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Sample records for level phylogenetic alterations

  1. Phylogenetic diversity of plants alters the effect of species richness on invertebrate herbivory.

    PubMed

    Dinnage, Russell

    2013-01-01

    Long-standing ecological theory proposes that diverse communities of plants should experience a decrease in herbivory. Yet previous empirical examinations of this hypothesis have revealed that plant species richness increases herbivory in just as many systems as it decreases it. In this study, I ask whether more insight into the role of plant diversity in promoting or suppressing herbivory can be gained by incorporating information about the evolutionary history of species in a community. In an old field system in southern Ontario, I surveyed communities of plants and measured levels of leaf damage on 27 species in 38 plots. I calculated a measure of phylogenetic diversity (PSE) that encapsulates information about the amount of evolutionary history represented in each of the plots and looked for a relationship between levels of herbivory and both species richness and phylogenetic diversity using a generalized linear mixed model (GLMM) that could account for variation in herbivory levels between species. I found that species richness was positively associated with herbivore damage at the plot-level, in keeping with the results from several other recent studies on this question. On the other hand, phylogenetic diversity was associated with decreased herbivory. Importantly, there was also an interaction between species richness and phylogenetic diversity, such that plots with the highest levels of herbivory were plots which had many species but only if those species tended to be closely related to one another. I propose that these results are the consequence of interactions with herbivores whose diets are phylogenetically specialized (for which I introduce the term cladophage), and how phylogenetic diversity may alter their realized host ranges. These results suggest that incorporating a phylogenetic perspective can add valuable additional insight into the role of plant diversity in explaining or predicting levels of herbivory at a whole-community scale.

  2. Convergent phylogenetic and functional responses to altered fire regimes in mesic savanna grasslands of North America and South Africa.

    PubMed

    Forrestel, Elisabeth J; Donoghue, Michael J; Smith, Melinda D

    2014-08-01

    The importance of fire in the creation and maintenance of mesic grassland communities is well recognized. Improved understanding of how grasses--the dominant clade in these important ecosystems--will respond to alterations in fire regimes is needed in the face of anthropogenically driven climate and land-use change. Here, we examined how grass communities shift in response to experimentally manipulated fire regimes at multiple levels of community diversity--taxonomic, phylogenetic and functional--in C4-dominanted mesic savanna grassland sites with similar structure and physiognomy, yet disparate biogeographic histories. We found that the grass communities were similar in their phylogenetic response and aspects of their functional response to high fire frequency. Both sites exhibited phylogenetic clustering of highly abundant species in annually burned plots, driven by species of the Andropogoneae, and a narrow range of functional strategies associated with rapid post-fire regeneration in a high-light, nitrogen-limited environment. By examining multiple facets of diversity in a comparative context, we identified convergent phylogenetic and functional responses to altered fire regimes in two mesic savanna grasslands. Our results highlight the importance of a common filtering process associated with fire that is consistent across grasslands of disparate biogeographic histories and taxonomic representation.

  3. Comparative Analysis of Begonia Plastid Genomes and Their Utility for Species-Level Phylogenetics.

    PubMed

    Harrison, Nicola; Harrison, Richard J; Kidner, Catherine A

    2016-01-01

    Recent, rapid radiations make species-level phylogenetics difficult to resolve. We used a multiplexed, high-throughput sequencing approach to identify informative genomic regions to resolve phylogenetic relationships at low taxonomic levels in Begonia from a survey of sixteen species. A long-range PCR method was used to generate draft plastid genomes to provide a strong phylogenetic backbone, identify fast evolving regions and provide informative molecular markers for species-level phylogenetic studies in Begonia.

  4. Comparative Analysis of Begonia Plastid Genomes and Their Utility for Species-Level Phylogenetics

    PubMed Central

    Harrison, Nicola; Harrison, Richard J.

    2016-01-01

    Recent, rapid radiations make species-level phylogenetics difficult to resolve. We used a multiplexed, high-throughput sequencing approach to identify informative genomic regions to resolve phylogenetic relationships at low taxonomic levels in Begonia from a survey of sixteen species. A long-range PCR method was used to generate draft plastid genomes to provide a strong phylogenetic backbone, identify fast evolving regions and provide informative molecular markers for species-level phylogenetic studies in Begonia. PMID:27058864

  5. Erosion of phylogenetic signal in tunicate mitochondrial genomes on different levels of analysis.

    PubMed

    Stach, Thomas; Braband, Anke; Podsiadlowski, Lars

    2010-06-01

    The molecular phylogenetic position of Tunicata and internal interrelationship of higher tunicate taxa is controversial. High substitution rates and extreme gene order variability hamper phylogenetic analyses. We describe the sequence and organization of the mitochondrial genome of the aplousobranch ascidian Clavelina lepadiformis and use mitochondrial genomes to investigate phylogenetic information content on different molecular levels of comparison. Despite agreement in phylogenetic analyses of nucleotide and amino acid sequences, split analyses revealed little phylogenetic signal. Split analyses on molecular data sets deemed increasingly conservative, demonstrated that the lack of signal pervades all levels and that it is Tunicata the taxon of interest that introduces noise in the data sets. The strongest signal present in our molecular data sets as revealed by split analyses is not present in the optimal cladograms and supports a sister group relationship between cephalochordates and craniates. Phylogenetic analysis of gene order using common interval algorithms shows that phylogenetic signal is also eroded in respect of gene positions. Even functional constraints, such as partial gene overlap as exemplified in the case of the commonly observed adjacency between cox2 and cytb are subjected to homoplasy. However, rare phylogenetic events like this hold some promise to retain phylogenetic information even in such cases of extreme variability. We therefore caution to rely on sequence analysis alone and recommend investigation into the signal content of molecular data sets in order to assess the strength of phylogenetic signal.

  6. Phylogenetic diversity and co-evolutionary signals among trophic levels change across a habitat edge.

    PubMed

    Peralta, Guadalupe; Frost, Carol M; Didham, Raphael K; Varsani, Arvind; Tylianakis, Jason M

    2015-03-01

    Incorporating the evolutionary history of species into community ecology enhances understanding of community composition, ecosystem functioning and responses to environmental changes. Phylogenetic history might partly explain the impact of fragmentation and land-use change on assemblages of interacting organisms and even determine potential cascading effects across trophic levels. However, it remains unclear whether phylogenetic diversity of basal resources is reflected at higher trophic levels in the food web. In particular, phylogenetic determinants of community structure have never been incorporated into habitat edge studies, even though edges are recognized as key factors affecting communities in fragmented landscapes. Here, we test whether phylogenetic diversity at different trophic levels (plants, herbivores and parasitoids) and signals of co-evolution (i.e. phylogenetic congruence) among interacting trophic levels change across an edge gradient between native and plantation forests. To ascertain whether there is a signal of co-evolution across trophic levels, we test whether related consumer species generally feed on related resource species. We found differences across trophic levels in how their phylogenetic diversity responded to the habitat edge gradient. Plant and native parasitoid phylogenetic diversity changed markedly across habitats, while phylogenetic variability of herbivores (which were predominantly native) did not change across habitats, though phylogenetic evenness declined in plantation interiors. Related herbivore species did not appear to feed disproportionately on related plant species (i.e. there was no signal of co-evolution) even when considering only native species, potentially due to the high trophic generality of herbivores. However, related native parasitoid species tended to feed on related herbivore species, suggesting the presence of a co-evolutionary signal at higher trophic levels. Moreover, this signal was stronger in

  7. Disturbance alters the phylogenetic composition and structure of plant communities in an old field system.

    PubMed

    Dinnage, Russell

    2009-09-18

    The changes in phylogenetic composition and structure of communities during succession following disturbance can give us insights into the forces that are shaping communities over time. In abandoned agricultural fields, community composition changes rapidly when a field is plowed, and is thought to reflect a relaxation of competition due to the elimination of dominant species which take time to re-establish. Competition can drive phylogenetic overdispersion, due to phylogenetic conservation of 'niche' traits that allow species to partition resources. Therefore, undisturbed old field communities should exhibit higher phylogenetic dispersion than recently disturbed systems, which should be relatively 'clustered' with respect to phylogenetic relationships. Several measures of phylogenetic structure between plant communities were measured in recently plowed areas and nearby 'undisturbed' sites. There was no difference in the absolute values of these measures between disturbed and 'undisturbed' sites. However, there was a difference in the 'expected' phylogenetic structure between habitats, leading to significantly lower than expected phylogenetic diversity in disturbed plots, and no difference from random expectation in 'undisturbed' plots. This suggests that plant species characteristic of each habitat are fairly evenly distributed on the shared species pool phylogeny, but that once the initial sorting of species into the two habitat types has occurred, the processes operating on them affect each habitat differently. These results were consistent with an analysis of correlation between phylogenetic distance and co-occurrence indices of species pairs in the two habitat types. This study supports the notion that disturbed plots are more clustered than expected, rather than 'undisturbed' plots being more overdispersed, suggesting that disturbed plant communities are being more strongly influenced by environmental filtering of conserved niche traits.

