl)methylidene]-1-benzofuran-3-one) as a major response to yeast elicitor. Parallel, large-scale transcriptome profiling indicated that three peroxidases, MtPRX1, MtPRX2, and MtPRX3, were coordinately induced with the accumulation of hispidol. MtPRX1 and MtPRX2 exhibited aurone synthase activity based upon in vitro substrate specificity and product profiles of recombinant proteins expressed in Escherichia coli. Hispidol possessed significant antifungal activity relative to other M. truncatula phenylpropanoids tested but has not been reported in this species before and was not found in differentiated roots in which high levels of the peroxidase transcripts accumulated. We propose that hispidol is formed in cell cultures by metabolic spillover when the pool of its precursor, isoliquiritigenin, builds up as a result of an imbalance between the upstream and downstream segments of the phenylpropanoid pathway, reflecting the plasticity of plant secondary metabolism. The results illustrate that integration of metabolomics and transcriptomics in genetically reprogrammed plant cell cultures is a powerful approach for the discovery of novel bioactive secondary metabolites and the mechanisms underlying their generation. PMID:19571306

Potential of in vivo real-time gastric gas profiling: a pilot evaluation of heat-stress and modulating dietary cinnamon effect in an animal model

PubMed Central

Ou, Jian Zhen; Cottrell, Jeremy J.; Ha, Nam; Pillai, Naresh; Yao, Chu K.; Berean, Kyle J.; Ward, Stephanie A.; Grando, Danilla; Muir, Jane G.; Harrison, Christopher J.; Wijesiriwardana, Udani; Dunshea, Frank R.; Gibson, Peter R.; Kalantar-zadeh, Kourosh

2016-01-01

Gastroenterologists are still unable to differentiate between some of the most ordinary disorders of the gut and consequently patients are misdiagnosed. We have developed a swallowable gas sensor capsule for addressing this. The gases of the gut are the by-product of the fermentation processes during digestion, affected by the gut state and can consequently provide the needed information regarding the health of the gut. Here we present the first study on gas sensor capsules for revealing the effect of a medical supplement in an animal (pig) model. We characterise the real-time alterations of gastric-gas in response to environmental heat-stress and dietary cinnamon and use the gas profiles for understanding the bio-physiological changes. Under no heat-stress, feeding increases gastric CO2 concentration, while dietary cinnamon reduces it due to decrease in gastric acid and pepsin secretion. Alternatively, heat-stress leads to hyperventilation in pigs, which reduces CO2 concentration and with the cinnamon treatment, CO2 diminishes even more, resulting in health improvement outcomes. Overall, a good repeatability in gas profiles is also observed. The model demonstrates the strong potential of real-time gas profiler in providing new physiological information that will impact understanding of therapeutics, presenting a highly reliable device for monitoring/diagnostics of gastrointestinal disorders. PMID:27633400

Antiphospholipid Antibody Syndrome Associated with Graves’ Disease Presenting As Inferior Vena Cava Thrombosis with Bilateral Lower Limb DVT

PubMed Central

Jain, Ankur

2014-01-01

We report a case of a 60-year-old lady who presented with bilateral lower limb swelling and a thyroid swelling with clinical features consistent with thyrotoxicosis. Investigations revealed the presence of a thrombus in bilateral external, internal iliac veins, and inferior vena cava extending up to its infrahepatic part. Hormone profile and radioiodine uptake scan confirmed the diagnosis of Graves’ disease. Further workup revealed the presence of antiphospholipid antibodies (confirmed after a repeat test at 12 weeks). The patient was treated with antithyroid drugs and anticoagulants. The patient improved with normalization of thyroid function and partial recanalization of the infrahepatic part of inferior vena cava. Hyperthyroidism has been implicated as a potential hypercoagulable state; however, the association of Graves’ disease with antiphospholipid antibody syndrome is limited to isolated case reports. This case highlights a new mechanism underlying hypercoagulability associated with Graves’ disease. PMID:24812529

A three-dimensional single-cell-resolution whole-brain atlas using CUBIC-X expansion microscopy and tissue clearing.

PubMed

Murakami, Tatsuya C; Mano, Tomoyuki; Saikawa, Shu; Horiguchi, Shuhei A; Shigeta, Daichi; Baba, Kousuke; Sekiya, Hiroshi; Shimizu, Yoshihiro; Tanaka, Kenji F; Kiyonari, Hiroshi; Iino, Masamitsu; Mochizuki, Hideki; Tainaka, Kazuki; Ueda, Hiroki R

2018-04-01

A three-dimensional single-cell-resolution mammalian brain atlas will accelerate systems-level identification and analysis of cellular circuits underlying various brain functions. However, its construction requires efficient subcellular-resolution imaging throughout the entire brain. To address this challenge, we developed a fluorescent-protein-compatible, whole-organ clearing and homogeneous expansion protocol based on an aqueous chemical solution (CUBIC-X). The expanded, well-cleared brain enabled us to construct a point-based mouse brain atlas with single-cell annotation (CUBIC-Atlas). CUBIC-Atlas reflects inhomogeneous whole-brain development, revealing a significant decrease in the cerebral visual and somatosensory cortical areas during postnatal development. Probabilistic activity mapping of pharmacologically stimulated Arc-dVenus reporter mouse brains onto CUBIC-Atlas revealed the existence of distinct functional structures in the hippocampal dentate gyrus. CUBIC-Atlas is shareable by an open-source web-based viewer, providing a new platform for whole-brain cell profiling.

Cross-Comparison of Leaching Strains Isolated from Two Different Regions: Chambishi and Dexing Copper Mines

PubMed Central

Ngom, Baba; Liang, Yili; Liu, Xueduan

2014-01-01

A cross-comparison of six strains isolated from two different regions, Chambishi copper mine (Zambia, Africa) and Dexing copper mine (China, Asia), was conducted to study the leaching efficiency of low grade copper ores. The strains belong to the three major species often encountered in bioleaching of copper sulfide ores under mesophilic conditions: Acidithiobacillus ferrooxidans, Acidithiobacillus thiooxidans, and Leptospirillum ferriphilum. Prior to their study in bioleaching, the different strains were characterized and compared at physiological level. The results revealed that, except for copper tolerance, strains within species presented almost similar physiological traits with slight advantages of Chambishi strains. However, in terms of leaching efficiency, native strains always achieved higher cell density and greater iron and copper extraction rates than the foreign microorganisms. In addition, microbial community analysis revealed that the different mixed cultures shared almost the same profile, and At. ferrooxidans strains always outcompeted the other strains. PMID:25478575

Genomic Characterization and Transcriptional Studies of the Starch-Utilizing Strain Bifidobacterium adolescentis 22L

PubMed Central

Duranti, Sabrina; Turroni, Francesca; Lugli, Gabriele Andrea; Milani, Christian; Viappiani, Alice; Mangifesta, Marta; Gioiosa, Laura; Palanza, Paola; van Sinderen, Douwe

2014-01-01

Bifidobacteria are members of the gut microbiota, but the genetic basis for their adaptation to the human gut is poorly understood. The analysis of the 2,203,222-bp genome of Bifidobacterium adolescentis 22L revealed a nutrient acquisition strategy that targets diet/plant-derived glycans, in particular starch and starch-like carbohydrates. Starch-like carbohydrates were shown to support the growth of B. adolescentis 22L. Transcriptome profiling of 22L cultures grown under in vitro conditions or during colonization of the murine gut by RNA sequencing and quantitative real-time PCR assays revealed the expression of a set of chromosomal loci responsible for starch metabolism as well as for pilus production. Such extracellular structures include so-called sortase-dependent and type IVb pili, which may be involved in gut colonization of 22L through adhesion to extracellular matrix proteins. PMID:25063659

Transcript Profiling Reveals the Presence of Abiotic Stress and Developmental Stage Specific Ascorbate Oxidase Genes in Plants

PubMed Central

Batth, Rituraj; Singh, Kapil; Kumari, Sumita; Mustafiz, Ananda

2017-01-01

Abiotic stress and climate change is the major concern for plant growth and crop yield. Abiotic stresses lead to enhanced accumulation of reactive oxygen species (ROS) consequently resulting in cellular damage and major losses in crop yield. One of the major scavengers of ROS is ascorbate (AA) which acts as first line of defense against external oxidants. An enzyme named ascorbate oxidase (AAO) is known to oxidize AA and deleteriously affect the plant system in response to stress. Genome-wide analysis of AAO gene family has led to the identification of five, three, seven, four, and six AAO genes in Oryza sativa, Arabidopsis, Glycine max, Zea mays, and Sorghum bicolor genomes, respectively. Expression profiling of these genes was carried out in response to various abiotic stresses and during various stages of vegetative and reproductive development using publicly available microarray database. Expression analysis in Oryza sativa revealed tissue specific expression of AAO genes wherein few members were exclusively expressed in either root or shoot. These genes were found to be regulated by both developmental cues as well as diverse stress conditions. The qRT-PCR analysis in response to salinity and drought stress in rice shoots revealed OsAAO2 to be the most stress responsive gene. On the other hand, OsAAO3 and OsAAO4 genes showed enhanced expression in roots under salinity/drought stresses. This study provides lead about important stress responsive AAO genes in various crop plants, which could be used to engineer climate resilient crop plants. PMID:28261251

Dynamic Cytology and Transcriptional Regulation of Rice Lamina Joint Development1[OPEN

PubMed Central

2017-01-01

Rice (Oryza sativa) leaf angle is determined by lamina joint and is an important agricultural trait determining leaf erectness and, hence, the photosynthesis efficiency and grain yield. Genetic studies reveal a complex regulatory network of lamina joint development; however, the morphological changes, cytological transitions, and underlying transcriptional programming remain to be elucidated. A systemic morphological and cytological study reveals a dynamic developmental process and suggests a common but distinct regulation of the lamina joint. Successive and sequential cell division and expansion, cell wall thickening, and programmed cell death at the adaxial or abaxial sides form the cytological basis of the lamina joint, and the increased leaf angle results from the asymmetric cell proliferation and elongation. Analysis of the gene expression profiles at four distinct developmental stages ranging from initiation to senescence showed that genes related to cell division and growth, hormone synthesis and signaling, transcription (transcription factors), and protein phosphorylation (protein kinases) exhibit distinct spatiotemporal patterns during lamina joint development. Phytohormones play crucial roles by promoting cell differentiation and growth at early stages or regulating the maturation and senescence at later stages, which is consistent with the quantitative analysis of hormones at different stages. Further comparison with the gene expression profile of leaf inclination1, a mutant with decreased auxin and increased leaf angle, indicates the coordinated effects of hormones in regulating lamina joint. These results reveal a dynamic cytology of rice lamina joint that is fine-regulated by multiple factors, providing informative clues for illustrating the regulatory mechanisms of leaf angle and plant architecture. PMID:28500269

Dynamic Cytology and Transcriptional Regulation of Rice Lamina Joint Development.

PubMed

Zhou, Li-Juan; Xiao, Lang-Tao; Xue, Hong-Wei

2017-07-01

Rice ( Oryza sativa ) leaf angle is determined by lamina joint and is an important agricultural trait determining leaf erectness and, hence, the photosynthesis efficiency and grain yield. Genetic studies reveal a complex regulatory network of lamina joint development; however, the morphological changes, cytological transitions, and underlying transcriptional programming remain to be elucidated. A systemic morphological and cytological study reveals a dynamic developmental process and suggests a common but distinct regulation of the lamina joint. Successive and sequential cell division and expansion, cell wall thickening, and programmed cell death at the adaxial or abaxial sides form the cytological basis of the lamina joint, and the increased leaf angle results from the asymmetric cell proliferation and elongation. Analysis of the gene expression profiles at four distinct developmental stages ranging from initiation to senescence showed that genes related to cell division and growth, hormone synthesis and signaling, transcription (transcription factors), and protein phosphorylation (protein kinases) exhibit distinct spatiotemporal patterns during lamina joint development. Phytohormones play crucial roles by promoting cell differentiation and growth at early stages or regulating the maturation and senescence at later stages, which is consistent with the quantitative analysis of hormones at different stages. Further comparison with the gene expression profile of leaf inclination1 , a mutant with decreased auxin and increased leaf angle, indicates the coordinated effects of hormones in regulating lamina joint. These results reveal a dynamic cytology of rice lamina joint that is fine-regulated by multiple factors, providing informative clues for illustrating the regulatory mechanisms of leaf angle and plant architecture. © 2017 American Society of Plant Biologists. All Rights Reserved.

Impact of land management on soil structure and soil hydraulic properties

NASA Astrophysics Data System (ADS)

Kodesova, Radka; Jirku, Veronika; Nikodem, Antonin; Muhlhanselova, Marcela; Zigova, Anna

2010-05-01

Study is focused on a comparison of a soil structure and soil hydraulic properties within soil profiles of a same soil type under different land management. Study was performed in Haplic Luvisol in Hnevceves the Czech Republic. Two soil profiles, which were in close distance from each other, were chosen: 1. under the conventional tillage, 2. under the permanent (30 years) grass cover. Soil sampling and field experiments were carried out immediately after the harvest of winter barley in 2008. The micromorphological images were used to evaluate the soil structure of all Ap, Bt1, Bt2 and C diagnostic horizons. The hydraulic properties of the diagnostic horizons were studied in the laboratory using multistep outflow experiments performed on the undisturbed 100-cm3 soil samples. A tension disc infiltrometer (with a disc radius of 10 cm) and minidisc tension infiltrometers (with a disc radius of 2.2 cm) were used to measure cumulative water infiltration under unsaturated conditions created using a pressure head of -2 cm. Measurements were performed at a depths of 5, 45, 75 and 110 cm, which corresponded to the Ap, Bt1, Bt2 and C horizons of studied Haplic Luvisol at both locations. The Guelph permeameter was used to measure cumulative water flux under surface ponding conditions. The depth of the drilled well was 10, 50, 80 and 115 cm, the well radius was 3 cm, and the well ponding depth was 5 cm. Both tests were used to evaluate hydraulic conductivity (K for h=-2cm, and Ks) values. Results showed, that while properties in the Bt2 and C horizons of both soil profiles were relatively similar, properties in the Ap and Bt1 horizons were different. The fraction of gravitational pores (which may cause preferential flow) in the Ap and Bt1 horizons of the soil profile under the convectional tillage was large than those in the Ap and Bt1 horizons of the soil profile under the permanent grass. This influenced for instance the Ks values measured using the Guelph permeametr. The Ks values were higher and more variable in the soil profile under the convectional tillage than those in the soil profile under the permanent grass. On the other hand, due to the periodical tillage and consequent soil structure breakdown, the fraction of the large capillary pores were smaller in the Ap horizon of the soil profile under the convectional tillage than that in the Ap horizon of the soil profile under the permanent grass. As result the K (h=-2cm) values measured using the tension infiltrometer in the soil profile under the permanent grass was higher than those in the soil profile under the convectional tillage. However, the fraction of the large capillary pores and K (h=-2cm) values were similar in the Bt1 horizons of both soil profiles. Thus the land management impacted both macropores and matrix pores in the Ap horizon and macropores (prismatic structure and biopores) in the Bt1 horizon. Acknowledgement: Authors acknowledge the financial support of the Grant Agency of the Czech Republic (grant No. GA CR 526/08/0434) and the Ministry of Education, Youth and Sports of the Czech Republic (grant No. MSM 6046070901).

Dryline on 22 May 2002 During IHOP: Convective Scale Measurements at the Profiling Site

NASA Technical Reports Server (NTRS)

Demoz, Belay; Flamant, Cyrille; Miller, David; Evans, Keith; Fabry, Federic; DiGirolamo, Paolo; Whiteman, David; Geerts, Bart; Weckwerth, Tammy; Brown, William

2004-01-01

A unique set of measurements of wind, water vapor mixing ratio and boundary layer height variability was observed during the first MOP dryline mission of 22 May 2002. Water vapor mixing ratio from the Scanning Raman Lidar (SRL), high-resolution profiles of aerosol backscatter from the HARLIE and wind profiles from the GLOW are combined with the vertical velocity derived from the NCAR/ISS/MAPR and the high-resolution FMCW radar to reveal the convective variability of the cumulus cloud-topped boundary layer. A combined analysis of the in-situ and remote sensing data from aircraft, radiosonde, lidars, and radars reveals moisture variability within boundary layer updraft and downdraft regions as well as characterizes the boundary layer height variability in the dry and moist sides of the dryline. The profiler site measurements will be tied to aircraft data to reveal the relative intensity and location of these updrafts to the dry line. This study provides unprecedented high temporal and spatial resolution measurements of wind, moisture and backscatter within a dryline and the associated convective boundary layer.

Functional morphology of the lower esophageal sphincter and crural diaphragm determined by three-dimensional high-resolution esophago-gastric junction pressure profile and CT imaging.

PubMed

Mittal, Ravinder K; Zifan, Ali; Kumar, Dushyant; Ledgerwood-Lee, Melissa; Ruppert, Erika; Ghahremani, Gary

2017-09-01

The smooth muscles of the lower esophageal sphincter (LES) and skeletal muscles of the crural diaphragm (CD) provide a closure/antireflux barrier mechanism at the esophago-gastric junction (EGJ). A number of questions in regard to the pressure profile of the LES and CD remain unclear, e.g., 1 ) Why is the LES pressure profile circumferentially asymmetric, 2 ) Is the crural diaphragm (CD) contraction also circumferentially asymmetric, and 3 ) Where is the LES and CD pressure profile located in the anatomy of the esophagus and stomach? The three-dimensional (3-D) high-resolution esophageal manometry (HRM) catheter can record a detailed profile of the EGJ pressure; however, it does not allow the determination of the circumferential orientation of individual pressure transducers in vivo. We used computed tomography (CT) scan imaging in combination with 3-D EGJ pressure recordings to determine the functional morphology of the LES and CD and its relationship to the EGJ anatomy. A 3-D-HRM catheter with 96 transducers (12 rings, 7.5 mm apart, located over 9-cm length of the catheter, with eight transducers in each ring, 45° apart (Medtronics), was used to record the EGJ pressure in 10 healthy subjects. A 0.5-mm diameter metal ball (BB) was taped to the catheter, adjacent to transducer 1 of the catheter. The EGJ was recorded under the following conditions: 1 ) end-expiration (LES pressure) before swallow, after swallow, and after edrophonium hydrochloride; and 2 ) peak inspiration (crural diaphragm contraction) for tidal inspiration and forced maximal inspiration. A CT scan was performed to localize the circumferential orientation of the BB. The CT scan imaging allowed the determination of the circumferential orientation of the LES and CD pressure profiles. The LES pressure under the three end-expiration conditions were different; however, the shape of the pressure profile was unique with the LES length longer toward the lesser curvature of the stomach as compared with the greater curvature. The pressure profile revealed circular and axial pressure asymmetry, with greatest pressure and shortest cranio-caudal length on the left (close to the angle of His). The CD contraction with tidal and forced inspiration increases pressure in the cranial half of the LES pressure profile, and it was placed horizontally across the recording. The CD, esophagus, and stomach were outlined in the CT scan images to construct a 3-D anatomy of the region; it revealed that the hiatus (CD) is placed obliquely across the esophagus; however, because of the bend of the esophagus to the left at the upper edge of the hiatus, the two were placed at right angle to each other, which resulted in a horizontal pressure profile of the CD on the LES. Our observations suggest a unique shape of the LES, CD, and the anatomical relationship between the two, which provides a possible explanation as to why the LES pressure shows circumferential and axial asymmetry. Our findings have implication for the length and circumferential orientation of myotomy incision required for the ablation of LES pressure in achalasia esophagus. NEW & NOTEWORTHY We used computed tomography scan imaging with three-dimensional esophago-gastric junction (EGJ) pressure recordings to determine functional morphology of the lower esophageal sphincter (LES) and crural diaphragm and its relationship to EGJ anatomy. The LES pressure profile was unique with the LES length longer and pressures lower toward the lesser curvature of the stomach, as compared with the greater curvature. Our findings have implications for the length and circumferential orientation of myotomy incision required for the ablation of LES pressure in the achalasia esophagus. Copyright © 2017 the American Physiological Society.

Metabonomics revealed xanthine oxidase-induced oxidative stress and inflammation in the pathogenesis of diabetic nephropathy.

PubMed

Liu, Jingping; Wang, Chengshi; Liu, Fang; Lu, Yanrong; Cheng, Jingqiu

2015-03-01

Diabetic nephropathy (DN) is a serious complication of diabetes mellitus (DM), which is a major public health problem in the world. To reveal the metabolic changes associated with DN, we analyzed the serum, urine, and renal extracts obtained from control and streptozotocin (STZ)-induced DN rats by (1)H NMR-based metabonomics and multivariate data analysis. A significant difference between control and DN rats was revealed in metabolic profiles, and we identified several important DN-related metabolites including increased levels of allantoin and uric acid (UA) in the DN rats, suggesting that disturbed purine metabolism may be involved in the DN. Combined with conventional histological and biological methods, we further demonstrated that xanthine oxidase (XO), a key enzyme for purine catabolism, was abnormally activated in the kidney of diabetic rats by hyperglycemia. The highly activated XO increased the level of intracellular ROS, which caused renal injury by direct oxidative damage to renal cells, and indirect inducing inflammatory responses via activating NF-κB signaling pathway. Our study highlighted that metabonomics is a promising tool to reveal the metabolic changes and the underlying mechanism involved in the pathogenesis of DN.

Metabolic profiling of PPARalpha-/- mice reveals defects in carnitine and amino acid homeostasis that are partially reversed by oral carnitine supplementation.

PubMed

Makowski, Liza; Noland, Robert C; Koves, Timothy R; Xing, Weibing; Ilkayeva, Olga R; Muehlbauer, Michael J; Stevens, Robert D; Muoio, Deborah M

2009-02-01

Peroxisome proliferator-activated receptor-alpha (PPARalpha) is a master transcriptional regulator of beta-oxidation and a prominent target of hypolipidemic drugs. To gain deeper insights into the systemic consequences of impaired fat catabolism, we used quantitative, mass spectrometry-based metabolic profiling to investigate the fed-to-fasted transition in PPARalpha(+/+) and PPARalpha(-/-) mice. Compared to PPARalpha(+/+) animals, acylcarnitine profiles of PPARalpha(-/-) mice revealed 2- to 4-fold accumulation of long-chain species in the plasma, whereas short-chain species were reduced by as much as 69% in plasma, liver, and skeletal muscle. These results reflect a metabolic bottleneck downstream of carnitine palmitoyltransferase-1, a mitochondrial enzyme that catalyzes the first step in beta-oxidation. Organic and amino acid profiles of starved PPARalpha(-/-) mice suggested compromised citric acid cycle flux, enhanced urea cycle activity, and increased amino acid catabolism. PPARalpha(-/-) mice had 40-50% lower plasma and tissue levels of free carnitine, corresponding with diminished hepatic expression of genes involved in carnitine biosynthesis and transport. One week of oral carnitine supplementation conferred partial metabolic recovery in the PPARalpha(-/-) mice. In summary, comprehensive metabolic profiling revealed novel biomarkers of defective fat oxidation, while also highlighting the potential value of supplemental carnitine as a therapy and diagnostic tool for metabolic disorders.

Profiling under UNIX by patching

NASA Technical Reports Server (NTRS)

Bishop, Matt

1986-01-01

Profiling under UNIX is done by inserting counters into programs either before or during the compilation or assembly phases. A fourth type of profiling involves monitoring the execution of a program, and gathering relevant statistics during the run. This method and an implementation of this method are examined, and its advantages and disadvantages are discussed.

Plasma Free Amino Acid Profiling of Five Types of Cancer Patients and Its Application for Early Detection

PubMed Central

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 assay and imposes a lower physical burden on subjects when compared to existing screening methods. PMID:21915291

Transcriptome display during tilapia sex determination and differentiation as revealed by RNA-Seq analysis.

PubMed

Tao, Wenjing; Chen, Jinlin; Tan, Dejie; Yang, Jing; Sun, Lina; Wei, Jing; Conte, Matthew A; Kocher, Thomas D; Wang, Deshou

2018-05-15

The factors determining sex in teleosts are diverse. Great efforts have been made to characterize the underlying genetic network in various species. However, only seven master sex-determining genes have been identified in teleosts. While the function of a few genes involved in sex determination and differentiation has been studied, we are far from fully understanding how genes interact to coordinate in this process. To enable systematic insights into fish sexual differentiation, we generated a dynamic co-expression network from tilapia gonadal transcriptomes at 5, 20, 30, 40, 90, and 180 dah (days after hatching), plus 45 and 90 dat (days after treatment) and linked gene expression profiles to both development and sexual differentiation. Transcriptomic profiles of female and male gonads at 5 and 20 dah exhibited high similarities except for a small number of genes that were involved in sex determination, while drastic changes were observed from 90 to 180 dah, with a group of differently expressed genes which were involved in gonadal differentiation and gametogenesis. Weighted gene correlation network analysis identified changes in the expression of Borealin, Gtsf1, tesk1, Zar1, Cdn15, and Rpl that were correlated with the expression of genes previously known to be involved in sex differentiation, such as Foxl2, Cyp19a1a, Gsdf, Dmrt1, and Amh. Global gonadal gene expression kinetics during sex determination and differentiation have been extensively profiled in tilapia. These findings provide insights into the genetic framework underlying sex determination and sexual differentiation, and expand our current understanding of developmental pathways during teleost sex determination.

Spatial variation in deposition rate coefficients of an adhesion-deficient bacterial strain in quartz sand.

PubMed

Tong, Meiping; Camesano, Terri A; Johnson, William P

2005-05-15

The transport of bacterial strain DA001 was examined in packed quartz sand under a variety of environmentally relevant ionic strength and flow conditions. Under all conditions, the retained bacterial concentrations decreased with distance from the column inlet at a rate that was faster than loglinear, indicating that the deposition rate coefficient decreased with increasing transport distance. The hyperexponential retained profile contrasted againstthe nonmonotonic retained profiles that had been previously observed for this same bacterial strain in glass bead porous media, demonstrating that the form of deviation from log-linear behavior is highly sensitive to system conditions. The deposition rate constants in quartz sand were orders of magnitude below those expected from filtration theory, even in the absence of electrostatic energy barriers. The degree of hyperexponential deviation of the retained profiles from loglinear behavior did not decrease with increasing ionic strength in quartz sand. These observations demonstrate thatthe observed low adhesion and deviation from log-linear behavior was not driven by electrostatic repulsion. Measurements of the interaction forces between DA001 cells and the silicon nitride tip of an atomic force microscope (AFM) showed that the bacterium possesses surface polymers with an average equilibrium length of 59.8 nm. AFM adhesion force measurements revealed low adhesion affinities between silicon nitride and DA001 polymers with approximately 95% of adhesion forces having magnitudes < 0.8 nN. Steric repulsion due to surface polymers was apparently responsible for the low adhesion to silicon nitride, indicating that steric interactions from extracellular polymers controlled DA001 adhesion deficiency and deviation from log-linear behavior on quartz sand.

Refining the tobacco dependence phenotype using the Wisconsin Inventory of Smoking Dependence Motives (WISDM)

PubMed Central

Piper, Megan E.; Bolt, Daniel M.; Kim, Su-Young; Japuntich, Sandra J.; Smith, Stevens S.; Niederdeppe, Jeff; Cannon, Dale S.; Baker, Timothy B.

2008-01-01

The construct of tobacco dependence is important from both scientific and public health perspectives, but it is poorly understood. The current research integrates person-centered analyses (e.g., latent profile analysis) and variable-centered analyses (e.g., exploratory factor analysis) to understand better the latent structure of dependence and to guide distillation of the phenotype. Using data from four samples of smokers (including treatment and non-treatment samples), latent profiles were derived using the Wisconsin Inventory of Smoking Dependence Motives (WISDM) subscale scores. Across all four samples, results revealed a unique latent profile that had relative elevations on four dependence motive subscales (Automaticity, Craving, Loss of Control, and Tolerance). Variable-centered analyses supported the uniqueness of these four subscales both as measures of a common factor distinct from that underlying the other nine subscales, and as the strongest predictors of relapse, withdrawal and other dependence criteria. Conversely, the remaining nine motives carried little unique predictive validity regarding dependence. Applications of a factor mixture model further support the presence of a unique class of smokers in relation to a common factor underlying the four subscales. The results illustrate how person-centered analyses may be useful as a supplement to variable-centered analyses for uncovering variables that are necessary and/or sufficient predictors of disorder criteria, as they may uncover small segments of a population in which the variables are uniquely distributed. The results also suggest that severe dependence is associated with a pattern of smoking that is heavy, pervasive, automatic and relatively unresponsive to instrumental contingencies. PMID:19025223

PGPR-mediated expression of salt tolerance gene in soybean through volatiles under sodium nitroprusside.

PubMed

Vaishnav, Anukool; Kumari, Sarita; Jain, Shekhar; Varma, Ajit; Tuteja, Narendra; Choudhary, Devendra Kumar

2016-11-01

Increasing evidence shows that nitric oxide (NO), a typical signaling molecule plays important role in development of plant and in bacteria-plant interaction. In the present study, we tested the effect of sodium nitroprusside (SNP)-a nitric oxide donor, on bacterial metabolism and its role in establishment of PGPR-plant interaction under salinity condition. In the present study, we adopted methods namely, biofilm formation assay, GC-MS analysis of bacterial volatiles, chemotaxis assay of root exudates (REs), measurement of electrolyte leakage and lipid peroxidation, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) for gene expression. GC-MS analysis revealed that three new volatile organic compounds (VOCs) were expressed after treatment with SNP. Two VOCs namely, 4-nitroguaiacol and quinoline were found to promote soybean seed germination under 100 mM NaCl stress. Chemotaxis assay revealed that SNP treatment, altered root exudates profiling (SS-RE), found more attracted to Pseudomonas simiae bacterial cells as compared to non-treated root exudates (S-RE) under salt stress. Expression of Peroxidase (POX), catalase (CAT), vegetative storage protein (VSP), and nitrite reductase (NR) genes were up-regulated in T6 treatment seedlings, whereas, high affinity K + transporter (HKT1), lipoxygenase (LOX), polyphenol oxidase (PPO), and pyrroline-5-carboxylate synthase (P5CS) genes were down-regulated under salt stress. The findings suggest that NO improves the efficiency and establishment of PGPR strain in the plant environment during salt condition. This strategy may be applied on soybean plants to increase their growth during salinity stress. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

DNA profiling analysis of endometrial and ovarian cell lines reveals misidentification, redundancy and contamination.

PubMed

Korch, Christopher; Spillman, Monique A; Jackson, Twila A; Jacobsen, Britta M; Murphy, Susan K; Lessey, Bruce A; Jordan, V Craig; Bradford, Andrew P

2012-10-01

Cell lines derived from human ovarian and endometrial cancers, and their immortalized non-malignant counterparts, are critical tools to investigate and characterize molecular mechanisms underlying gynecologic tumorigenesis, and facilitate development of novel therapeutics. To determine the extent of misidentification, contamination and redundancy, with evident consequences for the validity of research based upon these models, we undertook a systematic analysis and cataloging of endometrial and ovarian cell lines. Profiling of cell lines by analysis of DNA microsatellite short tandem repeats (STR), p53 nucleotide polymorphisms and microsatellite instability was performed. Fifty-one ovarian cancer lines were profiled with ten found to be redundant and five (A2008, OV2008, C13, SK-OV-4 and SK-OV-6) identified as cervical cancer cells. Ten endometrial cell lines were analyzed, with RL-92, HEC-1A, HEC-1B, HEC-50, KLE, and AN3CA all exhibiting unique, uncontaminated STR profiles. Multiple variants of Ishikawa and ECC-1 endometrial cancer cell lines were genotyped and analyzed by sequencing of mutations in the p53 gene. The profile of ECC-1 cells did not match the EnCa-101 tumor, from which it was reportedly derived, and all ECC-1 isolates were genotyped as Ishikawa cells, MCF-7 breast cancer cells, or a combination thereof. Two normal, immortalized endometrial epithelial cell lines, HES cells and the hTERT-EEC line, were identified as HeLa cervical carcinoma and MCF-7 breast cancer cells, respectively. Results demonstrate significant misidentification, duplication, and loss of integrity of endometrial and ovarian cancer cell lines. Authentication by STR DNA profiling is a simple and economical method to verify and validate studies undertaken with these models. Copyright © 2012 Elsevier Inc. All rights reserved.

Gene Expression Profiling of Monkeypox Virus-Infected Cells Reveals Novel Interfaces for Host-Virus Interactions

DTIC Science & Technology

2010-07-28

expression is plotted on Y -axis after normalization to mock-treated samples. Results plotted to compare calculated fold change in expression of each gene ...RESEARCH Open Access Gene expression profiling of monkeypox virus-infected cells reveals novel interfaces for host-virus interactions Abdulnaser...suppress antiviral cell defenses, exploit host cell machinery, and delay infection-induced cell death. However, a comprehensive study of all host genes

Dielectric collapse at the LaAlO 3/SrTiO 3 (001) heterointerface under applied electric field

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

Minohara, M.; Hikita, Y.; Bell, C.

The fascinating interfacial transport properties at the LaAlO 3/SrTiO 3 heterointerface have led to intense investigations of this oxide system. Exploiting the large dielectric constant of SrTiO 3 at low temperatures, tunability in the interfacial conductivity over a wide range has been demonstrated using a back-gate device geometry. In order to understand the effect of back-gating, it is crucial to assess the interface band structure and its evolution with external bias. In this study, we report measurements of the gate-bias dependent interface band alignment, especially the confining potential profile, at the conducting LaAlO 3/SrTiO 3 (001) heterointerface using soft andmore » hard x-ray photoemission spectroscopy in conjunction with detailed model simulations. Depth-profiling analysis incorporating the electric field dependent dielectric constant in SrTiO 3 reveals that a significant potential drop on the SrTiO 3 side of the interface occurs within ~2 nm of the interface under negative gate-bias. These results demonstrate gate control of the collapse of the dielectric permittivity at the interface, and explain the dramatic loss of electron mobility with back-gate depletion.« less

Comparative transcriptome profiling of chilling stress responsiveness in grafted watermelon seedlings.

PubMed

Xu, Jinhua; Zhang, Man; Liu, Guang; Yang, Xingping; Hou, Xilin

2016-12-01

Rootstock grafting may improve the resistance of watermelon plants to low temperatures. However, information regarding the molecular responses of rootstock grafted plants to chilling stress is limited. To elucidate the molecular mechanisms of chilling tolerance in grafted plants, the transcriptomic responses of grafted watermelon under chilling stress were analyzed using RNA-seq analysis. Sequencing data were used for digital gene expression (DGE) analysis to characterize the transcriptomic responses in grafted watermelon seedlings. A total of 702 differentially-expressed genes (DEGs) were found in rootstock grafted (RG) watermelon relative to self-grafted (SG) watermelon; among these genes, 522 genes were up-regulated and 180 were down-regulated. Additionally, 164 and 953 genes were found to specifically expressed in RG and SG seedlings under chilling stress, respectively. Functional annotations revealed that up-regulated DEGs are involved in protein processing, plant-pathogen interaction and the spliceosome, whereas down-regulated DEGs are associated with photosynthesis. Moreover, 13 DEGs were randomly selected for quantitative real time PCR (qRT-PCR) analysis. The expression profiles of these 13 DEGs were consistent with those detected by the DGE analysis, supporting the reliability of the DGE data. This work provides additional insight into the molecular basis of grafted watermelon responses to chilling stress. Copyright © 2016. Published by Elsevier Masson SAS.

Global Expressions Landscape of NAC Transcription Factor Family and Their Responses to Abiotic Stresses in Citrullus lanatus

PubMed Central

Lv, Xiaolong; Lan, Shanrong; Guy, Kateta Malangisha; Yang, Jinghua; Zhang, Mingfang; Hu, Zhongyuan

2016-01-01

Watermelon (Citrullus lanatus) is one xerophyte that has relative higher tolerance to drought and salt stresses as well as more sensitivity to cold stress, compared with most model plants. These characteristics facilitate it a potential model crop for researches on salt, drought or cold tolerance. In this study, a genome-wide comprehensive analysis of the ClNAC transcription factor (TF) family was carried out for the first time, to investigate their transcriptional profiles and potential functions in response to these abiotic stresses. The expression profiling analysis reveals that several NAC TFs are highly responsive to abiotic stresses and development, for instance, subfamily IV NACs may play roles in maintaining water status under drought or salt conditions, as well as water and metabolites conduction and translocation toward fruit. In contrast, rapid and negative responses of most of the ClNACs to low-temperature adversity may be related to the sensitivity to cold stress. Crosstalks among these abiotic stresses and hormone (abscisic acid and jasmonic acid) pathways were also discussed based on the expression of ClNAC genes. Our results will provide useful insights for the functional mining of NAC family in watermelon, as well as into the mechanisms underlying abiotic tolerance in other cash crops. PMID:27491393

Global Expressions Landscape of NAC Transcription Factor Family and Their Responses to Abiotic Stresses in Citrullus lanatus.

PubMed

Lv, Xiaolong; Lan, Shanrong; Guy, Kateta Malangisha; Yang, Jinghua; Zhang, Mingfang; Hu, Zhongyuan

2016-08-05

Watermelon (Citrullus lanatus) is one xerophyte that has relative higher tolerance to drought and salt stresses as well as more sensitivity to cold stress, compared with most model plants. These characteristics facilitate it a potential model crop for researches on salt, drought or cold tolerance. In this study, a genome-wide comprehensive analysis of the ClNAC transcription factor (TF) family was carried out for the first time, to investigate their transcriptional profiles and potential functions in response to these abiotic stresses. The expression profiling analysis reveals that several NAC TFs are highly responsive to abiotic stresses and development, for instance, subfamily IV NACs may play roles in maintaining water status under drought or salt conditions, as well as water and metabolites conduction and translocation toward fruit. In contrast, rapid and negative responses of most of the ClNACs to low-temperature adversity may be related to the sensitivity to cold stress. Crosstalks among these abiotic stresses and hormone (abscisic acid and jasmonic acid) pathways were also discussed based on the expression of ClNAC genes. Our results will provide useful insights for the functional mining of NAC family in watermelon, as well as into the mechanisms underlying abiotic tolerance in other cash crops.

Global Metabolic Regulation of the Snow Alga Chlamydomonas nivalis in Response to Nitrate or Phosphate Deprivation by a Metabolome Profile Analysis.

PubMed

Lu, Na; Chen, Jun-Hui; Wei, Dong; Chen, Feng; Chen, Gu

2016-05-10

In the present work, Chlamydomonas nivalis, a model species of snow algae, was used to illustrate the metabolic regulation mechanism of microalgae under nutrient deprivation stress. The seed culture was inoculated into the medium without nitrate or phosphate to reveal the cell responses by a metabolome profile analysis using gas chromatography time-of-flight mass spectrometry (GC/TOF-MS). One hundred and seventy-one of the identified metabolites clustered into five groups by the orthogonal partial least squares discriminant analysis (OPLS-DA) model. Among them, thirty of the metabolites in the nitrate-deprived group and thirty-nine of the metabolites in the phosphate-deprived group were selected and identified as "responding biomarkers" by this metabolomic approach. A significant change in the abundance of biomarkers indicated that the enhanced biosynthesis of carbohydrates and fatty acids coupled with the decreased biosynthesis of amino acids, N-compounds and organic acids in all the stress groups. The up- or down-regulation of these biomarkers in the metabolic network provides new insights into the global metabolic regulation and internal relationships within amino acid and fatty acid synthesis, glycolysis, the tricarboxylic acid cycle (TCA) and the Calvin cycle in the snow alga under nitrate or phosphate deprivation stress.

Exact Analytical Solution of the Peristaltic Nanofluids Flow in an Asymmetric Channel with Flexible Walls and Slip Condition: Application to the Cancer Treatment

PubMed Central

Ebaid, Abdelhalim; Aly, Emad H.

2013-01-01

In the cancer treatment, magnetic nanoparticles are injected into the blood vessel nearest to the cancer's tissues. The dynamic of these nanoparticles occurs under the action of the peristaltic waves generated on the flexible walls of the blood vessel. Studying such nanofluid flow under this action is therefore useful in treating tissues of the cancer. In this paper, the mathematical model describing the slip peristaltic flow of nanofluid was analytically investigated. Exact expressions were deduced for the temperature distribution and nano-particle concentration. In addition, the effects of the slip, thermophoresis, and Brownian motion parameters on the temperature and nano-particle concentration profiles were discussed and further compared with other approximate results in the literatures. In particular, these results have been obtained at the same values of the physical examined parameters that was considered in Akbar et al., “Peristaltic flow of a nanofluid with slip effects,” 2012. The results reveal that remarkable differences are detected between the exact current results and those approximately obtained in the literatures for behaviour of the temperature profile and nano-particles concentration. Accordingly, the current analysis and results are considered as optimal and therefore may be taken as a base for any future comparisons. PMID:24151526

Systematic profiling of alternative splicing signature reveals prognostic predictor for ovarian cancer.

PubMed

Zhu, Junyong; Chen, Zuhua; Yong, Lei

2018-02-01

The majority of genes are alternatively spliced and growing evidence suggests that alternative splicing is modified in cancer and is associated with cancer progression. Systematic analysis of alternative splicing signature in ovarian cancer is lacking and greatly needed. We profiled genome-wide alternative splicing events in 408 ovarian serous cystadenocarcinoma (OV) patients in TCGA. Seven types of alternative splicing events were curated and prognostic analyses were performed with predictive models and splicing network built for OV patients. Among 48,049 mRNA splicing events in 10,582 genes, we detected 2,611 alternative splicing events in 2,036 genes which were significant associated with overall survival of OV patients. Exon skip events were the most powerful prognostic factors among the seven types. The area under the curve of the receiver-operator characteristic curve for prognostic predictor, which was built with top significant alternative splicing events, was 0.937 at 2,000 days of overall survival, indicating powerful efficiency in distinguishing patient outcome. Interestingly, splicing correlation network suggested obvious trends in the role of splicing factors in OV. In summary, we built powerful prognostic predictors for OV patients and uncovered interesting splicing networks which could be underlying mechanisms. Copyright © 2017 Elsevier Inc. All rights reserved.

Dielectric collapse at the LaAlO 3/SrTiO 3 (001) heterointerface under applied electric field

DOE PAGES

Minohara, M.; Hikita, Y.; Bell, C.; ...

2017-08-25

The fascinating interfacial transport properties at the LaAlO 3/SrTiO 3 heterointerface have led to intense investigations of this oxide system. Exploiting the large dielectric constant of SrTiO 3 at low temperatures, tunability in the interfacial conductivity over a wide range has been demonstrated using a back-gate device geometry. In order to understand the effect of back-gating, it is crucial to assess the interface band structure and its evolution with external bias. In this study, we report measurements of the gate-bias dependent interface band alignment, especially the confining potential profile, at the conducting LaAlO 3/SrTiO 3 (001) heterointerface using soft andmore » hard x-ray photoemission spectroscopy in conjunction with detailed model simulations. Depth-profiling analysis incorporating the electric field dependent dielectric constant in SrTiO 3 reveals that a significant potential drop on the SrTiO 3 side of the interface occurs within ~2 nm of the interface under negative gate-bias. These results demonstrate gate control of the collapse of the dielectric permittivity at the interface, and explain the dramatic loss of electron mobility with back-gate depletion.« less

The changing profile of disability in the U.S. Army: 1981-2005.

PubMed

Bell, Nicole S; Schwartz, Carolyn E; Harford, Thomas; Hollander, Ilyssa E; Amoroso, Paul J

2008-01-01

we sought to provide a profile of U.S. Army soldiers discharged with a permanent disability and to clarify whether underlying demographic changes explain increasing risks. frequency distributions and logistic regression analyses describe active-duty Army soldiers discharged with a disability (January 1981 through December 2005; N = 108,119). Time-series analysis describes temporal changes in demographic factors associated with disability. disability risk has increased 7-fold over the past 25 years. In 2005, there were 1,262 disability discharges per 100,000 active-duty soldiers. Risk factors include female gender, lower rank, married or formerly married, high school education or less, and age 40 or younger. Army population demographics changed during this time; the average age and tenure of soldiers increased, and the proportion of soldiers who were officers, women, and college educated grew. Adjusting for these demographic changes did not explain the rapidly increasing risk of disability. Time-series models revealed that disability among women is increasing independently of the increasing number of women in the Army; disability is also increasing at a faster pace for younger, lower-ranked, enlisted, and shorter-tenured soldiers. disability is costly and growing in the Army. Temporal changes in underlying Army population demographics do not explain overall disability increases. Disability is increasing most rapidly among female, junior enlisted, and younger soldiers.

Individual neurophysiological profile in external effects investigation

NASA Astrophysics Data System (ADS)

Schastlivtseva, Daria; Tatiana Kotrovskaya, D..

Cortex biopotentials are the significant elements in human psychophysiological individuality. Considered that cortical biopotentials are diverse and individually stable, therefore there is the existence of certain dependence between the basic properties of higher nervous activity and cerebral bioelectric activity. The main purpose of the study was to reveal the individual neurophysiological profile and CNS initial functional state manifestation in human electroencephalogram (EEG) under effect of inert gases (argon, xenon, helium), hypoxia, pressure changes (0.02 and 0.2 MPa). We obtained 5-minute eyes closed background EEG on 19 scalp positions using Ag/AgCl electrodes mounted in an electrode cap. All EEG signals were re-referenced to average earlobes; Fast Furies Transformation analysis was used to calculate the relative power spectrum of delta-, theta-, alpha- and beta frequency band in artifact-free EEG. The study involved 26 healthy men who provided written informed consent, aged 20 to 35 years. Data obtained depend as individual EEG type and initial central nervous functional state as intensity, duration and mix of factors. Pronounced alpha rhythm in the raw EEG correlated with their adaptive capacity under studied factor exposure. Representation change and zonal distribution perversion of EEG alpha rhythm were accompanied by emotional instability, increased anxiety and difficulty adapting subjects. High power factor or combination factor with psychological and emotional or physical exertion minimizes individual EEG pattern.

RNA-sequencing and pathway analysis reveal alteration of hepatic steroid biosynthesis and retinol metabolism by tributyltin exposure in male rare minnow (Gobiocypris rarus).

PubMed

Zhang, Jiliang; Zhang, Chunnuan; Sun, Ping; Huang, Maoxian; Fan, Mingzhen; Liu, Min

2017-07-01

Tributyltin (TBT) is widely spread in aquatic ecosystems. Although adverse effects of TBT on reproduction and lipogenesis are observed in fishes, the underlying mechanisms, especially in livers, are still scarce and inconclusive. Thus, RNA-sequencing runs were performed on the hepatic libraries of adult male rare minnow (Gobiocypris rarus) after TBT exposure for 60d. After differentially expressed genes were identified, enrichment analysis and validation by quantitative real-time PCR were conducted. The results showed that TBT up-regulated the profile of hepatic genes in the steroid biosynthesis pathway and down-regulated the profile of hepatic genes in the retinol metabolism pathway. In the hepatic steroid biosynthesis pathway, TBT might induce biosynthesis of cholesterol, which could affect the bioavailability of steroid hormones. More important, 3beta-hydroxysteroid 3-dehydrogenase, a key enzyme in the biosynthesis of all active steroid hormones, was up-regulated by TBT exposure. In the hepatic retinol metabolism pathway, TBT impaired retinoic acid homeostasis which plays essential roles in both reproduction and lipogenesis. The results of two pathways offered new mechanisms underlying the toxicology of TBT and represented a starting point from which detailed mechanistic links should be explored. Copyright © 2017 Elsevier B.V. All rights reserved.

Demonstration of Aerosol Property Profiling by Multi-wavelength Lidar Under Varying Relative Humidity Conditions

NASA Technical Reports Server (NTRS)

Whiteman, D.N.; Veselovskii, I.; Kolgotin, A.; Korenskii, M.; Andrews, E.

2008-01-01

The feasibility of using a multi-wavelength Mie-Raman lidar based on a tripled Nd:YAG laser for profiling aerosol physical parameters in the planetary boundary layer (PBL) under varying conditions of relative humidity (RH) is studied. The lidar quantifies three aerosol backscattering and two extinction coefficients and from these optical data the particle parameters such as concentration, size and complex refractive index are retrieved through inversion with regularization. The column-integrated, lidar-derived parameters are compared with results from the AERONET sun photometer. The lidar and sun photometer agree well in the characterization of the fine mode parameters, however the lidar shows less sensitivity to coarse mode. The lidar results reveal a strong dependence of particle properties on RH. The height regions with enhanced RH are characterized by an increase of backscattering and extinction coefficient and a decrease in the Angstrom exponent coinciding with an increase in the particle size. We present data selection techniques useful for selecting cases that can support the calculation of hygroscopic growth parameters using lidar. Hygroscopic growth factors calculated using these techniques agree with expectations despite the lack of co-located radiosonde data. Despite this limitation, the results demonstrate the potential of multi-wavelength Raman lidar technique for study of aerosol humidification process.

Analysis of force profile during a maximum voluntary isometric contraction task.

PubMed

Househam, Elizabeth; McAuley, John; Charles, Thompson; Lightfoot, Timothy; Swash, Michael

2004-03-01

This study analyses maximum voluntary isometric contraction (MVIC) and its measurement by recording the force profile during maximal-effort, 7-s hand-grip contractions. Six healthy subjects each performed three trials repeated at short intervals to study variation from fatigue. These three trials were performed during three separate sessions at daily intervals to look at random variation. A pattern of force development during a trial was identified. An initiation phase, with or without an initiation peak, was followed by a maintenance phase, sometimes with secondary pulses and an underlying decline in force. Of these three MVIC parameters, maximum force during the maintenance phase showed less random variability compared to intertrial fatigue variability than did maximum force during the initiation phase or absolute maximum force. Analysis of MVIC as a task, rather than a single, maximal value reveals deeper levels of motor control in its generation. Thus, force parameters other than the absolute maximum force may be better suited to quantification of muscle performance in health and disease.

Metabolic profiling and systematic identification of flavonoids and isoflavonoids in roots and cell suspension cultures of Medicago truncatula using HPLC-UV-ESI-MS and GC-MS.

PubMed

Farag, Mohamed A; Huhman, David V; Lei, Zhentian; Sumner, Lloyd W

2007-02-01

An integrated approach utilizing HPLC-UV-ESI-MS and GC-MS was used for the large-scale and systematic identification of polyphenols in Medicago truncatula root and cell culture. Under optimized conditions, we were able to simultaneously quantify and identify 35 polyphenols including 26 isoflavones, 3 flavones, 2 flavanones, 2 aurones and a chalcone. All identifications were based upon UV spectra, mass spectral characteristics of protonated molecules, tandem mass spectral data, mass measurements obtained using a quadrupole time-of-flight mass spectrometer (QtofMS), and confirmed through the co-characterization of authentic compounds. In specific instances where the stereochemistry of sugar conjugates was uncertain, subsequent enzymatic hydrolysis of the conjugate followed by GC-MS was used to assign the sugar stereochemical configuration. Comparative metabolic profiling of Medicago truncatula root and cell cultures was then performed and revealed significant differences in the isoflavonoid composition of these two tissues.

Strains, functions, and dynamics in the expanded Human Microbiome Project

PubMed Central

Lloyd-Price, Jason; Mahurkar, Anup; Rahnavard, Gholamali; Crabtree, Jonathan; Orvis, Joshua; Hall, A. Brantley; Brady, Arthur; Creasy, Heather H.; McCracken, Carrie; Giglio, Michelle G.; McDonald, Daniel; Franzosa, Eric A.; Knight, Rob; White, Owen; Huttenhower, Curtis

2018-01-01

Summary The characterization of baseline microbial and functional diversity in the human microbiome has enabled studies of microbiome-related disease, microbial population diversity, biogeography, and molecular function. The NIH Human Microbiome Project (HMP) has provided one of the broadest such characterizations to date. Here, we introduce an expanded second phase of the study, abbreviated HMP1-II, comprising 1,631 new metagenomic samples (2,355 total) targeting diverse body sites with multiple time points in 265 individuals. We applied updated profiling and assembly methods to these data to provide new characterizations of microbiome personalization. Strain identification revealed distinct subspecies clades specific to body sites; it also quantified species with phylogenetic diversity under-represented in isolate genomes. Body-wide functional profiling classified pathways into universal, human-enriched, and body site-enriched subsets. Finally, temporal analysis decomposed microbial variation into rapidly variable, moderately variable, and stable subsets. This study furthers our knowledge of baseline human microbial diversity, thus enabling an understanding of personalized microbiome function and dynamics. PMID:28953883

Genome-wide transcriptional profiling of human glioblastoma cells in response to ITE treatment

PubMed Central

Kang, Bo; Zhou, Yanwen; Zheng, Min; Wang, Ying-Jie

2015-01-01

A ligand-activated transcription factor aryl hydrocarbon receptor (AhR) is recently revealed to play a key role in embryogenesis and tumorigenesis (Feng et al. [1], Safe et al. [2]) and 2-(1′H-indole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) (Song et al. [3]) is an endogenous AhR ligand that possesses anti-tumor activity. In order to gain insights into how ITE acts via the AhR in embryogenesis and tumorigenesis, we analyzed the genome-wide transcriptional profiles of the following three groups of cells: the human glioblastoma U87 parental cells, U87 tumor sphere cells treated with vehicle (DMSO) and U87 tumor sphere cells treated with ITE. Here, we provide the details of the sample gathering strategy and show the quality controls and the analyses associated with our gene array data deposited into the Gene Expression Omnibus (GEO) under the accession code of GSE67986. PMID:26484269

Vertical distribution of 137Cs in alluvial soils of the Lokna River floodplain (Tula oblast) long after the Chernobyl accident and its simulation

NASA Astrophysics Data System (ADS)

Mamikhin, S. V.; Golosov, V. N.; Paramonova, T. A.; Shamshurina, E. N.; Ivanov, M. M.

2016-12-01

Profiles of vertical 137Cs distribution in alluvial meadow soils on the low and medium levels of the Lokna River floodplain (central part of the Plavsk radioactive spot in Tula oblast) 28 years after the Chernobyl fallout have been studied. A significant increase in the 137Cs pool is revealed on the low floodplain areas compared to the soils of interfluves due to the accumulation of alluvium, which hampers the reduction of the total radionuclide pool in alluvial soils because of radioactive decay. The rate of alluvium accumulation in the soil on the medium floodplain level is lower by three times on average. An imitation prognostic model has been developed, which considers the flooding and climatic conditions in the region under study. Numerical experiments have quantitatively confirmed the deciding role of low-mobile forms in the migration of maximum 137Cs content along the soil profile in the absence of manifested erosion-accumulation processes.

Distinct polyadenylation landscapes of diverse human tissues revealed by a modified PA-seq strategy

PubMed Central

2013-01-01

Background Polyadenylation is a key regulatory step in eukaryotic gene expression and one of the major contributors of transcriptome diversity. Aberrant polyadenylation often associates with expression defects and leads to human diseases. Results To better understand global polyadenylation regulation, we have developed a polyadenylation sequencing (PA-seq) approach. By profiling polyadenylation events in 13 human tissues, we found that alternative cleavage and polyadenylation (APA) is prevalent in both protein-coding and noncoding genes. In addition, APA usage, similar to gene expression profiling, exhibits tissue-specific signatures and is sufficient for determining tissue origin. A 3′ untranslated region shortening index (USI) was further developed for genes with tandem APA sites. Strikingly, the results showed that different tissues exhibit distinct patterns of shortening and/or lengthening of 3′ untranslated regions, suggesting the intimate involvement of APA in establishing tissue or cell identity. Conclusions This study provides a comprehensive resource to uncover regulated polyadenylation events in human tissues and to characterize the underlying regulatory mechanism. PMID:24025092

Formation of Close-in Super-Earths in an Evolving Disk Due to Disk Winds

NASA Astrophysics Data System (ADS)

Ogihara, Masahiro; Kokubo, Eiichiro; Suzuki, Takeru; Morbidelli, Alessandro

2018-04-01

Planets with masses larger than Mars mass undergo rapid inward migration (type I migration) in a standard protoplanetary disk. Recent magnetohydrodynamical simulations revealed the presence of magnetically-driven disk winds, which would alter the disk profile and the type I migration in the close-in region (r<1 au). We investigate orbital evolution of planetary embryos in a disk that viscously evolves under effects of magnetically-driven disk winds. The aim is to examine whether observed distributions of close-in super-Earths can be reproduced by simulations. We find that the type I migration is significantly suppressed in a disk with flat surface density profile. After planetary embryos undergo slow inward migration, they are captured in a resonant chain. The resonant chain undergoes late orbital instability during the gas depletion, leading to a non-resonant configuration. We also find that observed distributions of close-in super-Earths (e.g., period ratio, mass ratio) can be reproduced by results of simulations.

An experimental study of adsorption interference in binary mixtures flowing through activated carbon

NASA Technical Reports Server (NTRS)

Madey, R.; Photinos, P. J.

1983-01-01

The isothermal transmission through activated carbon adsorber beds at 25 C of acetaldehyde-propane and acetylene-ethane mixtures in a helium carrier gas was measured. The inlet concentration of each component was in the range between 10 ppm and 500 ppm. The constant inlet volumetric flow rate was controlled at 200 cc (STP)/min in the acetaldehyde-propane experiments and at 50 cc (STP)/min in the acetaldehyde-ethane experiments. Comparison of experimental results with the corresponding single-component experiments under similar conditions reveals interference phenomena between the components of the mixtures as evidenced by changes in both the adsorption capacity and the dispersion number. Propane was found to displace acetaldehyde from the adsorbed state. The outlet concentration profiles of propane in the binary mixtures tend to become more diffuse than the corresponding concentration profiles of the one-component experiments. Similar features were observed with mixtures of acetylene and ethane; however, the displacement of acetylene by ethane is less pronounced.

Inhibition of Super-Enhancer Activity in Autoinflammatory Site-Derived T Cells Reduces Disease-Associated Gene Expression.

PubMed

Peeters, Janneke G C; Vervoort, Stephin J; Tan, Sander C; Mijnheer, Gerdien; de Roock, Sytze; Vastert, Sebastiaan J; Nieuwenhuis, Edward E S; van Wijk, Femke; Prakken, Berent J; Creyghton, Menno P; Coffer, Paul J; Mokry, Michal; van Loosdregt, Jorg

2015-09-29

The underlying molecular mechanisms for many autoimmune diseases are poorly understood. Juvenile idiopathic arthritis (JIA) is an exceptionally well-suited model for studying autoimmune diseases due to its early onset and the possibility to analyze cells derived from the site of inflammation. Epigenetic profiling, utilizing primary JIA patient-derived cells, can contribute to the understanding of autoimmune diseases. With H3K27ac chromatin immunoprecipitation, we identified a disease-specific, inflammation-associated, typical enhancer and super-enhancer signature in JIA patient synovial-fluid-derived CD4(+) memory/effector T cells. RNA sequencing of autoinflammatory site-derived patient T cells revealed that BET inhibition, utilizing JQ1, inhibited immune-related super-enhancers and preferentially reduced disease-associated gene expression, including cytokine-related processes. Altogether, these results demonstrate the potential use of enhancer profiling to identify disease mediators and provide evidence for BET inhibition as a possible therapeutic approach for the treatment of autoimmune diseases. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

In-situ pyrogenic production of biodiesel from swine fat.

PubMed

Lee, Jechan; Tsang, Yiu Fai; Jung, Jong-Min; Oh, Jeong-Ik; Kim, Hyung-Wook; Kwon, Eilhann E

2016-11-01

In-situ production of fatty acid methyl esters from swine fat via thermally induced pseudo-catalytic transesterification on silica was investigated in this study. Instead of methanol, dimethyl carbonate (DMC) was used as acyl acceptor to achieve environmental benefits and economic viability. Thermo-gravimetric analysis of swine fat reveals that swine fat contains 19.57wt.% of water and impurities. Moreover, the fatty acid profiles obtained under various conditions (extracted swine oil+methanol+NaOH, extracted swine oil+DMC+pseudo-catalytic, and swine fat+DMC+pseudo-catalytic) were compared. These profiles were identical, showing that the introduced in-situ transesterification is technically feasible. This also suggests that in-situ pseudo-catalytic transesterification has a high tolerance against impurities. This study also shows that FAME yield via in-situ pseudo-catalytic transesterification of swine fat reached up to 97.2% at 380°C. Therefore, in-situ pseudo-catalytic transesterification can be applicable to biodiesel production of other oil-bearing biomass feedstocks. Copyright © 2016 Elsevier Ltd. All rights reserved.

Computed versus measured ion velocity distribution functions in a Hall effect thruster

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

Garrigues, L.; CNRS, LAPLACE, F-31062 Toulouse; Mazouffre, S.

2012-06-01

We compare time-averaged and time-varying measured and computed ion velocity distribution functions in a Hall effect thruster for typical operating conditions. The ion properties are measured by means of laser induced fluorescence spectroscopy. Simulations of the plasma properties are performed with a two-dimensional hybrid model. In the electron fluid description of the hybrid model, the anomalous transport responsible for the electron diffusion across the magnetic field barrier is deduced from the experimental profile of the time-averaged electric field. The use of a steady state anomalous mobility profile allows the hybrid model to capture some properties like the time-averaged ion meanmore » velocity. Yet, the model fails at reproducing the time evolution of the ion velocity. This fact reveals a complex underlying physics that necessitates to account for the electron dynamics over a short time-scale. This study also shows the necessity for electron temperature measurements. Moreover, the strength of the self-magnetic field due to the rotating Hall current is found negligible.« less

Untargeted Metabolic Quantitative Trait Loci Analyses Reveal a Relationship between Primary Metabolism and Potato Tuber Quality1[W][OA

PubMed Central

Carreno-Quintero, Natalia; Acharjee, Animesh; Maliepaard, Chris; Bachem, Christian W.B.; Mumm, Roland; Bouwmeester, Harro; Visser, Richard G.F.; Keurentjes, Joost J.B.

2012-01-01

Recent advances in -omics technologies such as transcriptomics, metabolomics, and proteomics along with genotypic profiling have permitted dissection of the genetics of complex traits represented by molecular phenotypes in nonmodel species. To identify the genetic factors underlying variation in primary metabolism in potato (Solanum tuberosum), we have profiled primary metabolite content in a diploid potato mapping population, derived from crosses between S. tuberosum and wild relatives, using gas chromatography-time of flight-mass spectrometry. In total, 139 polar metabolites were detected, of which we identified metabolite quantitative trait loci for approximately 72% of the detected compounds. In order to obtain an insight into the relationships between metabolic traits and classical phenotypic traits, we also analyzed statistical associations between them. The combined analysis of genetic information through quantitative trait locus coincidence and the application of statistical learning methods provide information on putative indicators associated with the alterations in metabolic networks that affect complex phenotypic traits. PMID:22223596

Expression profile and distribution of Efhc1 gene transcript during rodent brain development.

PubMed

Conte, Fábio F; Ribeiro, Patrícia A O; Marchesini, Rafael B; Pascoal, Vinícius D B; Silva, Joelcimar M; Oliveira, Amanda R; Gilioli, Rovílson; Sbragia, Lourenço; Bittencourt, Jackson C; Lopes-Cendes, Iscia

2009-09-01

One of the putative causative genes for juvenile myoclonic epilepsy (JME) is EFHC1. We report here the expression profile and distribution of Efhc1 messenger RNA (mRNA) during mouse and rat brain development. Real-time polymerase chain reaction revealed that there is no difference in the expression of Efhc1 mRNA between right and left hemispheres in both species. In addition, the highest levels of Efhc1 mRNA were found at intra-uterine stages in mouse and in adulthood in rat. In common, there was a progressive decrease in Efhc1 expression from 1-day-old neonates to 14-day-old animals in both species. In situ hybridization studies showed that rat and mouse Efhc1 mRNAs are expressed in ependymal cells of ventricle walls. Our findings suggest that Efhc1 expression is more important during initial phases of brain development and that at this stage it could be involved in key developmental mechanisms underlying JME.

Metabolomics Profiling of Serum and Urine in Three Beef Cattle Breeds Revealed Different Levels of Tolerance to Heat Stress.

PubMed

Liao, Yupeng; Hu, Rui; Wang, Zhisheng; Peng, Quanhui; Dong, Xianwen; Zhang, Xiangfei; Zou, Huawei; Pu, Qijian; Xue, Bai; Wang, Lizhi

2018-06-25

This study was to determine differences in the global metabolic profiles of serum and urine of Xuanhan yellow cattle, Simmental crossbred cattle (Simmental × Xuanhan yellow cattle), and cattle-yaks (Jersey × Maiwa yak) under heat stress (temperature-humidity index remained above 80 for 1 week). A total of 55 different metabolites associated with the three breeds were identified in the serum and urine samples by gas chromatography-mass spectrometry. The metabolic adaptations to heat stress are heterogeneous. Cattle-yaks mobilize a greater amount of body protein to release glucogenic amino acids to supply energy, whereas the tricarboxylic acid cycle is inhibited. Simmental crossbred cattle mobilize a greater amount of body fat to use free fatty acids as an energy source. In comparison with Simmental crossbred cattle and cattle-yaks, Xuanhan yellow cattle have higher glycolytic activity and possess a stronger antioxidant defense system and are, in conclusion, more adapted to hot and humid environments.

Effect of moisture on the fatigue behavior of graphite/epoxy composite laminates

NASA Technical Reports Server (NTRS)

Ramani, S. V.; Nelson, H. G.

1979-01-01

The form of the moisture distribution in the specimen (gradient and flat profile) was considered to establish the influence of accelerated moisture conditioning on fatigue behavior. For the gradient specimens having an average moisture content of 1.4 percent, fatigue life was reduced by a factor of 8 at all stress levels investigated. Corresponding reduction in fatigue life for the flat moisture profile specimens at the same average moisture content was comparatively smaller, being about a factor of 5 from the value in dry specimens. X-ray radiographic analysis of damage accumulation in compression-compression fatigue revealed interlaminar cracking to be the dominant mode of failure responsible for the observed enhanced cyclic degradation of moisture-conditioned specimens. This finding was corroborated by the observed systematic reduction in interlaminar shear strength as a function of moisture content, which, in turn, increased the propensity for delamination under cyclic compressive loads. Residual strength measurements on cycled specimens indicated significant strength reductions at long lives, particularly in moisture conditioned specimens.

Reasoning about geography.

PubMed

Friedman, A; Brown, N R

2000-06-01

To understand the nature and etiology of biases in geographical judgments, the authors asked people to estimate latitudes (Experiments 1 and 2) and longitudes (Experiments 3 and 4) of cities throughout the Old and New Worlds. They also examined how people's biased geographical judgments change after they receive accurate information ("seeds") about actual locations. Location profiles constructed from the pre- and postseeding location estimates conveyed detailed information about the representations underlying geography knowledge, including the subjective positioning and subregionalization of regions within continents; differential seeding effects revealed between-region dependencies. The findings implicate an important role for conceptual knowledge and plausible-reasoning processes in tasks that use subjective geographical information.

Probe into the origin, development and evolution model of shelf desertizational environment in the last stage of Late Pleistocene

NASA Astrophysics Data System (ADS)

Yu, Hong-Jun; Liu, Jing-Pu; Shan, Qiu-Mei

1998-12-01

Based on study of China's shelf paleoenvironment, this paper summarises the definition of shelf desertization that occurred in the last stage of Late Pleistocene, and discusses the background of its formation and evolution process. Study of shallow layer profiler records and core data revealed that cold-dry aeolian erosion was the major exogenic force on the exposed shelf. Under the prevailing paleo-winter monsoon, part of the exposed marine stratum disintegrated into sand and then desertization occurred. The fine sediments were blown away and deposited on the leeward to form derivative loess deposits.

Minor Structural Change to Tertiary Sulfonamide RORc Ligands Led to Opposite Mechanisms of Action

PubMed Central

2014-01-01

A minor structural change to tertiary sulfonamide RORc ligands led to distinct mechanisms of action. Co-crystal structures of two compounds revealed mechanistically consistent protein conformational changes. Optimized phenylsulfonamides were identified as RORc agonists while benzylsulfonamides exhibited potent inverse agonist activity. Compounds behaving as agonists in our biochemical assay also gave rise to an increased production of IL-17 in human PBMCs whereas inverse agonists led to significant suppression of IL-17 under the same assay conditions. The most potent inverse agonist compound showed >180-fold selectivity over the ROR isoforms as well as all other nuclear receptors that were profiled. PMID:25815138

Travelling fronts of the CO oxidation on Pd(111) with coverage-dependent diffusion

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

Cisternas, Jaime, E-mail: jecisternas@miuandes.cl; Karpitschka, Stefan; Wehner, Stefan

2014-10-28

In this work, we study a surface reaction on Pd(111) crystals under ultra-high-vacuum conditions that can be modeled by two coupled reaction-diffusion equations. In the bistable regime, the reaction exhibits travelling fronts that can be observed experimentally using photo electron emission microscopy. The spatial profile of the fronts reveals a coverage-dependent diffusivity for one of the species. We propose a method to solve the nonlinear eigenvalue problem and compute the direction and the speed of the fronts based on a geometrical construction in phase-space. This method successfully captures the dependence of the speed on control parameters and diffusivities.

Lysosomal metabolomics reveals V-ATPase- and mTOR-dependent regulation of amino acid efflux from lysosomes.

PubMed

Abu-Remaileh, Monther; Wyant, Gregory A; Kim, Choah; Laqtom, Nouf N; Abbasi, Maria; Chan, Sze Ham; Freinkman, Elizaveta; Sabatini, David M

2017-11-10

The lysosome degrades and recycles macromolecules, signals to the cytosol and nucleus, and is implicated in many diseases. Here, we describe a method for the rapid isolation of mammalian lysosomes and use it to quantitatively profile lysosomal metabolites under various cell states. Under nutrient-replete conditions, many lysosomal amino acids are in rapid exchange with those in the cytosol. Loss of lysosomal acidification through inhibition of the vacuolar H + -adenosine triphosphatase (V-ATPase) increased the luminal concentrations of most metabolites but had no effect on those of the majority of essential amino acids. Instead, nutrient starvation regulates the lysosomal concentrations of these amino acids, an effect we traced to regulation of the mechanistic target of rapamycin (mTOR) pathway. Inhibition of mTOR strongly reduced the lysosomal efflux of most essential amino acids, converting the lysosome into a cellular depot for them. These results reveal the dynamic nature of lysosomal metabolites and that V-ATPase- and mTOR-dependent mechanisms exist for controlling lysosomal amino acid efflux. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Metabolomics profiles delineate uridine deficiency contributes to mitochondria-mediated apoptosis induced by celastrol in human acute promyelocytic leukemia cells

PubMed Central

Li, Lei; Huan, Fei; Li, Aiping; Liu, Yanqing; Xia, Yankai; Duan, Jin-ao; Ma, Shiping

2016-01-01

Celastrol, extracted from “Thunder of God Vine”, is a promising anti-cancer natural product. However, its effect on acute promyelocytic leukemia (APL) and underlying molecular mechanism are poorly understood. The purpose of this study was to explore its effect on APL and underlying mechanism based on metabolomics. Firstly, multiple assays indicated that celastrol could induce apoptosis of APL cells via p53-activated mitochondrial pathway. Secondly, unbiased metabolomics revealed that uridine was the most notable changed metabolite. Further study verified that uridine could reverse the apoptosis induced by celastrol. The decreased uridine was caused by suppressing the expression of gene encoding Dihydroorotate dehydrogenase, whose inhibitor could also induce apoptosis of APL cells. At last, mouse model confirmed that celastrol inhibited tumor growth through enhanced apoptosis. Celastrol could also decrease uridine and DHODH protein level in tumor tissues. Our in vivo study also indicated that celastrol had no systemic toxicity at pharmacological dose (2 mg/kg, i.p., 21 days). Altogether, our metabolomics study firstly reveals that uridine deficiency contributes to mitochondrial apoptosis induced by celastrol in APL cells. Celastrol shows great potential for the treatment of APL. PMID:27374097

Perceived Discrimination and Diurnal Cortisol: Examining Relations among Mexican American Adolescents

PubMed Central

Zeiders, Katharine H.; Doane, Leah D.; Roosa, Mark W.

2012-01-01

Perceived discrimination remains a salient and significant environmental stressor for ethnic and racial minority youth. Although many studies have examined the impact of racial/ethnic discrimination on mental health symptomatology and physical health, little is known of the potential physiological processes underlying such experiences, especially during adolescence. In an attempt to understand how varying perceptions of discrimination relate to functioning of the hypothalamic-pituitary-adrenal axis (HPA axis), the current study examined the relation between Mexican American adolescents’ (N= 100, Mage = 15.3 years old) perceptions of discrimination and aspects of their diurnal cortisol profiles. Three salivary samples (wakeup, +30 waking, bedtime) were collected across three days (total of 9 samples). Utilizing multi-level modeling, results revealed that adolescents’ perceived discrimination related to greater overall cortisol output (area under the curve; AUC) after controlling for other life stressors, depressive symptoms, family income, acculturation level, daily stress levels and daily behaviors. Findings also revealed that perceived discrimination was marginally related to a steeper cortisol awakening response (CAR). Together, these findings suggest that perceived discrimination is a salient and impactful stressor for Mexican American adolescents. Understanding the physiological correlates of discrimination can provide insight into larger health disparities among ethnic and racial minority individuals. PMID:22342577

Self-diffusion in 69Ga121Sb/71Ga123Sb isotope heterostructures

NASA Astrophysics Data System (ADS)

Bracht, H.; Nicols, S. P.; Haller, E. E.; Silveira, J. P.; Briones, F.

2001-05-01

Gallium and antimony self-diffusion experiments have been performed in undoped 69Ga121Sb/71Ga123Sb isotope heterostructures at temperatures between 571 and 708 °C under Sb- and Ga-rich ambients. Ga and Sb profiles measured with secondary ion mass spectrometry reveal that Ga diffuses faster than Sb by several orders of magnitude. This strongly suggests that the two self-atom species diffuse independently on their own sublattices. Experimental results lead us to conclude that Ga and Sb diffusion are mediated by Ga vacancies and Sb interstitials, respectively, and not by the formation of a triple defect proposed earlier by Weiler and Mehrer [Philos. Mag. A 49, 309 (1984)]. The extremely slow diffusion of Sb up to the melting temperature of GaSb is proposed to be a consequence of amphoteric transformations between native point defects which suppress the formation of those native defects which control Sb diffusion. Preliminary experiments exploring the effect of Zn indiffusion at 550 °C on Ga and Sb diffusion reveal an enhanced intermixing of the Ga isotope layers compared to undoped GaSb. However, under the same conditions the diffusion of Sb was not significantly affected.

1H NMR-based metabolic profiling reveals the effects of fluoxetine on lipid and amino acid metabolism in astrocytes.

PubMed

Bai, Shunjie; Zhou, Chanjuan; Cheng, Pengfei; Fu, Yuying; Fang, Liang; Huang, Wen; Yu, Jia; Shao, Weihua; Wang, Xinfa; Liu, Meiling; Zhou, Jingjing; Xie, Peng

2015-04-15

Fluoxetine, a selective serotonin reuptake inhibitor (SSRI), is a prescribed and effective antidepressant and generally used for the treatment of depression. Previous studies have revealed that the antidepressant mechanism of fluoxetine was related to astrocytes. However, the therapeutic mechanism underlying its mode of action in astrocytes remains largely unclear. In this study, primary astrocytes were exposed to 10 µM fluoxetine; 24 h post-treatment, a high-resolution proton nuclear magnetic resonance (1H NMR)-based metabolomic approach coupled with multivariate statistical analysis was used to characterize the metabolic variations of intracellular metabolites. The orthogonal partial least-squares discriminant analysis (OPLS-DA) score plots of the spectra demonstrated that the fluoxetine-treated astrocytes were significantly distinguished from the untreated controls. In total, 17 differential metabolites were identified to discriminate the two groups. These key metabolites were mainly involved in lipids, lipid metabolism-related molecules and amino acids. This is the first study to indicate that fluoxetine may exert antidepressant action by regulating the astrocyte's lipid and amino acid metabolism. These findings should aid our understanding of the biological mechanisms underlying fluoxetine therapy.