  8. Increasing phylogenetic resolution at low taxonomic levels using massively parallel sequencing of chloroplast genomes

    PubMed Central

    2009-01-01

    Background Molecular evolutionary studies share the common goal of elucidating historical relationships, and the common challenge of adequately sampling taxa and characters. Particularly at low taxonomic levels, recent divergence, rapid radiations, and conservative genome evolution yield limited sequence variation, and dense taxon sampling is often desirable. Recent advances in massively parallel sequencing make it possible to rapidly obtain large amounts of sequence data, and multiplexing makes extensive sampling of megabase sequences feasible. Is it possible to efficiently apply massively parallel sequencing to increase phylogenetic resolution at low taxonomic levels? Results We reconstruct the infrageneric phylogeny of Pinus from 37 nearly-complete chloroplast genomes (average 109 kilobases each of an approximately 120 kilobase genome) generated using multiplexed massively parallel sequencing. 30/33 ingroup nodes resolved with ≥ 95% bootstrap support; this is a substantial improvement relative to prior studies, and shows massively parallel sequencing-based strategies can produce sufficient high quality sequence to reach support levels originally proposed for the phylogenetic bootstrap. Resampling simulations show that at least the entire plastome is necessary to fully resolve Pinus, particularly in rapidly radiating clades. Meta-analysis of 99 published infrageneric phylogenies shows that whole plastome analysis should provide similar gains across a range of plant genera. A disproportionate amount of phylogenetic information resides in two loci (ycf1, ycf2), highlighting their unusual evolutionary properties. Conclusion Plastome sequencing is now an efficient option for increasing phylogenetic resolution at lower taxonomic levels in plant phylogenetic and population genetic analyses. With continuing improvements in sequencing capacity, the strategies herein should revolutionize efforts requiring dense taxon and character sampling, such as phylogeographic

  9. Ecosystem functions across trophic levels are linked to functional and phylogenetic diversity.

    PubMed

    Thompson, Patrick L; Davies, T Jonathan; Gonzalez, Andrew

    2015-01-01

    In experimental systems, it has been shown that biodiversity indices based on traits or phylogeny can outperform species richness as predictors of plant ecosystem function. However, it is unclear whether this pattern extends to the function of food webs in natural ecosystems. Here we tested whether zooplankton functional and phylogenetic diversity explains the functioning of 23 natural pond communities. We used two measures of ecosystem function: (1) zooplankton community biomass and (2) phytoplankton abundance (Chl a). We tested for diversity-ecosystem function relationships within and across trophic levels. We found a strong correlation between zooplankton diversity and ecosystem function, whereas local environmental conditions were less important. Further, the positive diversity-ecosystem function relationships were more pronounced for measures of functional and phylogenetic diversity than for species richness. Zooplankton and phytoplankton biomass were best predicted by different indices, suggesting that the two functions are dependent upon different aspects of diversity. Zooplankton community biomass was best predicted by zooplankton trait-based functional richness, while phytoplankton abundance was best predicted by zooplankton phylogenetic diversity. Our results suggest that the positive relationship between diversity and ecosystem function can extend across trophic levels in natural environments, and that greater insight into variation in ecosystem function can be gained by combining functional and phylogenetic diversity measures.

  10. Specimen-level phylogenetics in paleontology using the Fossilized Birth-Death model with sampled ancestors

    PubMed Central

    2017-01-01

    Bayesian phylogenetic methods integrating simultaneously morphological and stratigraphic information have been applied increasingly among paleontologists. Most of these studies have used Bayesian methods as an alternative to the widely-used parsimony analysis, to infer macroevolutionary patterns and relationships among species-level or higher taxa. Among recently introduced Bayesian methodologies, the Fossilized Birth-Death (FBD) model allows incorporation of hypotheses on ancestor-descendant relationships in phylogenetic analyses including fossil taxa. Here, the FBD model is used to infer the relationships among an ingroup formed exclusively by fossil individuals, i.e., dipnoan tooth plates from four localities in the Ain el Guettar Formation of Tunisia. Previous analyses of this sample compared the results of phylogenetic analysis using parsimony with stratigraphic methods, inferred a high diversity (five or more genera) in the Ain el Guettar Formation, and interpreted it as an artifact inflated by depositional factors. In the analysis performed here, the uncertainty on the chronostratigraphic relationships among the specimens was included among the prior settings. The results of the analysis confirm the referral of most of the specimens to the taxa Asiatoceratodus, Equinoxiodus, Lavocatodus and Neoceratodus, but reject those to Ceratodus and Ferganoceratodus. The resulting phylogeny constrained the evolution of the Tunisian sample exclusively in the Early Cretaceous, contrasting with the previous scenario inferred by the stratigraphically-calibrated topology resulting from parsimony analysis. The phylogenetic framework also suggests that (1) the sampled localities are laterally equivalent, (2) but three localities are restricted to the youngest part of the section; both results are in agreement with previous stratigraphic analyses of these localities. The FBD model of specimen-level units provides a novel tool for phylogenetic inference among fossils but also

  11. Specimen-level phylogenetics in paleontology using the Fossilized Birth-Death model with sampled ancestors.

    PubMed

    Cau, Andrea

    2017-01-01

    Bayesian phylogenetic methods integrating simultaneously morphological and stratigraphic information have been applied increasingly among paleontologists. Most of these studies have used Bayesian methods as an alternative to the widely-used parsimony analysis, to infer macroevolutionary patterns and relationships among species-level or higher taxa. Among recently introduced Bayesian methodologies, the Fossilized Birth-Death (FBD) model allows incorporation of hypotheses on ancestor-descendant relationships in phylogenetic analyses including fossil taxa. Here, the FBD model is used to infer the relationships among an ingroup formed exclusively by fossil individuals, i.e., dipnoan tooth plates from four localities in the Ain el Guettar Formation of Tunisia. Previous analyses of this sample compared the results of phylogenetic analysis using parsimony with stratigraphic methods, inferred a high diversity (five or more genera) in the Ain el Guettar Formation, and interpreted it as an artifact inflated by depositional factors. In the analysis performed here, the uncertainty on the chronostratigraphic relationships among the specimens was included among the prior settings. The results of the analysis confirm the referral of most of the specimens to the taxa Asiatoceratodus, Equinoxiodus, Lavocatodus and Neoceratodus, but reject those to Ceratodus and Ferganoceratodus. The resulting phylogeny constrained the evolution of the Tunisian sample exclusively in the Early Cretaceous, contrasting with the previous scenario inferred by the stratigraphically-calibrated topology resulting from parsimony analysis. The phylogenetic framework also suggests that (1) the sampled localities are laterally equivalent, (2) but three localities are restricted to the youngest part of the section; both results are in agreement with previous stratigraphic analyses of these localities. The FBD model of specimen-level units provides a novel tool for phylogenetic inference among fossils but also

  12. Arbuscular mycorrhizal fungal phylogenetic groups differ in affecting host plants along heavy metal levels.

    PubMed

    He, Lei; Yang, Haishui; Yu, Zhenxing; Tang, Jianjun; Xu, Ligen; Chen, Xin

    2014-10-01

    Arbuscular mycorrhizal fungi (AMF) are important components of soil microbial communities, and play important role in plant growth. However, the effects of AMF phylogenetic groups (Glomeraceae and non-Glomeraceae) on host plant under various heavy metal levels are not clear. Here we conducted a meta-analysis to compare symbiotic relationship between AMF phylogenetic groups (Glomeraceae and non-Glomeraceae) and host plant functional groups (herbs vs. trees, and non-legumes vs. legumes) at three heavy metal levels. In the meta-analysis, we calculate the effect size (ln(RR)) by taking the natural logarithm of the response ratio of inoculated to non-inoculated shoot biomass from each study. We found that the effect size of Glomeraceae increased, but the effect size of non-Glomeraceae decreased under high level of heavy metal compared to low level. According to the effect size, both Glomeraceae and non-Glomeraceae promoted host plant growth, but had different effects under various heavy metal levels. Glomeraceae provided more benefit to host plants than non-Glomeraceae did under heavy metal condition, while non-Glomeraceae provided more benefit to host plants than Glomeraceae did under no heavy metal. AMF phylogenetic groups also differed in promoting plant functional groups under various heavy metal levels. Interacting with Glomeraceae, herbs and legumes grew better than trees and non-legumes did under high heavy metal level, while trees and legumes grew better than herbs and non-legumes did under medium heavy metal level. Interacting with non-Glomeraceae, herbs and legumes grew better than trees and non-legumes did under no heavy metal. We suggested that the combination of legume with Glomeraceae could be a useful way in the remediation of heavy metal polluted environment.

  13. Reconstruction of Family-Level Phylogenetic Relationships within Demospongiae (Porifera) Using Nuclear Encoded Housekeeping Genes

    PubMed Central

    Hill, Malcolm S.; Hill, April L.; Lopez, Jose; Peterson, Kevin J.; Pomponi, Shirley; Diaz, Maria C.; Thacker, Robert W.; Adamska, Maja; Boury-Esnault, Nicole; Cárdenas, Paco; Chaves-Fonnegra, Andia; Danka, Elizabeth; De Laine, Bre-Onna; Formica, Dawn; Hajdu, Eduardo; Lobo-Hajdu, Gisele; Klontz, Sarah; Morrow, Christine C.; Patel, Jignasa; Picton, Bernard; Pisani, Davide; Pohlmann, Deborah; Redmond, Niamh E.; Reed, John; Richey, Stacy; Riesgo, Ana; Rubin, Ewelina; Russell, Zach; Rützler, Klaus; Sperling, Erik A.; di Stefano, Michael; Tarver, James E.; Collins, Allen G.

    2013-01-01

    Background Demosponges are challenging for phylogenetic systematics because of their plastic and relatively simple morphologies and many deep divergences between major clades. To improve understanding of the phylogenetic relationships within Demospongiae, we sequenced and analyzed seven nuclear housekeeping genes involved in a variety of cellular functions from a diverse group of sponges. Methodology/Principal Findings We generated data from each of the four sponge classes (i.e., Calcarea, Demospongiae, Hexactinellida, and Homoscleromorpha), but focused on family-level relationships within demosponges. With data for 21 newly sampled families, our Maximum Likelihood and Bayesian-based approaches recovered previously phylogenetically defined taxa: Keratosap, Myxospongiaep, Spongillidap, Haploscleromorphap (the marine haplosclerids) and Democlaviap. We found conflicting results concerning the relationships of Keratosap and Myxospongiaep to the remaining demosponges, but our results strongly supported a clade of Haploscleromorphap+Spongillidap+Democlaviap. In contrast to hypotheses based on mitochondrial genome and ribosomal data, nuclear housekeeping gene data suggested that freshwater sponges (Spongillidap) are sister to Haploscleromorphap rather than part of Democlaviap. Within Keratosap, we found equivocal results as to the monophyly of Dictyoceratida. Within Myxospongiaep, Chondrosida and Verongida were monophyletic. A well-supported clade within Democlaviap, Tetractinellidap, composed of all sampled members of Astrophorina and Spirophorina (including the only lithistid in our analysis), was consistently revealed as the sister group to all other members of Democlaviap. Within Tetractinellidap, we did not recover monophyletic Astrophorina or Spirophorina. Our results also reaffirmed the monophyly of order Poecilosclerida (excluding Desmacellidae and Raspailiidae), and polyphyly of Hadromerida and Halichondrida. Conclusions/Significance These results, using an

  14. Phylogenetic Classification at Generic Level in the Absence of Distinct Phylogenetic Patterns of Phenotypical Variation: A Case Study in Graphidaceae (Ascomycota)

    PubMed Central

    Parnmen, Sittiporn; Lücking, Robert; Lumbsch, H. Thorsten

    2012-01-01

    Molecular phylogenies often reveal that taxa circumscribed by phenotypical characters are not monophyletic. While re-examination of phenotypical characters often identifies the presence of characters characterizing clades, there is a growing number of studies that fail to identify diagnostic characters, especially in organismal groups lacking complex morphologies. Taxonomists then can either merge the groups or split taxa into smaller entities. Due to the nature of binomial nomenclature, this decision is of special importance at the generic level. Here we propose a new approach to choose among classification alternatives using a combination of morphology-based phylogenetic binning and a multiresponse permutation procedure to test for morphological differences among clades. We illustrate the use of this method in the tribe Thelotremateae focusing on the genus Chapsa, a group of lichenized fungi in which our phylogenetic estimate is in conflict with traditional classification and the morphological and chemical characters do not show a clear phylogenetic pattern. We generated 75 new DNA sequences of mitochondrial SSU rDNA, nuclear LSU rDNA and the protein-coding RPB2. This data set was used to infer phylogenetic estimates using maximum likelihood and Bayesian approaches. The genus Chapsa was found to be polyphyletic, forming four well-supported clades, three of which clustering into one unsupported clade, and the other, supported clade forming two supported subclades. While these clades cannot be readily separated morphologically, the combined binning/multiresponse permutation procedure showed that accepting the four clades as different genera each reflects the phenotypical pattern significantly better than accepting two genera (or five genera if splitting the first clade). Another species within the Thelotremateae, Thelotrema petractoides, a unique taxon with carbonized excipulum resembling Schizotrema, was shown to fall outside Thelotrema. Consequently, the new

  15. Family-Level Sampling of Mitochondrial Genomes in Coleoptera: Compositional Heterogeneity and Phylogenetics.

    PubMed

    Timmermans, Martijn J T N; Barton, Christopher; Haran, Julien; Ahrens, Dirk; Culverwell, C Lorna; Ollikainen, Alison; Dodsworth, Steven; Foster, Peter G; Bocak, Ladislav; Vogler, Alfried P

    2015-12-08

    Mitochondrial genomes are readily sequenced with recent technology and thus evolutionary lineages can be densely sampled. This permits better phylogenetic estimates and assessment of potential biases resulting from heterogeneity in nucleotide composition and rate of change. We gathered 245 mitochondrial sequences for the Coleoptera representing all 4 suborders, 15 superfamilies of Polyphaga, and altogether 97 families, including 159 newly sequenced full or partial mitogenomes. Compositional heterogeneity greatly affected 3rd codon positions, and to a lesser extent the 1st and 2nd positions, even after RY coding. Heterogeneity also affected the encoded protein sequence, in particular in the nad2, nad4, nad5, and nad6 genes. Credible tree topologies were obtained with the nhPhyML ("nonhomogeneous") algorithm implementing a model for branch-specific equilibrium frequencies. Likelihood searches using RAxML were improved by data partitioning by gene and codon position. Finally, the PhyloBayes software, which allows different substitution processes for amino acid replacement at various sites, produced a tree that best matched known higher level taxa and defined basal relationships in Coleoptera. After rooting with Neuropterida outgroups, suborder relationships were resolved as (Polyphaga (Myxophaga (Archostemata + Adephaga))). The infraorder relationships in Polyphaga were (Scirtiformia (Elateriformia ((Staphyliniformia + Scarabaeiformia) (Bostrichiformia (Cucujiformia))))). Polyphagan superfamilies were recovered as monophyla except Staphylinoidea (paraphyletic for Scarabaeiformia) and Cucujoidea, which can no longer be considered a valid taxon. The study shows that, although compositional heterogeneity is not universal, it cannot be eliminated for some mitochondrial genes, but dense taxon sampling and the use of appropriate Bayesian analyses can still produce robust phylogenetic trees.

  16. Family-Level Sampling of Mitochondrial Genomes in Coleoptera: Compositional Heterogeneity and Phylogenetics

    PubMed Central

    Timmermans, Martijn J. T. N.; Barton, Christopher; Haran, Julien; Ahrens, Dirk; Culverwell, C. Lorna; Ollikainen, Alison; Dodsworth, Steven; Foster, Peter G.; Bocak, Ladislav; Vogler, Alfried P.