1H NMR-Based Metabolic Profiling Reveals the Effects of Fluoxetine on Lipid and Amino Acid Metabolism in Astrocytes

PubMed Central

Bai, Shunjie; Zhou, Chanjuan; Cheng, Pengfei; Fu, Yuying; Fang, Liang; Huang, Wen; Yu, Jia; Shao, Weihua; Wang, Xinfa; Liu, Meiling; Zhou, Jingjing; Xie, Peng

2015-01-01

Fluoxetine, a selective serotonin reuptake inhibitor (SSRI), is a prescribed and effective antidepressant and generally used for the treatment of depression. Previous studies have revealed that the antidepressant mechanism of fluoxetine was related to astrocytes. However, the therapeutic mechanism underlying its mode of action in astrocytes remains largely unclear. In this study, primary astrocytes were exposed to 10 µM fluoxetine; 24 h post-treatment, a high-resolution proton nuclear magnetic resonance (1H NMR)-based metabolomic approach coupled with multivariate statistical analysis was used to characterize the metabolic variations of intracellular metabolites. The orthogonal partial least-squares discriminant analysis (OPLS-DA) score plots of the spectra demonstrated that the fluoxetine-treated astrocytes were significantly distinguished from the untreated controls. In total, 17 differential metabolites were identified to discriminate the two groups. These key metabolites were mainly involved in lipids, lipid metabolism-related molecules and amino acids. This is the first study to indicate that fluoxetine may exert antidepressant action by regulating the astrocyte’s lipid and amino acid metabolism. These findings should aid our understanding of the biological mechanisms underlying fluoxetine therapy. PMID:25884334

Autonomous, Controlled, and Amotivated Types of Academic Motivation: A Person-Oriented Analysis

ERIC Educational Resources Information Center

Ratelle, Catherine F.; Guay, Frederic; Vallerand, Robert J.; Larose, Simon; Senecal, Caroline

2007-01-01

The authors investigated students' profiles regarding autonomous, controlled, and amotivated regulation and tested whether profile groups differed on some academic adjustment outcomes. Studies 1 and 2 performed on high school students revealed 3 profiles: (a) students with high levels of both controlled motivation and amotivation but low levels of…

Metabolomic analysis based on 1H-nuclear magnetic resonance spectroscopy metabolic profiles in tuberculous, malignant and transudative pleural effusion

PubMed Central

Wang, Cheng; Peng, Jingjin; Kuang, Yanling; Zhang, Jiaqiang; Dai, Luming

2017-01-01

Pleural effusion is a common clinical manifestation with various causes. Current diagnostic and therapeutic methods have exhibited numerous limitations. By involving the analysis of dynamic changes in low molecular weight catabolites, metabolomics has been widely applied in various types of disease and have provided platforms to distinguish many novel biomarkers. However, to the best of our knowledge, there are few studies regarding the metabolic profiling for pleural effusion. In the current study, 58 pleural effusion samples were collected, among which 20 were malignant pleural effusions, 20 were tuberculous pleural effusions and 18 were transudative pleural effusions. The small molecule metabolite spectrums were obtained by adopting 1H nuclear magnetic resonance technology, and pattern-recognition multi-variable statistical analysis was used to screen out different metabolites. One-way analysis of variance, and Student-Newman-Keuls and the Kruskal-Wallis test were adopted for statistical analysis. Over 400 metabolites were identified in the untargeted metabolomic analysis and 26 metabolites were identified as significantly different among tuberculous, malignant and transudative pleural effusions. These metabolites were predominantly involved in the metabolic pathways of amino acids metabolism, glycometabolism and lipid metabolism. Statistical analysis revealed that eight metabolites contributed to the distinction between the three groups: Tuberculous, malignant and transudative pleural effusion. In the current study, the feasibility of identifying small molecule biochemical profiles in different types of pleural effusion were investigated reveal novel biological insights into the underlying mechanisms. The results provide specific insights into the biology of tubercular, malignant and transudative pleural effusion and may offer novel strategies for the diagnosis and therapy of associated diseases, including tuberculosis, advanced lung cancer and congestive heart failure. PMID:28627685

Differential Expression of In Vivo and In Vitro Protein Profile of Outer Membrane of Acidovorax avenae Subsp. avenae

PubMed Central

Qiu, Hui; Li, Bin; Jabeen, Amara; Li, Liping; Liu, He; Kube, Michael; Xie, Guanlin; Wang, Yanli; Sun, Guochang

2012-01-01

Outer membrane (OM) proteins play a significant role in bacterial pathogenesis. In this work, we examined and compared the expression of the OM proteins of the rice pathogen Acidovorax avenae subsp. avenae strain RS-1, a Gram-negative bacterium, both in an in vitro culture medium and in vivo rice plants. Global proteomic profiling of A. avenae subsp. avenae strain RS-1 comparing in vivo and in vitro conditions revealed the differential expression of proteins affecting the survival and pathogenicity of the rice pathogen in host plants. The shotgun proteomics analysis of OM proteins resulted in the identification of 97 proteins in vitro and 62 proteins in vivo by mass spectrometry. Among these OM proteins, there is a high number of porins, TonB-dependent receptors, lipoproteins of the NodT family, ABC transporters, flagellins, and proteins of unknown function expressed under both conditions. However, the major proteins such as phospholipase and OmpA domain containing proteins were expressed in vitro, while the proteins such as the surface anchored protein F, ATP-dependent Clp protease, OmpA and MotB domain containing proteins were expressed in vivo. This may indicate that these in vivo OM proteins have roles in the pathogenicity of A. avenae subsp. avenae strain RS-1. In addition, the LC-MS/MS identification of OmpA and MotB validated the in silico prediction of the existance of Type VI secretion system core components. To the best of our knowledge, this is the first study to reveal the in vitro and in vivo protein profiles, in combination with LC-MS/MS mass spectra, in silico OM proteome and in silico genome wide analysis, of pathogenicity or plant host required proteins of a plant pathogenic bacterium. PMID:23166741

Electrical structures in the northwest margin of the Junggar basin: Implications for its late Paleozoic geodynamics

NASA Astrophysics Data System (ADS)

Zhang, Sheng; Xu, Yixian; Jiang, Li; Yang, Bo; Liu, Ying; Griffin, W. L.; Luo, Yong; Huang, Rong; Zhou, Yong; Zhang, Liangliang

2017-10-01

Recent geological, geochemical and geophysical data have inclined to support the presence of a remnant Paleozoic oceanic lithosphere beneath the Western Junggar, southwestern Chinese Altaids. However, regional high-resolution geophysical data have been rarely deployed to image its geometry, making it difficult to trace its evolution and final geodynamic setting. Presently, two magnetotelluric (MT) profiles are deployed across the northwest margin of the Junggar basin and the southern Darbut belt to image the electrical structure of the crust and lithospheric mantle. High-quality data at 102 sites and the quasi-2D indications of phase tensor skew angles and impedance phase ellipses for relatively short periods (up to 500 s) allow us to invert the two profile data by a 2-D scheme. The resistivity cross-section of a NW-SE striking LINE2 sheds light on a fossil intraoceanic subduction system, and reveals the Miaoergou intrusions as a bowl-like pluton, indicating that the multi-phase intrusions primarily formed in a post-collisional setting. The resistivity cross-section of striking NE-SW LINE1 reveals a possible oceanic slab with relatively lower resistivity underlying the low-resistivity sedimentary strata and high-resistivity mélange. Given that the profile of LINE1 cuts the out-rise zone of a subducted slab developed during the late Paleozoic, the 2-D resistivity model may thus represent the zone that have experienced heterogeneous deformation, reflecting subduction with barrier variation parallel to the ancient trench. Moreover, as shown in previous results, the new MT data also illustrate that the Darbut Fault is a thin-skinned structure, which has been erased at depths during the subsequent magmatism.

Active BRAF-V600E is the key player in generation of a sessile serrated polyp-specific DNA methylation profile

PubMed Central

Dehghanizadeh, Somaye; Khoddami, Vahid; Mosbruger, Timothy L.; Hammoud, Sue S.; Edes, Kornelia; Berry, Therese S.; Done, Michelle; Samowitz, Wade S.; DiSario, James A.; Luba, Daniel G.; Burt, Randall W.

2018-01-01

Background Sessile serrated polyps (SSPs) have emerged as important precursors for a large number of sporadic colorectal cancers. They are difficult to detect during colonoscopy due to their flat shape and the excessive amounts of secreted mucin that cover the polyps. The underlying genetic and epigenetic basis for the emergence of SSPs is largely unknown with existing genetic studies confined to a limited number of oncogenes and tumor suppressors. A full characterization of the genetic and epigenetic landscape of SSPs would provide insight into their origin and potentially offer new biomarkers useful for detection of SSPs in stool samples. Methods We used a combination of genome-wide mutation detection, exome sequencing and DNA methylation profiling (via methyl-array and whole-genome bisulfite sequencing) to analyze multiple samples of sessile serrated polyps and compared these to familial adenomatous polyps. Results Our analysis revealed BRAF-V600E as the sole recurring somatic mutation in SSPs with no additional major genetic mutations detected. The occurrence of BRAF-V600E was coincident with a unique DNA methylation pattern revealing a set of DNA methylation markers showing significant (~3 to 30 fold) increase in their methylation levels, exclusively in SSP samples. These methylation patterns effectively distinguished sessile serrated polys from adenomatous polyps and did so more effectively than parallel gene expression profiles. Conclusions This study provides an important example of a single oncogenic mutation leading to reproducible global DNA methylation changes. These methylated markers are specific to SSPs and could be of important clinical relevance for the early diagnosis of SSPs using non-invasive approaches such as fecal DNA testing. PMID:29590112

Pharmacokinetics of two 6-mercaptopurine liquid formulations in children with acute lymphoblastic leukemia.

PubMed

Tolbert, Jaszianne A; Bai, Shasha; Abdel-Rahman, Susan M; August, Keith J; Weir, Scott J; Kearns, Gregory L; Neville, Kathleen A

2017-08-01

A liquid formulation of 6-mercaptopurine (6-MP) was recently approved by the Food and Drug Administration (Purixan®) based on bioavailability (BA) data from healthy adults. We examined the pharmacokinetics (PK) and BA of 6-MP in children with acute lymphoblastic leukemia (ALL) comparing a marketed tablet, two extemporaneously prepared liquid formulations, and data from the approved liquid formulation. Twenty-two children (6-17 years) participated in a randomized two-way, crossover study of two cohorts. Group 1 (n = 11; five males) received a 5 mg/ml liquid formulation and the marketed 50 mg 6-MP tablet on separate occasions, and Group 2 (n = 11; five males) received a 50 mg/ml liquid formulation and the marketed tablet. The usual prescribed 6-MP dose (25-115 mg/m 2 ) was given after an 8-hr fast. Serial blood samples were collected over 8 hr postdose. Plasma 6-MP concentrations were determined using a good laboratory practice (GLP)-validated liquid chromatography-tandem mass spectrometry method. PK parameters were calculated using noncompartmental analysis and compared within and between cohorts, and thiopurine methyltransferase (TPMT) genotype was analyzed. No patient had a TPMT genotype reflective of a poor metabolizer phenotype. Comparison of PK parameters between 5 and 50 mg/ml treatments revealed significant differences (P <0.05) in AUC N (where AUC is area under the curve), C maxN , and T max . Comparisons within each group revealed significant differences in AUC 0-∞ and T max in the 5 mg/ml group. Pharmacokinetic profiles of 6-MP established in healthy adults with the approved liquid formulation may not reflect the PK profile in children with ALL. Formulation-specific differences in PK may significantly impact the dose-exposure profile in these children and must be considered. © 2017 Wiley Periodicals, Inc.

Integrative Assessment of Chlorine-Induced Acute Lung Injury in Mice

PubMed Central

Pope-Varsalona, Hannah; Concel, Vincent J.; Liu, Pengyuan; Bein, Kiflai; Berndt, Annerose; Martin, Timothy M.; Ganguly, Koustav; Jang, An Soo; Brant, Kelly A.; Dopico, Richard A.; Upadhyay, Swapna; Di, Y. P. Peter; Hu, Zhen; Vuga, Louis J.; Medvedovic, Mario; Kaminski, Naftali; You, Ming; Alexander, Danny C.; McDunn, Jonathan E.; Prows, Daniel R.; Knoell, Daren L.

2012-01-01

The genetic basis for the underlying individual susceptibility to chlorine-induced acute lung injury is unknown. To uncover the genetic basis and pathophysiological processes that could provide additional homeostatic capacities during lung injury, 40 inbred murine strains were exposed to chlorine, and haplotype association mapping was performed. The identified single-nucleotide polymorphism (SNP) associations were evaluated through transcriptomic and metabolomic profiling. Using ≥ 10% allelic frequency and ≥ 10% phenotype explained as threshold criteria, promoter SNPs that could eliminate putative transcriptional factor recognition sites in candidate genes were assessed by determining transcript levels through microarray and reverse real-time PCR during chlorine exposure. The mean survival time varied by approximately 5-fold among strains, and SNP associations were identified for 13 candidate genes on chromosomes 1, 4, 5, 9, and 15. Microarrays revealed several differentially enriched pathways, including protein transport (decreased more in the sensitive C57BLKS/J lung) and protein catabolic process (increased more in the resistant C57BL/10J lung). Lung metabolomic profiling revealed 95 of the 280 metabolites measured were altered by chlorine exposure, and included alanine, which decreased more in the C57BLKS/J than in the C57BL/10J strain, and glutamine, which increased more in the C57BL/10J than in the C57BLKS/J strain. Genetic associations from haplotype mapping were strengthened by an integrated assessment using transcriptomic and metabolomic profiling. The leading candidate genes associated with increased susceptibility to acute lung injury in mice included Klf4, Sema7a, Tns1, Aacs, and a gene that encodes an amino acid carrier, Slc38a4. PMID:22447970

Hierarchical Status Predicts Behavioral Vulnerability and Nucleus Accumbens Metabolic Profile Following Chronic Social Defeat Stress.

PubMed

Larrieu, Thomas; Cherix, Antoine; Duque, Aranzazu; Rodrigues, João; Lei, Hongxia; Gruetter, Rolf; Sandi, Carmen

2017-07-24

Extensive data highlight the existence of major differences in individuals' susceptibility to stress [1-4]. While genetic factors [5, 6] and exposure to early life stress [7, 8] are key components for such neurobehavioral diversity, intriguing observations revealed individual differences in response to stress in inbred mice [9-12]. This raised the possibility that other factors might be critical in stress vulnerability. A key challenge in the field is to identify non-invasively risk factors for vulnerability to stress. Here, we investigated whether behavioral factors, emerging from preexisting dominance hierarchies, could predict vulnerability to chronic stress [9, 13-16]. We applied a chronic social defeat stress (CSDS) model of depression in C57BL/6J mice to investigate the predictive power of hierarchical status to pinpoint which individuals will exhibit susceptibility to CSDS. Given that the high social status of dominant mice would be the one particularly challenged by CSDS, we predicted and found that dominant individuals were the ones showing a strong susceptibility profile as indicated by strong social avoidance following CSDS, while subordinate mice were not affected. Data from 1 H-NMR spectroscopy revealed that the metabolic profile in the nucleus accumbens (NAc) relates to social status and vulnerability to stress. Under basal conditions, subordinates show lower levels of energy-related metabolites compared to dominants. In subordinates, but not dominants, levels of these metabolites were increased after exposure to CSDS. To the best of our knowledge, this is the first study that identifies non-invasively the origin of behavioral risk factors predictive of stress-induced depression-like behaviors associated with metabolic changes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cardiomyocyte-specific deletion of the G protein-coupled estrogen receptor (GPER) leads to left ventricular dysfunction and adverse remodeling: A sex-specific gene profiling analysis.

PubMed

Wang, Hao; Sun, Xuming; Chou, Jeff; Lin, Marina; Ferrario, Carlos M; Zapata-Sudo, Gisele; Groban, Leanne

2017-08-01

Activation of G protein-coupled estrogen receptor (GPER) by its agonist, G1, protects the heart from stressors such as pressure-overload, ischemia, a high-salt diet, estrogen loss, and aging, in various male and female animal models. Due to nonspecific effects of G1, the exact functions of cardiac GPER cannot be concluded from studies using systemic G1 administration. Moreover, global knockdown of GPER affects glucose homeostasis, blood pressure, and many other cardiovascular-related systems, thereby confounding interpretation of its direct cardiac actions. We generated a cardiomyocyte-specific GPER knockout (KO) mouse model to specifically investigate the functions of GPER in cardiomyocytes. Compared to wild type mice, cardiomyocyte-specific GPER KO mice exhibited adverse alterations in cardiac structure and impaired systolic and diastolic function, as measured by echocardiography. Gene deletion effects on left ventricular dimensions were more profound in male KO mice compared to female KO mice. Analysis of DNA microarray data from isolated cardiomyocytes of wild type and KO mice revealed sex-based differences in gene expression profiles affecting multiple transcriptional networks. Gene Set Enrichment Analysis (GSEA) revealed that mitochondrial genes are enriched in GPER KO females, whereas inflammatory response genes are enriched in GPER KO males, compared to their wild type counterparts of the same sex. The cardiomyocyte-specific GPER KO mouse model provides us with a powerful tool to study the functions of GPER in cardiomyocytes. The gene expression profiles of the GPER KO mice provide foundational information for further study of the mechanisms underlying sex-specific cardioprotection by GPER. Copyright © 2016 Elsevier B.V. All rights reserved.

Starch-coated magnetic liposomes as an inhalable carrier for accumulation of fasudil in the pulmonary vasculature.

PubMed

Nahar, Kamrun; Absar, Shahriar; Patel, Brijeshkumar; Ahsan, Fakhrul

2014-04-10

In this study, we tested the feasibility of magnetic liposomes as a carrier for pulmonary preferential accumulation of fasudil, an investigational drug for the treatment of pulmonary arterial hypertension (PAH). To develop an optimal inhalable formulation, various magnetic liposomes were prepared and characterized for physicochemical properties, storage stability and in vitro release profiles. Select formulations were evaluated for uptake by pulmonary arterial smooth muscle cells (PASMCs) - target cells - using fluorescence microscopy and HPLC. The efficacy of the magnetic liposomes in reducing hyperplasia was tested in 5-HT-induced proliferated PASMCs. The drug absorption profiles upon intratracheal administration were monitored in healthy rats. Optimized spherical liposomes - with mean size of 170 nm, zeta potential of -35mV and entrapment efficiency of 85% - exhibited an 80% cumulative drug release over 120 h. Fluorescence microscopic study revealed an enhanced uptake of liposomes by PASMCs under an applied magnetic field: the uptake was 3-fold greater compared with that observed in the absence of magnetic field. PASMC proliferation was reduced by 40% under the influence of the magnetic field. Optimized liposomes appeared to be safe when incubated with PASMCs and bronchial epithelial cells. Compared with plain fasudil, intratracheal magnetic liposomes containing fasudil extended the half-life and area under the curve by 27- and 14-fold, respectively. Magnetic-liposomes could be a viable delivery system for site-specific treatment of PAH. Copyright © 2014 Elsevier B.V. All rights reserved.

Local Context Finder (LCF) reveals multidimensional relationships among mRNA expression profiles of Arabidopsis responding to pathogen infection

PubMed Central

Katagiri, Fumiaki; Glazebrook, Jane

2003-01-01

A major task in computational analysis of mRNA expression profiles is definition of relationships among profiles on the basis of similarities among them. This is generally achieved by pattern recognition in the distribution of data points representing each profile in a high-dimensional space. Some drawbacks of commonly used pattern recognition algorithms stem from their use of a globally linear space and/or limited degrees of freedom. A pattern recognition method called Local Context Finder (LCF) is described here. LCF uses nonlinear dimensionality reduction for pattern recognition. Then it builds a network of profiles based on the nonlinear dimensionality reduction results. LCF was used to analyze mRNA expression profiles of the plant host Arabidopsis interacting with the bacterial pathogen Pseudomonas syringae. In one case, LCF revealed two dimensions essential to explain the effects of the NahG transgene and the ndr1 mutation on resistant and susceptible responses. In another case, plant mutants deficient in responses to pathogen infection were classified on the basis of LCF analysis of their profiles. The classification by LCF was consistent with the results of biological characterization of the mutants. Thus, LCF is a powerful method for extracting information from expression profile data. PMID:12960373

Comparative transcriptome analysis of pepper (Capsicum annuum) revealed common regulons in multiple stress conditions and hormone treatments.

PubMed

Lee, Sanghyeob; Choi, Doil

2013-09-01

Global transcriptome analysis revealed common regulons for biotic/abiotic stresses, and some of these regulons encoding signaling components in both stresses were newly identified in this study. In this study, we aimed to identify plant responses to multiple stress conditions and discover the common regulons activated under a variety of stress conditions. Global transcriptome analysis revealed that salicylic acid (SA) may affect the activation of abiotic stress-responsive genes in pepper. Our data indicate that methyl jasmonate (MeJA) and ethylene (ET)-responsive genes were primarily activated by biotic stress, while abscisic acid (ABA)-responsive genes were activated under both types of stresses. We also identified differentially expressed gene (DEG) responses to specific stress conditions. Biotic stress induces more DEGs than those induced by abiotic and hormone applications. The clustering analysis using DEGs indicates that there are common regulons for biotic or abiotic stress conditions. Although SA and MeJA have an antagonistic effect on gene expression levels, SA and MeJA show a largely common regulation as compared to the regulation at the DEG expression level induced by other hormones. We also monitored the expression profiles of DEG encoding signaling components. Twenty-two percent of these were commonly expressed in both stress conditions. The importance of this study is that several genes commonly regulated by both stress conditions may have future applications for creating broadly stress-tolerant pepper plants. This study revealed that there are complex regulons in pepper plant to both biotic and abiotic stress conditions.

Integrated lipidomics and transcriptomic analysis of peripheral blood reveals significantly enriched pathways in type 2 diabetes mellitus.

PubMed

Zhao, Chen; Mao, Jinghe; Ai, Junmei; Shenwu, Ming; Shi, Tieliu; Zhang, Daqing; Wang, Xiaonan; Wang, Yunliang; Deng, Youping

2013-01-01

Insulin resistance is a key element in the pathogenesis of type 2 diabetes mellitus. Plasma free fatty acids were assumed to mediate the insulin resistance, while the relationship between lipid and glucose disposal remains to be demonstrated across liver, skeletal muscle and blood. We profiled both lipidomics and gene expression of 144 total peripheral blood samples, 84 from patients with T2D and 60 from healthy controls. Then, factor and partial least squares models were used to perform a combined analysis of lipidomics and gene expression profiles to uncover the bioprocesses that are associated with lipidomic profiles in type 2 diabetes. According to factor analysis of the lipidomic profile, several species of lipids were found to be correlated with different phenotypes, including diabetes-related C23:2CE, C23:3CE, C23:4CE, ePE36:4, ePE36:5, ePE36:6; race-related (African-American) PI36:1; and sex-related PE34:1 and LPC18:2. The major variance of gene expression profile was not caused by known factors and no significant difference can be directly derived from differential gene expression profile. However, the combination of lipidomic and gene expression analyses allows us to reveal the correlation between the altered lipid profile with significantly enriched pathways, such as one carbon pool by folate, arachidonic acid metabolism, insulin signaling pathway, amino sugar and nucleotide sugar metabolism, propanoate metabolism, and starch and sucrose metabolism. The genes in these pathways showed a good capability to classify diabetes samples. Combined analysis of gene expression and lipidomic profiling reveals type 2 diabetes-associated lipid species and enriched biological pathways in peripheral blood, while gene expression profile does not show direct correlation. Our findings provide a new clue to better understand the mechanism of disordered lipid metabolism in association with type 2 diabetes.

Harnessing BET Inhibitor Sensitivity Reveals AMIGO2 as a Melanoma Survival Gene.

PubMed

Fontanals-Cirera, Barbara; Hasson, Dan; Vardabasso, Chiara; Di Micco, Raffaella; Agrawal, Praveen; Chowdhury, Asif; Gantz, Madeleine; de Pablos-Aragoneses, Ana; Morgenstern, Ari; Wu, Pamela; Filipescu, Dan; Valle-Garcia, David; Darvishian, Farbod; Roe, Jae-Seok; Davies, Michael A; Vakoc, Christopher R; Hernando, Eva; Bernstein, Emily

2017-11-16

Bromodomain and extraterminal domain inhibitors (BETi) represent promising therapeutic agents for metastatic melanoma, yet their mechanism of action remains unclear. Here we interrogated the transcriptional effects of BETi and identified AMIGO2, a transmembrane molecule, as a BET target gene essential for melanoma cell survival. AMIGO2 is upregulated in melanoma cells and tissues compared to human melanocytes and nevi, and AMIGO2 silencing in melanoma cells induces G1/S arrest followed by apoptosis. We identified the pseudokinase PTK7 as an AMIGO2 interactor whose function is regulated by AMIGO2. Epigenomic profiling and genome editing revealed that AMIGO2 is regulated by a melanoma-specific BRD2/4-bound promoter and super-enhancer configuration. Upon BETi treatment, BETs are evicted from these regulatory elements, resulting in AMIGO2 silencing and changes in PTK7 proteolytic processing. Collectively, this study uncovers mechanisms underlying the therapeutic effects of BETi in melanoma and reveals the AMIGO2-PTK7 axis as a targetable pathway for metastatic melanoma. Copyright © 2017 Elsevier Inc. All rights reserved.

Clinical Profile of Children and Adolescents Attending the Behavioural Paediatrics Unit OPD in a Tertiary Care Set up

ERIC Educational Resources Information Center

Jayaprakash, R.

2012-01-01

Background: There are limited studies on the clinical profile of children attending child guidance clinic under Paediatric background. Aims: To study clinical profile of Children & adolescents attending the Behavioural Paediatrics Unit (BPU) OPD under department of Paediatrics in a tertiary care set up. Methods: Monthly average turnover in the…

The Effect of Small Additions of Carbon Nanotubes on the Mechanical Properties of Epoxy Polymers under Static and Dynamic Loads

NASA Astrophysics Data System (ADS)

Tarasov, A. E.; Badamshina, E. R.; Anokhin, D. V.; Razorenov, S. V.; Vakorina, G. S.

2018-01-01

The results of measurements of the mechanical characteristics of cured epoxy composites containing small and ultrasmall additions of single-walled carbon nanotubes in the concentration range from 0 to 0.133 wt % under static and dynamic loads are presented. Static measurements of strength characteristics have been carried out under standard test conditions. Measurements of the Hugoniot elastic limit and spall strength were performed under a shock wave loading of the samples at a deformation rate of (0.8-1.5) ß 105 s-1 before the fracture using explosive devices by recording and subsequent analyzing the evolution of the full wave profiles. It has been shown that agglomerates of nanotubes present in the structure of the composites after curing cause a significant scatter of the measured strength parameters, both in the static and in the dynamic test modes. However, the effects of carbon nanotube additions in the studied concentration interval on the physical and mechanical characteristics of the parameters were not revealed for both types of loading.

Tocopherols in Sunflower Seedlings under Light and Dark Conditions.

PubMed

del Moral, Lidia; Pérez-Vich, Begoña; Velasco, Leonardo

2015-01-01

The objective of this study was to evaluate the dynamics of tocopherols in cotyledons and radicles from sunflower seeds with high and low total tocopherol content, mainly in the α-tocopherol form, and from seeds with increased proportions of β-, γ-, and δ-tocopherol, both under dark and light conditions. Tocopherol content was measured every 24 h from 1 to 12 days after sowing. In all cases, the content of individual tocopherol forms in the cotyledons and radicles was reduced along the sampling period, which was more pronounced under light conditions. The presence of light had a slightly greater effect on α- and γ-tocopherol than on β- and δ-tocopherol. A marked light effect was also observed on total tocopherol content, with light promoting the reduction of tocopherol content in cotyledons and radicles. The study revealed only slight differences in the patterns of tocopherol losses in lines with different tocopherol profiles, both under dark and light conditions, which suggested that the partial replacement of α-tocopherol by other tocopherol forms had no great impact on the protection against oxidative damage in seedlings.

Tocopherols in Sunflower Seedlings under Light and Dark Conditions

PubMed Central

del Moral, Lidia; Pérez-Vich, Begoña

2015-01-01

The objective of this study was to evaluate the dynamics of tocopherols in cotyledons and radicles from sunflower seeds with high and low total tocopherol content, mainly in the α-tocopherol form, and from seeds with increased proportions of β-, γ-, and δ-tocopherol, both under dark and light conditions. Tocopherol content was measured every 24 h from 1 to 12 days after sowing. In all cases, the content of individual tocopherol forms in the cotyledons and radicles was reduced along the sampling period, which was more pronounced under light conditions. The presence of light had a slightly greater effect on α- and γ-tocopherol than on β- and δ-tocopherol. A marked light effect was also observed on total tocopherol content, with light promoting the reduction of tocopherol content in cotyledons and radicles. The study revealed only slight differences in the patterns of tocopherol losses in lines with different tocopherol profiles, both under dark and light conditions, which suggested that the partial replacement of α-tocopherol by other tocopherol forms had no great impact on the protection against oxidative damage in seedlings. PMID:26347898

Identifying the bad guy in a lineup using confidence judgments under deadline pressure.

PubMed

Brewer, Neil; Weber, Nathan; Wootton, David; Lindsay, D Stephen

2012-10-01

Eyewitness-identification tests often culminate in witnesses not picking the culprit or identifying innocent suspects. We tested a radical alternative to the traditional lineup procedure used in such tests. Rather than making a positive identification, witnesses made confidence judgments under a short deadline about whether each lineup member was the culprit. We compared this deadline procedure with the traditional sequential-lineup procedure in three experiments with retention intervals ranging from 5 min to 1 week. A classification algorithm that identified confidence criteria that optimally discriminated accurate from inaccurate decisions revealed that decision accuracy was 24% to 66% higher under the deadline procedure than under the traditional procedure. Confidence profiles across lineup stimuli were more informative than were identification decisions about the likelihood that an individual witness recognized the culprit or correctly recognized that the culprit was not present. Large differences between the maximum and the next-highest confidence value signaled very high accuracy. Future support for this procedure across varied conditions would highlight a viable alternative to the problematic lineup procedures that have traditionally been used by law enforcement.

A Comprehensive Approach to Sequence-oriented IsomiR annotation (CASMIR): demonstration with IsomiR profiling in colorectal neoplasia.

PubMed

Wu, Chung Wah; Evans, Jared M; Huang, Shengbing; Mahoney, Douglas W; Dukek, Brian A; Taylor, William R; Yab, Tracy C; Smyrk, Thomas C; Jen, Jin; Kisiel, John B; Ahlquist, David A

2018-05-25

MicroRNA (miRNA) profiling is an important step in studying biological associations and identifying marker candidates. miRNA exists in isoforms, called isomiRs, which may exhibit distinct properties. With conventional profiling methods, limitations in assay and analysis platforms may compromise isomiR interrogation. We introduce a comprehensive approach to sequence-oriented isomiR annotation (CASMIR) to allow unbiased identification of global isomiRs from small RNA sequencing data. In this approach, small RNA reads are maintained as independent sequences instead of being summarized under miRNA names. IsomiR features are identified through step-wise local alignment against canonical forms and precursor sequences. Through customizing the reference database, CASMIR is applicable to isomiR annotation across species. To demonstrate its application, we investigated isomiR profiles in normal and neoplastic human colorectal epithelia. We also ran miRDeep2, a popular miRNA analysis algorithm to validate isomiRs annotated by CASMIR. With CASMIR, specific and biologically relevant isomiR patterns could be identified. We note that specific isomiRs are often more abundant than their canonical forms. We identify isomiRs that are commonly up-regulated in both colorectal cancer and advanced adenoma, and illustrate advantages in targeting isomiRs as potential biomarkers over canonical forms. Studying miRNAs at the isomiR level could reveal new insight into miRNA biology and inform assay design for specific isomiRs. CASMIR facilitates comprehensive annotation of isomiR features in small RNA sequencing data for isomiR profiling and differential expression analysis.

Depth profiling of mechanical degradation of PV backsheets after UV exposure

NASA Astrophysics Data System (ADS)

Gu, Xiaohong; Krommenhoek, Peter J.; Lin, Chiao-Chi; Yu, Li-Chieh; Nguyen, Tinh; Watson, Stephanie S.

2015-09-01

Polymeric multilayer backsheets protect the photovoltaic modules from damage of moisture and ultraviolet (UV) while providing electrical insulation. Due to the multilayer structures, the properties of the inner layers of the backsheets, including their interfaces, during weathering are not well known. In this study, a commercial type of PPE (polyethylene terephthalate (PET)/PET/ethylene vinyl acetate (EVA)) backsheet films was selected as a model system for a depth profiling study of mechanical properties of a backsheet film during UV exposure. The NIST SPHERE (Simulated Photodegradation via High Energy Radiant Exposure) was used for the accelerated laboratory exposure of the materials with UV at 85°C and two relative humidities (RH) of 5 % (dry) and 60 % (humid). Cryomicrotomy was used to obtain cross-sectional PPE samples. Mechanical depth profiling of the cross-sections of aged and unaged samples was conducted by nanoindentation, and a peak-force based quantitative nanomechanical atomic force microscopy (QNM-AFM) mapping techniquewas used to investigate the microstructure and adhesion properties of the adhesive tie layers. The nanoindentation results show the stiffening of the elastic modulus in the PET outer and pigmented EVA layers. From QNM-AFM, the microstructures and adhesion properties of the adhesive layers between PET outer and core layers and between PET core and EVA inner layers are revealed and found to degrade significantly after aging under humidity environment. The results from mechanical depth profiling of the PPE backsheet are further related to the previous chemical depth profiling of the same material, providing new insights into the effects of accelerated UV and humidity on the degradation of multilayer backsheet.

Taxonomic characterization of the cellulose-degrading bacterium NCIB 10462

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

Dees, C.; Ringleberg, D.; Scott, T.C.

The gram negative cellulase-producing bacterium NCIB 10462 has been previously named Pseudomonas fluorescens subsp. or var. cellulosa. Since there is renewed interest in cellulose-degrading bacteria for use in bioconversion of cellulose to chemical feed stocks and fuels, we re-examined the characteristics of this microorganism to determine its proper taxonomic characterization and to further define it`s true metabolic potential. Metabolic and physical characterization of NCIB 10462 revealed that this was an alkalophilic, non-fermentative, gram negative, oxidase positive, motile, cellulose-degrading bacterium. The aerobic substrate utilization profile of this bacterium was found to have few characteristics consistent with a classification of P. fluorescensmore » with a very low probability match with the genus Sphingomonas. Total lipid analysis did not reveal that any sphingolipid bases are produced by this bacterium. NCIB 10462 was found to grow best aerobically but also grows well in complex media under reducing conditions. NCIB 10462 grew slowly under full anaerobic conditions on complex media but growth on cellulosic media was found only under aerobic conditions. Total fatty acid analysis (MIDI) of NCIB 10462 failed to group this bacterium with a known pseudomonas species. However, fatty acid analysis of the bacteria when grown at temperatures below 37{degrees}C suggest that the organism is a pseudomonad. Since a predominant characteristic of this bacterium is it`s ability to degrade cellulose, we suggest it be called Pseudomonas cellulosa.« less

Disruption of TCA Cycle and Glutamate Metabolism Identified by Metabolomics in an In Vitro Model of Amyotrophic Lateral Sclerosis.

PubMed

Veyrat-Durebex, Charlotte; Corcia, Philippe; Piver, Eric; Devos, David; Dangoumau, Audrey; Gouel, Flore; Vourc'h, Patrick; Emond, Patrick; Laumonnier, Frédéric; Nadal-Desbarats, Lydie; Gordon, Paul H; Andres, Christian R; Blasco, Hélène

2016-12-01

This study aims to develop a cellular metabolomics model that reproduces the pathophysiological conditions found in amyotrophic lateral sclerosis in order to improve knowledge of disease physiology. We used a co-culture model combining the motor neuron-like cell line NSC-34 and the astrocyte clone C8-D1A, with each over-expressing wild-type or G93C mutant human SOD1, to examine amyotrophic lateral sclerosis (ALS) physiology. We focused on the effects of mutant human SOD1 as well as oxidative stress induced by menadione on intracellular metabolism using a metabolomics approach through gas chromatography coupled with mass spectrometry (GC-MS) analysis. Preliminary non-supervised analysis by Principal Component Analysis (PCA) revealed that cell type, genetic environment, and time of culture influenced the metabolomics profiles. Supervised analysis using orthogonal partial least squares discriminant analysis (OPLS-DA) on data from intracellular metabolomics profiles of SOD1 G93C co-cultures produced metabolites involved in glutamate metabolism and the tricarboxylic acid cycle (TCA) cycle. This study revealed the feasibility of using a metabolomics approach in a cellular model of ALS. We identified potential disruption of the TCA cycle and glutamate metabolism under oxidative stress, which is consistent with prior research in the disease. Analysis of metabolic alterations in an in vitro model is a novel approach to investigation of disease physiology.

Genome-wide Expression Profiling, In Vivo DNA Binding Analysis, and Probabilistic Motif Prediction Reveal Novel Abf1 Target Genes during Fermentation, Respiration, and Sporulation in Yeast

PubMed Central

Schlecht, Ulrich; Erb, Ionas; Demougin, Philippe; Robine, Nicolas; Borde, Valérie; van Nimwegen, Erik; Nicolas, Alain

2008-01-01

The autonomously replicating sequence binding factor 1 (Abf1) was initially identified as an essential DNA replication factor and later shown to be a component of the regulatory network controlling mitotic and meiotic cell cycle progression in budding yeast. The protein is thought to exert its functions via specific interaction with its target site as part of distinct protein complexes, but its roles during mitotic growth and meiotic development are only partially understood. Here, we report a comprehensive approach aiming at the identification of direct Abf1-target genes expressed during fermentation, respiration, and sporulation. Computational prediction of the protein's target sites was integrated with a genome-wide DNA binding assay in growing and sporulating cells. The resulting data were combined with the output of expression profiling studies using wild-type versus temperature-sensitive alleles. This work identified 434 protein-coding loci as being transcriptionally dependent on Abf1. More than 60% of their putative promoter regions contained a computationally predicted Abf1 binding site and/or were bound by Abf1 in vivo, identifying them as direct targets. The present study revealed numerous loci previously unknown to be under Abf1 control, and it yielded evidence for the protein's variable DNA binding pattern during mitotic growth and meiotic development. PMID:18305101

Differential expression profile of membrane proteins in L-02 cells exposed to trichloroethylene.

PubMed

Hong, Wen-Xu; Huang, Aibo; Lin, Sheng; Yang, Xifei; Yang, Linqing; Zhou, Li; Huang, Haiyan; Wu, Desheng; Huang, Xinfeng; Xu, Hua; Liu, Jianjun

2016-10-01

Trichloroethylene (TCE), a halogenated organic solvent widely used in industries, is known to cause severe hepatotoxicity. However, the mechanisms underlying TCE hepatotoxicity are still not well understood. It is predicted that membrane proteins are responsible for key biological functions, and recent studies have revealed that TCE exposure can induce abnormal levels of membrane proteins in body fluids and cultured cells. The aim of this study is to investigate the TCE-induced alterations of membrane proteins profiles in human hepatic L-02 liver cells. A comparative membrane proteomics analysis was performed in combination with two-dimensional fluorescence difference gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry. A total of 15 proteins were identified as differentially expressed (4 upregulated and 11 downregulated) between TCE-treated cells and normal controls. Among this, 14 of them are suggested as membrane-associated proteins by their transmembrane domain and/or subcellular location. Furthermore, the differential expression of β subunit of adenosine triphosphate synthase (ATP5B) and prolyl 4-hydroxylase, β polypeptide (P4HB) were verified by Western blot analysis in TCE-treated L-02 cells. Our work not only reveals the association between TCE exposure and altered expression of membrane proteins but also provides a novel strategy to discover membrane biomarkers and elucidate the potential mechanisms involving with membrane proteins response to chemical-induced toxic effect. © The Author(s) 2015.