    2016-01-01

    Mitochondrial genomes are readily sequenced with recent technology and thus evolutionary lineages can be densely sampled. This permits better phylogenetic estimates and assessment of potential biases resulting from heterogeneity in nucleotide composition and rate of change. We gathered 245 mitochondrial sequences for the Coleoptera representing all 4 suborders, 15 superfamilies of Polyphaga, and altogether 97 families, including 159 newly sequenced full or partial mitogenomes. Compositional heterogeneity greatly affected 3rd codon positions, and to a lesser extent the 1st and 2nd positions, even after RY coding. Heterogeneity also affected the encoded protein sequence, in particular in the nad2, nad4, nad5, and nad6 genes. Credible tree topologies were obtained with the nhPhyML (“nonhomogeneous”) algorithm implementing a model for branch-specific equilibrium frequencies. Likelihood searches using RAxML were improved by data partitioning by gene and codon position. Finally, the PhyloBayes software, which allows different substitution processes for amino acid replacement at various sites, produced a tree that best matched known higher level taxa and defined basal relationships in Coleoptera. After rooting with Neuropterida outgroups, suborder relationships were resolved as (Polyphaga (Myxophaga (Archostemata + Adephaga))). The infraorder relationships in Polyphaga were (Scirtiformia (Elateriformia ((Staphyliniformia + Scarabaeiformia) (Bostrichiformia (Cucujiformia))))). Polyphagan superfamilies were recovered as monophyla except Staphylinoidea (paraphyletic for Scarabaeiformia) and Cucujoidea, which can no longer be considered a valid taxon. The study shows that, although compositional heterogeneity is not universal, it cannot be eliminated for some mitochondrial genes, but dense taxon sampling and the use of appropriate Bayesian analyses can still produce robust phylogenetic trees. PMID:26645679

  17. Tributyltin exposure alters cytokine levels in mouse serum.

    PubMed

    Lawrence, Shanieek; Pellom, Samuel T; Shanker, Anil; Whalen, Margaret M

    2016-11-01

    Tributyltin (TBT), a toxic environmental contaminant, has been widely utilized for various industrial, agricultural and household purposes. Its usage has led to a global contamination and its bioaccumulation in aquatic organisms and terrestrial mammals. Previous studies suggest that TBT has debilitating effects on the overall immune function of animals, rendering them more vulnerable to diseases. TBT (at concentrations that have been detected in human blood) alters secretion of inflammatory cytokines from human lymphocytes ex vivo. Thus, it is important to determine if specified levels of TBT can alter levels of cytokines in an in vivo system. Mice were exposed to biologically relevant concentrations of TBT (200, 100 or 25 nM final concentrations). The quantitative determination of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL2, IL5, IL7, IL12βp40, IL13, IL15, keratinocyte chemoattractant (KC), macrophage inflammatory protein 1β (MIP), MIP2 and regulated on activation normal T-cell-expressed and secreted (RANTES) was performed in mouse sera by MAGPIX analysis and Western blot. Results indicated alterations (both decreases and increases) in several cytokines. The pro-inflammatory cytokines IFNγ, TNFα, IL-1β, IL-2, IL5, IL12βp40 and IL-15 were altered as were the chemokines MIP-1 and RANTES and the anti-inflammatory cytokine IL-13. Increases in IFNγ and TNFα were seen in the serum of mice exposed to TBT for less than 24 h. Levels of IL1β, IL-12 βp40, IL-5 and IL-15 were also modulated in mouse serum, depending on the specific experiment and exposure level. IL-2 was consistently decreased in mouse serum when animals were exposed to TBT. There were also TBT-induced increases in MIP-1β, RANTES and IL-13. These results from human and murine samples clearly suggest that TBT exposures modulate the secretion inflammatory cytokines.

  18. Copper deficiency in neonatal mice alters brain catecholamine levels

    SciTech Connect

    Bailey, W.R.; Prohaska, J.R. )

    1991-03-15

    Copper (Cu) deficiency was investigated in Swiss albino mice to develop a model that alters brain catecholamine metabolism without serious growth impairment. Cu deficiency was induced by feeding a diet low in Cu to dams beginning either 7 days (d) prior, 4d prior, 4d after, or on the day of parturition. All 4-week-old male Cu-deficient ({minus}Cu) offspring were anemic and exhibited biochemical characteristics of Cu deficiency when compared to their respective +Cu control mice. However, the best model, which resulted in altered catecholamine metabolism characterized by elevation of dopamine (DA) and depression in norepinephrine (NE) in brain, heart, and spleen, was when treatment began 4d prior to birth. Body and brain weight were not altered. However, levels of Cu in brain and liver of {minus}Cu mice were markedly reduced to 21% and 31% of those measured in +Cu controls, respectively. Furthermore, brain NE and DA concentrations of {minus}Cu mice were 72% and 132% of those quantified in +Cu offspring, respectively. A plausible explanation is that dietary Cu deficiency results in lower activity of brain dopamine-{beta}-monooxygenase, the Cu dependent enzyme that catalyzes conversion of DA to NE. It is not yet known if these changes in Ne and DA pool size altered the quantity or characteristics of the neuronal catecholamine receptors, and more importantly, whether or not the observed changes are reversible by nutritional intervention.

  19. Enhanced heat stability and kinetic parameters of maize endosperm ADPglucose pyrophosphorylase by alteration of phylogenetically identified amino acids.

    PubMed

    Boehlein, Susan K; Shaw, Janine R; Georgelis, Nikolaos; Hannah, L Curtis

    2014-02-01

    ADP-glucose pyrophosphorylase (AGPase) controls the rate-limiting step in starch biosynthesis and is regulated at various levels. Cereal endosperm enzymes, in contrast to other plant AGPases, are particularly heat labile and transgenic studies highlight the importance of temperature for cereal yield. Previously, a phylogenetic approach identified Type II and positively selected amino acid positions in the large subunit of maize endosperm AGPase. Glycogen content, kinetic parameters and heat stability were measured in AGPases having mutations in these sites and interesting differences were observed. This study expands on our earlier evolutionary work by determining how all Type II and positively selected sites affect kinetic constants, heat stability and catalytic rates at increased temperatures. Variants with enhanced properties were identified and combined into one gene, designated Sh2-E. Enhanced properties include: heat stability, enhanced activity at 37 °C, activity at 55 °C, reduced Ka and activity in the absence of activator. The resulting enzyme exhibited all improved properties of the various individual changes. Additionally, Sh2-E was expressed with a small subunit variant with enhanced enzyme properties resulting in an enzyme that has exceptional heat stability, a high catalytic rate at increased temperatures and significantly decreased Km values for both substrates in the absence of the activator.

  20. Salt stress alters DNA methylation levels in alfalfa (Medicago spp).

    PubMed

    Al-Lawati, A; Al-Bahry, S; Victor, R; Al-Lawati, A H; Yaish, M W

    2016-02-26

    Modification of DNA methylation status is one of the mechanisms used by plants to adjust gene expression at both the transcriptional and posttranscriptional levels when plants are exposed to suboptimal conditions. Under abiotic stress, different cultivars often show heritable phenotypic variation accompanied by epigenetic polymorphisms at the DNA methylation level. This variation may provide the raw materials for plant breeding programs that aim to enhance abiotic stress tolerance, including salt tolerance. In this study, methylation-sensitive amplified polymorphism (MSAP) analysis was used to assess cytosine methylation levels in alfalfa (Medicago spp) roots exposed to increasing NaCl concentrations (0.0, 8.0, 12.0, and 20.0 dS/m). Eleven indigenous landraces were analyzed, in addition to a salt-tolerant cultivar that was used as a control. There was a slight increase in DNA methylation upon exposure to high levels of soil salinity. Phylogenetic analysis using MSAP showed epigenetic variation within and between the alfalfa landraces when exposed to saline conditions. Based on MSAP and enzyme-linked immunosorbent assay results, we found that salinity increased global DNA methylation status, particularly in plants exposed to the highest level of salinity (20 dS/m). Quantitative reverse transcription-polymerase chain reaction indicated that this might be mediated by the overexpression of methyltransferase homolog genes after exposure to saline conditions. DNA demethylation using 5-azacytidine reduced seedling lengths and dry and fresh weights, indicating a possible decrease in salinity tolerance. These results suggest that salinity affects DNA methylation flexibility.