Proteomic Analysis of Interactions between a Deep-Sea Thermophilic Bacteriophage and Its Host at High Temperature ▿ †

PubMed Central

Wei, Dahai; Zhang, Xiaobo

2010-01-01

The virus-host interaction is essential to understanding the role that viruses play in ecological and geochemical processes in deep-sea vent ecosystems. Virus-induced changes in cellular gene expression and host physiology have been studied extensively. However, the molecular mechanism of interaction between a bacteriophage and its host at high temperature remains poorly understood. In the present study, the virus-induced gene expression profile of Geobacillus sp. E263, a thermophile isolated from a deep-sea hydrothermal ecosystem, was characterized. Based on proteomic analysis and random arbitrarily primed PCR (RAP-PCR) of Geobacillus sp. E263 cultured under non-bacteriophage GVE2 infection and GVE2 infection conditions, there were two types of protein/gene profiles in response to GVE2 infection. Twenty differentially expressed genes and proteins were revealed that could be grouped into 3 different categories based on cellular function, suggesting a coordinated response to infection. These differentially expressed genes and proteins were further confirmed by Northern blot analysis. To characterize the host proteins in response to virus infection, aspartate aminotransferase (AST) was inactivated to construct the AST mutant of Geobacillus sp. E263. The results showed that the AST protein was essential in virus infection. Thus, transcriptional and proteomic analyses and functional analysis revealed previously unknown host responses to deep-sea thermophilic virus infection. PMID:20015994

Fruit ripening mutants reveal cell metabolism and redox state during ripening.

PubMed

Kumar, Vinay; Irfan, Mohammad; Ghosh, Sumit; Chakraborty, Niranjan; Chakraborty, Subhra; Datta, Asis

2016-03-01

Ripening which leads to fruit senescence is an inimitable process characterized by vivid changes in color, texture, flavor, and aroma of the fleshy fruits. Our understanding of the mechanisms underlying the regulation of fruit ripening and senescence is far from complete. Molecular and biochemical studies on tomato (Solanum lycopersicum) ripening mutants such as ripening inhibitor (rin), nonripening (nor), and never ripe (Nr) have been useful in our understanding of fruit development and ripening. The MADS-box transcription factor RIN, a global regulator of fruit ripening, is vital for the broad aspects of ripening, in both ethylene-dependent and independent manners. Here, we have carried out microarray analysis to study the expression profiles of tomato genes during ripening of wild type and rin mutant fruits. Analysis of the differentially expressed genes revealed the role of RIN in regulation of several molecular and biochemical events during fruit ripening including fruit specialized metabolism and cellular redox state. The role of reactive oxygen species (ROS) during fruit ripening and senescence was further examined by determining the changes in ROS level during ripening of wild type and mutant fruits and by analyzing expression profiles of the genes involved in maintaining cellular redox state. Taken together, our findings suggest an important role of ROS during fruit ripening and senescence, and therefore, modulation of ROS level during ripening could be useful in achieving desired fruit quality.

TGFβ1-Induced Differentiation of Human Bone Marrow-Derived MSCs Is Mediated by Changes to the Actin Cytoskeleton.

PubMed

Elsafadi, Mona; Manikandan, Muthurangan; Almalki, Sami; Mobarak, Mohammad; Atteya, Muhammad; Iqbal, Zafar; Hashmi, Jamil Amjad; Shaheen, Sameerah; Alajez, Nehad; Alfayez, Musaad; Kassem, Moustapha; Dawud, Raed Abu; Mahmood, Amer

2018-01-01

TGF β is a potent regulator of several biological functions in many cell types, but its role in the differentiation of human bone marrow-derived skeletal stem cells (hMSCs) is currently poorly understood. In the present study, we demonstrate that a single dose of TGF β 1 prior to induction of osteogenic or adipogenic differentiation results in increased mineralized matrix or increased numbers of lipid-filled mature adipocytes, respectively. To identify the mechanisms underlying this TGF β -mediated enhancement of lineage commitment, we compared the gene expression profiles of TGF β 1-treated hMSC cultures using DNA microarrays. In total, 1932 genes were upregulated, and 1298 genes were downregulated. Bioinformatics analysis revealed that TGF β l treatment was associated with an enrichment of genes in the skeletal and extracellular matrix categories and the regulation of the actin cytoskeleton. To investigate further, we examined the actin cytoskeleton following treatment with TGF β 1 and/or cytochalasin D. Interestingly, cytochalasin D treatment of hMSCs enhanced adipogenic differentiation but inhibited osteogenic differentiation. Global gene expression profiling revealed a significant enrichment of pathways related to osteogenesis and adipogenesis and of genes regulated by both TGF β 1 and cytochalasin D. Our study demonstrates that TGF β 1 enhances hMSC commitment to either the osteogenic or adipogenic lineages by reorganizing the actin cytoskeleton.

Correlates of Vaccine-Induced Protection against Mycobacterium tuberculosis Revealed in Comparative Analyses of Lymphocyte Populations

PubMed Central

Kurtz, Sherry L.

2015-01-01

A critical hindrance to the development of a novel vaccine against Mycobacterium tuberculosis is a lack of understanding of protective correlates of immunity and of host factors involved in a successful adaptive immune response. Studies from our group and others have used a mouse-based in vitro model system to assess correlates of protection. Here, using this coculture system and a panel of whole-cell vaccines with varied efficacy, we developed a comprehensive approach to understand correlates of protection. We compared the gene and protein expression profiles of vaccine-generated immune peripheral blood lymphocytes (PBLs) to the profiles found in immune splenocytes. PBLs not only represent a clinically relevant cell population, but comparing the expression in these populations gave insight into compartmentally specific mechanisms of protection. Additionally, we performed a direct comparison of host responses induced when immune cells were cocultured with either the vaccine strain Mycobacterium bovis BCG or virulent M. tuberculosis. These comparisons revealed host-specific and bacterium-specific factors involved in protection against virulent M. tuberculosis. Most significantly, we identified a set of 13 core molecules induced in the most protective vaccines under all of the conditions tested. Further validation of this panel of mediators as a predictor of vaccine efficacy will facilitate vaccine development, and determining how each promotes adaptive immunity will advance our understanding of antimycobacterial immune responses. PMID:26269537

An Examination of the Changes in Science Teaching Orientations and Technology-Enhanced Tools for Student Learning in the Context of Professional Development

NASA Astrophysics Data System (ADS)

Campbell, Todd; Zuwallack, Rebecca; Longhurst, Max; Shelton, Brett E.; Wolf, Paul G.

2014-07-01

This research examines how science teaching orientations and beliefs about technology-enhanced tools change over time in professional development (PD). The primary data sources for this study came from learning journals of 8 eighth grade science teachers at the beginning and conclusion of a year of PD. Based on the analysis completed, Information Transmission (IT) and Struggling with Standards-Based Reform (SSBR) profiles were found at the beginning of the PD, while SSBR and Standards-Based Reform (SBR) profiles were identified at the conclusion of PD. All profiles exhibited Vision I beliefs about the goals and purposes for science education, while only the SBR profile exhibited Vision II goals and purposes for science teaching. The IT profile demonstrated naïve or unrevealed beliefs about the nature of science, while the SSBR and SBR profiles had more sophisticated beliefs in this area. The IT profile was grounded in more teacher-centered beliefs about science teaching and learning as the other two profiles revealed more student-centered beliefs. While no beliefs about technology-enhanced tools were found for the IT profile, these were found for the other two profiles. Our findings suggest promising implications for (a) Roberts' Vision II as a central support for reform efforts, (b) situating technology-enhanced tools within the beliefs about science teaching and learning dimension of science teaching orientations, and (c) revealing how teacher orientations develop as a result of PD.

Developing Coping Typologies of Minority Adolescents: A Latent Profile Analysis

ERIC Educational Resources Information Center

Aldridge, Arianna A.; Roesch, Scott C.

2008-01-01

Latent profile analysis (LPA) was used to develop a coping typology of minority adolescents (M = 15.5 years). A multiethnic sample (n = 354) was recruited from a program aimed at serving low-income students. LPA revealed three distinct coping profiles. The first comprised adolescents who used a number of specific coping strategies at a low level…

Effect of Dietary Forage to Concentrate Ratios on Dynamic Profile Changes and Interactions of Ruminal Microbiota and Metabolites in Holstein Heifers

PubMed Central

Zhang, Jun; Shi, Haitao; Wang, Yajing; Li, Shengli; Cao, Zhijun; Ji, Shoukun; He, Yuan; Zhang, Hongtao

2017-01-01

A better understanding of global ruminal microbiota and metabolites under extensive feeding conditions is a prerequisite for optimizing rumen function and improving ruminant feed efficiency. Furthermore, the gap between the information on the ruminal microbiota and metabolites needs to be bridged. The aim of this study was to investigate the effects of a wide range of forage to concentrate ratios (F:C) on changes and interactions of ruminal microbiota and metabolites. Four diets with different F:C (80:20, 60:40, 40:60, and 20:80) were limit-fed to 24 Holstein heifers, and Illumina MiSeq sequencing and gas chromatography time-of-flight/mass spectrometry were used to investigate the profile changes of the ruminal microbes and metabolites, and the interaction between them. The predominant bacterial phyla in the rumen were Bacteroidetes (57.2 ± 2.6%) and Firmicutes (26.8 ± 1.6%), and the predominant anaerobic fungi were Neocallimastigomycota (64.3 ± 3.8%) and Ascomycota (22.6 ± 2.4%). In total, 44, 9, 25, and 2 genera, respectively, were identified as the core rumen bacteria, ciliate protozoa, anaerobic fungi, and archaea communities across all samples. An increased concentrate level linearly decreased the relative abundance of cellulolytic bacteria and ciliates, namely Fibrobacter, Succinimonas, Polyplastron, and Ostracodinium (q < 0.05), and linearly increased the relative abundance of Entodinium (q = 0.04), which is a non-fibrous carbohydrate degrader. Dietary F:C had no effect on the communities of anaerobic fungi and archaea. Rumen metabolomics analysis revealed that ruminal amino acids, lipids, organic acids, and carbohydrates were altered significantly by altering the dietary F:C. With increasing dietary concentrate levels, the proportions of propionate and butyrate linearly increased in the rumen (P ≤ 0.01). Correlation analysis revealed that there was some utilization relationship or productive association between candidate metabolites and affected microbe groups. This study provides a better understanding of ruminal microbiota and metabolites under a wide range of dietary F:C, which could further reveal integrative information of rumen function and lead to an improvement in ruminant production. PMID:29170660

Novel use of a Dektak 150 surface profiler unmasks differences in resorption pit profiles between control and Charcot patient osteoclasts.

PubMed

Petrova, Nina L; Petrov, Peter K; Edmonds, Michael E; Shanahan, Catherine M

2014-04-01

We hypothesized that newly formed osteoclasts from patients with acute Charcot osteoarthropathy can resorb surfaces of bone more extensively compared with controls. Peripheral blood monocytes, isolated from eight Charcot patients and nine controls, were cultured in vitro on 24-well plates and bovine bone discs in duplicate with macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor κβ ligand (RANKL). Osteoclast formation was assessed by tartrate-resistant acid phosphatase staining (TRAcP) at day 17. Resorption was measured at day 21 after toluidine blue staining by two methods: (1) area of resorption at the surface by image analysis (%) and (2) area of resorption under the surface (μm(2)) measured by a Dektak 150 Surface Profiler. Ten 1,000 μm-long scans were performed per disc. Pits were classified as unidented, bidented, and multidented according to their shape. Although the number of newly formed TRAcP positive multinucleated cells (>3 nuclei) was similar in M-CSF + RANKL-treated cultures between controls and Charcot patients, the latter exhibited increased resorbing activity. The area of resorption on the surface by image analysis was significantly greater in Charcot patients compared with controls (21.1 % [14.5-26.2] vs. 40.8 % [35.4-46.0], median [25-75th percentile], p < 0.01), as was the area of resorption under the surface (2.7 x 10(3) μm(2) [1.6 x 10(3)- 3.9 x 10(3)] vs. 8.3 x 10(3) μm (2) [5.6 x 10(3)- 10.6 x 10(3), [corrected] p < 0.01) after profilometry. In Charcot patients pits were deeper and wider and more frequently presented as multidented pits. This application of the Dektak 150 Surface Profiler revealed novel differences in resorption pit profile from osteoclasts derived from Charcot patients compared with controls. Resorption in Charcot patients was mediated by highly aggressive newly formed osteoclasts from monocytes eroding large and deep areas of bone.

An EST-based analysis identifies new genes and reveals distinctive gene expression features of Coffea arabica and Coffea canephora

PubMed Central

2011-01-01

Background Coffee is one of the world's most important crops; it is consumed worldwide and plays a significant role in the economy of producing countries. Coffea arabica and C. canephora are responsible for 70 and 30% of commercial production, respectively. C. arabica is an allotetraploid from a recent hybridization of the diploid species, C. canephora and C. eugenioides. C. arabica has lower genetic diversity and results in a higher quality beverage than C. canephora. Research initiatives have been launched to produce genomic and transcriptomic data about Coffea spp. as a strategy to improve breeding efficiency. Results Assembling the expressed sequence tags (ESTs) of C. arabica and C. canephora produced by the Brazilian Coffee Genome Project and the Nestlé-Cornell Consortium revealed 32,007 clusters of C. arabica and 16,665 clusters of C. canephora. We detected different GC3 profiles between these species that are related to their genome structure and mating system. BLAST analysis revealed similarities between coffee and grape (Vitis vinifera) genes. Using KA/KS analysis, we identified coffee genes under purifying and positive selection. Protein domain and gene ontology analyses suggested differences between Coffea spp. data, mainly in relation to complex sugar synthases and nucleotide binding proteins. OrthoMCL was used to identify specific and prevalent coffee protein families when compared to five other plant species. Among the interesting families annotated are new cystatins, glycine-rich proteins and RALF-like peptides. Hierarchical clustering was used to independently group C. arabica and C. canephora expression clusters according to expression data extracted from EST libraries, resulting in the identification of differentially expressed genes. Based on these results, we emphasize gene annotation and discuss plant defenses, abiotic stress and cup quality-related functional categories. Conclusion We present the first comprehensive genome-wide transcript profile study of C. arabica and C. canephora, which can be freely assessed by the scientific community at http://www.lge.ibi.unicamp.br/coffea. Our data reveal the presence of species-specific/prevalent genes in coffee that may help to explain particular characteristics of these two crops. The identification of differentially expressed transcripts offers a starting point for the correlation between gene expression profiles and Coffea spp. developmental traits, providing valuable insights for coffee breeding and biotechnology, especially concerning sugar metabolism and stress tolerance. PMID:21303543

Relationships between physical education students' motivational profiles, enjoyment, state anxiety, and self-reported physical activity.

PubMed

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?

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

PubMed

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.

Profound Effect of Profiling Platform and Normalization Strategy on Detection of Differentially Expressed MicroRNAs – A Comparative Study

PubMed Central

Meyer, Swanhild U.; Kaiser, Sebastian; Wagner, Carola; Thirion, Christian; Pfaffl, Michael W.

2012-01-01

Background Adequate normalization minimizes the effects of systematic technical variations and is a prerequisite for getting meaningful biological changes. However, there is inconsistency about miRNA normalization performances and recommendations. Thus, we investigated the impact of seven different normalization methods (reference gene index, global geometric mean, quantile, invariant selection, loess, loessM, and generalized procrustes analysis) on intra- and inter-platform performance of two distinct and commonly used miRNA profiling platforms. Methodology/Principal Findings We included data from miRNA profiling analyses derived from a hybridization-based platform (Agilent Technologies) and an RT-qPCR platform (Applied Biosystems). Furthermore, we validated a subset of miRNAs by individual RT-qPCR assays. Our analyses incorporated data from the effect of differentiation and tumor necrosis factor alpha treatment on primary human skeletal muscle cells and a murine skeletal muscle cell line. Distinct normalization methods differed in their impact on (i) standard deviations, (ii) the area under the receiver operating characteristic (ROC) curve, (iii) the similarity of differential expression. Loess, loessM, and quantile analysis were most effective in minimizing standard deviations on the Agilent and TLDA platform. Moreover, loess, loessM, invariant selection and generalized procrustes analysis increased the area under the ROC curve, a measure for the statistical performance of a test. The Jaccard index revealed that inter-platform concordance of differential expression tended to be increased by loess, loessM, quantile, and GPA normalization of AGL and TLDA data as well as RGI normalization of TLDA data. Conclusions/Significance We recommend the application of loess, or loessM, and GPA normalization for miRNA Agilent arrays and qPCR cards as these normalization approaches showed to (i) effectively reduce standard deviations, (ii) increase sensitivity and accuracy of differential miRNA expression detection as well as (iii) increase inter-platform concordance. Results showed the successful adoption of loessM and generalized procrustes analysis to one-color miRNA profiling experiments. PMID:22723911

Enzymatically Modified Starch Ameliorates Postprandial Serum Triglycerides and Lipid Metabolome in Growing Pigs.

PubMed

Metzler-Zebeli, Barbara U; Eberspächer, Eva; Grüll, Dietmar; Kowalczyk, Lidia; Molnar, Timea; Zebeli, Qendrim

2015-01-01

Developing host digestion-resistant starches to promote human health is of great research interest. Chemically modified starches (CMS) are widely used in processed foods and although the modification of the starch molecule allows specific reduction in digestibility, the metabolic effects of CMS have been less well described. This short-term study evaluated the impact of enzymatically modified starch (EMS) on fasting and postprandial profiles of blood glucose, insulin and lipids, and serum metabolome in growing pigs. Eight jugular-vein catheterized pigs (initial body weight, 37.4 kg; 4 months of age) were fed 2 diets containing 72% purified starch (EMS or waxy corn starch (control)) in a cross-over design for 7 days. On day 8, an 8-hour meal tolerance test (MTT) was performed with serial blood samplings. Besides biochemical analysis, serum was analysed for 201 metabolites through targeted mass spectrometry-based metabolomic approaches. Pigs fed the EMS diet showed increased (P<0.05) immediate serum insulin and plasma glucose response compared to pigs fed the control diet; however, area-under-the-curves for insulin and glucose were not different among diets. Results from MTT indicated reduced postprandial serum triglycerides with EMS versus control diet (P<0.05). Likewise, serum metabolome profiling identified characteristic changes in glycerophospholipid, lysophospholipids, sphingomyelins and amino acid metabolome profiles with EMS diet compared to control diet. Results showed rapid adaptations of blood metabolites to dietary starch shifts within 7 days. In conclusion, EMS ingestion showed potential to attenuate postprandial raise in serum lipids and suggested constant alteration in the synthesis or breakdown of sphingolipids and phospholipids which might be a health benefit of EMS consumption. Because serum insulin was not lowered, more research is warranted to reveal possible underlying mechanisms behind the observed changes in the profile of serum lipid metabolome in response to EMS consumption.

Enzymatically Modified Starch Ameliorates Postprandial Serum Triglycerides and Lipid Metabolome in Growing Pigs

PubMed Central

Metzler-Zebeli, Barbara U.; Eberspächer, Eva; Grüll, Dietmar; Kowalczyk, Lidia; Molnar, Timea; Zebeli, Qendrim

2015-01-01

Developing host digestion-resistant starches to promote human health is of great research interest. Chemically modified starches (CMS) are widely used in processed foods and although the modification of the starch molecule allows specific reduction in digestibility, the metabolic effects of CMS have been less well described. This short-term study evaluated the impact of enzymatically modified starch (EMS) on fasting and postprandial profiles of blood glucose, insulin and lipids, and serum metabolome in growing pigs. Eight jugular-vein catheterized pigs (initial body weight, 37.4 kg; 4 months of age) were fed 2 diets containing 72% purified starch (EMS or waxy corn starch (control)) in a cross-over design for 7 days. On day 8, an 8-hour meal tolerance test (MTT) was performed with serial blood samplings. Besides biochemical analysis, serum was analysed for 201 metabolites through targeted mass spectrometry-based metabolomic approaches. Pigs fed the EMS diet showed increased (P<0.05) immediate serum insulin and plasma glucose response compared to pigs fed the control diet; however, area-under-the-curves for insulin and glucose were not different among diets. Results from MTT indicated reduced postprandial serum triglycerides with EMS versus control diet (P<0.05). Likewise, serum metabolome profiling identified characteristic changes in glycerophospholipid, lysophospholipids, sphingomyelins and amino acid metabolome profiles with EMS diet compared to control diet. Results showed rapid adaptations of blood metabolites to dietary starch shifts within 7 days. In conclusion, EMS ingestion showed potential to attenuate postprandial raise in serum lipids and suggested constant alteration in the synthesis or breakdown of sphingolipids and phospholipids which might be a health benefit of EMS consumption. Because serum insulin was not lowered, more research is warranted to reveal possible underlying mechanisms behind the observed changes in the profile of serum lipid metabolome in response to EMS consumption. PMID:26076487

Systematic analysis of Ca2+ homeostasis in Saccharomyces cerevisiae based on chemical-genetic interaction profiles

PubMed Central

Ghanegolmohammadi, Farzan; Yoshida, Mitsunori; Ohnuki, Shinsuke; Sukegawa, Yuko; Okada, Hiroki; Obara, Keisuke; Kihara, Akio; Suzuki, Kuninori; Kojima, Tetsuya; Yachie, Nozomu; Hirata, Dai; Ohya, Yoshikazu

2017-01-01

We investigated the global landscape of Ca2+ homeostasis in budding yeast based on high-dimensional chemical-genetic interaction profiles. The morphological responses of 62 Ca2+-sensitive (cls) mutants were quantitatively analyzed with the image processing program CalMorph after exposure to a high concentration of Ca2+. After a generalized linear model was applied, an analysis of covariance model was used to detect significant Ca2+–cls interactions. We found that high-dimensional, morphological Ca2+–cls interactions were mixed with positive (86%) and negative (14%) chemical-genetic interactions, whereas one-dimensional fitness Ca2+–cls interactions were all negative in principle. Clustering analysis with the interaction profiles revealed nine distinct gene groups, six of which were functionally associated. In addition, characterization of Ca2+–cls interactions revealed that morphology-based negative interactions are unique signatures of sensitized cellular processes and pathways. Principal component analysis was used to discriminate between suppression and enhancement of the Ca2+-sensitive phenotypes triggered by inactivation of calcineurin, a Ca2+-dependent phosphatase. Finally, similarity of the interaction profiles was used to reveal a connected network among the Ca2+ homeostasis units acting in different cellular compartments. Our analyses of high-dimensional chemical-genetic interaction profiles provide novel insights into the intracellular network of yeast Ca2+ homeostasis. PMID:28566553

Measurements of Martian dust devil winds with HiRISE

USGS Publications Warehouse

Choi, D.S.; Dundas, C.M.

2011-01-01

We report wind measurements within Martian dust devils observed in plan view from the High Resolution Imaging Science Experiment (HiRISE) orbiting Mars. The central color swath of the HiRISE instrument has three separate charge-coupled devices (CCDs) and color filters that observe the surface in rapid cadence. Active features, such as dust devils, appear in motion when observed by this region of the instrument. Our image animations reveal clear circulatory motion within dust devils that is separate from their translational motion across the Martian surface. Both manual and automated tracking of dust devil clouds reveal tangential winds that approach 20-30 m s -1 in some cases. These winds are sufficient to induce a ???1% decrease in atmospheric pressure within the dust devil core relative to ambient, facilitating dust lifting by reducing the threshold wind speed for particle elevation. Finally, radial velocity profiles constructed from our automated measurements test the Rankine vortex model for dust devil structure. Our profiles successfully reveal the solid body rotation component in the interior, but fail to conclusively illuminate the profile in the outer regions of the vortex. One profile provides evidence for a velocity decrease as a function of r -1/2, instead of r -1, suggestive of surface friction effects. However, other profiles do not support this observation, or do not contain enough measurements to produce meaningful insights. Copyright 2011 by the American Geophysical Union.

The Use of TOC Reconciliation as a Means of Establishing the Degree to Which Chromatographic Screening of Plastic Material Extracts for Organic Extractables Is Complete.

PubMed

Jenke, Dennis; Couch, Thomas R; Robinson, Sarah J; Volz, Trent J; Colton, Raymond H

2014-01-01

Extracts of plastic packaging, manufacturing, and delivery systems (or their materials of construction) are analyzed by chromatographic methods to establish the system's extractables profile. The testing strategy consists of multiple orthogonal chromatographic methods, for example, gas and liquid chromatography with multiple detection strategies. Although this orthogonal testing strategy is comprehensive, it is not necessarily complete and members of the extractables profile can elude detection and/or accurate identification/quantification. Because the chromatographic methods rarely indicate that some extractables have been missed, another means of assessing the completeness of the profiling activity must be established. If the extracts are aqueous and contain no organic additives (e.g., pH buffers), then they can be analyzed for their total organic carbon content (TOC). Additionally, the TOC of an extract can be calculated based on the extractables revealed by the screening analyses. The measured and calculated TOC can be reconciled to establish the completeness and accuracy of the extractables profile. If the reconciliation is poor, then the profile is either incomplete or inaccurate and additional testing is needed to establish the complete and accurate profile. Ten test materials and components of systems were extracted and their extracts characterized for organic extractables using typical screening procedures. Measured and calculated TOC was reconciled to establish the completeness of the revealed extractables profile. When the TOC reconciliation was incomplete, the profiling was augmented with additional analytical testing to reveal the missing members of the organic extractables profile. This process is illustrated via two case studies involving aqueous extracts of sterile filters. Plastic materials and systems used to manufacture, contain, store, and deliver pharmaceutical products are extracted and the extracts analyzed to establish the materials' (or systems') organic extractables profile. Such testing typically consists of multiple chromatographic approaches whose differences help to ensure that all organic extractables are revealed, measured, and identified. Nevertheless, this rigorous screening process is not infallible and certain organic extractables may elude detection. If the extraction medium is aqueous, the process of total organic carbon (TOC) reconciliation is proposed as a means of establishing when some organic extractables elude detection. In the reconciliation, the TOC of the extracts is both directly measured and calculated from the chromatographic data. The measured and calculated TOC is compared (or reconciled), and the degree of reconciliation is an indication of the completeness and accuracy of the organic extractables profiling. If the reconciliation is poor, then the extractables profile is either incomplete or inaccurate and additional testing must be performed to establish the complete and accurate profile. This article demonstrates the TOC reconciliation process by considering aqueous extracts of 10 different test articles. Incomplete reconciliations were augmented with additional testing to produce a more complete TOC reconciliation. © PDA, Inc. 2014.

Control of the U and Th behaviour in forest soils

NASA Astrophysics Data System (ADS)

Rihs, Sophie; Gontier, Adrien; Chabaux, François; Pelt, Eric; Turpault, Marie-Pierre

2015-04-01

U- and Th-series disequilibria and U, Th, Fe and Al speciation, were measured in several soil profiles from the experimental forest site of Breuil (Morvan, France) in order to address the impact of the vegetation on U and Th nuclides behaviour in soils. Thirty-five years after an experimental clear-felling of the native forest, the soil developed under two replacing mono-specific plantations (Oak and Douglas fir) were therefore compared to the undisturbed native forest soil. The analogous physical and chemical properties of these soils before the replacement were formerly demonstrated. Our results suggest that a shift in the Iron distribution seems to occur under the stand replaced by Oaks, with a significant replacement of Fe-bearing silicates by well crystallized Fe oxides. In contrast, such evolution was not demonstrated in the soils under Douglas fir. The concurrent loss of U and Th from the soils under Oak was tentatively related to the dissolution of Fe-bearing minerals. A mass balance calculation demonstrates that the observed increase in U oxalate-extracted fractions can quantitatively be explained through the entire profiles by a mere dissolution of up to 20% of U-Fe-bearing silicated minerals, without significant re-adsorption onto the amorphous Fe-Al oxides for U. Beside this primary release from Fe-bearing silicate minerals, the mobility of U and Th seems more likely controlled by Al phases rather than Fe oxides in surface layers during further pedogenic processes. Indeed, some of the U- and Th series disequilibria seem to be strongly related to Al dynamic in these layers. This relationship can be seen in the native forest profiles as well as in the replaced profiles, suggesting that this feature is not linked to the cover change. The redistribution of U and Th isotopes through these pedogenic processes therefore rule out the use of U-series for weathering rate determination in shallowest soils layers. In contrast, below 25 cm, the release of U and Th as well as the change of their distribution among the soil phases does not affect U- and Th series disequilibria. The activity ratios measured in oxalate leachates and the residues allow to demonstrate that the dissolution of a U-bearing silicate mineral and the consequent release of up to 20% of U would shift the (234U/238U) and (230Th/234U) ratios by less than 2%. These results therefore reveal that, after 35 years, no significant impact of the cover change on U-series disequilibria was recorded in the main part of the soil profiles, which, at this stage, justify the use of these nuclides as chronometers for weathering determination.

The effect of dys-1 mutation on miRNA expression profile in Caenorhabditis elegans during Shenzhou-8 mission

NASA Astrophysics Data System (ADS)

Xu, Dan; Sun, Yeqing; Gao, Ying; Xing, Yanfang

microRNAs (miRNAs) is reported to be sensitive to radiation exposure and altered gravity, involved in a variety of biological processes through negative regulation of gene expression. Dystrophin-like dys-1 gene is expressed and required in muscle tissue, which plays a vital role in mechanical transduction when gravity varies. In the present study, we investigated the effect of dys-1 mutation on miRNA expression profile in Caenorhabditis elegans (C. elegans) under space radiation associated with microgravity (R+M) and radiation alone (R) environment during Shenzhou-8 mission. We performed miRNA microarray analysis in dys-1 mutant and wide-type (WT) of dauer larvae and found that 27 miRNAs changed in abundance after spaceflight. Compared with WT, there was different miRNA expression pattern in different treatments in dys-1 mutant. Cel-miR-796 and miR-124 were reversely expressed under R+M and R environment in WT and dys-1 mutant, respectively, indicating they might be affected by microgravity. Mutation of dys-1 remarkably reduced the number of altered miRNAs under space environment, resulting in the decrease of genes in biological categories of “body morphogenesis”, “behavior”, “cell adhesion” and so on. Particularly, we found that those genes controlling regulation of locomotion in WT were lost in dys-1 mutant, while genes in positive regulation of developmental process only existed in dys-1 mutant. miR-796 was predicted to target genes ace-1 and dyc-1 that are functionally linked to dys-1. Integration analysis of miRNA and mRNA expression profile revealed that miR-56 and miR-124 were involved in behavior and locomotion by regulating different target genes under space environment, among which nep-11, deb-1, C07H4.1 and F11H8.2 might be associated with neuromuscular system. Our findings suggest that dys-1 could cause alteration of miRNAs and target genes, involved in regulating the response of C. elegans to space microgravity in neuromuscular system. This research will provide new insight for better understanding of the mechanism in microgravity-induced muscular dystrophy.

A Novel Counter Sheet-flow Sandwich Cell Culture Device for Mammalian Cell Growth in Space

NASA Astrophysics Data System (ADS)

Sun, Shujin; Gao, Yuxin; Shu, Nanjiang; Tang, Zemei; Tao, Zulai; Long, Mian

2008-08-01

Cell culture and growth in space is crucial to understand the cellular responses under microgravity. The effects of microgravity were coupled with such environment restrictions as medium perfusion, in which the underlying mechanism has been poorly understood. In the present work, a customer-made counter sheet-flow sandwich cell culture device was developed upon a biomechanical concept from fish gill breathing. The sandwich culture unit consists of two side chambers where the medium flow is counter-directional, a central chamber where the cells are cultured, and two porous polycarbonate membranes between side and central chambers. Flow dynamics analysis revealed the symmetrical velocity profile and uniform low shear rate distribution of flowing medium inside the central culture chamber, which promotes sufficient mass transport and nutrient supply for mammalian cell growth. An on-orbit experiment performed on a recovery satellite was used to validate the availability of the device.

Genetic, molecular and physiological basis of variation in Drosophila gut immunocompetence.

PubMed

Bou Sleiman, Maroun S; Osman, Dani; Massouras, Andreas; Hoffmann, Ary A; Lemaitre, Bruno; Deplancke, Bart

2015-07-27

Gut immunocompetence involves immune, stress and regenerative processes. To investigate the determinants underlying inter-individual variation in gut immunocompetence, we perform enteric infection of 140 Drosophila lines with the entomopathogenic bacterium Pseudomonas entomophila and observe extensive variation in survival. Using genome-wide association analysis, we identify several novel immune modulators. Transcriptional profiling further shows that the intestinal molecular state differs between resistant and susceptible lines, already before infection, with one transcriptional module involving genes linked to reactive oxygen species (ROS) metabolism contributing to this difference. This genetic and molecular variation is physiologically manifested in lower ROS activity, lower susceptibility to ROS-inducing agent, faster pathogen clearance and higher stem cell activity in resistant versus susceptible lines. This study provides novel insights into the determinants underlying population-level variability in gut immunocompetence, revealing how relatively minor, but systematic genetic and transcriptional variation can mediate overt physiological differences that determine enteric infection susceptibility.

Gene expression profiling of flax (Linum usitatissimum L.) under edaphic stress.

PubMed

Dmitriev, Alexey A; Kudryavtseva, Anna V; Krasnov, George S; Koroban, Nadezhda V; Speranskaya, Anna S; Krinitsina, Anastasia A; Belenikin, Maxim S; Snezhkina, Anastasiya V; Sadritdinova, Asiya F; Kishlyan, Natalya V; Rozhmina, Tatiana A; Yurkevich, Olga Yu; Muravenko, Olga V; Bolsheva, Nadezhda L; Melnikova, Nataliya V

2016-11-16

Cultivated flax (Linum usitatissimum L.) is widely used for production of textile, food, chemical and pharmaceutical products. However, various stresses decrease flax production. Search for genes, which are involved in stress response, is necessary for breeding of adaptive cultivars. Imbalanced concentration of nutrient elements in soil decrease flax yields and also results in heritable changes in some flax lines. The appearance of Linum Insertion Sequence 1 (LIS-1) is the most studied modification. However, LIS-1 function is still unclear. High-throughput sequencing of transcriptome of flax plants grown under normal (N), phosphate deficient (P), and nutrient excess (NPK) conditions was carried out using Illumina platform. The assembly of transcriptome was performed, and a total of 34924, 33797, and 33698 unique transcripts for N, P, and NPK sequencing libraries were identified, respectively. We have not revealed any LIS-1 derived mRNA in our sequencing data. The analysis of high-throughput sequencing data allowed us to identify genes with potentially differential expression under imbalanced nutrition. For further investigation with qPCR, 15 genes were chosen and their expression levels were evaluated in the extended sampling of 31 flax plants. Significant expression alterations were revealed for genes encoding WRKY and JAZ protein families under P and NPK conditions. Moreover, the alterations of WRKY family genes differed depending on LIS-1 presence in flax plant genome. Besides, we revealed slight and LIS-1 independent mRNA level changes of KRP2 and ING1 genes, which are adjacent to LIS-1, under nutrition stress. Differentially expressed genes were identified in flax plants, which were grown under phosphate deficiency and excess nutrition, on the basis of high-throughput sequencing and qPCR data. We showed that WRKY and JAS gene families participate in flax response to imbalanced nutrient content in soil. Besides, we have not identified any mRNA, which could be derived from LIS-1, in our transcriptome sequencing data. Expression of LIS-1 flanking genes, ING1 and KRP2, was suggested not to be nutrient stress-induced. Obtained results provide new insights into edaphic stress response in flax and the role of LIS-1 in these process.

DNA profiling, telomere analysis and antioxidant properties as tools for monitoring ex situ seed longevity

PubMed Central

Donà, M.; Balestrazzi, A.; Mondoni, A.; Rossi, G.; Ventura, L.; Buttafava, A.; Macovei, A.; Sabatini, M. E.; Valassi, A.; Carbonera, D.

2013-01-01

Background and Aims The germination test currently represents the most used method to assess seed viability in germplasm banks, despite the difficulties caused by the occurrence of seed dormancy. Furthermore, seed longevity can vary considerably across species and populations from different environments, and studies related to the eco-physiological processes underlying such variations are still limited in their depth. The aim of the present work was the identification of reliable molecular markers that might help in monitoring seed deterioration. Methods Dry seeds were subjected to artificial ageing and collected at different time points for molecular/biochemical analyses. DNA damage was measured using the RAPD (random amplified polymorphic DNA) approach while the seed antioxidant profile was obtained using both the DPPH (1,1-diphenyl, 2-picrylhydrazyl) assay and the Folin–Ciocalteu reagent method. Electron paramagnetic resonance (EPR) provided profiles of free radicals. Quantitative real-time polymerase chain reaction (QRT-PCR) was used to assess the expression profiles of the antioxidant genes MT2 (type 2 metallothionein) and SOD (superoxide dismutase). A modified QRT-PCR protocol was used to determine telomere length. Key Results The RAPD profiles highlighted different capacities of the two Silene species to overcome DNA damage induced by artificial ageing. The antioxidant profiles of dry and rehydrated seeds revealed that the high-altitude taxon Silene acaulis was characterized by a lower antioxidant specific activity. Significant upregulation of the MT2 and SOD genes was observed only in the rehydrated seeds of the low-altitude species. Rehydration resulted in telomere lengthening in both Silene species. Conclusions Different seed viability markers have been selected for plant species showing inherent variation of seed longevity. RAPD analysis, quantification of redox activity of non-enzymatic antioxidant compounds and gene expression profiling provide deeper insights to study seed viability during storage. Telomere lengthening is a promising tool to discriminate between short- and long-lived species. PMID:23532044

40 CFR 141.709 - Developing the disinfection profile and benchmark.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 23 2011-07-01 2011-07-01 false Developing the disinfection profile... Cryptosporidium Disinfection Profiling and Benchmarking Requirements § 141.709 Developing the disinfection profile and benchmark. (a) Systems required to develop disinfection profiles under § 141.708 must follow the...

40 CFR 141.709 - Developing the disinfection profile and benchmark.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 23 2014-07-01 2014-07-01 false Developing the disinfection profile... Cryptosporidium Disinfection Profiling and Benchmarking Requirements § 141.709 Developing the disinfection profile and benchmark. (a) Systems required to develop disinfection profiles under § 141.708 must follow the...

40 CFR 141.709 - Developing the disinfection profile and benchmark.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 24 2012-07-01 2012-07-01 false Developing the disinfection profile... Cryptosporidium Disinfection Profiling and Benchmarking Requirements § 141.709 Developing the disinfection profile and benchmark. (a) Systems required to develop disinfection profiles under § 141.708 must follow the...

40 CFR 141.709 - Developing the disinfection profile and benchmark.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 24 2013-07-01 2013-07-01 false Developing the disinfection profile... Cryptosporidium Disinfection Profiling and Benchmarking Requirements § 141.709 Developing the disinfection profile and benchmark. (a) Systems required to develop disinfection profiles under § 141.708 must follow the...

Translational Profiles of Medullary Myofibroblasts during Kidney Fibrosis

PubMed Central

Grgic, Ivica; Krautzberger, A. Michaela; Hofmeister, Andreas; Lalli, Matthew; DiRocco, Derek P.; Fleig, Susanne V.; Liu, Jing; Duffield, Jeremy S.; McMahon, Andrew P.; Aronow, Bruce

2014-01-01

Myofibroblasts secrete matrix during chronic injury, and their ablation ameliorates fibrosis. Development of new biomarkers and therapies for CKD will be aided by a detailed analysis of myofibroblast gene expression during the early stages of fibrosis. However, dissociating myofibroblasts from fibrotic kidney is challenging. We therefore adapted translational ribosome affinity purification (TRAP) to isolate and profile mRNA from myofibroblasts and their precursors during kidney fibrosis. We generated and characterized a transgenic mouse expressing an enhanced green fluorescent protein (eGFP)–tagged L10a ribosomal subunit protein under control of the collagen1α1 promoter. We developed a one-step procedure for isolation of polysomal RNA from collagen1α1-eGFPL10a mice subject to unilateral ureteral obstruction and analyzed and validated the resulting transcriptional profiles. Pathway analysis revealed strong gene signatures for cell proliferation, migration, and shape change. Numerous novel genes and candidate biomarkers were upregulated during fibrosis, specifically in myofibroblasts, and we validated these results by quantitative PCR, in situ, and Western blot analysis. This study provides a comprehensive analysis of early myofibroblast gene expression during kidney fibrosis and introduces a new technique for cell-specific polysomal mRNA isolation in kidney injury models that is suited for RNA-sequencing technologies. PMID:24652793

Label-free Quantitative Protein Profiling of vastus lateralis Muscle During Human Aging*

PubMed Central

Théron, Laëtitia; Gueugneau, Marine; Coudy, Cécile; Viala, Didier; Bijlsma, Astrid; Butler-Browne, Gillian; Maier, Andrea; Béchet, Daniel; Chambon, Christophe

2014-01-01

Sarcopenia corresponds to the loss of muscle mass occurring during aging, and is associated with a loss of muscle functionality. Proteomic links the muscle functional changes with protein expression pattern. To better understand the mechanisms involved in muscle aging, we performed a proteomic analysis of Vastus lateralis muscle in mature and older women. For this, a shotgun proteomic method was applied to identify soluble proteins in muscle, using a combination of high performance liquid chromatography and mass spectrometry. A label-free protein profiling was then conducted to quantify proteins and compare profiles from mature and older women. This analysis showed that 35 of the 366 identified proteins were linked to aging in muscle. Most of the proteins were under-represented in older compared with mature women. We built a functional interaction network linking the proteins differentially expressed between mature and older women. The results revealed that the main differences between mature and older women were defined by proteins involved in energy metabolism and proteins from the myofilament and cytoskeleton. This is the first time that label-free quantitative proteomics has been applied to study of aging mechanisms in human skeletal muscle. This approach highlights new elements for elucidating the alterations observed during aging and may lead to novel sarcopenia biomarkers. PMID:24217021

Label-free quantitative protein profiling of vastus lateralis muscle during human aging.

PubMed

Théron, Laëtitia; Gueugneau, Marine; Coudy, Cécile; Viala, Didier; Bijlsma, Astrid; Butler-Browne, Gillian; Maier, Andrea; Béchet, Daniel; Chambon, Christophe

2014-01-01

Sarcopenia corresponds to the loss of muscle mass occurring during aging, and is associated with a loss of muscle functionality. Proteomic links the muscle functional changes with protein expression pattern. To better understand the mechanisms involved in muscle aging, we performed a proteomic analysis of Vastus lateralis muscle in mature and older women. For this, a shotgun proteomic method was applied to identify soluble proteins in muscle, using a combination of high performance liquid chromatography and mass spectrometry. A label-free protein profiling was then conducted to quantify proteins and compare profiles from mature and older women. This analysis showed that 35 of the 366 identified proteins were linked to aging in muscle. Most of the proteins were under-represented in older compared with mature women. We built a functional interaction network linking the proteins differentially expressed between mature and older women. The results revealed that the main differences between mature and older women were defined by proteins involved in energy metabolism and proteins from the myofilament and cytoskeleton. This is the first time that label-free quantitative proteomics has been applied to study of aging mechanisms in human skeletal muscle. This approach highlights new elements for elucidating the alterations observed during aging and may lead to novel sarcopenia biomarkers.

Salivary Alpha-Amylase Reactivity in Breast Cancer Survivors

PubMed Central

Wan, Cynthia; Couture-Lalande, Marie-Ève; Narain, Tasha A.; Lebel, Sophie; Bielajew, Catherine

2016-01-01

The two main components of the stress system are the hypothalamic-pituitary-adrenal (HPA) and sympathetic-adrenal-medullary (SAM) axes. While cortisol has been commonly used as a biomarker of HPA functioning, much less attention has been paid to the role of the SAM in this context. Studies have shown that long-term breast cancer survivors display abnormal reactive cortisol patterns, suggesting a dysregulation of their HPA axis. To fully understand the integrity of the stress response in this population, this paper explored the diurnal and acute alpha-amylase profiles of 22 breast cancer survivors and 26 women with no history of cancer. Results revealed that breast cancer survivors displayed identical but elevated patterns of alpha-amylase concentrations in both diurnal and acute profiles relative to that of healthy women, F (1, 39) = 17.95, p < 0.001 and F (1, 37) = 7.29, p = 0.010, respectively. The average area under the curve for the diurnal and reactive profiles was 631.54 ± 66.94 SEM and 1238.78 ± 111.84 SEM, respectively. This is in sharp contrast to their cortisol results, which showed normal diurnal and blunted acute patterns. The complexity of the stress system necessitates further investigation to understand the synergistic relationship of the HPA and SAM axes. PMID:27023572

Salivary Alpha-Amylase Reactivity in Breast Cancer Survivors.

PubMed

Wan, Cynthia; Couture-Lalande, Marie-Ève; Narain, Tasha A; Lebel, Sophie; Bielajew, Catherine

2016-03-23

The two main components of the stress system are the hypothalamic-pituitary-adrenal (HPA) and sympathetic-adrenal-medullary (SAM) axes. While cortisol has been commonly used as a biomarker of HPA functioning, much less attention has been paid to the role of the SAM in this context. Studies have shown that long-term breast cancer survivors display abnormal reactive cortisol patterns, suggesting a dysregulation of their HPA axis. To fully understand the integrity of the stress response in this population, this paper explored the diurnal and acute alpha-amylase profiles of 22 breast cancer survivors and 26 women with no history of cancer. Results revealed that breast cancer survivors displayed identical but elevated patterns of alpha-amylase concentrations in both diurnal and acute profiles relative to that of healthy women, F (1, 39) = 17.95, p < 0.001 and F (1, 37) = 7.29, p = 0.010, respectively. The average area under the curve for the diurnal and reactive profiles was 631.54 ± 66.94 SEM and 1238.78 ± 111.84 SEM, respectively. This is in sharp contrast to their cortisol results, which showed normal diurnal and blunted acute patterns. The complexity of the stress system necessitates further investigation to understand the synergistic relationship of the HPA and SAM axes.

Gas Chromatography-Mass Spectrometry-Based Metabolite Profiling of Salmonella enterica Serovar Typhimurium Differentiates between Biofilm and Planktonic Phenotypes

PubMed Central

Maker, Garth L.; Trengove, Robert D.; O'Handley, Ryan M.

2015-01-01

The aim of this study was to utilize gas chromatography coupled with mass spectrometry (GC-MS) to compare and identify patterns of biochemical change between Salmonella cells grown in planktonic and biofilm phases and Salmonella biofilms of different ages. Our results showed a clear separation between planktonic and biofilm modes of growth. The majority of metabolites contributing to variance between planktonic and biofilm supernatants were identified as amino acids, including alanine, glutamic acid, glycine, and ornithine. Metabolites contributing to variance in intracellular profiles were identified as succinic acid, putrescine, pyroglutamic acid, and N-acetylglutamic acid. Principal-component analysis revealed no significant differences between the various ages of intracellular profiles, which would otherwise allow differentiation of biofilm cells on the basis of age. A shifting pattern across the score plot was illustrated when analyzing extracellular metabolites sampled from different days of biofilm growth, and amino acids were again identified as the metabolites contributing most to variance. An understanding of biofilm-specific metabolic responses to perturbations, especially antibiotics, can lead to the identification of novel drug targets and potential therapies for combating biofilm-associated diseases. We concluded that under the conditions of this study, GC-MS can be successfully applied as a high-throughput technique for “bottom-up” metabolomic biofilm research. PMID:25636852

Metabolomic profile of systemic sclerosis patients.

PubMed

Murgia, Federica; Svegliati, Silvia; Poddighe, Simone; Lussu, Milena; Manzin, Aldo; Spadoni, Tatiana; Fischetti, Colomba; Gabrielli, Armando; Atzori, Luigi

2018-05-16

Systemic sclerosis (SSc) is an autoimmune disease of unknown aetiology characterized by vascular lesions, immunological alterations and diffuse fibrosis of the skin and internal organs. Since recent evidence suggests that there is a link between metabolomics and immune mediated disease, serum metabolic profile of SSc patients and healthy controls was investigated by 1 H-NMR and GC-MS techniques. The results indicated a lower level of aspartate, alanine, choline, glutamate, and glutarate in SSc patients compared with healthy controls. Moreover, comparing patients affected by limited SSc (lcSSc) and diffuse SSc (dcSSc), 6 discriminant metabolites were identified. The multivariate analysis performed using all the metabolites significantly different revealed glycolysis, gluconeogenesis, energetic pathways, glutamate metabolism, degradation of ketone bodies and pyruvate metabolism as the most important networks. Aspartate, alanine and citrate yielded a high area under receiver-operating characteristic (ROC) curves (AUC of 0.81; CI 0.726-0.93) for discriminating SSc patients from controls, whereas ROC curve generated with acetate, fructose, glutamate, glutamine, glycerol and glutarate (AUC of 0.84; CI 0.7-0.98) discriminated between lcSSc and dcSSc. These results indicated that serum NMR-based metabolomics profiling method is sensitive and specific enough to distinguish SSc from healthy controls and provided a feasible diagnostic tool for the diagnosis and classification of the disease.

Evaluating the Cognition, Behavior, and Social Profile of an Adolescent With Learning Disabilities and Assessing the Effectiveness of an Individualized Educational Program

PubMed Central

Tabitha Louis, Preeti; Arnold Emerson, Isaac

2014-01-01

Objective: The present study seeks to outline a holistic assessment method that was used in understanding problems experienced by an adolescent boy and in designing and implementing an individualized educational program. Methods: An adolescent child referred for concerns in learning was screened for learning disability using standardized inventories and test batteries. The Connors Parent and Teacher Rating Scales (short forms), Wechsler's Intelligence Scale for Children (WISC), the Vineland Social Maturity Scale (VSMS), and the Kinetic Family Drawing (KFD) test were used to assess the behavior, cognition, and social profile of the child. An individualized educational program was designed and this intervention was provided for 6 months by using parents as co-therapists. Participant and parent interview schedules were used in identifying underlying issues of concern. The child was reassessed 6 months after the intervention was provided. Results: Findings on the Connors Parent Rating Scale revealed scores that were greater than the 50th percentile on the domains of inattention and cognitive problems. On the Connors Teacher Rating Scale, we observed scores greater than the 50th percentile on the hyperactivity, cognitive problems, and the inattention domains. The WISC revealed that the child had a "Dull Normal" Intellectual functioning and there was also a deficit of 2 years on the social skills as tested by the Vineland Social Maturity Scale (VSMS). The Kinetic Family Drawing Test revealed negative emotions within the child. Post intervention, we noticed a remarkable improvement in the scores across all domains of behavior, social, and cognitive functioning. Conclusion: Designing an individualized education program that is tailored to the specific needs of the child and using parents as co-therapists proved to be an effective intervention. PMID:25053954

Molecular analysis of microbiota along the digestive tract of juvenile Atlantic salmon (Salmo salar L.).

PubMed

Navarrete, P; Espejo, R T; Romero, J

2009-04-01

Dominant bacterial microbiota of the gut of juvenile farmed Atlantic salmon was investigated using a combination of molecular approaches. Bacterial community composition from the stomach, the pyloric caeca, and the intestine was assessed by extracting DNA directly from each gut compartment. Temporal temperature gradient gel electrophoresis (TTGE) analysis of 16S ribosomal DNA (rDNA) amplicons showed very similar bacterial compositions throughout the digestive tract. Band sequencing revealed a narrow diversity of species with a dominance of Pseudomonas in the three compartments. However, cloning revealed more diversity among the Pseudomonas sequences. To confirm these results, we analyzed the bacterial community by amplifying the variable 16S-23S rDNA intergenic spacer region (ITS). Similar ITS profiles were observed among gastrointestinal compartments of salmon, confirming the TTGE results. Moreover, the dominant ITS band at 650 bp, identified as Pseudomonas, was observed in the ITS profile from fish collected in two seasons (July 2003 and 2004). In contrast, aerobic culture analysis revealed Shewanella spp. as the most prevalent isolate. This discrepancy was resolved by evaluating 16S rDNA and ITS polymerase chain reaction amplification efficiency from both Shewanella and Pseudomonas isolates. Very similar efficiencies were observed in the two bacteria. Hence, this discrepancy may be explained by preferential cultivation of Shewanella spp. under the experimental conditions. Also, we included analyses of pelleted feed and the water influent to explore environmental influences on the bacterial composition of the gut microbiota. Overall, these results indicate a homogeneous composition of the bacterial community composition along the gastrointestinal tract of reared juvenile salmon. This community is mainly composed of Pseudomonas spp., which could be derived from water influent and may be selectively associated with salmon in this hatchery.

Flowfield measurements in a separated and reattached flat plate turbulent boundary layer

NASA Technical Reports Server (NTRS)

Patrick, William P.

1987-01-01

The separation and reattachment of a large-scale, two-dimensional turbulent boundary layer at low subsonic speed on a flat plate has been studied experimentally. The separation bubble was 55 cm long and had a maximum bubble thickness, measured to the height of the mean dividing streamline, of 17 cm, which was twice the thickness of the inlet boundary layer. A combination of laser velocimetry, hot-wire anemometry, pneumatic probing techniques, and flow visualization were used as diagnostics. Principal findings were that an outer inviscid rotational flow was defined which essentially convected over the blockage associated with the inner, viscously dominated bubble recirculation region. A strong backflow region in which the flow moved upstream 100 percent of the time was measured near the test surface over the central 35 percent of the bubble. A laminar backflow boundary layer having pseudo-turbulent characteristics including a log-linear velocity profile was generated under the highly turbulent backflow. Velocity profile shapes in the reversed flow region matched a previously developed universal backflow profile at the upstream edge of the separation region but not in the steady backflow region downstream. A smoke flow visualization movie and hot-film measurements revealed low frequency nonperiodic flapping at reattachment. However, forward flow fraction data at reattachment and mean velocity profiles in the redeveloping boundary layer downstream of reattachment correlated with backward-facing step data when the axial dimension was scaled by the distance from the maximum bubble thickness to reattachment.

Determining buried grid street system and native of the remains with GPR and petrography, in ancient Nysa city, Aydin - Turkey

NASA Astrophysics Data System (ADS)

Kadioglu, Selma; Kadioglu, Musa; Kadioglu, Yusuf K.

2010-05-01

Nysa, is one of the most important ancient cities of the region of Caria in Anatolia (Asia Minor), was built on the slopes on the sides of the stream called Tekkecik, in a 3 km North of Sultanhisar, East of Aydın city of Turkey. The buildings, streets and public squares of the ancient city were supported by vaulted substructures adapted to the topographic conditions. There are important ruins on the site from the Hellenistic and the Roman periods and the Byzantine era. Now the Greek theatre and its walled entrance are intact. Other important remains are the gymnasium, stadium, library, temple, nymphaeum, bridge a tunnel like structure and the Byzantine churches in the West; the agora, Bouleuterion / Gerontikon, and the Roman public baths in the East. The first aim of the study was to determine the locations of the buried streets thought grid system according to the some excavated results already in the east and west side of the Nysa. Therefore the GPR studies were realized selected areas, which could include the streets, around the Bouleuterion / Gerontikon and at the South of the library. Two dimensional (2D) GPR data were measured on the parallel GPR profiles spaced 1m apart on each part of the study areas using 250 MHz shielded antennas. The processed parallel profile data set was formed through a solid 3D view by aligning the profiles respectively. A simplified amplitude-color range and appropriate opacity function were constructed to activate buried remains. Interactive interpretation was done with time slices and transparent sub-blocks of the 3D volume by arranging an opaque function. It was known that the maximum amplitudes represented the remains. So, weak amplitude range around the zero amplitude was eliminated by giving zero opacity value and transparent 3D imaging was obtained. The second known was that the amplitudes were decreased according to time. Therefore, amplitude scale could be weighted by a constant coefficient changing with the time range of the 3D sub-volumes, which was bigger than one and smaller than two and had a decimal number. As a result, all remains could be imaged in the transparent 3D depth-volumes where the street could be revealed clearly. Finally three streets were revealed in the depth volumes. The first street was on the West part and the second street, which was parallel of the first street, was on the Southwest part of the Bouleuterion / Gerontikon and the third street was on the South of the library. Diggings on the West and Southwest parts of the research area encouraged the 3D image results. The second aim of the study was to find out native rocks of the Nysa remains and sources. The small rock samples were collected from the theatre, stadium, basement of agora and the tomb and analyzed under polarized microscope and confocal Raman spectroscopy. The results of the studies revealed that the main rocks of these remains composed of white color marble. These marbles have granoblastic texture composed of mainly pressure twinned calcite as coarse grain size under the polarized microscope. The confocal Raman spectroscopical studies revealed that the marble remains of Nysa ancient city were mainly built from Jurassic- Cretaceous carbonate rocks of Western Anatolia marble quarry in the vicinity region. This study was supported by the Scientific and Technological Research Council of Turkey (TUBITAK) under grant no. 107K523 and Earth Sciences Application and Research Center of Ankara University (YEBIM).

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

PubMed

Thomas, Pious; Sekhar, Aparna Chandra

2017-05-01

The interior of plants constitutes a unique environment for microorganisms with various organisms inhabiting as endophytes. Unlike subterranean plant parts, aboveground parts are relatively less explored for endophytic microbial diversity. We employed a combination of cultivation and molecular approaches to study the endophytic bacterial diversity in banana shoot-tips. Cultivable bacteria from 20 sucker shoot-tips of cv. Grand Naine included 37 strains under 16 genera and three phyla (Proteobacteria, Actinobacteria, Firmicutes). 16S rRNA gene-ribotyping approach on 799f and 1492r PCR-amplicons to avoid plant organelle sequences was ineffective showing limited bacterial diversity. 16S rRNA metagene profiling targeting the V3-V4 hypervariable region after filtering out the chloroplast (74.2 %), mitochondrial (22.9 %), and unknown sequences (1.1 %) revealed enormous bacterial diversity. Proteobacteria formed the predominant phylum (64 %) succeeded by Firmicutes (12.1 %), Actinobacteria (9.5 %), Bacteroidetes (6.4 %), Planctomycetes, Cyanobacteria, and minor shares (<1 %) of 14 phyla including several candidate phyla besides the domain Euryarchaeota (0.2 %). Microbiome analysis of single shoot-tips through 16S rRNA V3 region profiling showed similar taxonomic richness and diversity and was less affected by plant sequence interferences. DNA extraction kit ominously influenced the phylogenetic diversity. The study has revealed vast diversity of normally uncultivable endophytic bacteria prevailing in banana shoot-tips (20 phyla, 46 classes) with about 2.6 % of the deciphered 269 genera and 1.5 % of the 656 observed species from the same source of shoot-tips attained through cultivation. The predominant genera included several agriculturally important bacteria. The study reveals an immense ecosystem of endophytic bacteria in banana shoot tissues endorsing the earlier documentation of intracellular "Cytobacts" and "Peribacts" with possible roles in plant holobiome and hologenome.

Multidimensional profiles of health locus of control in Hispanic Americans

PubMed Central

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

2016-01-01

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. PMID:25855212

Synergistic effect of allyl isothiocyanate (AITC) on cisplatin efficacy in vitro and in vivo

PubMed Central

Ling, Xiang; Westover, David; Cao, Felicia; Cao, Shousong; He, Xiang; Kim, Hak-Ryul; Zhang, Yuesheng; Chan, Daniel CF; Li, Fengzhi

2015-01-01

Although in vitro studies have shown that isothiocyanates (ITCs) can synergistically sensitize cancer cells to cisplatin treatment, the underlying mechanisms have not been well defined, and there are no in vivo demonstrations of this synergy. Here, we report the in vitro and in vivo data for the combination of allyl isothiocyanate (AITC), one of the most common naturally occurring ITCs, with cisplatin. Our study revealed that cisplatin and AITC combination synergistically inhibits cancer cell growth and colony formation, and enhances apoptosis in association with the downregulation of antiapoptotic proteins Bcl-2 and survivin. Importantly, the in vivo combination treatment suppresses human tumor growth in animal models without observable increases in toxicity (body weight loss) in comparison with single agent treatment. Furthermore, our data revealed that addition of AITC to cisplatin treatment changes the profile of G2/M arrest (e.g. increase in M phase cell number) and significantly extends the duration of G2/M arrest in comparison with cisplatin treatment alone. To explore the underlying mechanism, we found that AITC treatment rapidly depletes b-tubulin. Combination of AITC and cisplatin inhibits the expression of G2/M checkpoint-relevant proteins including CDC2, cyclin B1 and CDC25. Together, our findings reveal a novel mechanism for AITC enhancing cisplatin efficacy and provides the first in vivo evidence to support ITCs as potential candidates for developing new regimens to overcome platinum resistance. PMID:26396928

Ribosome A and P sites revealed by length analysis of ribosome profiling data

PubMed Central

Martens, Andrew T.; Taylor, James; Hilser, Vincent J.

2015-01-01

The high-throughput sequencing of nuclease-protected mRNA fragments bound to ribosomes, a technique known as ribosome profiling, quantifies the relative frequencies with which different regions of transcripts are translated. This technique has revealed novel translation initiation sites with unprecedented scope and has furthered investigations into the connections between codon biases and translation rates. Yet the location of the codon being decoded in ribosome footprints is still unknown, and has been complicated by the recent observation of footprints with non-canonical lengths. Here we show how taking into account the variations in ribosome footprint lengths can reveal the ribosome aminoacyl (A) and peptidyl (P) site locations. These location assignments are in agreement with the proposed mechanisms for various ribosome pauses and further enhance the resolution of the profiling data. We also show that GC-rich motifs at the 5′ ends of footprints are found in yeast, calling into question the anti-Shine-Dalgarno effect's role in ribosome pausing. PMID:25805170

The Application of Ultra-High-Performance Liquid Chromatography Coupled with a LTQ-Orbitrap Mass Technique to Reveal the Dynamic Accumulation of Secondary Metabolites in Licorice under ABA Stress.

PubMed

Li, Da; Xu, Guojie; Ren, Guangxi; Sun, Yufeng; Huang, Ying; Liu, Chunsheng

2017-10-20

The traditional medicine licorice is the most widely consumed herbal product in the world. Although much research work on studying the changes in the active compounds of licorice has been reported, there are still many areas, such as the dynamic accumulation of secondary metabolites in licorice, that need to be further studied. In this study, the secondary metabolites from licorice under two different methods of stress were investigated by ultra-high-performance liquid chromatography coupled with hybrid linear ion trap-Orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap-MS). A complex continuous coordination of flavonoids and triterpenoids in a network was modulated by different methods of stress during growth. The results showed that a total of 51 secondary metabolites were identified in licorice under ABA stress. The partial least squares-discriminate analysis (PLS-DA) revealed the distinction of obvious compounds among stress-specific districts relative to ABA stress. The targeted results showed that there were significant differences in the accumulation patterns of the deeply targeted 41 flavonoids and 10 triterpenoids compounds by PCA and PLS-DA analyses. To survey the effects of flavonoid and triterpenoid metabolism under ABA stress, we inspected the stress-specific metabolic changes. Our study testified that the majority of flavonoids and triterpenoids were elevated in licorice under ABA stress, while the signature metabolite affecting the dynamic accumulation of secondary metabolites was detected. Taken together, our results suggest that ABA-specific metabolite profiling dynamically changed in terms of the biosynthesis of flavonoids and triterpenoids, which may offer new trains of thought on the regular pattern of dynamic accumulation of secondary metabolites in licorice at the metabolite level. Our results also provide a reference for clinical applications and directional planting and licorice breeding.

Metabolic Profile and Inflammatory Responses in Dairy Cows with Left Displaced Abomasum Kept under Small-Scaled Farm Conditions

PubMed Central

Klevenhusen, Fenja; Humer, Elke; Metzler-Zebeli, Barbara; Podstatzky-Lichtenstein, Leopold; Wittek, Thomas; Zebeli, Qendrim

2015-01-01

Simple Summary This research established an association between lactation number and milk production and metabolic and inflammatory responses in high-producing dairy cows affected by left abomasal displacement in small-scaled dairy farms. The study showed metabolic alterations, liver damage, and inflammation in the sick cows, which were further exacerbated with increasing lactation number and milk yield of the cows. Abstract Left displaced abomasum (LDA) is a severe metabolic disease of cattle with a strong negative impact on production efficiency of dairy farms. Metabolic and inflammatory alterations associated with this disease have been reported in earlier studies, conducted mostly in large dairy farms. This research aimed to: (1) evaluate metabolic and inflammatory responses in dairy cows affected by LDA in small-scaled dairy farms; and (2) establish an association between lactation number and milk production with the outcome of metabolic variables. The cows with LDA had lower serum calcium (Ca), but greater concentrations of non-esterified fatty acids (NEFA) and beta-hydroxy-butyrate (BHBA), in particular when lactation number was >2. Cows with LDA showed elevated levels of aspartate aminotransferase, glutamate dehydrogenase, and serum amyloid A (SAA), regardless of lactation number. In addition, this study revealed strong associations between milk yield and the alteration of metabolic profile but not with inflammation in the sick cows. Results indicate metabolic alterations, liver damage, and inflammation in LDA cows kept under small-scale farm conditions. Furthermore, the data suggest exacerbation of metabolic profile and Ca metabolism but not of inflammation and liver health with increasing lactation number and milk yield in cows affected by LDA. PMID:26479481

Alteration of the exopolysaccharide production and the transcriptional profile of free-living Frankia strain CcI3 under nitrogen-fixing conditions.

PubMed

Lee, Hae-In; Donati, Andrew J; Hahn, Dittmar; Tisa, Louis S; Chang, Woo-Suk

2013-12-01

We investigated the effect of different nitrogen (N) sources on exopolysaccharide (EPS) production and composition by Frankia strain CcI3, a N2-fixing actinomycete that forms root nodules with Casuarina species. Frankia cells grown in the absence of NH4Cl (i.e., under N2-fixing conditions) produced 1.7-fold more EPS, with lower galactose (45.1 vs. 54.7 mol%) and higher mannose (17.3 vs. 9.7 mol%) contents than those grown in the presence of NH4Cl as a combined N-source. In the absence of the combined N-source, terminally linked and branched residue contents were nearly twice as high with 32.8 vs. 15.1 mol% and 15.1 vs. 8.7 mol%, respectively, than in its presence, while the content of linearly linked residues was lower with 52.1 mol% compared to 76.2 mol%. To find out clues for the altered EPS production at the transcriptional level, we performed whole-gene expression profiling using quantitative reverse transcription PCR and microarray technology. The transcription profiles of Frankia strain CcI3 grown in the absence of NH4Cl revealed up to 2 orders of magnitude higher transcription of nitrogen fixation-related genes compared to those of CcI3 cells grown in the presence of NH4Cl. Unexpectedly, microarray data did not provide evidence for transcriptional regulation as a mechanism for differences in EPS production. These findings indicate effects of nitrogen fixation on the production and composition of EPS in Frankia strain CcI3 and suggest posttranscriptional regulation of enhanced EPS production in the absence of the combined N-source.

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

Machado, Thales R.; QIO-UJI, Universitat Jaume I, 12071 Castellón; Sczancoski, Júlio C.

Defect-related photoluminescence (PL) in materials have attracted interest for applications including near ultraviolet (NUV) excitable light-emitting diodes and in biomedical field. In this paper, hydroxyapatite [Ca{sub 10}(PO{sub 4}){sub 6}(OH){sub 2}] nanorods with intense PL bands (bluish- and yellowish-white emissions) were obtained when excited under NUV radiation at room temperature. These nanoparticles were synthesized via chemical precipitation at 90 °C followed by distinct heat treatments temperatures (200–800 °C). Intense and broad emission profiles were achieved at 350 °C (380–750 nm) and 400 °C (380–800 nm). UV–Vis spectroscopy revealed band gap energies (5.58–5.78 eV) higher than the excitation energies (~3.54 and ~2.98more » eV at 350 and 415 nm, respectively), confirming the contribution of defect energy levels within the forbidden zone for PL emissions. The structural features were characterized by X-ray diffraction, Rietveld refinement, thermogravimetric analysis, and Fourier transform infrared spectroscopy. By means of these techniques, the relation between structural order-disorder induced by defects, chemical reactions at both lattice and surface of the materials as well as the PL, without activator centers, was discussed in details. - Graphical abstract: The self-activated photoluminescence emissions of chemically precipitated hydroxyapatite nanorods were improved by different heat treatment temperatures. - Highlights: • HA nanorods were synthesized with improved self-activated PL at room temperature. • PL profile and intensity dependents on the temperature of posterior heat treatments. • Bluish- and yellowish-white emissions under NUV excitation (350 and 415 nm). • Broad and intense profiles achieved at 350 °C (380–750 nm) and 400 °C (380–800 nm). • PL from the e′–h{sup •} recombination between defect energy levels within the band gap.« less

Near-Surface Profiles of Water Stable Isotope Components and Indicated Transitional History of Ice-Wedge Polygons Near Barrow

NASA Astrophysics Data System (ADS)

Iwahana, G.; Wilson, C.; Newman, B. D.; Heikoop, J. M.; Busey, R.

2017-12-01

Wetlands associated with ice-wedge polygons are commonly distributed across the Arctic Coastal Plain of northern Alaska, a region underlain by continuous permafrost. Micro-topography of the ice-wedge polygons controls local hydrology, and the micro-topography could be altered due to factors such like surface vegetation, wetness, freeze-thaw cycles, and permafrost degradation/aggradation under climate change. Understanding status of the wetlands in the near future is important because it determines biogeochemical cycle, which drives release of greenhouse gases from the ground. However, transitional regime of the ice-wedge polygons under the changing climate is not fully understood. In this study, we analyzed geochemistry of water extracted from frozen soil cores sampled down to about 1m depth in 2014 March at NGEE-Arctic sites in the Barrow Environmental Observatory. The cores were sampled from troughs/rims/centers of five different low-centered or flat-centered polygons. The frozen cores are divided into 5-10cm cores for each location, thawed in sealed plastic bags, and then extracted water was stored in vials. Comparison between the profiles of geochemistry indicated connection of soil water in the active layer at different location in a polygon, while it revealed that distinctly different water has been stored in permafrost layer at troughs/rims/centers of some polygons. Profiles of volumetric water content (VWC) showed clear signals of freeze-up desiccation in the middle of saturated active layers as low VWC anomalies at most sampling points. Water in the active layer and near-surface permafrost was classified into four categories: ice wedge / fresh meteoric / transitional / highly fractionated water. The overall results suggested prolonged separation of water in the active layer at the center of low-centered polygons without lateral connection in water path in the past.

Pure axial flow of viscoelastic fluids in rectangular microchannels under combined effects of electro-osmosis and hydrodynamics

NASA Astrophysics Data System (ADS)

Reshadi, Milad; Saidi, Mohammad Hassan; Ebrahimi, Abbas

2018-02-01

This paper presents an analysis of the combined electro-osmotic and pressure-driven axial flows of viscoelastic fluids in a rectangular microchannel with arbitrary aspect ratios. The rheological behavior of the fluid is described by the complete form of Phan-Thien-Tanner (PTT) model with the Gordon-Schowalter convected derivative which covers the upper convected Maxwell, Johnson-Segalman and FENE-P models. Our numerical simulation is based on the computation of 2D Poisson-Boltzmann, Cauchy momentum and PTT constitutive equations. The solution of these governing nonlinear coupled set of equations is obtained by using the second-order central finite difference method in a non-uniform grid system and is verified against 1D analytical solution of the velocity profile with less than 0.06% relative error. Also, a parametric study is carried out to investigate the effect of channel aspect ratio (width to height), wall zeta potential and the Debye-Hückel parameter on 2D velocity profile, volumetric flow rate and the Poiseuille number in the mixed EO/PD flows of viscoelastic fluids with different Weissenberg numbers. Our results show that, for low channel aspect ratios, the previous 1D analytical models underestimate the velocity profile at the channel half-width centerline in the case of favorable pressure gradients and overestimate it in the case of adverse pressure gradients. The results reveal that the inapplicability of the Debye-Hückel approximation at high zeta potentials is more significant for higher Weissenberg number fluids. Also, it is found that, under the specified values of electrokinetic parameters, there is a threshold for velocity scale ratio in which the Poiseuille number is approximately independent of channel aspect ratio.

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EPA's Greenhouse Gas Reporting Program periodically produces detailed profiles of the various industries that report under the program. These profiles contain detailed analyses. This page hosts data highlights for all sectors.

Transcriptomics and physiological analyses reveal co-ordinated alteration of metabolic pathways in Jatropha curcas drought tolerance.

PubMed

Sapeta, Helena; Lourenço, Tiago; Lorenz, Stefan; Grumaz, Christian; Kirstahler, Philipp; Barros, Pedro M; Costa, Joaquim Miguel; Sohn, Kai; Oliveira, M Margarida

2016-02-01

Jatropha curcas, a multipurpose plant attracting a great deal of attention due to its high oil content and quality for biofuel, is recognized as a drought-tolerant species. However, this drought tolerance is still poorly characterized. This study aims to contribute to uncover the molecular background of this tolerance, using a combined approach of transcriptional profiling and morphophysiological characterization during a period of water-withholding (49 d) followed by rewatering (7 d). Morphophysiological measurements showed that J. curcas plants present different adaptation strategies to withstand moderate and severe drought. Therefore, RNA sequencing was performed for samples collected under moderate and severe stress followed by rewatering, for both roots and leaves. Jatropha curcas transcriptomic analysis revealed shoot- and root-specific adaptations across all investigated conditions, except under severe stress, when the dramatic transcriptomic reorganization at the root and shoot level surpassed organ specificity. These changes in gene expression were clearly shown by the down-regulation of genes involved in growth and water uptake, and up-regulation of genes related to osmotic adjustments and cellular homeostasis. However, organ-specific gene variations were also detected, such as strong up-regulation of abscisic acid synthesis in roots under moderate stress and of chlorophyll metabolism in leaves under severe stress. Functional validation further corroborated the differential expression of genes coding for enzymes involved in chlorophyll metabolism, which correlates with the metabolite content of this pathway. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

[Effects of chronic experimental stress and endogenous opioids on histophysiological parameters of the thyroid gland].

PubMed

Krasnoperov, R A; Glumova, V A; Riashchikov, S N; Proshutina, N E

1992-01-01

In adult rabbits stress was modelled by electrostimulation of the hypothalamus ventromedial nucleus (15-hour-long session during 30 days) and medulla's raphe big nucleus which is one of the central places of the opioid peptides synthesis was irritated. It is revealed, that under stress thyroid gland responds by serum T3 increase in comparison with control animals with statistically significant variability of the T4 profile. Chronicity of the emotional agitation involves destructive changes in the thyroid parenchyma the hurting effect of the negative emotional factor is expressed less during opioid peptides complex activation. It is suggested that there are its own stress-limiting mechanisms in thyroid gland.

Phase controlled homodyne infrared near-field microscopy and spectroscopy reveal inhomogeneity within and among individual boron nitride nanotubes.

PubMed

Xu, Xiaoji G; Tanur, Adrienne E; Walker, Gilbert C

2013-04-25

We propose a practical method to obtain near-field infrared absorption spectra in apertureless near-field scanning optical microscopy (aNSOM) through homodyne detection with a specific choice of reference phase. The underlying mechanism of the method is illustrated by theoretical and numeric models to show its ability to obtain absorptive rather than dispersive profiles in near-field infrared vibrational microscopy. The proposed near-field nanospectroscopic method is applied to obtain infrared spectra from regions of individual multiwall boron nitride nanotubes (BNNTs) in spatial regions smaller than the diffraction limit of the light source. The spectra suggest variations in interwall spacing within the individual tubes probed.

Sub-nA spatially resolved conductivity profiling of surface and interface defects in ceria films

DOE PAGES

Farrow, Tim; Yang, Nan; Doria, Sandra; ...

2015-03-17

Spatial variability of conductivity in ceria is explored using scanning probe microscopy with galvanostatic control. Ionically blocking electrodes are used to probe the conductivity under opposite polarities to reveal possible differences in the defect structure across a thin film of CeO2. Data suggest the existence of a large spatial inhomogeneity that could give rise to constant phase elements during standard electrochemical characterization, potentially affecting the overall conductivity of films on the macroscale. The approach discussed here can also be utilized for other mixed ionic electronic conductor systems including memristors and electroresistors, as well as physical systems such as ferroelectric tunnelingmore » barriers« less

Protonation-dependent base flipping in the catalytic triad of a small RNA

NASA Astrophysics Data System (ADS)

Sun, Zhaoxi; Wang, Xiaohui; Zhang, John Z. H.