  1. Human traumatic brain injury alters plasma microRNA levels.

    PubMed

    Redell, John B; Moore, Anthony N; Ward, Norman H; Hergenroeder, Georgene W; Dash, Pramod K

    2010-12-01

    Circulating microRNAs (miRNAs) present in the serum/plasma are characteristically altered in many pathological conditions, and have been employed as diagnostic markers for specific diseases. We examined if plasma miRNA levels are altered in patients with traumatic brain injury (TBI) relative to matched healthy volunteers, and explored their potential for use as diagnostic TBI biomarkers. The plasma miRNA profiles from severe TBI patients (Glasgow Coma Scale [GCS] score ≤8) and age-, gender-, and race-matched healthy volunteers were compared by microarray analysis. Of the 108 miRNAs identified in healthy volunteer plasma, 52 were altered after severe TBI, including 33 with decreased and 19 with increased relative abundance. An additional 8 miRNAs were detected only in the TBI plasma. We used quantitative RT-PCR to determine if plasma miRNAs could identify TBI patients within the first 24 h post-injury. Receiver operating characteristic curve analysis indicated that miR-16, miR-92a, and miR-765 were good markers of severe TBI (0.89, 0.82, and 0.86 AUC values, respectively). Multiple logistic regression analysis revealed that combining these miRNAs markedly increased diagnostic accuracy (100% specificity and 100% sensitivity), compared to either healthy volunteers or orthopedic injury patients. In mild TBI patients (GCS score > 12), miR-765 levels were unchanged, while the plasma levels of miR-92a and miR-16 were significantly increased within the first 24 h of injury compared to healthy volunteers, and had AUC values of 0.78 and 0.82, respectively. Our results demonstrate that circulating miRNA levels are altered after TBI, providing a rich new source of potential molecular biomarkers. Plasma-derived miRNA biomarkers, used in combination with established clinical practices such as imaging, neurocognitive, and motor examinations, have the potential to improve TBI patient classification and possibly management.

  2. Diversity of Phylogenetic Information According to the Locus and the Taxonomic Level: An Example from a Parasitic Mesostigmatid Mite Genus

    PubMed Central

    Roy, Lise; Dowling, Ashley P.G.; Chauve, Claude Marie; Buronfosse, Thierry

    2010-01-01

    Molecular markers for cladistic analyses may perform differently according to the taxonomic group considered and the historical level under investigation. Here we evaluate the phylogenetic potential of five different markers for resolving evolutionary relationships within the ectoparasitic genus Dermanyssus at the species level, and their ability to address questions about the evolution of specialization. COI provided 9–18% divergence between species (up to 9% within species), 16S rRNA 10–16% (up to 4% within species), ITS1 and 2 2–9% (up to 1% within species) and Tropomyosin intron n 8–20% (up to 6% within species). EF-1α revealed different non-orthologous copies within individuals of Dermanyssus and Ornithonyssus. Tropomyosin intron n was shown containing consistent phylogenetic signal at the specific level within Dermanyssus and represents a promising marker for future prospects in phylogenetics of Acari. Phylogenetic analyses revealed that the generalist condition is apomorphic and D. gallinae might represent a complex of hybridized lineages. The split into hirsutus-group and gallinae-group in Dermanyssus does not seem to be appropriate based upon these results and D. longipes appears to be composed of two different entities. PMID:20480038

  3. Diversification of land plants: insights from a family-level phylogenetic analysis

    PubMed Central

    2011-01-01

    Background Some of the evolutionary history of land plants has been documented based on the fossil record and a few broad-scale phylogenetic analyses, especially focusing on angiosperms and ferns. Here, we reconstructed phylogenetic relationships among all 706 families of land plants using molecular data. We dated the phylogeny using multiple fossils and a molecular clock technique. Applying various tests of diversification that take into account topology, branch length, numbers of extant species as well as extinction, we evaluated diversification rates through time. We also compared these diversification profiles against the distribution of the climate modes of the Phanerozoic. Results We found evidence for the radiations of ferns and mosses in the shadow of angiosperms coinciding with the rather warm Cretaceous global climate. In contrast, gymnosperms and liverworts show a signature of declining diversification rates during geological time periods of cool global climate. Conclusions This broad-scale phylogenetic analysis helps to reveal the successive waves of diversification that made up the diversity of land plants we see today. Both warm temperatures and wet climate may have been necessary for the rise of the diversity under a successive lineage replacement scenario. PMID:22103931

  4. Complete generic-level phylogenetic analyses of palms (Arecaceae) with comparisons of supertree and supermatrix approaches.

    PubMed

    Baker, William J; Savolainen, Vincent; Asmussen-Lange, Conny B; Chase, Mark W; Dransfield, John; Forest, Félix; Harley, Madeline M; Uhl, Natalie W; Wilkinson, Mark

    2009-04-01

    Supertree and supermatrix methods have great potential in the quest to build the tree of life and yet they remain controversial, with most workers opting for one approach or the other, but rarely both. Here, we employed both methods to construct phylogenetic trees of all genera of palms (Arecaceae/Palmae), an iconic angiosperm family of great economic importance. We assembled a supermatrix consisting of 16 partitions, comprising DNA sequence data, plastid restriction fragment length polymorphism data, and morphological data for all genera, from which a highly resolved and well-supported phylogenetic tree was built despite abundant missing data. To construct supertrees, we used variants of matrix representation with parsimony (MRP) analysis based on input trees generated directly from subsamples of the supermatrix. All supertrees were highly resolved. Standard MRP with bootstrap-weighted matrix elements performed most effectively in this case, generating trees with the greatest congruence with the supermatrix tree and fewest clades unsupported by any input tree. Nonindependence due to input trees based on combinations of data partitions was an acceptable trade-off for improvements in supertree performance. Irreversible MRP and the use of strictly independent input trees only provided no obvious benefits. Contrary to previous claims, we found that unsupported clades are not infrequent under some MRP implementations, with up to 13% of clades lacking support from any input tree in some irreversible MRP supertrees. To build a formal synthesis, we assessed the cross-corroboration between supermatrix trees and the variant supertrees using semistrict consensus, enumerating shared clades and compatible clades. The semistrict consensus of the supermatrix tree and the most congruent supertree contained 160 clades (of a maximum of 204), 137 of which were present in both trees. The relationships recovered by these trees strongly support the current phylogenetic classification

  5. Serum Levels of Acylcarnitines Are Altered in Prediabetic Conditions

    PubMed Central

    Mai, Manuel; Tönjes, Anke; Kovacs, Peter; Stumvoll, Michael; Fiedler, Georg Martin; Leichtle, Alexander Benedikt

    2013-01-01

    Objective The role of mitochondrial function in the complex pathogenesis of type 2 diabetes is not yet completely understood. Therefore, the aim of this study was to investigate serum concentrations of short-, medium- and long-chain acylcarnitines as markers of mitochondrial function in volunteers with normal, impaired or diabetic glucose control. Methods Based on a 75 g oral glucose tolerance test, 1019 studied subjects were divided into a group with normal glucose tolerance (NGT; n = 636), isolated impaired fasting glycaemia (IFG; n = 184), impaired glucose tolerance (IGT; n = 87) or type 2 diabetes (T2D; n = 112). Serum concentrations of free carnitine and 24 acylcarnitines were measured by mass spectrometry. Results Serum levels of acetylcarnitine (C2), propionylcarnitine (C3), octanoylcarnitine (C8), malonylcarnitine/hydroxybutyrylcarnitine (C3DC+C4OH), hexanoylcarnitine (C6), octenoylcarnitine (C8:1), decanoylcarnitine (C10), decenoylcarnitine (C10:1), dodecanoylcarnitine (C12), tetradecenoylcarnitine (C14:1), tetradecadienylcarnitine (C14:2), hydroxytetradecanoylcarnitine (C14OH), hydroxyhexadecanoylcarnitine (C16OH) and octadecenoylcarnitine (C18:1) were significantly different among the groups (all p<0.05 adjusted for age, gender and BMI). Between the prediabetic states C14:1, C14:2 and C18:1 showed significantly higher serum concentrations in persons with IGT (p<0.05). Compared to T2D the IFG and the IGT subjects showed lower serum concentrations of malonylcarnitine/hydroxybutyrylcarnitine (C3DC+C4OH) (p<0.05). Conclusion Alterations in serum concentrations of several acylcarnitines, in particular tetradecenoylcarnitine (C14:1), tetradecadienylcarnitine (C14:2), octadecenoylcarnitine (C18:1) and malonylcarnitine/hydroxybutyrylcarnitine (C3DC+C4OH) are associated not only with T2D but also with prediabetic states. PMID:24358186

  6. Large multi-gene phylogenetic trees of the grasses (Poaceae): progress towards complete tribal and generic level sampling.