2017-09-01

Protonation dependent base flipping in RNA has never been studied theoretically. In this work we studied protonation-dependent behavior of the base flipping in the catalytic triad of a single-stranded RNA which was previously characterized by NMR experiment. Molecular dynamics simulation reveals that the GA mismatch in this region accounts for this behavior. Free energy profiles show that the stable point for flipping dihedral shifts about 35° and the free energy barrier along the flipping pathway is elevated upon protonation. The orientation of Guanine from syn to anti conformation is coupled with protonation-dependent base flipping and G-HA+ base pair is formed under acidic condition.

Indexcov: fast coverage quality control for whole-genome sequencing.

PubMed

Pedersen, Brent S; Collins, Ryan L; Talkowski, Michael E; Quinlan, Aaron R

2017-11-01

The BAM and CRAM formats provide a supplementary linear index that facilitates rapid access to sequence alignments in arbitrary genomic regions. Comparing consecutive entries in a BAM or CRAM index allows one to infer the number of alignment records per genomic region for use as an effective proxy of sequence depth in each genomic region. Based on these properties, we have developed indexcov, an efficient estimator of whole-genome sequencing coverage to rapidly identify samples with aberrant coverage profiles, reveal large-scale chromosomal anomalies, recognize potential batch effects, and infer the sex of a sample. Indexcov is available at https://github.com/brentp/goleft under the MIT license. © The Authors 2017. Published by Oxford University Press.

On the Regularities of the Polar Profiles of Proteins Related to Ebola Virus Infection and their Functional Domains.

PubMed

Polanco, Carlos; Samaniego Mendoza, José Lino; Buhse, Thomas; Uversky, Vladimir N; Bañuelos Chao, Ingrid Paola; Bañuelos Cedano, Marcela Angola; Tavera, Fernando Michel; Tavera, Daniel Michel; Falconi, Manuel; Ponce de León, Abelardo Vela

2018-03-06

The number of fatalities and economic losses caused by the Ebola virus infection across the planet culminated in the havoc that occurred between August and November 2014. However, little is known about the molecular protein profile of this devastating virus. This work represents a thorough bioinformatics analysis of the regularities of charge distribution (polar profiles) in two groups of proteins and their functional domains associated with Ebola virus disease: Ebola virus proteins and Human proteins interacting with Ebola virus. Our analysis reveals that a fragment exists in each of these proteins-one named the "functional domain"-with the polar profile similar to the polar profile of the protein that contains it. Each protein is formed by a group of short sub-sequences, where each fragment has a different and distinctive polar profile and where the polar profile between adjacent short sub-sequences changes orderly and gradually to coincide with the polar profile of the whole protein. When using the charge distribution as a metric, it was observed that it effectively discriminates the proteins from their functional domains. As a counterexample, the same test was applied to a set of synthetic proteins built for that purpose, revealing that any of the regularities reported here for the Ebola virus proteins and human proteins interacting with Ebola virus were not present in the synthetic proteins. Our results indicate that the polar profile of each protein studied and its corresponding functional domain are similar. Thus, when building each protein from its functional domai-adding one amino acid at a time and plotting each time its polar profile-it was observed that the resulting graphs can be divided into groups with similar polar profiles.

Continuous culture methodology for the screening of microalgae for oil.

PubMed

Del Río, Esperanza; Armendáriz, Ana; García-Gómez, Elena; García-González, Mercedes; Guerrero, Miguel G

2015-02-10

A basic criterion in the selection of microalgae suitable as source of oil for biodiesel should be their actual capacity to produce lipids or, more properly, the fatty acid yield. Performance assessment of 10 preselected microalgae under both batch and continuous culture points to the latter approach as the most adequate for evaluating fatty acid productivity. Differences were patent in continuous culture among strains that otherwise had analogous oil accumulation potential under batch culture. Some promising strains under batch culture (like Muriella aurantiaca and Monoraphidium braunii) exhibited, however, values for actual fatty acid productivity lower than 40 mgL(-1)d(-1) in continuous regime. The analysis performed in photochemostat under continuous culture regime revealed the great potential of Chlorococcum olefaciens, Pseudokirchneriella subcapitata and Scenedesmus almeriensis as oil producing microalgae. Fatty acid productivity levels over 90 mgL(-1)d(-1) were recorded for the latter strains under moderate nitrogen limitation, conditions which led to an enrichment in saturated and monounsaturated fatty acids, a more suitable profile as raw material for biodiesel. The continuous culture methodology employed represents a sound procedure for screening microalgae for biofuel production, providing a reliable evaluation of their fatty acid production capacity, under conditions close to those of outdoor production systems. Copyright © 2015 Elsevier B.V. All rights reserved.

Mass Spectrometry Analysis of Spatial Protein Networks by Colocalization Analysis (COLA).

PubMed

Mardakheh, Faraz K

2017-01-01

A major challenge in systems biology is comprehensive mapping of protein interaction networks. Crucially, such interactions are often dynamic in nature, necessitating methods that can rapidly mine the interactome across varied conditions and treatments to reveal change in the interaction networks. Recently, we described a fast mass spectrometry-based method to reveal functional interactions in mammalian cells on a global scale, by revealing spatial colocalizations between proteins (COLA) (Mardakheh et al., Mol Biosyst 13:92-105, 2017). As protein localization and function are inherently linked, significant colocalization between two proteins is a strong indication for their functional interaction. COLA uses rapid complete subcellular fractionation, coupled with quantitative proteomics to generate a subcellular localization profile for each protein quantified by the mass spectrometer. Robust clustering is then applied to reveal significant similarities in protein localization profiles, indicative of colocalization.

Young Athletes’ Motivational Profiles

PubMed Central

Murcia, Juan Antonio Moreno; Gimeno, Eduardo Cervelló; Coll, David González-Cutre

2007-01-01

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. Key pointsThe “self-determined profile ”was characterized by high task orientation, high task-involving climate perception and 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 characterized by high ego orientation, high ego-involving climate perception and was more customary of males and athletes practising team sports as well as those training two or three days a week.Both profiles revealed a moderate tendency toward dispositional flow, with no significant differences between the two profiles.The “low self-determined and low non-self-determined profile ”had low scores on all of the variables in the study. PMID:24149326

GHGRP Minerals Sector Industrial Profile

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GHGRP Chemicals Sector Industrial Profile

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GHGRP Metals Sector Industrial Profile

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EPA's Greenhouse Gas Reporting Program periodically produces detailed profiles of the various industries that report under the program. The profiles available for download below contain detailed analyses for the Metals industry.

Are there differential symptom profiles that improve in response to different pharmacological treatments of premenstrual syndrome/premenstrual dysphoric disorder?

PubMed

Halbreich, Uriel; O'Brien, P M Shaughn; Eriksson, Elias; Bäckström, Torbjörn; Yonkers, Kimberly A; Freeman, Ellen W

2006-01-01

Current evidence suggests that the accepted treatments for premenstrual syndrome (PMS)/premenstrual dysphoric disorder (PMDD) have similar overall efficacy. While these treatments are more effective than placebo, response rates associated with them are far from satisfactory (<60%), such that, irrespective of treatment modality, there remain a significant number of women who are unresponsive to current conventional pharmacological therapy. The available data on response rates of specific types of premenstrual symptoms to, or symptom profiles that are most amenable to, each treatment modality are limited and not well defined because most studies were not designed to assess specific symptom profiles. Those studies that have attempted to evaluate which symptom profiles respond to specific therapies have revealed variations within the individual modalities, as well as between the different modalities. It appears that suppression of ovulation ameliorates a broad range of behavioural as well as physical premenstrual symptoms. SSRIs are most effective for irritability and anxiety symptoms, with lesser efficacy for 'atypical' premenstrual symptoms. GABAergic compounds are most efficacious for anxiety and anxious/depressive symptoms, while dopamine agonists, particularly bromocriptine, are perhaps most efficacious for mastalgia. Overall treatment response rates may improve if treatments are targeted at well-defined subgroups of patients. Re-analysis of available datasets from randomised clinical trials may shed more light on the notion that targeting women with specific premenstrual symptom profiles for specific treatment modalities would improve response rates beyond the current ceiling of approximately 60%. Such information would also improve understanding of the putative pathophysiological mechanisms underlying PMS and PMDD, and may point to a more specific diagnosis of these conditions.

Geophysical imaging and thermal modeling of subsurface morphology and thaw evolution of discontinuous permafrost

NASA Astrophysics Data System (ADS)

McClymont, Alastair F.; Hayashi, Masaki; Bentley, Laurence R.; Christensen, Brendan S.

2013-09-01

our current understanding of permafrost thaw in subarctic regions in response to rising air temperatures, little is known about the subsurface geometry and distribution of discontinuous permafrost bodies in peat-covered, wetland-dominated terrains and their responses to rising temperature. Using electrical resistivity tomography, ground-penetrating radar profiling, and thermal-conduction modeling, we show how the land cover distributions influence thawing of discontinuous permafrost at a study site in the Northwest Territories, Canada. Permafrost bodies in this region occur under forested peat plateaus and have thicknesses of 5-13 m. Our geophysical data reveal different stages of thaw resulting from disturbances within the active layer: from widening and deepening of differential thaw features under small frost-table depressions to complete thaw of permafrost under an isolated bog. By using two-dimensional geometric constraints derived from our geophysics profiles and meteorological data, we model seasonal and interannual changes to permafrost distribution in response to contemporary climatic conditions and changes in land cover. Modeling results show that in this environment (1) differences in land cover have a strong influence on subsurface thermal gradients such that lateral thaw dominates over vertical thaw and (2) in accordance with field observations, thaw-induced subsidence and flooding at the lateral margins of peat plateaus represents a positive feedback that leads to enhanced warming along the margins of peat plateaus and subsequent lateral heat conduction. Based on our analysis, we suggest that subsurface energy transfer processes (and feedbacks) at scales of 1-100 m have a strong influence on overall permafrost degradation rates at much larger scales.

Physiological Investigation and Transcriptome Analysis of Polyethylene Glycol (PEG)-Induced Dehydration Stress in Cassava.

PubMed

Fu, Lili; Ding, Zehong; Han, Bingying; Hu, Wei; Li, Yajun; Zhang, Jiaming

2016-02-25

Cassava is an important tropical and sub-tropical root crop that is adapted to drought environment. However, severe drought stress significantly influences biomass accumulation and starchy root production. The mechanism underlying drought-tolerance remains obscure in cassava. In this study, changes of physiological characters and gene transcriptome profiles were investigated under dehydration stress simulated by polyethylene glycol (PEG) treatments. Five traits, including peroxidase (POD) activity, proline content, malondialdehyde (MDA), soluble sugar and soluble protein, were all dramatically induced in response to PEG treatment. RNA-seq analysis revealed a gradient decrease of differentially expressed (DE) gene number in tissues from bottom to top of a plant, suggesting that cassava root has a quicker response and more induced/depressed DE genes than leaves in response to drought. Overall, dynamic changes of gene expression profiles in cassava root and leaves were uncovered: genes related to glycolysis, abscisic acid and ethylene biosynthesis, lipid metabolism, protein degradation, and second metabolism of flavonoids were significantly induced, while genes associated with cell cycle/organization, cell wall synthesis and degradation, DNA synthesis and chromatin structure, protein synthesis, light reaction of photosynthesis, gibberelin pathways and abiotic stress were greatly depressed. Finally, novel pathways in ABA-dependent and ABA-independent regulatory networks underlying PEG-induced dehydration response in cassava were detected, and the RNA-Seq results of a subset of fifteen genes were confirmed by real-time PCR. The findings will improve our understanding of the mechanism related to dehydration stress-tolerance in cassava and will provide useful candidate genes for breeding of cassava varieties better adapted to drought environment.

Physiological Investigation and Transcriptome Analysis of Polyethylene Glycol (PEG)-Induced Dehydration Stress in Cassava

PubMed Central

Fu, Lili; Ding, Zehong; Han, Bingying; Hu, Wei; Li, Yajun; Zhang, Jiaming

2016-01-01

Cassava is an important tropical and sub-tropical root crop that is adapted to drought environment. However, severe drought stress significantly influences biomass accumulation and starchy root production. The mechanism underlying drought-tolerance remains obscure in cassava. In this study, changes of physiological characters and gene transcriptome profiles were investigated under dehydration stress simulated by polyethylene glycol (PEG) treatments. Five traits, including peroxidase (POD) activity, proline content, malondialdehyde (MDA), soluble sugar and soluble protein, were all dramatically induced in response to PEG treatment. RNA-seq analysis revealed a gradient decrease of differentially expressed (DE) gene number in tissues from bottom to top of a plant, suggesting that cassava root has a quicker response and more induced/depressed DE genes than leaves in response to drought. Overall, dynamic changes of gene expression profiles in cassava root and leaves were uncovered: genes related to glycolysis, abscisic acid and ethylene biosynthesis, lipid metabolism, protein degradation, and second metabolism of flavonoids were significantly induced, while genes associated with cell cycle/organization, cell wall synthesis and degradation, DNA synthesis and chromatin structure, protein synthesis, light reaction of photosynthesis, gibberelin pathways and abiotic stress were greatly depressed. Finally, novel pathways in ABA-dependent and ABA-independent regulatory networks underlying PEG-induced dehydration response in cassava were detected, and the RNA-Seq results of a subset of fifteen genes were confirmed by real-time PCR. The findings will improve our understanding of the mechanism related to dehydration stress-tolerance in cassava and will provide useful candidate genes for breeding of cassava varieties better adapted to drought environment. PMID:26927071

Field versus laboratory experiments to evaluate the fate of azoxystrobin in an amended vineyard soil.

PubMed

Herrero-Hernández, E; Marín-Benito, J M; Andrades, M S; Sánchez-Martín, M J; Rodríguez-Cruz, M S

2015-11-01

This study reports the effect that adding spent mushroom substrate (SMS) to a representative vineyard soil from La Rioja region (Spain) has on the behaviour of azoxystrobin in two different environmental scenarios. Field dissipation experiments were conducted on experimental plots amended at rates of 50 and 150 t ha(-1), and similar dissipation experiments were simultaneously conducted in the laboratory to identify differences under controlled conditions. Azoxystrobin dissipation followed biphasic kinetics in both scenarios, although the initial dissipation phase was much faster in the field than in the laboratory experiments, and the half-life (DT50) values obtained in the two experiments were 0.34-46.3 days and 89.2-148 days, respectively. Fungicide residues in the soil profile increased in the SMS amended soil and they were much higher in the top two layers (0-20 cm) than in deeper layers. The persistence of fungicide in the soil profile is consistent with changes in azoxystrobin adsorption by unamended and amended soils over time. Changes in the dehydrogenase activity (DHA) of soils under different treatments assayed in the field and in the laboratory indicated that SMS and the fungicide had a stimulatory effect on soil DHA. The results reveal that the laboratory studies usually reported in the literature to explain the fate of pesticides in amended soils are insufficient to explain azoxystrobin behaviour under real conditions. Field studies are necessary to set up efficient applications of SMS and fungicide, with a view to preventing the possible risk of water contamination. Copyright © 2015 Elsevier Ltd. All rights reserved.

Improving suicide mortality statistics in Tarragona (Catalonia, Spain) between 2004-2012.

PubMed

Barbería, Eneko; Gispert, Rosa; Gallo, Belén; Ribas, Gloria; Puigdefàbregas, Anna; Freitas, Adriana; Segú, Elena; Torralba, Pilar; García-Sayago, Francisco; Estarellas, Aina

2016-07-20

Monitoring and preventing suicidal behaviour requires, among other data, knowing suicide deaths precisely. They often appear under-reported or misclassified in the official mortality statistics. The aim of this study is to analyse the under-reporting found in the suicide mortality statistics of Tarragona (a province of Catalonia, Spain). The analysis takes into account all suicide deaths that occurred in the Tarragona Area of the Catalan Institute of Legal Medicine and Forensic Sciences (TA-CILMFS) between 2004 and 2012. The sources of information were the death data files of the Catalan Mortality Register, as well as the Autopsies Files of the TA-CILMFS. Suicide rates and socio-demographic profiles were statistically compared between the suicide initially reported and the final one. The mean percentage of non-reported cases in the period was 16.2%, with a minimum percentage of 2.2% in 2005 and a maximum of 26.8% in 2009. The crude mortality rate by suicide rose from 6.6 to 7.9 per 100,000 inhabitants once forensic data were incorporated. Small differences were detected between the socio-demographic profile of the suicide initially reported and the final one. Supplementary information was obtained on the suicide method, which revealed a significant increase in poisoning and suicides involving trains. An exhaustive review of suicide deaths data from forensic sources has led to an improvement in the under-reported statistical information. It also improves the knowledge of the method of suicide and personal characteristics. Copyright © 2016 SEP y SEPB. Publicado por Elsevier España, S.L.U. All rights reserved.

Effect of sublethal preculturing on the survival of probiotics and metabolite formation in set-yoghurt.

PubMed

Settachaimongkon, Sarn; van Valenberg, Hein J F; Winata, Vera; Wang, Xiaoxi; Nout, M J Robert; van Hooijdonk, Toon C M; Zwietering, Marcel H; Smid, Eddy J

2015-08-01

The objective of this study was to investigate the effect of preculturing of Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp. lactis BB12 under sublethal stress conditions on their survival and metabolite formation in set-yoghurt. Prior to co-cultivation with yoghurt starters in milk, the two probiotic strains were precultured under sublethal stress conditions (combinations of elevated NaCl and low pH) in a batch fermentor. The activity of sublethally precultured probiotics was evaluated during fermentation and refrigerated storage by monitoring bacterial population dynamics, milk acidification and changes in volatile and non-volatile metabolite profiles of set-yoghurt. The results demonstrated adaptive stress responses of the two probiotic strains resulting in their viability improvement without adverse influence on milk acidification. A complementary metabolomic approach using SPME-GC/MS and (1)H-NMR resulted in the identification of 35 volatiles and 43 non-volatile polar metabolites, respectively. Principal component analysis revealed substantial impact of the activity of sublethally precultured probiotics on metabolite formation demonstrated by distinctive volatile and non-volatile metabolite profiles of set-yoghurt. Changes in relative abundance of various aroma compounds suggest that incorporation of stress-adapted probiotics considerably influences the organoleptic quality of product. This study provides new information on the application of stress-adapted probiotics in an actual food-carrier environment. Copyright © 2015 Elsevier Ltd. All rights reserved.

Terahertz Pulsed Imaging and Magnetic Resonance Imaging as Tools to Probe Formulation Stability

PubMed Central

Zhang, Qilei; Gladden, Lynn F.; Avalle, Paolo; Zeitler, J. Axel; Mantle, Michael D.

2013-01-01

Dissolution stability over the entire shelf life duration is of critical importance to ensure the quality of solid dosage forms. Changes in the drug release profile during storage may affect the bioavailability of drug products. This study investigated the stability of a commercial tablet (Lescol® XL) when stored under accelerated conditions (40 °C/75% r.h.). Terahertz pulsed imaging (TPI) was used to investigate the structure of the tablet coating before and after the accelerated aging process. The results indicate that the coating was reduced in thickness and exhibited a higher density after being stored under accelerated conditions for four weeks. In situ magnetic resonance imaging (MRI) of the water penetration processes during tablet dissolution in a USP-IV dissolution cell equipped with an in-line UV-vis analyzer was carried out to study local differences in water uptake into the tablet matrix between the stressed and unstressed state. The drug release profiles of the Lescol® XL tablet before and after the accelerated storage stability testing were compared using a “difference” factor f1 and a “similarity” factor f2. The results reveal that even though the physical properties of the coating layers changed significantly during the stress testing, the coating protected the tablet matrix and the densification of the coating polymer had no adverse effect on the drug release performance. PMID:24300564

Mechanisms of crystalline silica-induced pulmonary toxicity revealed by global gene expression profiling

PubMed Central

Sellamuthu, Rajendran; Umbright, Christina; Li, Shengqiao; Kashon, Michael; Joseph, Pius

2015-01-01

A proper understanding of the mechanisms underlying crystalline silica-induced pulmonary toxicity has implications in the management and potential prevention of the adverse health effects associated with silica exposure including silicosis, cancer and several auto-immune diseases. Human lung type II epithelial cells and rat lungs exposed to crystalline silica were employed as experimental models to determine global gene expression changes in order to understand the molecular mechanisms underlying silica-induced pulmonary toxicity. The differential gene expression profile induced by silica correlated with its toxicity in the A549 cells. The biological processes perturbed by silica exposure in the A549 cells and rat lungs, as identified by the bioinformatics analysis of the differentially expressed genes, demonstrated significant similarity. Functional categorization of the differentially expressed genes identified cancer, cellular movement, cellular growth and proliferation, cell death, inflammatory response, cell cycle, cellular development, and genetic disorder as top ranking biological functions perturbed by silica exposure in A549 cells and rat lungs. Results of our study, in addition to confirming several previously identified molecular targets and mechanisms involved in silica toxicity, identified novel molecular targets and mechanisms potentially involved in silica-induced pulmonary toxicity. Further investigations, including those focused on the novel molecular targets and mechanisms identified in the current study may result in better management and, possibly, reduction and/or prevention of the potential adverse health effects associated with crystalline silica exposure. PMID:22087542

Cervical Spinal Cord Atrophy Profile in Adult SMN1-Linked SMA

PubMed Central

El Mendili, Mohamed-Mounir; Lenglet, Timothée; Stojkovic, Tanya; Behin, Anthony; Guimarães-Costa, Raquel; Salachas, François; Meininger, Vincent; Bruneteau, Gaelle; Le Forestier, Nadine; Laforêt, Pascal; Lehéricy, Stéphane; Benali, Habib; Pradat, Pierre-François

2016-01-01

Purpose The mechanisms underlying the topography of motor deficits in spinal muscular atrophy (SMA) remain unknown. We investigated the profile of spinal cord atrophy (SCA) in SMN1-linked SMA, and its correlation with the topography of muscle weakness. Materials and Methods Eighteen SMN1-linked SMA patients type III/V and 18 age/gender-matched healthy volunteers were included. Patients were scored on manual muscle testing and functional scales. Spinal cord was imaged using 3T MRI system. Radial distance (RD) and cord cross-sectional area (CSA) measurements in SMA patients were compared to those in controls and correlated with strength and disability scores. Results CSA measurements revealed a significant cord atrophy gradient mainly located between C3 and C6 vertebral levels with a SCA rate ranging from 5.4% to 23% in SMA patients compared to controls. RD was significantly lower in SMA patients compared to controls in the anterior-posterior direction with a maximum along C4 and C5 vertebral levels (p-values < 10−5). There were no correlations between atrophy measurements, strength and disability scores. Conclusions Spinal cord atrophy in adult SMN1-linked SMA predominates in the segments innervating the proximal muscles. Additional factors such as neuromuscular junction or intrinsic skeletal muscle defects may play a role in more complex mechanisms underlying weakness in these patients. PMID:27089520

Evaluation of characteristics of high-energy electron beams using N-isopropyl-acrylamide gel dosimeter

NASA Astrophysics Data System (ADS)

Shih, Tian-Yu; Yen, Tsung-Hsien; Liu, Yan-Lin; Luzhbin, Dmytro; Wu, Jay

2017-11-01

The advantage of electron beam radiotherapy is that the absorbed dose rapidly decreases with the increasing depth, which can prevent damage to deeper organs and tissues. Accurately evaluating the absorbed dose in the superficial tumor is imperative. This study assessed the characteristics of electron beams by using the N-isopropyl-acrylamide (n-NIPAM) gel dosimeter. The n-NIPAM gel was composed of 6% gelatin, 5% monomer, and 2.5% cross-linker with 5 mM tetrakis (hydroxymethyl) phosphonium chloride for deoxygenation. The gel was irradiated with 6-, 9-, and 12-MeV electron beams with dose rates of 100-600 MU/min, respectively. The energy dependence and dose rate dependence were assessed. The beam profiles and percentage depth doses were measured and compared with the results of the Gafchromic film and ionization chamber. The linearity of the n-NIPAM gel under 6-, 9-, and 12-MeV electrons was larger than 0.990 with 2% variation in sensitivity. The sensitivity of the gel under 100-600 MU/min showed 5% variations. The energy and dose rate dependence can be negligible. The beam profiles and percentage depth doses measured by the n-NIPAM gel matched well with the results of the ionization chamber and film. This study reveals the possibility of using the n-NIPAM gel dosimeter for electron beam measurements in clinical radiotherapy.

Gene expression profile analysis of rat cerebellum under acute alcohol intoxication.

PubMed

Zhang, Yu; Wei, Guangkuan; Wang, Yuehong; Jing, Ling; Zhao, Qingjie

2015-02-25

Acute alcohol intoxication, a common disease causing damage to the central nervous system (CNS) has been primarily studied on the aspects of alcohol addiction and chronic alcohol exposure. The understanding of gene expression change in the CNS during acute alcohol intoxication is still lacking. We established a model for acute alcohol intoxication in SD rats by oral gavage. A rat cDNA microarray was used to profile mRNA expression in the cerebella of alcohol-intoxicated rats (experimental group) and saline-treated rats (control group). A total of 251 differentially expressed genes were identified in response to acute alcohol intoxication, in which 208 of them were up-regulated and 43 were down-regulated. Gene ontology (GO) term enrichment analysis and pathway analysis revealed that the genes involved in the biological processes of immune response and endothelial integrity are among the most severely affected in response to acute alcohol intoxication. We discovered five transcription factors whose consensus binding motifs are overrepresented in the promoter region of differentially expressed genes. Additionally, we identified 20 highly connected hub genes by co-expression analysis, and validated the differential expression of these genes by real-time quantitative PCR. By determining novel biological pathways and transcription factors that have functional implication to acute alcohol intoxication, our study substantially contributes to the understanding of the molecular mechanism underlying the pathology of acute alcoholism. Copyright © 2014 Elsevier B.V. All rights reserved.

Transcriptional Profiling of Nitrogen Fixation in Azotobacter vinelandii▿†

PubMed Central

Hamilton, Trinity L.; Ludwig, Marcus; Dixon, Ray; Boyd, Eric S.; Dos Santos, Patricia C.; Setubal, João C.; Bryant, Donald A.; Dean, Dennis R.; Peters, John W.

2011-01-01

Most biological nitrogen (N2) fixation results from the activity of a molybdenum-dependent nitrogenase, a complex iron-sulfur enzyme found associated with a diversity of bacteria and some methanogenic archaea. Azotobacter vinelandii, an obligate aerobe, fixes nitrogen via the oxygen-sensitive Mo nitrogenase but is also able to fix nitrogen through the activities of genetically distinct alternative forms of nitrogenase designated the Vnf and Anf systems when Mo is limiting. The Vnf system appears to replace Mo with V, and the Anf system is thought to contain Fe as the only transition metal within the respective active site metallocofactors. Prior genetic analyses suggest that a number of nif-encoded components are involved in the Vnf and Anf systems. Genome-wide transcription profiling of A. vinelandiicultured under nitrogen-fixing conditions under various metal amendments (e.g., Mo or V) revealed the discrete complement of genes associated with each nitrogenase system and the extent of cross talk between the systems. In addition, changes in transcript levels of genes not directly involved in N2fixation provided insight into the integration of central metabolic processes and the oxygen-sensitive process of N2fixation in this obligate aerobe. The results underscored significant differences between Mo-dependent and Mo-independent diazotrophic growth that highlight the significant advantages of diazotrophic growth in the presence of Mo. PMID:21724999

EXPRESSION PROFILING OF FIVE RAT STRAINS REVEAL TRANSCRIPTIONAL MODES IN THE ANTIGEN PROCESSING PATHWAY

EPA Science Inventory

Comparative gene expression profiling of rat strains with genetic predisposition to diverse cardiovascular diseases can help decode the transcriptional program that governs cellular behavior. We hypothesized that co-transcribed, intra-pathway, functionally coherent genes can be r...

Comprehensive circular RNA profiling reveals that circular RNA100783 is involved in chronic CD28-associated CD8(+)T cell ageing.

PubMed

Wang, Yu-Hong; Yu, Xu-Hui; Luo, Shan-Shun; Han, Hui

2015-01-01

Ageing brings about the gradual deterioration of the immune system, also known as immunosenescence. The role of non-coding circular RNA in immunosenescence is under studied. Using circular RNA microarray data, we assembled Comparison groups (C1, C2, C3 and C4) that allowed us to compare the circular RNA expression profiles between CD28(+)CD8(+) T cells and CD28(-)CD8(+) T cells isolated from healthy elderly or adult control subjects. Using a step-wise biomathematical strategy, the differentially-expressed circRNAs were identified in C1 (CD28(+)CD8(+) vs CD28(-)CD8(+)T cells in the elderly) and C4 (CD28(-)CD8(+)T cells in the elderly vs in the adult), and the commonly-expressed circRNA species from these profiles were optimized as immunosenescence biomarkers. Four overlapping upregulated circular RNAs (100550, 100783, 101328 and 102592) expressed in cross-comparison between C1 and C4 were validated using quantitative polymerase chain reaction. Of these, only circular RNA100783 exhibited significant validation. None of the down-regulated circular RNAs were expressed in the C1 and the C4 cross-comparisons. Therefore, we further predicted circular RNA100783-targeted miRNA-gene interactions using online DAVID annotation. The analysis revealed that a circular RNA100783-targeted miRNA-mRNA network may be involved in alternative splicing, the production of splice variants, and in the regulation of phosphoprotein expression. Considering the hypothesis of splicing-related biogenesis of circRNAs, we propose that circular RNA100783 may play a role in phosphoprotein-associated functions duringCD28-related CD8(+) T cell ageing. This study is the first to employ circular RNA profiling to investigate circular RNA-micro RNA interactions in ageing human CD8(+)T cell populations and the accompanying loss of CD28 expression. The overlapping expression of circular RNA100783 may represent a novel biomarker for the longitudinal tracking ofCD28-related CD8(+) T cell ageing and global immunosenescence.

Adeno-Associated Virus Type 2 Wild-Type and Vector-Mediated Genomic Integration Profiles of Human Diploid Fibroblasts Analyzed by Third-Generation PacBio DNA Sequencing

PubMed Central

Hüser, Daniela; Gogol-Döring, Andreas; Chen, Wei

2014-01-01

ABSTRACT Genome-wide analysis of adeno-associated virus (AAV) type 2 integration in HeLa cells has shown that wild-type AAV integrates at numerous genomic sites, including AAVS1 on chromosome 19q13.42. Multiple GAGY/C repeats, resembling consensus AAV Rep-binding sites are preferred, whereas rep-deficient AAV vectors (rAAV) regularly show a random integration profile. This study is the first study to analyze wild-type AAV integration in diploid human fibroblasts. Applying high-throughput third-generation PacBio-based DNA sequencing, integration profiles of wild-type AAV and rAAV are compared side by side. Bioinformatic analysis reveals that both wild-type AAV and rAAV prefer open chromatin regions. Although genomic features of AAV integration largely reproduce previous findings, the pattern of integration hot spots differs from that described in HeLa cells before. DNase-Seq data for human fibroblasts and for HeLa cells reveal variant chromatin accessibility at preferred AAV integration hot spots that correlates with variant hot spot preferences. DNase-Seq patterns of these sites in human tissues, including liver, muscle, heart, brain, skin, and embryonic stem cells further underline variant chromatin accessibility. In summary, AAV integration is dependent on cell-type-specific, variant chromatin accessibility leading to random integration profiles for rAAV, whereas wild-type AAV integration sites cluster near GAGY/C repeats. IMPORTANCE Adeno-associated virus type 2 (AAV) is assumed to establish latency by chromosomal integration of its DNA. This is the first genome-wide analysis of wild-type AAV2 integration in diploid human cells and the first to compare wild-type to recombinant AAV vector integration side by side under identical experimental conditions. Major determinants of wild-type AAV integration represent open chromatin regions with accessible consensus AAV Rep-binding sites. The variant chromatin accessibility of different human tissues or cell types will have impact on vector targeting to be considered during gene therapy. PMID:25031342

Changes of multi-scale structure during mimicked DSC heating reveal the nature of starch gelatinization

NASA Astrophysics Data System (ADS)

Wang, Shujun; Zhang, Xiu; Wang, Shuo; Copeland, Les

2016-06-01

A thorough understanding of starch gelatinization is extremely important for precise control of starch functional properties for food processing and human nutrition. Here we reveal the molecular mechanism of starch gelatinization by differential scanning calorimetry (DSC) in conjunction with a protocol using the rapid viscosity analyzer (RVA) to generate material for analysis under conditions that simulated the DSC heating profiles. The results from DSC, FTIR, Raman, X-ray diffraction and small angle X-ray scattering (SAXS) analyses all showed that residual structural order remained in starch that was heated to the DSC endotherm end temperature in starch:water mixtures of 0.5 to 4:1 (v/w). We conclude from this study that the DSC endotherm of starch at a water:starch ratio of 2 to 4 (v/w) does not represent complete starch gelatinization. The DSC endotherm of starch involves not only the water uptake and swelling of amorphous regions, but also the melting of starch crystallites.

RNA-Seq Mouse Brain Regions Expression Data Analysis: Focus on ApoE Functional Network

PubMed

Babenko, Vladimir N; Smagin, Dmitry A; Kudryavtseva, Natalia N

2017-09-13

ApoE expression status was proved to be a highly specific marker of energy metabolism rate in the brain. Along with its neighbor, Translocase of Outer Mitochondrial Membrane 40 kDa (TOMM40) which is involved in mitochondrial metabolism, the corresponding genomic region constitutes the neuroenergetic hotspot. Using RNA-Seq data from a murine model of chronic stress a significant positive expression coordination of seven neighboring genes in ApoE locus in five brain regions was observed. ApoE maintains one of the highest absolute expression values genome-wide, implying that ApoE can be the driver of the neighboring gene expression alteration observed under stressful loads. Notably, we revealed the highly statistically significant increase of ApoE expression in the hypothalamus of chronically aggressive (FDR < 0.007) and defeated (FDR < 0.001) mice compared to the control. Correlation analysis revealed a close association of ApoE and proopiomelanocortin (Pomc) gene expression profiles implying the putative neuroendocrine stress response background of ApoE expression elevation therein.

NAC-NOR mutations in tomato Penjar accessions attenuate multiple metabolic processes and prolong the fruit shelf life.

PubMed

Kumar, Rakesh; Tamboli, Vajir; Sharma, Rameshwar; Sreelakshmi, Yellamaraju

2018-09-01

Several Penjar accessions of tomato grown in the Mediterranean exhibit prolonged shelf life and harbor alcobaca mutation. To uncover the metabolic basis underlying shelf life, we compared four Penjar accessions to Ailsa Craig. Three accessions bore alcobaca mutation, whereas the fourth was a novel NAC-NOR allele. Cuticle composition of Penjars varied widely during fruit ripening. All Penjars exhibited delayed ripening, prolonged on-vine and off-vine shelf life, low ethylene emission, and carotenoid levels. Metabolic profiling revealed shifts in Krebs cycle intermediates, amino acids, and γ-aminobutyric acid levels indicating the attenuation of respiration in Penjars during post-harvest storage. Penjar fruits also showed concerted downregulation of several cell-wall modifying genes and related metabolites. The high ABA and sucrose levels at the onset of senescence in Penjar fruits likely contribute to reduced water loss. Our analyses reveal that the attenuation of various metabolic processes by NAC-NOR mutation likely prolongs the shelf life of Penjar fruits. Copyright © 2018 Elsevier Ltd. All rights reserved.

Three-Dimensional Adipose Tissue Imaging Reveals Regional Variation in Beige Fat Biogenesis and PRDM16-Dependent Sympathetic Neurite Density.

PubMed

Chi, Jingyi; Wu, Zhuhao; Choi, Chan Hee J; Nguyen, Lily; Tegegne, Saba; Ackerman, Sarah E; Crane, Audrey; Marchildon, François; Tessier-Lavigne, Marc; Cohen, Paul

2018-01-09

While the cell-intrinsic pathways governing beige adipocyte development and phenotype have been increasingly delineated, comparatively little is known about how beige adipocytes interact with other cell types in fat. Here, we introduce a whole-tissue clearing method for adipose that permits immunolabeling and three-dimensional profiling of structures including thermogenic adipocytes and sympathetic innervation. We found that tissue architecture and sympathetic innervation differ significantly between subcutaneous and visceral depots. Subcutaneous fat demonstrates prominent regional variation in beige fat biogenesis with localization of UCP1 + beige adipocytes to areas with dense sympathetic neurites. We present evidence that the density of sympathetic projections is dependent on PRDM16 in adipocytes, providing another potential mechanism underlying the metabolic benefits mediated by PRDM16. This powerful imaging tool highlights the interaction of tissue components during beige fat biogenesis and reveals a previously undescribed mode of regulation of the sympathetic nervous system by adipocytes. Copyright © 2017 Elsevier Inc. All rights reserved.

Macro-fingerprint analysis-through-separation of licorice based on FT-IR and 2DCOS-IR

NASA Astrophysics Data System (ADS)

Wang, Yang; Wang, Ping; Xu, Changhua; Yang, Yan; Li, Jin; Chen, Tao; Li, Zheng; Cui, Weili; Zhou, Qun; Sun, Suqin; Li, Huifen

2014-07-01

In this paper, a step-by-step analysis-through-separation method under the navigation of multi-step IR macro-fingerprint (FT-IR integrated with second derivative IR (SD-IR) and 2DCOS-IR) was developed for comprehensively characterizing the hierarchical chemical fingerprints of licorice from entirety to single active components. Subsequently, the chemical profile variation rules of three parts (flavonoids, saponins and saccharides) in the separation process were holistically revealed and the number of matching peaks and correlation coefficients with standards of pure compounds was increasing along the extracting directions. The findings were supported by UPLC results and a verification experiment of aqueous separation process. It has been demonstrated that the developed multi-step IR macro-fingerprint analysis-through-separation approach could be a rapid, effective and integrated method not only for objectively providing comprehensive chemical characterization of licorice and all its separated parts, but also for rapidly revealing the global enrichment trend of the active components in licorice separation process.

Changes of multi-scale structure during mimicked DSC heating reveal the nature of starch gelatinization

PubMed Central

Wang, Shujun; Zhang, Xiu; Wang, Shuo; Copeland, Les

2016-01-01

A thorough understanding of starch gelatinization is extremely important for precise control of starch functional properties for food processing and human nutrition. Here we reveal the molecular mechanism of starch gelatinization by differential scanning calorimetry (DSC) in conjunction with a protocol using the rapid viscosity analyzer (RVA) to generate material for analysis under conditions that simulated the DSC heating profiles. The results from DSC, FTIR, Raman, X-ray diffraction and small angle X-ray scattering (SAXS) analyses all showed that residual structural order remained in starch that was heated to the DSC endotherm end temperature in starch:water mixtures of 0.5 to 4:1 (v/w). We conclude from this study that the DSC endotherm of starch at a water:starch ratio of 2 to 4 (v/w) does not represent complete starch gelatinization. The DSC endotherm of starch involves not only the water uptake and swelling of amorphous regions, but also the melting of starch crystallites. PMID:27319782

Neural congruence between intertemporal and interpersonal self-control: Evidence from delay and social discounting.

PubMed

Hill, Paul F; Yi, Richard; Spreng, R Nathan; Diana, Rachel A

2017-11-15

Behavioral studies using delay and social discounting as indices of self-control and altruism, respectively, have revealed functional similarities between farsighted and social decisions. However, neural evidence for this functional link is lacking. Twenty-five young adults completed a delay and social discounting task during fMRI scanning. A spatiotemporal partial least squares analysis revealed that both forms of discounting were well characterized by a pattern of brain activity in areas comprising frontoparietal control, default, and mesolimbic reward networks. Both forms of discounting appear to draw on common neurocognitive mechanisms, regardless of whether choices involve intertemporal or interpersonal outcomes. We also observed neural profiles differentiating between high and low discounters. High discounters were well characterized by increased medial temporal lobe and limbic activity. In contrast, low discount rates were associated with activity in the medial prefrontal cortex and right temporoparietal junction. This pattern may reflect biological mechanisms underlying behavioral heterogeneity in discount rates. Copyright © 2017 Elsevier Inc. All rights reserved.

Mechanistic investigation in ultrasound induced enhancement of enzymatic hydrolysis of invasive biomass species.

PubMed

Borah, Arup Jyoti; Agarwal, Mayank; Poudyal, Manisha; Goyal, Arun; Moholkar, Vijayanand S

2016-08-01

This study has assessed four invasive weeds, viz. Saccharum spontaneum (SS), Mikania micrantha (MM), Lantana camara (LC) and Eichhornia crassipes (EC) for enzymatic hydrolysis prior to bioalcohol fermentation. Enzymatic hydrolysis of pretreated biomasses of weeds has been conducted with mechanical agitation and sonication under constant (non-optimum) conditions. Profiles of total reducible sugar release have been fitted to HCH-1 model of enzymatic hydrolysis using Genetic Algorithm. Trends in parameters of this model reveal physical mechanism of ultrasound-induced enhancement of enzymatic hydrolysis. Sonication accelerates hydrolysis kinetics by ∼10-fold. This effect is contributed by several causes, attributed to intense micro-convection generated during sonication: (1) increase in reaction velocity, (2) increase in enzyme-substrate affinity, (3) reduction in product inhibition, and (4) enhancement of enzyme activity due to conformational changes in its secondary structure. Enhancement effect of sonication is revealed to be independent of conditions of enzymatic hydrolysis - whether optimum or non-optimum. Copyright © 2016 Elsevier Ltd. All rights reserved.

Fate of Eight Different Polymers under Uncontrolled Composting Conditions: Relationships Between Deterioration, Biofilm Formation, and the Material Surface Properties.

PubMed

Mercier, Anne; Gravouil, Kevin; Aucher, Willy; Brosset-Vincent, Sandra; Kadri, Linette; Colas, Jenny; Bouchon, Didier; Ferreira, Thierry

2017-02-21

With the ever-increasing volume of polymer wastes and their associated detrimental impacts on the environment, the plastic life cycle has drawn increasing attention. Here, eight commercial polymers selected from biodegradable to environmentally persistent materials, all formulated under a credit card format, were incubated in an outdoor compost to evaluate their fate over time and to profile the microbial communities colonizing their surfaces. After 450 days in compost, the samples were all colonized by multispecies biofilms, these latest displaying different amounts of adhered microbial biomass and significantly distinct bacterial and fungal community compositions depending on the substrate. Interestingly, colonization experiments on the eight polymers revealed a large core of shared microbial taxa, predominantly composed of microorganisms previously reported from environments contaminated with petroleum hydrocarbons or plastics debris. These observations suggest that biofilms may contribute to the alteration process of all the polymers studied. Actually, four substrates, independently of their assignment to a polymer group, displayed a significant deterioration, which might be attributed to biologically mediated mechanisms. Relevantly, the deterioration appears strongly associated with the formation of a high-cell density biofilm onto the polymer surfaces. The analysis of various surface properties revealed that roughness and hydrophilicity are likely prominent parameters for driving the biological interactions with the polymers.

Transient exposure to oxygen or nitrate reveals ecophysiology of fermentative and sulfate‐reducing benthic microbial populations

PubMed Central

Saad, Sainab; Bhatnagar, Srijak; Tegetmeyer, Halina E.; Geelhoed, Jeanine S.; Strous, Marc

2017-01-01

Summary For the anaerobic remineralization of organic matter in marine sediments, sulfate reduction coupled to fermentation plays a key role. Here, we enriched sulfate‐reducing/fermentative communities from intertidal sediments under defined conditions in continuous culture. We transiently exposed the cultures to oxygen or nitrate twice daily and investigated the community response. Chemical measurements, provisional genomes and transcriptomic profiles revealed trophic networks of microbial populations. Sulfate reducers coexisted with facultative nitrate reducers or aerobes enabling the community to adjust to nitrate or oxygen pulses. Exposure to oxygen and nitrate impacted the community structure, but did not suppress fermentation or sulfate reduction as community functions, highlighting their stability under dynamic conditions. The most abundant sulfate reducer in all cultures, related to Desulfotignum balticum, appeared to have coupled both acetate‐ and hydrogen oxidation to sulfate reduction. We describe a novel representative of the widespread uncultured candidate phylum Fermentibacteria (formerly candidate division Hyd24‐12). For this strictly anaerobic, obligate fermentative bacterium, we propose the name ‘USabulitectum silens’ and identify it as a partner of sulfate reducers in marine sediments. Overall, we provide insights into the function of fermentative, as well as sulfate‐reducing microbial communities and their adaptation to a dynamic environment. PMID:28836729

Causal Genetic Variation Underlying Metabolome Differences.

PubMed

Swain-Lenz, Devjanee; Nikolskiy, Igor; Cheng, Jiye; Sudarsanam, Priya; Nayler, Darcy; Staller, Max V; Cohen, Barak A

2017-08-01

An ongoing challenge in biology is to predict the phenotypes of individuals from their genotypes. Genetic variants that cause disease often change an individual's total metabolite profile, or metabolome. In light of our extensive knowledge of metabolic pathways, genetic variants that alter the metabolome may help predict novel phenotypes. To link genetic variants to changes in the metabolome, we studied natural variation in the yeast Saccharomyces cerevisiae We used an untargeted mass spectrometry method to identify dozens of metabolite Quantitative Trait Loci (mQTL), genomic regions containing genetic variation that control differences in metabolite levels between individuals. We mapped differences in urea cycle metabolites to genetic variation in specific genes known to regulate amino acid biosynthesis. Our functional assays reveal that genetic variation in two genes, AUA1 and ARG81 , cause the differences in the abundance of several urea cycle metabolites. Based on knowledge of the urea cycle, we predicted and then validated a new phenotype: sensitivity to a particular class of amino acid isomers. Our results are a proof-of-concept that untargeted mass spectrometry can reveal links between natural genetic variants and metabolome diversity. The interpretability of our results demonstrates the promise of using genetic variants underlying natural differences in the metabolome to predict novel phenotypes from genotype. Copyright © 2017 by the Genetics Society of America.

Lysine acetylome profiling uncovers novel histone deacetylase substrate proteins in Arabidopsis.

PubMed

Hartl, Markus; Füßl, Magdalena; Boersema, Paul J; Jost, Jan-Oliver; Kramer, Katharina; Bakirbas, Ahmet; Sindlinger, Julia; Plöchinger, Magdalena; Leister, Dario; Uhrig, Glen; Moorhead, Greg Bg; Cox, Jürgen; Salvucci, Michael E; Schwarzer, Dirk; Mann, Matthias; Finkemeier, Iris

2017-10-23

Histone deacetylases have central functions in regulating stress defenses and development in plants. However, the knowledge about the deacetylase functions is largely limited to histones, although these enzymes were found in diverse subcellular compartments. In this study, we determined the proteome-wide signatures of the RPD3/HDA1 class of histone deacetylases in Arabidopsis Relative quantification of the changes in the lysine acetylation levels was determined on a proteome-wide scale after treatment of Arabidopsis leaves with deacetylase inhibitors apicidin and trichostatin A. We identified 91 new acetylated candidate proteins other than histones, which are potential substrates of the RPD3/HDA1-like histone deacetylases in Arabidopsis , of which at least 30 of these proteins function in nucleic acid binding. Furthermore, our analysis revealed that histone deacetylase 14 (HDA14) is the first organellar-localized RPD3/HDA1 class protein found to reside in the chloroplasts and that the majority of its protein targets have functions in photosynthesis. Finally, the analysis of HDA14 loss-of-function mutants revealed that the activation state of RuBisCO is controlled by lysine acetylation of RuBisCO activase under low-light conditions. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

A Sister Group Contrast Using Untargeted Global Metabolomic Analysis Delineates the Biochemical Regulation Underlying Desiccation Tolerance in Sporobolus stapfianus[C][W][OA

PubMed Central

Oliver, Melvin J.; Guo, Lining; Alexander, Danny C.; Ryals, John A.; Wone, Bernard W.M.; Cushman, John C.

2011-01-01

Understanding how plants tolerate dehydration is a prerequisite for developing novel strategies for improving drought tolerance. The desiccation-tolerant (DT) Sporobolus stapfianus and the desiccation-sensitive (DS) Sporobolus pyramidalis formed a sister group contrast to reveal adaptive metabolic responses to dehydration using untargeted global metabolomic analysis. Young leaves from both grasses at full hydration or at 60% relative water content (RWC) and from S. stapfianus at lower RWCs were analyzed using liquid and gas chromatography linked to mass spectrometry or tandem mass spectrometry. Comparison of the two species in the fully hydrated state revealed intrinsic differences between the two metabolomes. S. stapfianus had higher concentrations of osmolytes, lower concentrations of metabolites associated with energy metabolism, and higher concentrations of nitrogen metabolites, suggesting that it is primed metabolically for dehydration stress. Further reduction of the leaf RWC to 60% instigated a metabolic shift in S. stapfianus toward the production of protective compounds, whereas S. pyramidalis responded differently. The metabolomes of S. stapfianus leaves below 40% RWC were strongly directed toward antioxidant production, nitrogen remobilization, ammonia detoxification, and soluble sugar production. Collectively, the metabolic profiles obtained uncovered a cascade of biochemical regulation strategies critical to the survival of S. stapfianus under desiccation. PMID:21467579

Integration of Genome-Scale Modeling and Transcript Profiling Reveals Metabolic Pathways Underlying Light and Temperature Acclimation in Arabidopsis[C][W

PubMed Central

Töpfer, Nadine; Caldana, Camila; Grimbs, Sergio; Willmitzer, Lothar; Fernie, Alisdair R.; Nikoloski, Zoran

2013-01-01

Understanding metabolic acclimation of plants to challenging environmental conditions is essential for dissecting the role of metabolic pathways in growth and survival. As stresses involve simultaneous physiological alterations across all levels of cellular organization, a comprehensive characterization of the role of metabolic pathways in acclimation necessitates integration of genome-scale models with high-throughput data. Here, we present an integrative optimization-based approach, which, by coupling a plant metabolic network model and transcriptomics data, can predict the metabolic pathways affected in a single, carefully controlled experiment. Moreover, we propose three optimization-based indices that characterize different aspects of metabolic pathway behavior in the context of the entire metabolic network. We demonstrate that the proposed approach and indices facilitate quantitative comparisons and characterization of the plant metabolic response under eight different light and/or temperature conditions. The predictions of the metabolic functions involved in metabolic acclimation of Arabidopsis thaliana to the changing conditions are in line with experimental evidence and result in a hypothesis about the role of homocysteine-to-Cys interconversion and Asn biosynthesis. The approach can also be used to reveal the role of particular metabolic pathways in other scenarios, while taking into consideration the entirety of characterized plant metabolism. PMID:23613196

Metabolomic analysis reveals altered metabolic pathways in a rat model of gastric carcinogenesis.

PubMed

Gu, Jinping; Hu, Xiaomin; Shao, Wei; Ji, Tianhai; Yang, Wensheng; Zhuo, Huiqin; Jin, Zeyu; Huang, Huiying; Chen, Jiacheng; Huang, Caihua; Lin, Donghai

2016-09-13

Gastric cancer (GC) is one of the most malignant tumors with a poor prognosis. Alterations in metabolic pathways are inextricably linked to GC progression. However, the underlying molecular mechanisms remain elusive. We performed NMR-based metabolomic analysis of sera derived from a rat model of gastric carcinogenesis, revealed significantly altered metabolic pathways correlated with the progression of gastric carcinogenesis. Rats were histologically classified into four pathological groups (gastritis, GS; low-grade gastric dysplasia, LGD; high-grade gastric dysplasia, HGD; GC) and the normal control group (CON). The metabolic profiles of the five groups were clearly distinguished from each other. Furthermore, significant inter-metabolite correlations were extracted and used to reconstruct perturbed metabolic networks associated with the four pathological stages compared with the normal stage. Then, significantly altered metabolic pathways were identified by pathway analysis. Our results showed that oxidative stress-related metabolic pathways, choline phosphorylation and fatty acid degradation were continually disturbed during gastric carcinogenesis. Moreover, amino acid metabolism was perturbed dramatically in gastric dysplasia and GC. The GC stage showed more changed metabolite levels and more altered metabolic pathways. Two activated pathways (glycolysis; glycine, serine and threonine metabolism) substantially contributed to the metabolic alterations in GC. These results lay the basis for addressing the molecular mechanisms underlying gastric carcinogenesis and extend our understanding of GC progression.

LC-MS analysis of Hep-2 and Hek-293 cell lines treated with Brazilian red propolis reveals differences in protein expression.

PubMed

da Silva Frozza, Caroline O; da Silva Brum, Emyle; Alving, Anjali; Moura, Sidnei; Henriques, João A P; Roesch-Ely, Mariana

2016-08-01

Red propolis, an exclusive variety of propolis found in the northeast of Brazil has shown to present antitumour activity, among several other biological properties. This article aimed to help to evaluate the underlying molecular mechanisms of the potential anticancer effects of red propolis on tumour, Hep-2, and non-tumour cells, Hek-293. Differentially expressed proteins in human cell lines were identified through label-free quantitative MS-based proteomic platform, and cells were stained with Giemsa to show morphological changes. A total of 1336 and 773 proteins were identified for Hep-2 and Hek-293, respectively. Among the proteins here identified, 16 were regulated in the Hep-2 cell line and 04 proteins in the Hek-293 line. Over a total of 2000 proteins were identified under MS analysis, and approximately 1% presented differential expression patterns. The GO annotation using Protein Analysis THrough Evolutionary Relationships classification system revealed predominant molecular function of catalytic activity, and among the biological processes, the most prominent was associated to cell metabolism. The proteomic profile here presented should help to elucidate further molecular mechanisms involved in inhibition of cancer cell proliferation by red propolis, which remain unclear to date. © 2016 Royal Pharmaceutical Society.

Combining geomorphological mapping and near surface geophysics (GPR and ERT) to study piping systems

NASA Astrophysics Data System (ADS)

Bernatek-Jakiel, Anita; Kondracka, Marta

2016-12-01

This paper aims to provide a more comprehensive characterization of piping systems in mountainous areas under a temperate climate using geomorphological mapping and geophysical methods (electrical resistivity tomography - ERT and ground penetrating radar - GPR). The significance of piping in gully formation and hillslope hydrology has been discussed for many years, and most of the studies are based on surface investigations. However, it seems that most surface investigations underestimate this subsurface process. Therefore, our purpose was to estimate the scale of piping activity based on both surface and subsurface investigations. We used geophysical methods to detect the boundary of lateral water movement fostering pipe development and recognize the internal structure of the underlying materials. The survey was carried out in the Bereźnica Wyżna catchment, in the Bieszczady Mountains. (Eastern Carpathians, Poland), where pipes develop in Cambisols at a mean depth of about 0.7-0.8 m. The geophysical techniques that were used are shown to be successful in identifying pipes. GPR data suggest that the density of piping systems is much larger than that detectible from surface observations alone. Pipe length can be > 6.5-9.2% (maximum = 49%) higher than what surface mapping suggests. Thus, the significance of piping in hillslope hydrology and gully formation can be greater than previously assumed. These results also draw attention to the scale of piping activity in the Carpathians, where this process has been neglected for many years. The ERT profiles reveal areas affected by piping as places of higher resistivity values, which are an effect of a higher content of air-filled pores (due to higher soil porosity, intense biological activity, and well-developed soil structure). In addition, the ERT profiles show that the pipes in the study area develop at the soil-bedrock interface, probably above the layers of shales or mudstones which create a water restrictive layer. Our results illustrate the suitability and limitations of GPR and ERT to study soil piping. In general, geophysical surveying is useful for gathering more information on pipe density, potential pipe detection, and recognition of the internal structure of materials underlying the pipes. However, the interpretation of radargrams and ERT profiles should be always accompanied by detailed terrain mapping due to potential disturbances affecting geophysical profiles.

Differences in coagulation among Asians and Caucasians and the implication for reconstructive microsurgery.

PubMed

Singhal, Dhruv; Smorodinsky, Emmanuil; Guo, Lifei

2011-01-01

Microvascular reconstructive surgery has seen a revival with the introduction of muscle-sparing perforator flaps. Recognition of potential ethnic differences in coagulation profiles would be important to a microvascular surgeon. Based on clinical observations, we hypothesize that Asian patients have a less thrombogenic coagulation profile than Caucasians. An extensive retrospective review was performed. The annual incidence of venous thromboembolism in the United States is generally accepted to range from 70 to 120 events per 100,000 people versus 16 to 17 events per 100,000 persons in Asia. Autopsy analysis of pulmonary embolism incidence was noted to be 15% in North Americans and less than 1% in Asian populations. Thromboelastography analysis of Asian and Caucasian patients undergoing cholecystectomy revealed different hemostatic mechanisms. Comparison of Asians and Caucasians undergoing the Fontan procedure revealed significantly lower postoperative factor levels in Asians than Caucasians. Baseline comparison of factor and serum levels revealed Asians with the least thrombogenic profiles compared with other ethnic groups. Asians and Caucasians demonstrate different baseline rates of deep vein thrombosis and pulmonary embolism, different hemostatic responses to surgery, and different baseline levels of clotting factors. Further study may lead to better pre-, intra-, and postoperative care of the free flap patient based on their ethnic coagulation profile. © Thieme Medical Publishers.

Cyclin-dependent kinase 8 module expression profiling reveals requirement of mediator subunits 12 and 13 for transcription of Serpent-dependent innate immunity genes in Drosophila.

PubMed

Kuuluvainen, Emilia; Hakala, Heini; Havula, Essi; Sahal Estimé, Michelle; Rämet, Mika; Hietakangas, Ville; Mäkelä, Tomi P

2014-06-06

The Cdk8 (cyclin-dependent kinase 8) module of Mediator integrates regulatory cues from transcription factors to RNA polymerase II. It consists of four subunits where Med12 and Med13 link Cdk8 and cyclin C (CycC) to core Mediator. Here we have investigated the contributions of the Cdk8 module subunits to transcriptional regulation using RNA interference in Drosophila cells. Genome-wide expression profiling demonstrated separation of Cdk8-CycC and Med12-Med13 profiles. However, transcriptional regulation by Cdk8-CycC was dependent on Med12-Med13. This observation also revealed that Cdk8-CycC and Med12-Med13 often have opposite transcriptional effects. Interestingly, Med12 and Med13 profiles overlapped significantly with that of the GATA factor Serpent. Accordingly, mutational analyses indicated that GATA sites are required for Med12-Med13 regulation of Serpent-dependent genes. Med12 and Med13 were also found to be required for Serpent-activated innate immunity genes in defense to bacterial infection. The results reveal a novel role for the Cdk8 module in Serpent-dependent transcription and innate immunity. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

GHGRP Petroleum and Natural Gas Systems Sector Industrial Profile

EPA Pesticide Factsheets

EPA's Greenhouse Gas Reporting Program periodically produces detailed profiles of the various industries that report under the program. These profiles contain detailed analyses for Petroleum and Natural Gas Systems.

GHGRP Miscellaneous Combustion Sector Industrial Profile

EPA Pesticide Factsheets

EPA's Greenhouse Gas Reporting Program periodically produces detailed profiles of the various industries that report under the program. The profiles available for download below contain detailed analyses for the Miscellaneous Combustion industry.

Archive of GHGRP Refineries Sector Industrial Profile

EPA Pesticide Factsheets

EPA's Greenhouse Gas Reporting Program periodically produces detailed profiles of the various industries that report under the program. The profiles available for download below contain detailed analyses for the Refineries industry.

GHGRP Power Plants Sector Industrial Profiles

EPA Pesticide Factsheets

EPA's Greenhouse Gas Reporting Program periodically produces detailed profiles of the various industries that report under the program. These profiles, available for download below, contain detailed analyses for the Power Plants industry.

Archive of GHGRP Chemicals Sector Industrial Profile

EPA Pesticide Factsheets

EPA's Greenhouse Gas Reporting Program periodically produces detailed profiles of the various industries that report under the program. The profiles available for download below contain detailed analyses for the Chemicals industry.

GHGRP Electronics Manufacturing Sector Industrial Profile

EPA Pesticide Factsheets

EPA's Greenhouse Gas Reporting Program periodically produces detailed profiles of the various industries that report under the program. The profiles available for download below contain detailed analyses for the Electronics Manufacturing industry.

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.

PubMed

Jacewicz, R; Lewandowski, K; Rupa-Matysek, J; Jędrzejczyk, M; Berent, J

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.

Expression and secretory profile of buffalo fetal fibroblasts and Wharton's jelly feeder layers.

PubMed

Parmar, Mehtab S; Mishra, Smruti Ranjan; Somal, Anjali; Pandey, Sriti; Kumar, G Sai; Sarkar, Mihir; Chandra, Vikash; Sharma, G Taru

2017-05-01

The present study examined the comparative expression and secretory profile of vital signaling molecules in buffalo fetal fibroblasts (BFF) and Wharton's jelly (BWJ) feeder layers at different passages. Both feeder layers were expanded up to 8th passage. Signaling molecules viz. bone morphogenetic protein 4 (BMP4), fibroblast growth factor 2 (FGF2), leukemia inhibitory factor (LIF) and transforming growth factor beta 1 (TGFB1) and pluripotency-associated transcriptional factors (POU5F1, SOX2, NANOG, KLF4, MYC and FOXD3) were immunolocalized in the both feeder types. A clear variation in the expression pattern of key signaling molecules with passaging was registered in both feeders compared to primary culture (0 passage). The conditioned media (CM) was collected from different passages (2, 4, 6, 8) of both the feeder layers and was quantified using enzyme-linked immunosorbent assay (ELISA). Concomitant to expression profile, protein quantification also revealed differences in the concentration of signaling molecules at different time points. Conjointly, expression and secretory profile revealed that 2nd passage of BFF and 6th passage of BWJ exhibit optimal levels of key signaling molecules thus may be selected as best passages for embryonic stem cells (ESCs) propagation. Further, the effect of mitomycin-C (MMC) treatment on the expression profile of signaling molecules in the selected passages of BFF and BWJ revealed that MMC modulates the expression profile of these molecules. In conclusion, the results indicate that feeder layers vary in expression and secretory pattern of vital signaling molecules with passaging. Based on these findings, the appropriate feeder passages may be selected for the quality propagation of buffalo ESCs. Copyright © 2017 Elsevier B.V. All rights reserved.

Multidimensional profiles of health locus of control in Hispanic Americans.

PubMed

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.

The Dynamics of Internalizing and Externalizing Comorbidity Across the Early School Years

PubMed Central

Willner, Cynthia J.; Gatzke-Kopp, Lisa M.; Bray, Bethany C.

2017-01-01

High rates of comorbidity are observed between internalizing and externalizing problems, yet the developmental dynamics of comorbid symptom presentations are not yet well understood. This study explored the developmental course of latent profiles of internalizing and externalizing symptoms across kindergarten, 1st, and 2nd grade. The sample consisted of 336 children from an urban, low-income community, selected based on relatively high (61%) or low (39%) aggressive/oppositional behavior problems at school entry (64% male; 70% African American, 20% Hispanic). Teachers reported on children’s symptoms in each year. An exploratory latent profile analysis of children’s scores on aggression/oppositionality, hyperactivity/inattention, anxiety, and social withdrawal symptom factors revealed 4 latent symptom profiles: comorbid (48% of the sample in each year), internalizing (19–23%), externalizing (21–22%), and well-adjusted (7–11%). The developmental course of these symptom profiles was examined using a latent transition analysis, which revealed remarkably high continuity in the comorbid symptom profile (89% from one year to the next) and moderately high continuity in both the internalizing and externalizing profiles (80% and 71%, respectively). Internalizing children had a 20% probability of remitting to the well-adjusted profile by the following year, whereas externalizing children had a 25% probability of transitioning to the comorbid profile. These results are consistent with the hypothesis that a common vulnerability factor contributes to developmentally stable internalizing-externalizing comorbidity, while also suggesting that some children with externalizing symptoms are at risk for subsequently accumulating internalizing symptoms. PMID:27739391

Stigma toward schizophrenia: do all psychiatrists behave the same? Latent profile analysis of a national sample of psychiatrists in Brazil

PubMed Central

2013-01-01

Background An important issue concerning the worldwide fight against stigma is the evaluation of psychiatrists’ beliefs and attitudes toward schizophrenia and mental illness in general. However, there is as yet no consensus on this matter in the literature, and results vary according to the stigma dimension assessed and to the cultural background of the sample. The aim of this investigation was to search for profiles of stigmatizing beliefs related to schizophrenia in a national sample of psychiatrists in Brazil. Methods A sample of 1414 psychiatrists were recruited from among those attending the 2009 Brazilian Congress of Psychiatry. A questionnaire was applied in face-to-face interviews. The questionnaire addressed four stigma dimensions, all in reference to individuals with schizophrenia: stereotypes, restrictions, perceived prejudice and social distance. Stigma item scores were included in latent profile analyses; the resulting profiles were entered into multinomial logistic regression models with sociodemographics, in order to identify significant correlates. Results Three profiles were identified. The “no stigma” subjects (n = 337) characterized individuals with schizophrenia in a positive light, disagreed with restrictions, and displayed a low level of social distance. The “unobtrusive stigma” subjects (n = 471) were significantly younger and displayed the lowest level of social distance, although most of them agreed with involuntary admission and demonstrated a high level of perceived prejudice. The “great stigma” subjects (n = 606) negatively stereotyped individuals with schizophrenia, agreed with restrictions and scored the highest on the perceived prejudice and social distance dimensions. In comparison with the first two profiles, this last profile comprised a significantly larger number of individuals who were in frequent contact with a family member suffering from a psychiatric disorder, as well as comprising more individuals who had no such family member. Conclusions Our study not only provides additional data related to an under-researched area but also reveals that psychiatrists are a heterogeneous group regarding stigma toward schizophrenia. The presence of different stigma profiles should be evaluated in further studies; this could enable anti-stigma initiatives to be specifically designed to effectively target the stigmatizing group. PMID:23517184

[Spatial distribution and ecological significance of heavy metals in soils from Chatian mercury mining deposit, western Hunan province].

PubMed

Sun, Hong-Fei; Li, Yong-Hu; Ji, Yan-Fang; Yang, Lin-Sheng; Wang, Wu-Yi

2009-04-15

Ores, waste tailings and slag, together with three typical soil profiles (natural soil profiles far from mine entrance and near mine entrance, soil profile under slag) in Chatian mercury mining deposit (CMD), western Hunan province were sampled and their concentrations of mercury (Hg), arsenic (As), lead (Pb), cadmium (Cd), zinc (Zn) were determined by HG-ICP-AES and ICP-MS. Enrichment factor and correlation analysis were taken to investigate the origins, distribution and migration of Hg, as well as other heavy metals in the CMD. The results show that Hg is enriched in the bottom of the soil profile far from mine entrance but accumulated in the surface of soil profiles near mine entrance and under slag. The soil profiles near mine entrance and under slag are both contaminated by Hg, while the latter is contaminated more heavily. In the soil profile under slag, Hg concentration in the surface soil, Hg average concentration in the total profile, and the leaching depth of soil Hg are 640 microg x g(-1), (76.74 +/- 171.71) microg x g(-1), and more than 100 cm, respectively; while 6.5 microg x g(-1), (2.74 +/- 1.90) microg x g(-1), and 40 cm, respectively, are found in the soil profile near mine entrance. Soil in the mercury mine area is also polluted by Cd, As, Pb, Zn besides metallogenic element Hg, among which Cd pollution is relatively heavier than others. The mobility of the studied heavy metals in soil follows the order as Hg > Cd > As > Zn approximately equal to Pb. The leaching depth of the heavy metals is influenced by total concentration in the surface soil and soil physico-chemical parameters. The origins, distribution and migration of heavy metals in soil profile in the mining area are related to primary geological environment, and strongly influenced by human mining activities.

Receptive amusia: evidence for cross-hemispheric neural networks underlying music processing strategies.

PubMed

Schuppert, M; Münte, T F; Wieringa, B M; Altenmüller, E

2000-03-01

Perceptual musical functions were investigated in patients suffering from unilateral cerebrovascular cortical lesions. Using MIDI (Musical Instrument Digital Interface) technique, a standardized short test battery was established that covers local (analytical) as well as global perceptual mechanisms. These represent the principal cognitive strategies in melodic and temporal musical information processing (local, interval and rhythm; global, contour and metre). Of the participating brain-damaged patients, a total of 69% presented with post-lesional impairments in music perception. Left-hemisphere-damaged patients showed significant deficits in the discrimination of local as well as global structures in both melodic and temporal information processing. Right-hemisphere-damaged patients also revealed an overall impairment of music perception, reaching significance in the temporal conditions. Detailed analysis outlined a hierarchical organization, with an initial right-hemisphere recognition of contour and metre followed by identification of interval and rhythm via left-hemisphere subsystems. Patterns of dissociated and associated melodic and temporal deficits indicate autonomous, yet partially integrated neural subsystems underlying the processing of melodic and temporal stimuli. In conclusion, these data contradict a strong hemispheric specificity for music perception, but indicate cross-hemisphere, fragmented neural substrates underlying local and global musical information processing in the melodic and temporal dimensions. Due to the diverse profiles of neuropsychological deficits revealed in earlier investigations as well as in this study, individual aspects of musicality and musical behaviour very likely contribute to the definite formation of these widely distributed neural networks.

A Self-Powered Fast-Sampling Profiling Float in support of a Mesoscale Ocean Observing System in the Western North Pacific

NASA Astrophysics Data System (ADS)

Valdez, T.; Chao, Y.; Davis, R. E.; Jones, J.

2012-12-01

This talk will describe a new self-powered profiling float that can perform fast sampling over the upper ocean for long durations in support of a mesoscale ocean observing system in the Western North Pacific. The current state-of-the-art profiling floats can provide several hundreds profiles for the upper ocean every ten days. To quantify the role of the upper ocean in modulating the development of Typhoons requires at least an order of magnitude reduction for the sampling interval. With today's profiling float and battery technology, a fast sampling of one day or even a few hours will reduce the typical lifetime of profiling floats from years to months. Interactions between the ocean and typhoons often involves mesoscale eddies and fronts, which require a dense array of floats to reveal the 3-dimensional structure. To measure the mesoscale ocean over a large area like the Western North Pacific therefore requires a new technology that enables fast sampling and long duration at the same time. Harvesting the ocean renewable energy associated with the vertical temperature differentials has the potential to power profiling floats with fast sampling over long durations. Results from the development and deployment of a prototype self-powered profiling float (known as SOLO-TREC) will be presented. With eight hours sampling in the upper 500 meters, the upper ocean temperature and salinity reveal pronounced high frequency variations. Plans to use the SOLO-TREC technology in support of a dense array of fast sampling profiling floats in the Western North Pacific will be discussed.

Screening molecular associations with lipid membranes using natural abundance 13C cross-polarization magic-angle spinning NMR and principal component analysis.

PubMed

Middleton, David A; Hughes, Eleri; Madine, Jillian

2004-08-11

We describe an NMR approach for detecting the interactions between phospholipid membranes and proteins, peptides, or small molecules. First, 1H-13C dipolar coupling profiles are obtained from hydrated lipid samples at natural isotope abundance using cross-polarization magic-angle spinning NMR methods. Principal component analysis of dipolar coupling profiles for synthetic lipid membranes in the presence of a range of biologically active additives reveals clusters that relate to different modes of interaction of the additives with the lipid bilayer. Finally, by representing profiles from multiple samples in the form of contour plots, it is possible to reveal statistically significant changes in dipolar couplings, which reflect perturbations in the lipid molecules at the membrane surface or within the hydrophobic interior.

Salt composition of groundwater and reclaimed solonetzes in the Baraba Lowland

NASA Astrophysics Data System (ADS)

Semendyaeva, N. V.; Elizarov, N. V.

2017-10-01

Solonetzes of experimental trials established in 1981 and 1986 in the Baraba Lowland were examined. It was found that gypsum-based ameliorants improve the soil and lead to a decrease in the content of soluble salts in the soil profile. Exchange processes between cations of the soil adsorption complex and calcium of gypsum were particularly intensive in the first years after gypsum application. This resulted in a sharp rise in the content of soluble salts that migrated down the soil profile to the groundwater. In the following years, the reclaimed solonetzes were desalinized under the conditions of relatively stable groundwater level. On the 30th year after single gypsum application, the groundwater level sharply rose (to 50 cm), and the soil was subjected to the secondary salinization; the contents of bicarbonates, carbonates, and sodium in the soils increased. Spring leaching caused some desalinization, but the content of soluble salts in the upper soil meter increased again in the fall. A close correlation between the salt compositions of the groundwater and the reclaimed solonetzes was revealed.

Hypoxia-induced HIF1α targets in melanocytes reveal a molecular profile associated with poor melanoma prognosis

PubMed Central

Loftus, Stacie K.; Baxter, Laura L.; Cronin, Julia C.; Fufa, Temesgen D.; Pavan, William J.

2017-01-01

Summary Hypoxia and HIF1α signaling direct tissue-specific gene responses regulating tumor progression, invasion and metastasis. By integrating HIF1α knockdown and hypoxia-induced gene expression changes, this study identifies a melanocyte-specific, HIF1α-dependent/hypoxia-responsive gene expression signature. Integration of these gene expression changes with HIF1α ChIP-Seq analysis identifies 81 HIF1α direct target genes in melanocytes. The expression levels for ten of the HIF1α direct targets – GAPDH, PKM, PPAT, DARS, DTWD1, SEH1L, ZNF292, RLF, AGTRAP, and GPC6 – are significantly correlated with reduced time of Disease Free Status (DFS) in melanoma by logistic regression (P-value =0.0013) and ROC curve analysis (AUC= 0.826, P-value<0.0001). This HIF1α-regulated profile defines a melanocyte-specific response under hypoxia, and demonstrates the role of HIF1α as an invasive cell state gatekeeper in regulating cellular metabolism, chromatin and transcriptional regulation, vascularization and invasion. PMID:28168807

Genomic and Proteomic Profiling Reveals Reduced Mitochondrial Function and Disruption of the Neuromuscular Junction Driving Rat Sarcopenia

PubMed Central

Ibebunjo, Chikwendu; Chick, Joel M.; Kendall, Tracee; Eash, John K.; Li, Christine; Zhang, Yunyu; Vickers, Chad; Wu, Zhidan; Clarke, Brian A.; Shi, Jun; Cruz, Joseph; Fournier, Brigitte; Brachat, Sophie; Gutzwiller, Sabine; Ma, QiCheng; Markovits, Judit; Broome, Michelle; Steinkrauss, Michelle; Skuba, Elizabeth; Galarneau, Jean-Rene; Gygi, Steven P.

2013-01-01

Molecular mechanisms underlying sarcopenia, the age-related loss of skeletal muscle mass and function, remain unclear. To identify molecular changes that correlated best with sarcopenia and might contribute to its pathogenesis, we determined global gene expression profiles in muscles of rats aged 6, 12, 18, 21, 24, and 27 months. These rats exhibit sarcopenia beginning at 21 months. Correlation of the gene expression versus muscle mass or age changes, and functional annotation analysis identified gene signatures of sarcopenia distinct from gene signatures of aging. Specifically, mitochondrial energy metabolism (e.g., tricarboxylic acid cycle and oxidative phosphorylation) pathway genes were the most downregulated and most significantly correlated with sarcopenia. Also, perturbed were genes/pathways associated with neuromuscular junction patency (providing molecular evidence of sarcopenia-related functional denervation and neuromuscular junction remodeling), protein degradation, and inflammation. Proteomic analysis of samples at 6, 18, and 27 months confirmed the depletion of mitochondrial energy metabolism proteins and neuromuscular junction proteins. Together, these findings suggest that therapeutic approaches that simultaneously stimulate mitochondrogenesis and reduce muscle proteolysis and inflammation have potential for treating sarcopenia. PMID:23109432

Design of a soil cutting resistance sensor for application in site-specific tillage.

PubMed

Agüera, Juan; Carballido, Jacob; Gil, Jesús; Gliever, Chris J; Perez-Ruiz, Manuel

2013-05-10

One objective of precision agriculture is to provide accurate information about soil and crop properties to optimize the management of agricultural inputs to meet site-specific needs. This paper describes the development of a sensor equipped with RTK-GPS technology that continuously and efficiently measures soil cutting resistance at various depths while traversing the field. Laboratory and preliminary field tests verified the accuracy of this prototype soil strength sensor. The data obtained using a hand-operated soil cone penetrometer was used to evaluate this field soil compaction depth profile sensor. To date, this sensor has only been tested in one field under one gravimetric water content condition. This field test revealed that the relationships between the soil strength profile sensor (SSPS) cutting force and soil cone index values are assumed to be quadratic for the various depths considered: 0-10, 10-20 and 20-30 cm (r2 = 0.58, 0.45 and 0.54, respectively). Soil resistance contour maps illustrated its practical value. The developed sensor provides accurate, timely and affordable information on soil properties to optimize resources and improve agricultural economy.

A new one-dimensional radiative equilibrium model for investigating atmospheric radiation entropy flux.