    PubMed

    Bouchenak-Khelladi, Yanis; Salamin, Nicolas; Savolainen, Vincent; Forest, Felix; Bank, Michelle van der; Chase, Mark W; Hodkinson, Trevor R

    2008-05-01

    In this paper we included a very broad representation of grass family diversity (84% of tribes and 42% of genera). Phylogenetic inference was based on three plastid DNA regions rbcL, matK and trnL-F, using maximum parsimony and Bayesian methods. Our results resolved most of the subfamily relationships within the major clades (BEP and PACCMAD), which had previously been unclear, such as, among others the: (i) BEP and PACCMAD sister relationship, (ii) composition of clades and the sister-relationship of Ehrhartoideae and Bambusoideae + Pooideae, (iii) paraphyly of tribe Bambuseae, (iv) position of Gynerium as sister to Panicoideae, (v) phylogenetic position of Micrairoideae. With the presence of a relatively large amount of missing data, we were able to increase taxon sampling substantially in our analyses from 107 to 295 taxa. However, bootstrap support and to a lesser extent Bayesian inference posterior probabilities were generally lower in analyses involving missing data than those not including them. We produced a fully resolved phylogenetic summary tree for the grass family at subfamily level and indicated the most likely relationships of all included tribes in our analysis.

  7. A phylum-level phylogenetic classification of zygomycete fungi based on genome-scale data.

    PubMed

    Spatafora, Joseph W; Chang, Ying; Benny, Gerald L; Lazarus, Katy; Smith, Matthew E; Berbee, Mary L; Bonito, Gregory; Corradi, Nicolas; Grigoriev, Igor; Gryganskyi, Andrii; James, Timothy Y; O'Donnell, Kerry; Roberson, Robert W; Taylor, Thomas N; Uehling, Jessie; Vilgalys, Rytas; White, Merlin M; Stajich, Jason E

    2016-09-01

    Zygomycete fungi were classified as a single phylum, Zygomycota, based on sexual reproduction by zygospores, frequent asexual reproduction by sporangia, absence of multicellular sporocarps, and production of coenocytic hyphae, all with some exceptions. Molecular phylogenies based on one or a few genes did not support the monophyly of the phylum, however, and the phylum was subsequently abandoned. Here we present phylogenetic analyses of a genome-scale data set for 46 taxa, including 25 zygomycetes and 192 proteins, and we demonstrate that zygomycetes comprise two major clades that form a paraphyletic grade. A formal phylogenetic classification is proposed herein and includes two phyla, six subphyla, four classes and 16 orders. On the basis of these results, the phyla Mucoromycota and Zoopagomycota are circumscribed. Zoopagomycota comprises Entomophtoromycotina, Kickxellomycotina and Zoopagomycotina; it constitutes the earliest diverging lineage of zygomycetes and contains species that are primarily parasites and pathogens of small animals (e.g. amoeba, insects, etc.) and other fungi, i.e. mycoparasites. Mucoromycota comprises Glomeromycotina, Mortierellomycotina, and Mucoromycotina and is sister to Dikarya. It is the more derived clade of zygomycetes and mainly consists of mycorrhizal fungi, root endophytes, and decomposers of plant material. Evolution of trophic modes, morphology, and analysis of genome-scale data are discussed.

  8. A specimen-level phylogenetic analysis and taxonomic revision of Diplodocidae (Dinosauria, Sauropoda)

    PubMed Central

    Mateus, Octávio; Benson, Roger B.J.

    2015-01-01

    Diplodocidae are among the best known sauropod dinosaurs. Several species were described in the late 1800s or early 1900s from the Morrison Formation of North America. Since then, numerous additional specimens were recovered in the USA, Tanzania, Portugal, and Argentina, as well as possibly Spain, England, Georgia, Zimbabwe, and Asia. To date, the clade includes about 12 to 15 nominal species, some of them with questionable taxonomic status (e.g., ‘Diplodocus’ hayi or Dyslocosaurus polyonychius), and ranging in age from Late Jurassic to Early Cretaceous. However, intrageneric relationships of the iconic, multi-species genera Apatosaurus and Diplodocus are still poorly known. The way to resolve this issue is a specimen-based phylogenetic analysis, which has been previously implemented for Apatosaurus, but is here performed for the first time for the entire clade of Diplodocidae. The analysis includes 81 operational taxonomic units, 49 of which belong to Diplodocidae. The set of OTUs includes all name-bearing type specimens previously proposed to belong to Diplodocidae, alongside a set of relatively complete referred specimens, which increase the amount of anatomically overlapping material. Non-diplodocid outgroups were selected to test the affinities of potential diplodocid specimens that have subsequently been suggested to belong outside the clade. The specimens were scored for 477 morphological characters, representing one of the most extensive phylogenetic analyses of sauropod dinosaurs. Character states were figured and tables given in the case of numerical characters. The resulting cladogram recovers the classical arrangement of diplodocid relationships. Two numerical approaches were used to increase reproducibility in our taxonomic delimitation of species and genera. This resulted in the proposal that some species previously included in well-known genera like Apatosaurus and Diplodocus are generically distinct. Of particular note is that the famous genus

  9. A specimen-level phylogenetic analysis and taxonomic revision of Diplodocidae (Dinosauria, Sauropoda).

    PubMed

    Tschopp, Emanuel; Mateus, Octávio; Benson, Roger B J

    2015-01-01

    Diplodocidae are among the best known sauropod dinosaurs. Several species were described in the late 1800s or early 1900s from the Morrison Formation of North America. Since then, numerous additional specimens were recovered in the USA, Tanzania, Portugal, and Argentina, as well as possibly Spain, England, Georgia, Zimbabwe, and Asia. To date, the clade includes about 12 to 15 nominal species, some of them with questionable taxonomic status (e.g., 'Diplodocus' hayi or Dyslocosaurus polyonychius), and ranging in age from Late Jurassic to Early Cretaceous. However, intrageneric relationships of the iconic, multi-species genera Apatosaurus and Diplodocus are still poorly known. The way to resolve this issue is a specimen-based phylogenetic analysis, which has been previously implemented for Apatosaurus, but is here performed for the first time for the entire clade of Diplodocidae. The analysis includes 81 operational taxonomic units, 49 of which belong to Diplodocidae. The set of OTUs includes all name-bearing type specimens previously proposed to belong to Diplodocidae, alongside a set of relatively complete referred specimens, which increase the amount of anatomically overlapping material. Non-diplodocid outgroups were selected to test the affinities of potential diplodocid specimens that have subsequently been suggested to belong outside the clade. The specimens were scored for 477 morphological characters, representing one of the most extensive phylogenetic analyses of sauropod dinosaurs. Character states were figured and tables given in the case of numerical characters. The resulting cladogram recovers the classical arrangement of diplodocid relationships. Two numerical approaches were used to increase reproducibility in our taxonomic delimitation of species and genera. This resulted in the proposal that some species previously included in well-known genera like Apatosaurus and Diplodocus are generically distinct. Of particular note is that the famous genus

  10. Towards a phylogenetic generic classification of Thelypteridaceae: Additional sampling suggests alterations of neotropical taxa and further study of paleotropical genera.

    PubMed

    Almeida, Thaís Elias; Hennequin, Sabine; Schneider, Harald; Smith, Alan R; Batista, João Aguiar Nogueira; Ramalho, Aline Joseph; Proite, Karina; Salino, Alexandre

    2016-01-01

    Thelypteridaceae is one of the largest fern families, having about 950 species and a cosmopolitan distribution but with most species occurring in tropical and subtropical regions. Its generic classification remains controversial, with different authors recognizing from one up to 32 genera. Phylogenetic relationships within the family have not been exhaustively studied, but previous studies have confirmed the monophyly of the lineage. Thus far, sampling has been inadequate for establishing a robust hypothesis of infrafamilial relationships within the family. In order to understand phylogenetic relationships within Thelypteridaceae and thus to improve generic reclassification, we expand the molecular sampling, including new samples of Old World taxa and, especially, many additional neotropical representatives. We also explore the monophyly of exclusively or mostly neotropical genera Amauropelta, Goniopteris, Meniscium, and Steiropteris. Our sampling includes 68 taxa and 134 newly generated sequences from two plastid genomic regions (rps4-trnS and trnL-trnF), plus 73 rps4 and 72 trnL-trnF sequences from GenBank. These data resulted in a concatenated matrix of 1980 molecular characters for 149 taxa. The combined data set was analyzed using maximum parsimony and bayesian inference of phylogeny. Our results are consistent with the general topological structure found in previous studies, including two main lineages within the family: phegopteroid and thelypteroid. The thelypteroid lineage comprises two clades; one of these included the segregates Metathelypteris, Coryphopteris, and Amauropelta (including part of Parathelypteris), whereas the other comprises all segregates of Cyclosorus s.l., such as Goniopteris, Meniscium, and Steiropteris (including Thelypteris polypodioides, previously incertae sedis). The three mainly neotropical segregates were found to be monophyletic but nested in a broadly defined Cyclosorus. The fourth mainly neotropical segregate, Amauropelta

  11. Phylogenetic factorization of compositional data yields lineage-level associations in microbiome datasets

    PubMed Central

    Silverman, Justin D.; Leff, Jonathan W.; Bennett, Dominic J.; Darcy, John L.; Mukherjee, Sayan; Fierer, Noah; David, Lawrence A.