PubMed

Wu, Wei; Liu, Yangang

2010-05-12

A new one-dimensional radiative equilibrium model is built to analytically evaluate the vertical profile of the Earth's atmospheric radiation entropy flux under the assumption that atmospheric longwave radiation emission behaves as a greybody and shortwave radiation as a diluted blackbody. Results show that both the atmospheric shortwave and net longwave radiation entropy fluxes increase with altitude, and the latter is about one order in magnitude greater than the former. The vertical profile of the atmospheric net radiation entropy flux follows approximately that of the atmospheric net longwave radiation entropy flux. Sensitivity study further reveals that a 'darker' atmosphere with a larger overall atmospheric longwave optical depth exhibits a smaller net radiation entropy flux at all altitudes, suggesting an intrinsic connection between the atmospheric net radiation entropy flux and the overall atmospheric longwave optical depth. These results indicate that the overall strength of the atmospheric irreversible processes at all altitudes as determined by the corresponding atmospheric net entropy flux is closely related to the amount of greenhouse gases in the atmosphere.

A Metabolic Profiling Strategy for the Dissection of Plant Defense against Fungal Pathogens

PubMed Central

Aliferis, Konstantinos A.; Faubert, Denis; Jabaji, Suha

2014-01-01

Here we present a metabolic profiling strategy employing direct infusion Orbitrap mass spectrometry (MS) and gas chromatography-mass spectrometry (GC/MS) for the monitoring of soybean's (Glycine max L.) global metabolism regulation in response to Rhizoctonia solani infection in a time-course. Key elements in the approach are the construction of a comprehensive metabolite library for soybean, which accelerates the steps of metabolite identification and biological interpretation of results, and bioinformatics tools for the visualization and analysis of its metabolome. The study of metabolic networks revealed that infection results in the mobilization of carbohydrates, disturbance of the amino acid pool, and activation of isoflavonoid, α-linolenate, and phenylpropanoid biosynthetic pathways of the plant. Components of these pathways include phytoalexins, coumarins, flavonoids, signaling molecules, and hormones, many of which exhibit antioxidant properties and bioactivity helping the plant to counterattack the pathogen's invasion. Unraveling the biochemical mechanism operating during soybean-Rhizoctonia interaction, in addition to its significance towards the understanding of the plant's metabolism regulation under biotic stress, provides valuable insights with potential for applications in biotechnology, crop breeding, and agrochemical and food industries. PMID:25369450

An Outer Membrane Protein Involved in the Uptake of Glucose Is Essential for Cytophaga hutchinsonii Cellulose Utilization

PubMed Central

Zhou, Hong; Wang, Xia; Yang, Tengteng; Zhang, Weixin; Chen, Guanjun

2016-01-01

Cytophaga hutchinsonii specializes in cellulose digestion by employing a collection of novel cell-associated proteins. Here, we identified a novel gene locus, CHU_1276, that is essential for C. hutchinsonii cellulose utilization. Disruption of CHU_1276 in C. hutchinsonii resulted in complete deficiency in cellulose degradation, as well as compromised assimilation of cellobiose or glucose at a low concentration. Further analysis showed that CHU_1276 was an outer membrane protein that could be induced by cellulose and low concentrations of glucose. Transcriptional profiling revealed that CHU_1276 exerted a profound effect on the genome-wide response to both glucose and Avicel and that the mutant lacking CHU_1276 displayed expression profiles very different from those of the wild-type strain under different culture conditions. Specifically, comparison of their transcriptional responses to cellulose led to the identification of a gene set potentially regulated by CHU_1276. These results suggest that CHU_1276 plays an essential role in cellulose utilization, probably by coordinating the extracellular hydrolysis of cellulose substrate with the intracellular uptake of the hydrolysis product in C. hutchinsonii. PMID:26773084

Shotgun metabolomic approach based on mass spectrometry for hepatic mitochondria of mice under arsenic exposure.

PubMed

García-Sevillano, M A; García-Barrera, T; Navarro, F; Montero-Lobato, Z; Gómez-Ariza, J L

2015-04-01

Mass spectrometry (MS)-based toxicometabolomics requires analytical approaches for obtaining unbiased metabolic profiles. The present work explores the general application of direct infusion MS using a high mass resolution analyzer (a hybrid systems triple quadrupole-time-of-flight) and a complementary gas chromatography-MS analysis to mitochondria extracts from mouse hepatic cells, emphasizing on mitochondria isolation from hepatic cells with a commercial kit, sample treatment after cell lysis, comprehensive metabolomic analysis and pattern recognition from metabolic profiles. Finally, the metabolomic platform was successfully checked on a case-study based on the exposure experiment of mice Mus musculus to inorganic arsenic during 12 days. Endogenous metabolites alterations were recognized by partial least squares-discriminant analysis. Subsequently, metabolites were identified by combining MS/MS analysis and metabolomics databases. This work reports for the first time the effects of As-exposure on hepatic mitochondria metabolic pathways based on MS, and reveals disturbances in Krebs cycle, β-oxidation pathway, amino acids degradation and perturbations in creatine levels. This non-target analysis provides extensive metabolic information from mitochondrial organelle, which could be applied to toxicology, pharmacology and clinical studies.

High-Speed Boundary-Layer Transition Induced by an Isolated Roughness Element

NASA Technical Reports Server (NTRS)

Kegerise, Michael A.; Owens, Lewis R.; King, Rudolph A.

2010-01-01

Progress on an experimental effort to quantify the instability mechanisms associated with roughness-induced transition in a high-speed boundary layer is reported in this paper. To simulate the low-disturbance environment encountered during high-altitude flight, the experimental study was performed in the NASA-Langley Mach 3.5 Supersonic Low-Disturbance Tunnel. A flat plate trip sizing study was performed first to identify the roughness height required to force transition. That study, which included transition onset measurements under both quiet and noisy freestream conditions, confirmed the sensitivity of roughness-induced transition to freestream disturbance levels. Surveys of the laminar boundary layer on a 7deg half-angle sharp-tipped cone were performed via hot-wire anemometry and pitot-pressure measurements. The measured mean mass-flux and Mach-number profiles agreed very well with computed mean-flow profiles. Finally, surveys of the boundary layer developing downstream of an isolated roughness element on the cone were performed. The measurements revealed an instability in the far wake of the roughness element that grows exponentially and has peak frequencies in the 150 to 250 kHz range.

Altered gene expression of the innate immune, neuroendocrine, and nuclear factor-kappa B (NF-κB) systems is associated with posttraumatic stress disorder in military personnel.

PubMed

Guardado, Pedro; Olivera, Anlys; Rusch, Heather L; Roy, Michael; Martin, Christiana; Lejbman, Natasha; Lee, Hwyunhwa; Gill, Jessica M

2016-03-01

Whole transcriptome analysis provides an unbiased examination of biological activity, and likely, unique insight into the mechanisms underlying posttraumatic stress disorder (PTSD) and comorbid depression and traumatic brain injury. This study compared gene-expression profiles in military personnel with PTSD (n=28) and matched controls without PTSD (n=27) using HG-U133 Plus 2.0 microarrays (Affymetrix), which contain 54,675 probe sets representing more than 38,500 genes. Analysis of expression profiles revealed 203 differentially expressed genes in PTSD, of which 72% were upregulated. Using Partek Genomics Suite 6.6, differentially expressed transcription clusters were filtered based on a selection criterion of ≥1.5 relative fold change at a false discovery rate of ≤5%. Ingenuity Pathway Analysis (Qiagen) of the differentially expressed genes indicated a dysregulation of genes associated with the innate immune, neuroendocrine, and NF-κB systems. These findings provide novel insights that may lead to new pharmaceutical agents for PTSD treatments and help mitigate mental and physical comorbidity risk. Copyright © 2016. Published by Elsevier Ltd.

Rice Phospholipase A Superfamily: Organization, Phylogenetic and Expression Analysis during Abiotic Stresses and Development

PubMed Central

Singh, Amarjeet; Baranwal, Vinay; Shankar, Alka; Kanwar, Poonam; Ranjan, Rajeev; Yadav, Sandeep; Pandey, Amita; Kapoor, Sanjay; Pandey, Girdhar K.

2012-01-01

Background Phospholipase A (PLA) is an important group of enzymes responsible for phospholipid hydrolysis in lipid signaling. PLAs have been implicated in abiotic stress signaling and developmental events in various plants species. Genome-wide analysis of PLA superfamily has been carried out in dicot plant Arabidopsis. A comprehensive genome-wide analysis of PLAs has not been presented yet in crop plant rice. Methodology/Principal Findings A comprehensive bioinformatics analysis identified a total of 31 PLA encoding genes in the rice genome, which are divided into three classes; phospholipase A1 (PLA1), patatin like phospholipases (pPLA) and low molecular weight secretory phospholipase A2 (sPLA2) based on their sequences and phylogeny. A subset of 10 rice PLAs exhibited chromosomal duplication, emphasizing the role of duplication in the expansion of this gene family in rice. Microarray expression profiling revealed a number of PLA members expressing differentially and significantly under abiotic stresses and reproductive development. Comparative expression analysis with Arabidopsis PLAs revealed a high degree of functional conservation between the orthologs in two plant species, which also indicated the vital role of PLAs in stress signaling and plant development across different plant species. Moreover, sub-cellular localization of a few candidates suggests their differential localization and functional role in the lipid signaling. Conclusion/Significance The comprehensive analysis and expression profiling would provide a critical platform for the functional characterization of the candidate PLA genes in crop plants. PMID:22363522

Ribosome profiling reveals the rhythmic liver translatome and circadian clock regulation by upstream open reading frames

PubMed Central

Janich, Peggy; Arpat, Alaaddin Bulak; Castelo-Szekely, Violeta; Lopes, Maykel; Gatfield, David

2015-01-01

Mammalian gene expression displays widespread circadian oscillations. Rhythmic transcription underlies the core clock mechanism, but it cannot explain numerous observations made at the level of protein rhythmicity. We have used ribosome profiling in mouse liver to measure the translation of mRNAs into protein around the clock and at high temporal and nucleotide resolution. We discovered, transcriptome-wide, extensive rhythms in ribosome occupancy and identified a core set of approximately 150 mRNAs subject to particularly robust daily changes in translation efficiency. Cycling proteins produced from nonoscillating transcripts revealed thus-far-unknown rhythmic regulation associated with specific pathways (notably in iron metabolism, through the rhythmic translation of transcripts containing iron responsive elements), and indicated feedback to the rhythmic transcriptome through novel rhythmic transcription factors. Moreover, estimates of relative levels of core clock protein biosynthesis that we deduced from the data explained known features of the circadian clock better than did mRNA expression alone. Finally, we identified uORF translation as a novel regulatory mechanism within the clock circuitry. Consistent with the occurrence of translated uORFs in several core clock transcripts, loss-of-function of Denr, a known regulator of reinitiation after uORF usage and of ribosome recycling, led to circadian period shortening in cells. In summary, our data offer a framework for understanding the dynamics of translational regulation, circadian gene expression, and metabolic control in a solid mammalian organ. PMID:26486724

A circadian neuropeptide PDF in the honeybee, Apis mellifera: cDNA cloning and expression of mRNA.

PubMed

Sumiyoshi, Miho; Sato, Seiji; Takeda, Yukimasa; Sumida, Kazunori; Koga, Keita; Itoh, Tsunao; Nakagawa, Hiroyuki; Shimohigashi, Yasuyuki; Shimohigashi, Miki

2011-12-01

Pigment-dispersing factor (PDF) is a pacemaker hormone regulating the locomotor rhythm in insects. In the present study, we cloned the cDNAs encoding the Apis PDF precursor protein, and found that there are at least seven different pdf mRNAs yielded by an alternative splicing site and five alternative polyadenylation sites in the 5'UTR and 3'UTR regions. The amino acid sequence of Apis PDF peptide has a characteristic novel amino acid residue, aspargine (Asn), at position 17. Quantitative real-time PCR of total and 5'UTR insertion-type pdf mRNAs revealed, for the first time, that the expression levels change in a circadian manner with a distinct trough at the beginning of night in LD conditions, and at the subjective night under DD conditions. In contrast, the expression level of 5'UTR deletion-type pdf mRNAs was about half of that of the insertion type, and the expression profile failed to show a circadian rhythm. As the expression profile of the total pdf mRNA exhibited a circadian rhythm, transcription regulated at the promoter region was supposed to be controlled by some of the clock components. Whole mount in situ hybridization revealed that 14 lateral neurons at the frontal margin of the optic lobe express these mRNA isoforms. PDF expressing cells examined with a newly produced antibody raised against Apis PDF were also found to have a dense supply of axon terminals in the optic lobes and the central brain.

Differential proteome profiling in the hippocampus of amnesic mice.

PubMed

Baghel, Meghraj Singh; Thakur, Mahendra Kumar

2017-08-01

Amnesia or memory loss is associated with brain aging and several neurodegenerative pathologies including Alzheimer's disease (AD). This can be induced by a cholinergic antagonist scopolamine but the underlying molecular mechanism is poorly understood. This study of proteome profiling in the hippocampus could provide conceptual insights into the molecular mechanisms involved in amnesia. To reveal this, mice were administered scopolamine to induce amnesia and memory impairment was validated by novel object recognition test. Using two-dimensional gel electrophoresis coupled with MALDI-MS/MS, we have analyzed the hippocampal proteome and identified 18 proteins which were differentially expressed. Out of these proteins, 11 were downregulated and 7 were upregulated in scopolamine-treated mice as compared to control. In silico analysis showed that the majority of identified proteins are involved in metabolism, catalytic activity, and cytoskeleton architectural functions. STRING interaction network analysis revealed that majority of identified proteins exhibit common association with Actg1 cytoskeleton and Vdac1 energy transporter protein. Furthermore, interaction map analysis showed that Fascin1 and Coronin 1b individually interact with Actg1 and regulate the actin filament dynamics. Vdac1 was significantly downregulated in amnesic mice and showed interaction with other proteins in interaction network. Therefore, we silenced Vdac1 in the hippocampus of normal young mice and found similar impairment in recognition memory of Vdac1 silenced and scopolamine-treated mice. Thus, these findings suggest that Vdac1-mediated disruption of energy metabolism and cytoskeleton architecture might be involved in scopolamine-induced amnesia. © 2017 Wiley Periodicals, Inc.

MicroRNA profiling reveals unique miRNA signatures in IGF-1 treated embryonic striatal stem cell fate decisions in striatal neurogenesis in vitro.

PubMed

Pati, Soumya; Supeno, Nor Entan; Muthuraju, Sangu; Abdul Hadi, Raisah; Ghani, Abdul Rahman Izaini; Idris, Fauziah Mohamad; Maletic-Savatic, Mirjana; Abdullah, Jafri Malin; Jaafar, Hasnan

2014-01-01

The striatum is considered to be the central processing unit of the basal ganglia in locomotor activity and cognitive function of the brain. IGF-1 could act as a control switch for the long-term proliferation and survival of EGF+bFGF-responsive cultured embryonic striatal stem cell (ESSC), while LIF imposes a negative impact on cell proliferation. The IGF-1-treated ESSCs also showed elevated hTERT expression with demonstration of self-renewal and trilineage commitment (astrocytes, oligodendrocytes, and neurons). In order to decipher the underlying regulatory microRNA (miRNA)s in IGF-1/LIF-treated ESSC-derived neurogenesis, we performed in-depth miRNA profiling at 12 days in vitro and analyzed the candidates using the Partek Genome Suite software. The annotated miRNA fingerprints delineated the differential expressions of miR-143, miR-433, and miR-503 specific to IGF-1 treatment. Similarly, the LIF-treated ESSCs demonstrated specific expression of miR-326, miR-181, and miR-22, as they were nonsignificant in IGF-treated ESSCs. To elucidate the possible downstream pathways, we performed in silico mapping of the said miRNAs into ingenuity pathway analysis. Our findings revealed the important mRNA targets of the miRNAs and suggested specific interactomes. The above studies introduced a new genre of miRNAs for ESSC-based neuroregenerative therapeutic applications.

Oncogene-induced senescence results in marked metabolic and bioenergetic alterations

PubMed Central

Quijano, Celia; Cao, Liu; Fergusson, Maria M; Romero, Hector; Liu, Jie; Gutkind, Sarah; Rovira, Ilsa I; Mohney, Robert P; Karoly, Edward D

2012-01-01

Oncogene-induced senescence (OIS) is characterized by permanent growth arrest and the acquisition of a secretory, pro-inflammatory state. Increasingly, OIS is viewed as an important barrier to tumorgenesis. Surprisingly, relatively little is known about the metabolic changes that accompany and therefore may contribute to OIS. Here, we have performed a metabolomic and bioenergetic analysis of Ras-induced senescence. Profiling approximately 300 different intracellular metabolites reveals that cells that have undergone OIS develop a unique metabolic signature that differs markedly from cells undergoing replicative senescence. A number of lipid metabolites appear uniquely increased in OIS cells, including a marked increase in the level of certain intracellular long chain fatty acids. Functional studies reveal that this alteration in the metabolome reflects substantial changes in overall lipid metabolism. In particular, Ras-induced senescent cells manifest a decline in lipid synthesis and a significant increase in fatty acid oxidation. Increased fatty acid oxidation results in an unexpectedly high rate of basal oxygen consumption in cells that have undergone OIS. Pharmacological or genetic inhibition of carnitine palmitoyltransferase 1, the rate-limiting step in mitochondrial fatty acid oxidation, restores a presenescent metabolic rate and, surprisingly, selectively inhibits the secretory, pro-inflammatory state that accompanies OIS. Thus, Ras-induced senescent cells demonstrate profound alterations in their metabolic and bioenergetic profiles, particularly with regards to the levels, synthesis and oxidation of free fatty acids. Furthermore, the inflammatory phenotype that accompanies OIS appears to be related to these underlying changes in cellular metabolism. PMID:22421146

Comprehensive transcriptome-based characterization of differentially expressed genes involved in microsporogenesis of radish CMS line and its maintainer.

PubMed

Xie, Yang; Zhang, Wei; Wang, Yan; Xu, Liang; Zhu, Xianwen; Muleke, Everlyne M; Liu, Liwang

2016-09-01

Microsporogenesis is an indispensable period for investigating microspore development and cytoplasmic male sterility (CMS) occurrence. Radish CMS line plays a critical role in elite F1 hybrid seed production and heterosis utilization. However, the molecular mechanisms of microspore development and CMS occurrence have not been thoroughly uncovered in radish. In this study, a comparative analysis of radish floral buds from a CMS line (NAU-WA) and its maintainer (NAU-WB) was conducted using next generation sequencing (NGS) technology. Digital gene expression (DGE) profiling revealed that 3504 genes were significantly differentially expressed between NAU-WA and NAU-WB library, among which 1910 were upregulated and 1594 were downregulated. Gene ontology (GO) analysis showed that these differentially expressed genes (DEGs) were mainly enriched in extracellular region, catalytic activity, and response to stimulus. KEGG enrichment analysis revealed that the DEGs were predominantly associated with flavonoid biosynthesis, glycolysis, and biosynthesis of secondary metabolites. Real-time quantitative PCR analysis showed that the expression profiles of 13 randomly selected DEGs were in high agreement with results from Illumina sequencing. Several candidate genes encoding ATP synthase, auxin response factor (ARF), transcription factors (TFs), chalcone synthase (CHS), and male sterility (MS) were responsible for microsporogenesis. Furthermore, a schematic diagram for functional interaction of DEGs from NAU-WA vs. NAU-WB library in radish plants was proposed. These results could provide new information on the dissection of the molecular mechanisms underlying microspore development and CMS occurrence in radish.

RNA Sequencing Reveals the Alteration of the Expression of Novel Genes in Ethanol-Treated Embryoid Bodies.

PubMed

Mandal, Chanchal; Kim, Sun Hwa; Chai, Jin Choul; Oh, Seon Mi; Lee, Young Seek; Jung, Kyoung Hwa; Chai, Young Gyu

2016-01-01

Fetal alcohol spectrum disorder is a collective term representing fetal abnormalities associated with maternal alcohol consumption. Prenatal alcohol exposure and related anomalies are well characterized, but the molecular mechanism behind this phenomenon is not well characterized. In this present study, our aim is to profile important genes that regulate cellular development during fetal development. Human embryonic carcinoma cells (NCCIT) are cultured to form embryoid bodies and then treated in the presence and absence of ethanol (50 mM). We employed RNA sequencing to profile differentially expressed genes in the ethanol-treated embryoid bodies from NCCIT vs. EB, NCCIT vs. EB+EtOH and EB vs. EB+EtOH data sets. A total of 632, 205 and 517 differentially expressed genes were identified from NCCIT vs. EB, NCCIT vs. EB+EtOH and EB vs. EB+EtOH, respectively. Functional annotation using bioinformatics tools reveal significant enrichment of differential cellular development and developmental disorders. Furthermore, a group of 42, 15 and 35 transcription factor-encoding genes are screened from all of the differentially expressed genes obtained from NCCIT vs. EB, NCCIT vs. EB+EtOH and EB vs. EB+EtOH, respectively. We validated relative gene expression levels of several transcription factors from these lists by quantitative real-time PCR. We hope that our study substantially contributes to the understanding of the molecular mechanism underlying the pathology of alcohol-mediated anomalies and ease further research.

A general method to eliminate laboratory induced recombinants during massive, parallel sequencing of cDNA library.

PubMed

Waugh, Caryll; Cromer, Deborah; Grimm, Andrew; Chopra, Abha; Mallal, Simon; Davenport, Miles; Mak, Johnson

2015-04-09

Massive, parallel sequencing is a potent tool for dissecting the regulation of biological processes by revealing the dynamics of the cellular RNA profile under different conditions. Similarly, massive, parallel sequencing can be used to reveal the complexity of viral quasispecies that are often found in the RNA virus infected host. However, the production of cDNA libraries for next-generation sequencing (NGS) necessitates the reverse transcription of RNA into cDNA and the amplification of the cDNA template using PCR, which may introduce artefact in the form of phantom nucleic acids species that can bias the composition and interpretation of original RNA profiles. Using HIV as a model we have characterised the major sources of error during the conversion of viral RNA to cDNA, namely excess RNA template and the RNaseH activity of the polymerase enzyme, reverse transcriptase. In addition we have analysed the effect of PCR cycle on detection of recombinants and assessed the contribution of transfection of highly similar plasmid DNA to the formation of recombinant species during the production of our control viruses. We have identified RNA template concentrations, RNaseH activity of reverse transcriptase, and PCR conditions as key parameters that must be carefully optimised to minimise chimeric artefacts. Using our optimised RT-PCR conditions, in combination with our modified PCR amplification procedure, we have developed a reliable technique for accurate determination of RNA species using NGS technology.

The Utility of the MMPI-2 with Pedophiles.

ERIC Educational Resources Information Center

Mann, Jim; And Others

1992-01-01

Examined Minnesota Multiphasic Personality Inventory-2 (MMPI-2) profiles of incarcerated pedophiles in state prisons (n=60), federal prisons (n=24), and military confinement facilities (n=25), each offering different educational and social composition. Multivariate statistics revealed that three groups' profiles were significantly different,…

Trophic Mode-Dependent Proteomic Analysis Reveals Functional Significance of Light-Independent Chlorophyll Synthesis in Synechocystis sp. PCC 6803.

PubMed

Fang, Longfa; Ge, Haitao; Huang, Xiahe; Liu, Ye; Lu, Min; Wang, Jinlong; Chen, Weiyang; Xu, Wu; Wang, Yingchun

2017-01-09

The photosynthetic model organism Synechocystis sp. PCC 6803 can grow in different trophic modes, depending on the availability of light and exogenous organic carbon source. However, how the protein profile changes to facilitate the cells differentially propagate in different modes has not been comprehensively investigated. Using isobaric labeling-based quantitative proteomics, we simultaneously identified and quantified 45% Synechocystis proteome across four different trophic modes, i.e., autotrophic, heterotrophic, photoheterotrophic, and mixotrophic modes. Among the 155 proteins that are differentially expressed across four trophic modes, proteins involved in nitrogen assimilation and light-independent chlorophyll synthesis are dramatically upregulated in the mixotrophic mode, concomitant with a dramatic increase of P II phosphorylation that senses carbon and nitrogen assimilation status. Moreover, functional study using a mutant defective in light-independent chlorophyll synthesis revealed that this pathway is important for chlorophyll accumulation under a cycled light/dark illumination regime, a condition mimicking day/night cycles in certain natural habitats. Collectively, these results provide the most comprehensive information on trophic mode-dependent protein expression in cyanobacterium, and reveal the functional significance of light-independent chlorophyll synthesis in trophic growth. Copyright © 2017 The Author. Published by Elsevier Inc. All rights reserved.

Multiple Roles of Integrin-Linked Kinase in Epidermal Development, Maturation and Pigmentation Revealed by Molecular Profiling

PubMed Central

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

2012-01-01

Integrin-linked kinase (ILK) is an important scaffold protein that mediates a variety of cellular responses to integrin stimulation by extracellular matrix proteins. Mice with epidermis-restricted inactivation of the Ilk gene exhibit pleiotropic phenotypic defects, including impaired hair follicle morphogenesis, reduced epidermal adhesion to the basement membrane, compromised epidermal integrity, as well as wasting and failure to thrive leading to perinatal death. To better understand the underlying molecular mechanisms that cause such a broad range of alterations, we investigated the impact of Ilk gene inactivation on the epidermis transcriptome. Microarray analysis showed over 700 differentially regulated mRNAs encoding proteins involved in multiple aspects of epidermal function, including keratinocyte differentiation and barrier formation, inflammation, regeneration after injury, and fundamental epidermal developmental pathways. These studies also revealed potential effects on genes not previously implicated in ILK functions, including those important for melanocyte and melanoblast development and function, regulation of cytoskeletal dynamics, and homeobox genes. This study shows that ILK is a critical regulator of multiple aspects of epidermal function and homeostasis, and reveals the previously unreported involvement of ILK not only in epidermal differentiation and barrier formation, but also in melanocyte genesis and function. PMID:22574216

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

PubMed

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

2012-01-01

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

GCMS investigation of volatile compounds in green coffee affected by potato taste defect and the Antestia bug.

PubMed

Jackels, Susan C; Marshall, Eric E; Omaiye, Angelica G; Gianan, Robert L; Lee, Fabrice T; Jackels, Charles F

2014-10-22

Potato taste defect (PTD) is a flavor defect in East African coffee associated with Antestiopsis orbitalis feeding and 3-isopropyl-2-methoxypyrazine (IPMP) in the coffee. To elucidate the manifestation of PTD, surface and interior volatile compounds of PTD and non-PTD green coffees were sampled by headspace solid phase microextraction and analyzed by gas chromatography mass spectrometry. Principal component analysis of the chromatographic data revealed a profile of surface volatiles distinguishing PTD from non-PTD coffees dominated by tridecane, dodecane, and tetradecane. While not detected in surface volatiles, IPMP was found in interior volatiles of PTD coffee. Desiccated antestia bugs were analyzed by GCMS, revealing that the three most prevalent volatiles were tridecane, dodecane, and tetradecane, as was found in the surface profile PTD coffee. Coffee having visible insect damage exhibited both a PTD surface volatile profile and IPMP in interior volatiles, supporting the hypothesis linking antestia bug feeding activity with PTD profile compounds on the surface and IPMP in the interior of the beans.

Molecular profiles of pre- and postoperative breast cancer tumours reveal differentially expressed genes.

PubMed

Riis, Margit L H; Lüders, Torben; Markert, Elke K; Haakensen, Vilde D; Nesbakken, Anne-Jorun; Kristensen, Vessela N; Bukholm, Ida R K

2012-01-01

Gene expression studies on breast cancer have generally been performed on tissue obtained at the time of surgery. In this study, we have compared the gene expression profiles in preoperative tissue (core needle biopsies) while tumor is still in its normal milieu to postoperative tissue from the same tumor obtained during surgery. Thirteen patients were included of which eleven had undergone sentinel node diagnosis procedure before operation. Microarray gene expression analysis was performed using total RNA from all the samples. Paired significance analysis of microarrays revealed 228 differently expressed genes, including several early response stress-related genes such as members of the fos and jun families as well as genes of which the expression has previously been associated with cancer. The expression profiles found in the analyses of breast cancer tissue must be evaluated with caution. Different profiles may simply be the result of differences in the surgical trauma and timing of when samples are taken and not necessarily associated with tumor biology.

Molecular Profiles of Pre- and Postoperative Breast Cancer Tumours Reveal Differentially Expressed Genes

PubMed Central

Riis, Margit L. H.; Lüders, Torben; Markert, Elke K.; Haakensen, Vilde D.; Nesbakken, Anne-Jorun; Kristensen, Vessela N.; Bukholm, Ida R. K.

2012-01-01

Gene expression studies on breast cancer have generally been performed on tissue obtained at the time of surgery. In this study, we have compared the gene expression profiles in preoperative tissue (core needle biopsies) while tumor is still in its normal milieu to postoperative tissue from the same tumor obtained during surgery. Thirteen patients were included of which eleven had undergone sentinel node diagnosis procedure before operation. Microarray gene expression analysis was performed using total RNA from all the samples. Paired significance analysis of microarrays revealed 228 differently expressed genes, including several early response stress-related genes such as members of the fos and jun families as well as genes of which the expression has previously been associated with cancer. The expression profiles found in the analyses of breast cancer tissue must be evaluated with caution. Different profiles may simply be the result of differences in the surgical trauma and timing of when samples are taken and not necessarily associated with tumor biology. PMID:23227362

Gene expression profile analysis of Ligon lintless-1 (Li1) mutant reveals important genes and pathways in cotton leaf and fiber development.

PubMed

Ding, Mingquan; Jiang, Yurong; Cao, Yuefen; Lin, Lifeng; He, Shae; Zhou, Wei; Rong, Junkang

2014-02-10

Ligon lintless-1 (Li1) is a monogenic dominant mutant of Gossypium hirsutum (upland cotton) with a phenotype of impaired vegetative growth and short lint fibers. Despite years of research involving genetic mapping and gene expression profile analysis of Li1 mutant ovule tissues, the gene remains uncloned and the underlying pathway of cotton fiber elongation is still unclear. In this study, we report the whole genome-level deep-sequencing analysis of leaf tissues of the Li1 mutant. Differentially expressed genes in leaf tissues of mutant versus wild-type (WT) plants are identified, and the underlying pathways and potential genes that control leaf and fiber development are inferred. The results show that transcription factors AS2, YABBY5, and KANDI-like are significantly differentially expressed in mutant tissues compared with WT ones. Interestingly, several fiber development-related genes are found in the downregulated gene list of the mutant leaf transcriptome. These genes include heat shock protein family, cytoskeleton arrangement, cell wall synthesis, energy, H2O2 metabolism-related genes, and WRKY transcription factors. This finding suggests that the genes are involved in leaf morphology determination and fiber elongation. The expression data are also compared with the previously published microarray data of Li1 ovule tissues. Comparative analysis of the ovule transcriptomes of Li1 and WT reveals that a number of pathways important for fiber elongation are enriched in the downregulated gene list at different fiber development stages (0, 6, 9, 12, 15, 18dpa). Differentially expressed genes identified in both leaf and fiber samples are aligned with cotton whole genome sequences and combined with the genetic fine mapping results to identify a list of candidate genes for Li1. Copyright © 2013 Elsevier B.V. All rights reserved.

Integrated community profiling indicates long-term temporal stability of the predominant faecal microbiota in captive cheetahs.

PubMed

Becker, Anne A M J; Janssens, Geert P J; Snauwaert, Cindy; Hesta, Myriam; Huys, Geert

2015-01-01

Understanding the symbiotic relationship between gut microbes and their animal host requires characterization of the core microbiota across populations and in time. Especially in captive populations of endangered wildlife species such as the cheetah (Acinonyx jubatus), this knowledge is a key element to enhance feeding strategies and reduce gastrointestinal disorders. In order to investigate the temporal stability of the intestinal microbiota in cheetahs under human care, we conducted a longitudinal study over a 3-year period with bimonthly faecal sampling of 5 cheetahs housed in two European zoos. For this purpose, an integrated 16S rRNA DGGE-clone library approach was used in combination with a series of real-time PCR assays. Our findings disclosed a stable faecal microbiota, beyond intestinal community variations that were detected between zoo sample sets or between animals. The core of this microbiota was dominated by members of Clostridium clusters I, XI and XIVa, with mean concentrations ranging from 7.5-9.2 log10 CFU/g faeces and with significant positive correlations between these clusters (P<0.05), and by Lactobacillaceae. Moving window analysis of DGGE profiles revealed 23.3-25.6% change between consecutive samples for four of the cheetahs. The fifth animal in the study suffered from intermediate episodes of vomiting and diarrhea during the monitoring period and exhibited remarkably more change (39.4%). This observation may reflect the temporary impact of perturbations such as the animal's compromised health, antibiotic administration or a combination thereof, which temporarily altered the relative proportions of Clostridium clusters I and XIVa. In conclusion, this first long-term monitoring study of the faecal microbiota in feline strict carnivores not only reveals a remarkable compositional stability of this ecosystem, but also shows a qualitative and quantitative similarity in a defined set of faecal bacterial lineages across the five animals under study that may typify the core phylogenetic microbiome of cheetahs.

Integrated Community Profiling Indicates Long-Term Temporal Stability of the Predominant Faecal Microbiota in Captive Cheetahs

PubMed Central

Becker, Anne A. M. J.; Janssens, Geert P. J.; Snauwaert, Cindy; Hesta, Myriam; Huys, Geert

2015-01-01

Understanding the symbiotic relationship between gut microbes and their animal host requires characterization of the core microbiota across populations and in time. Especially in captive populations of endangered wildlife species such as the cheetah (Acinonyx jubatus), this knowledge is a key element to enhance feeding strategies and reduce gastrointestinal disorders. In order to investigate the temporal stability of the intestinal microbiota in cheetahs under human care, we conducted a longitudinal study over a 3-year period with bimonthly faecal sampling of 5 cheetahs housed in two European zoos. For this purpose, an integrated 16S rRNA DGGE-clone library approach was used in combination with a series of real-time PCR assays. Our findings disclosed a stable faecal microbiota, beyond intestinal community variations that were detected between zoo sample sets or between animals. The core of this microbiota was dominated by members of Clostridium clusters I, XI and XIVa, with mean concentrations ranging from 7.5-9.2 log10 CFU/g faeces and with significant positive correlations between these clusters (P<0.05), and by Lactobacillaceae. Moving window analysis of DGGE profiles revealed 23.3-25.6% change between consecutive samples for four of the cheetahs. The fifth animal in the study suffered from intermediate episodes of vomiting and diarrhea during the monitoring period and exhibited remarkably more change (39.4%). This observation may reflect the temporary impact of perturbations such as the animal’s compromised health, antibiotic administration or a combination thereof, which temporarily altered the relative proportions of Clostridium clusters I and XIVa. In conclusion, this first long-term monitoring study of the faecal microbiota in feline strict carnivores not only reveals a remarkable compositional stability of this ecosystem, but also shows a qualitative and quantitative similarity in a defined set of faecal bacterial lineages across the five animals under study that may typify the core phylogenetic microbiome of cheetahs. PMID:25905625

Defects in Mitochondrial Dynamics and Metabolomic Signatures of Evolving Energetic Stress in Mouse Models of Familial Alzheimer's Disease

PubMed Central

Trushina, Eugenia; Nemutlu, Emirhan; Zhang, Song; Christensen, Trace; Camp, Jon; Mesa, Janny; Siddiqui, Ammar; Tamura, Yasushi; Sesaki, Hiromi; Wengenack, Thomas M.; Dzeja, Petras P.; Poduslo, Joseph F.

2012-01-01

Background The identification of early mechanisms underlying Alzheimer's Disease (AD) and associated biomarkers could advance development of new therapies and improve monitoring and predicting of AD progression. Mitochondrial dysfunction has been suggested to underlie AD pathophysiology, however, no comprehensive study exists that evaluates the effect of different familial AD (FAD) mutations on mitochondrial function, dynamics, and brain energetics. Methods and Findings We characterized early mitochondrial dysfunction and metabolomic signatures of energetic stress in three commonly used transgenic mouse models of FAD. Assessment of mitochondrial motility, distribution, dynamics, morphology, and metabolomic profiling revealed the specific effect of each FAD mutation on the development of mitochondrial stress and dysfunction. Inhibition of mitochondrial trafficking was characteristic for embryonic neurons from mice expressing mutant human presenilin 1, PS1(M146L) and the double mutation of human amyloid precursor protein APP(Tg2576) and PS1(M146L) contributing to the increased susceptibility of neurons to excitotoxic cell death. Significant changes in mitochondrial morphology were detected in APP and APP/PS1 mice. All three FAD models demonstrated a loss of the integrity of synaptic mitochondria and energy production. Metabolomic profiling revealed mutation-specific changes in the levels of metabolites reflecting altered energy metabolism and mitochondrial dysfunction in brains of FAD mice. Metabolic biomarkers adequately reflected gender differences similar to that reported for AD patients and correlated well with the biomarkers currently used for diagnosis in humans. Conclusions Mutation-specific alterations in mitochondrial dynamics, morphology and function in FAD mice occurred prior to the onset of memory and neurological phenotype and before the formation of amyloid deposits. Metabolomic signatures of mitochondrial stress and altered energy metabolism indicated alterations in nucleotide, Krebs cycle, energy transfer, carbohydrate, neurotransmitter, and amino acid metabolic pathways. Mitochondrial dysfunction, therefore, is an underlying event in AD progression, and FAD mouse models provide valuable tools to study early molecular mechanisms implicated in AD. PMID:22393443

Translational Upregulation of an Individual p21Cip1 Transcript Variant by GCN2 Regulates Cell Proliferation and Survival under Nutrient Stress

PubMed Central

Lehman, Stacey L.; Cerniglia, George J.; Johannes, Gregg J.; Ye, Jiangbin; Ryeom, Sandra; Koumenis, Constantinos

2015-01-01

Multiple transcripts encode for the cell cycle inhibitor p21Cip1. These transcripts produce identical proteins but differ in their 5’ untranslated regions (UTRs). Although several stresses that induce p21 have been characterized, the mechanisms regulating the individual transcript variants and their functional significance are unknown. Here we demonstrate through 35S labeling, luciferase reporter assays, and polysome transcript profiling that activation of the Integrated Stress Response (ISR) kinase GCN2 selectively upregulates the translation of a p21 transcript variant containing 5’ upstream open reading frames (uORFs) through phosphorylation of the eukaryotic translation initiation factor eIF2α. Mutational analysis reveals that the uORFs suppress translation under basal conditions, but promote translation under stress. Functionally, ablation of p21 ameliorates G1/S arrest and reduces cell survival in response to GCN2 activation. These findings uncover a novel mechanism of p21 post-transcriptional regulation, offer functional significance for the existence of multiple p21 transcripts, and support a key role for GCN2 in regulating the cell cycle under stress. PMID:26102367