    2017-01-01

    Marker gene sequencing of microbial communities has generated big datasets of microbial relative abundances varying across environmental conditions, sample sites and treatments. These data often come with putative phylogenies, providing unique opportunities to investigate how shared evolutionary history affects microbial abundance patterns. Here, we present a method to identify the phylogenetic factors driving patterns in microbial community composition. We use the method, “phylofactorization,” to re-analyze datasets from the human body and soil microbial communities, demonstrating how phylofactorization is a dimensionality-reducing tool, an ordination-visualization tool, and an inferential tool for identifying edges in the phylogeny along which putative functional ecological traits may have arisen. PMID:28289558

  12. Sources of Signal in 62 Protein-Coding Nuclear Genes for Higher-Level Phylogenetics of Arthropods

    PubMed Central

    Regier, Jerome C.; Zwick, Andreas

    2011-01-01

    Background This study aims to investigate the strength of various sources of phylogenetic information that led to recent seemingly robust conclusions about higher-level arthropod phylogeny and to assess the role of excluding or downweighting synonymous change for arriving at those conclusions. Methodology/Principal Findings The current study analyzes DNA sequences from 68 gene segments of 62 distinct protein-coding nuclear genes for 80 species. Gene segments analyzed individually support numerous nodes recovered in combined-gene analyses, but few of the higher-level nodes of greatest current interest. However, neither is there support for conflicting alternatives to these higher-level nodes. Gene segments with higher rates of nonsynonymous change tend to be more informative overall, but those with lower rates tend to provide stronger support for deeper nodes. Higher-level nodes with bootstrap values in the 80% – 99% range for the complete data matrix are markedly more sensitive to substantial drops in their bootstrap percentages after character subsampling than those with 100% bootstrap, suggesting that these nodes are likely not to have been strongly supported with many fewer data than in the full matrix. Data set partitioning of total data by (mostly) synonymous and (mostly) nonsynonymous change improves overall node support, but the result remains much inferior to analysis of (unpartitioned) nonsynonymous change alone. Clusters of genes with similar nonsynonymous rate properties (e.g., faster vs. slower) show some distinct patterns of node support but few conflicts. Synonymous change is shown to contribute little, if any, phylogenetic signal to the support of higher-level nodes, but it does contribute nonphylogenetic signal, probably through its underlying heterogeneous nucleotide composition. Analysis of seemingly conservative indels does not prove useful. Conclusions Generating a robust molecular higher-level phylogeny of Arthropoda is currently possible

  13. Altered Serum Uric Acid Level in Lichen Planus Patients

    PubMed Central

    Chakraborti, Goutam; Biswas, Rabindranath; Chakraborti, Sandip; Sen, Pradyot Kumar

    2014-01-01

    Background: Lichen planus (LP) is a common disorder whose etiopathogenesis is not clear. Recently, it has been suggested that increased reactive oxygen species (ROS) play important roles in the underlying mechanism of LP. Objectives: The principal aim of this study was to evaluate serum uric acid (UA) levels as a measure of the antioxidant defense status in LP patients. Methods: Serum UA levels were determined in 58 LP patients and 61 controls. Results: Serum UA levels were significantly decreased in patients with respect to controls. Moreover, serum UA level was decreased according to increasing duration of disease. Conclusions: The results of our study suggest that LP is associated with decrease of UA levels in serum. UA may be a potential, useful biomarker of antioxidant status in LP for elaboration of treatment strategy and monitoring. PMID:25484383

  14. PHYLOGENETIC ANALYSIS OF PSEUDOCHLORODESMIS STRAINS REVEALS CRYPTIC DIVERSITY ABOVE THE FAMILY LEVEL IN THE SIPHONOUS GREEN ALGAE (BRYOPSIDALES, CHLOROPHYTA)(1).

    PubMed

    Verbruggen, Heroen; Vlaeminck, Caroline; Sauvage, Thomas; Sherwood, Alison R; Leliaert, Frederik; De Clerck, Olivier

    2009-06-01

    The genus Pseudochlorodesmis (Bryopsidales) is composed of diminutive siphons of extreme morphological simplicity. The discovery of Pseudochlorodesmis-like juveniles in more complex Bryopsidales (e.g., the Halimeda microthallus stage) jeopardized the recognition of this genus. Confronted with this uncertainty, taxonomists transferred many simple siphons into a new genus, Siphonogramen. In this study, we used a multimarker approach to clarify the phylogenetic and taxonomic affinities of the Pseudochlorodesmis-Siphonogramen (PS) complex within the more morphologically complex bryopsidalean taxa. Our analyses reveal a new layer of diversity largely distinct from the lineages containing the structurally complex genera. The PS complex shows profound cryptic diversity exceeding the family level. We discuss a potential link between thallus complexity and the prevalence and profundity of cryptic diversity. For taxonomic simplicity and as a first step toward clarifying the taxonomy of these simple siphons, we propose to maintain Pseudochlorodesmis as a form genus and subsume Siphonogramen and Botryodesmis therein.

  15. Light-Induced Alterations in Basil Ganglia Kynurenic Acid Levels

    NASA Technical Reports Server (NTRS)

    Sroufe, Angela E.; Whittaker, J. A.; Patrickson, J. W.; Orr, M. C.

    1997-01-01

    The metabolic synthesis, release and breakdown of several known CNS neurotransmitters have been shown to follow a circadian pattern entrained to the environmental light/dark cycle. The levels of excitatory amino acid (EAA) transmitters such as glutamate, have been shown to vary with environmental lighting conditions. Kynurenic Acid (KA), an endogenous tryptophan metabolite and glutamate receptor antagonist, has been reported to have neuroprotective effects against EAA-induced excitotoxic cell damage. Changes in KA's activity within the mammalian basal ganglia has been proposed as being contributory to neurotoxicity in Huntington's Disease. It is not known whether CNS KA levels follow a circadian pattern or exhibit light-induced fluctuations. However, because the symptoms of certain degenerative motor disorders seem to fluctuate with daily 24 hour rhythm, we initiated studies to determine if basal ganglia KA were influenced by the daily light/dark cycle and could influence motor function. Therefore in this study, HPLC-EC was utilized to determine if basal ganglia KA levels in tissue extracts from adult male Long-Evans rats (200-250g) entrained to 24 and 48 hours constant light and dark conditions, respectively. Samples were taken one hour before the onset of the subjective day and one hour prior to the onset of the subjective night in order to detect possible phase differences in KA levels and to allow for accumulation of factors expressed in association with the light or dark phase. Data analysis revealed that KA levels in the basal ganglia vary with environmental lighting conditions; being elevated generally during the dark. Circadian phase differences in KA levels were also evident during the subjective night and subjective day, respectively. Results from these studies are discussed with respect to potential cyclic changes in neuronal susceptibility to excitotoxic damage during the daily 24 hour cycle and its possible relevance to future therapeutic approaches in

  16. New molecular markers for fungal phylogenetics: Two genes for species level systematics in the Sordariomycetes (Ascomycota)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Although significant progress has been made resolving deep branches of the fungal tree of life in recent works, many fungal systematists are interested in species-level questions to both define species and to assess fungal biodiversity. Fungal genome sequences are a useful resource to systematic bio...

  17. Multilocus Phylogenetics Show High Levels of Endemic Fusaria Inhabiting Sardinian Soils (Tyrrhenian Islands)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Mediterranean island of Sardinia is well known for high levels of vascular plant diversity and endemism, but little is known about its microbial diversity. Under the hypothesis that Fusarium species would show similar patterns, we estimated variability in Fusarium species composition among ten ...

  18. Dietary protein source and level alters growth in neon tetras.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Nutritional studies for aquarium fish like the neon tetra are sparse in comparison with those for food fish. To determine the optimum dietary protein level and source for growth of neon tetras, diets were formulated to contain 25, 35, 45 and 55% dietary protein from either marine animal protein or ...

  19. Microsatellites: Evolutionary and methodological background and empirical applications at individual, population, and phylogenetic levels

    USGS Publications Warehouse

    Scribner, Kim T.; Pearce, John M.; Baker, Allan J.

    2000-01-01

    The recent proliferation and greater accessibility of molecular genetic markers has led to a growing appreciation of the ecological and evolutionary inferences that can be drawn from molecular characterizations of individuals and populations (Burke et al. 1992, Avise 1994). Different techniques have the ability to target DNA sequences which have different patterns of inheritance, different modes and rates of evolution and, concomitantly, different levels of variation. In the quest for 'the right marker for the right job', microsatellites have been widely embraced as the marker of choice for many empirical genetic studies. The proliferation of microsatellite loci for various species and the voluminous literature compiled in very few years associated with their evolution and use in various research applications, exemplifies their growing importance as a research tool in the biological sciences.The ability to define allelic states based on variation at the nucleotide level has afforded unparalleled opportunities to document the actual mutational process and rates of evolution at individual microsatellite loci. The scrutiny to which these loci have been subjected has resulted in data that raise issues pertaining to assumptions formerly stated, but largely untestable for other marker classes. Indeed this is an active arena for theoretical and empirical work. Given the extensive and ever-increasing literature on various statistical methodologies and cautionary notes regarding the uses of microsatellites, some consideration should be given to the unique characteristics of these loci when determining how and under what conditions they can be employed.

  20. Running on uneven ground: leg adjustments to altered ground level.

    PubMed

    Müller, Roy; Blickhan, Reinhard

    2010-08-01

    In locomotion, humans have to deal with changes in ground level like pavement or stairs. When they encounter uneven ground with changes in terrain height, they reduce their angle of attack and leg stiffness on a step. This strategy was found for the single step upward movement. However, are these adjustments the result of a general strategy? In our study we focused on leg adjustments while running up and down, implying permanent adaptation to a new track level. To investigate this, we measured ten healthy participants as they ran along a runway with 10 cm increased and 10 cm lowered steps. We found that ground reaction force, leg length, leg stiffness, and angle of attack were adjusted to the direction of the vertical disturbance (up or down) but also to its length. When running upwards, leg stiffness decreased by about 20.4% on the single step and by about 9.3% on the permanently elevated track step. In addition to that - when running downwards - leg stiffness decreased in preparation for the downward step by about 18.8%. We also observed that the angle of attack diminished on elevated contact from 61 degrees to 59 degrees, and increased on lowered contact from 61 degrees to 65 degrees. The adjustment of leg stiffness seemed to be actively achieved, whereas the angle of attack appeared to be passively adjusted, consistent with a running model that includes leg retraction in late swing phase.

  1. Chronic hyperammonemia alters the circadian rhythms of corticosteroid hormone levels and of motor activity in rats.

    PubMed

    Ahabrach, Hanan; Piedrafita, Blanca; Ayad, Abdelmalik; El Mlili, Nisrin; Errami, Mohammed; Felipo, Vicente; Llansola, Marta

    2010-05-15

    Patients with liver cirrhosis may present hepatic encephalopathy with a wide range of neurological disturbances and alterations in sleep quality and in the sleep-wake circadian rhythm. Hyperammonemia is a main contributor to the neurological alterations in hepatic encephalopathy. We have assessed, in an animal model of chronic hyperammonemia without liver failure, the effects of hyperammonemia per se on the circadian rhythms of motor activity, temperature, and plasma levels of adrenal corticosteroid hormones. Chronic hyperammonemia alters the circadian rhythms of locomotor activity and of cortisol and corticosterone levels in blood. Different types of motor activity are affected differentially. Hyperammonemia significantly alters the rhythm of spontaneous ambulatory activity, reducing strongly ambulatory counts and slightly average velocity during the night (the active phase) but not during the day, resulting in altered circadian rhythms. In contrast, hyperammonemia did not affect wheel running at all, indicating that it affects spontaneous but not voluntary activity. Vertical activity was affected only very slightly, indicating that hyperammonemia does not induce anxiety. Hyperammonemia abolished completely the circadian rhythm of corticosteroid hormones in plasma, completely eliminating the peaks of cortisol and corticosterone present in control rats at the start of the dark period. The data reported show that chronic hyperammonemia, similar to that present in patients with liver cirrhosis, alters the circadian rhythms of corticosteroid hormones and of motor activity. This suggests that hyperammonemia would be a relevant contributor to the alterations in corticosteroid hormones and in circadian rhythms in patients with liver cirrhosis.

  2. Fetal alcohol exposure alters neurosteroid levels in the developing rat brain.

    PubMed

    Caldeira, Jerri C; Wu, Yan; Mameli, Manuel; Purdy, Robert H; Li, Pui-Kai; Akwa, Yvette; Savage, Daniel D; Engen, John R; Valenzuela, C Fernando

    2004-09-01

    Neurosteroids are modulators of neuronal function that may play important roles in brain maturation. We determined whether chronic prenatal ethanol exposure altered neurosteroid levels in the developing brain. Rat dams were exposed to: (i) a 5% ethanol-containing liquid diet that produces peak maternal blood alcohol levels near the legal intoxication limit (approximately 0.08 g/dL); (ii) an isocaloric liquid diet containing maltose-dextrin instead of ethanol with pair-feeding; (iii) rat chow ad libitum. Neurosteroid levels were assessed in offspring brains using radioimmunoassay or gas chromatography-mass spectrometry techniques. A prenatal ethanol exposure-induced increase in pregnenolone sulfate levels, but not dehydroepiandrosterone sulfate levels, was evident at the earliest time point studied (embryonic day 14). This effect lasted until post-natal day 5. Levels of other neurosteroids were assessed at embryonic day 20; pregnenolone levels, but not allopregnanolone levels, were elevated. Pregnenolone sulfate levels were not altered in the maternal brain. Neither pregnenolone nor pregnenolone sulfate levels were significantly altered in the fetal liver, placenta and maternal blood, indicating that the effect of ethanol is not secondary to accumulation of peripherally-produced steroids. Fetal ethanol exposure has been shown to decrease both cellular and behavioral responsiveness to neurosteroids, and our findings provide a plausible explanation for this effect.

  3. Multilocus phylogenetic analysis of true morels (Morchella) reveals high levels of endemics in Turkey relative ot other regions of Europe

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The present study was conducted to better understand how the phylogenetic diversity of true morels (Morchella) in Turkey compares with species found in other regions of the world. The current research builds on our recently published survey of 10 Turkish provinces and another of the world in which D...

  4. Genome-Wide Survey of Nuclear Protein-Coding Markers for Beetle Phylogenetics and Their Application in Resolving both Deep and Shallow-Level Divergences.

    PubMed

    Che, Li-Heng; Zhang, Shao-Qian; Li, Yun; Liang, Dan; Pang, Hong; Ślipiński, Adam; Zhang, Peng

    2017-03-03

    Beetles (Coleoptera) are the most diverse and species-rich insect group, representing an impressive explosive radiation in the evolutionary history of insects, and their evolutionary relationships are often difficult to resolve. The amount of "traditional markers" (e.g., mitochondrial genes and nuclear rDNAs) for beetle phylogenetics is small and these markers often lack sufficient signals in resolving relationships for such a rapidly radiating lineage. Here, based on the available genome data of beetles and other related insect species, we performed a genome-wide survey to search nuclear protein-coding (NPC) genes suitable for research on beetle phylogenetics. As a result, we identified 1470 candidate loci, which provided a valuable data resource to the beetle evolutionary research community for NPC marker development. We randomly chose 180 candidate loci from the database to design primers and successfully developed 95 NPC markers which can be PCR amplified from standard genomic DNA extracts. These new nuclear markers are universally applicable across Coleoptera, with an average amplification success rate of 90%. To test the phylogenetic utility, we used them to investigate the backbone phylogeny of Coleoptera (18 families sampled) and the family Coccinellidae (39 species sampled). Both phylogenies are well resolved (average bootstrap support > 95%), showing that our markers can be used to address phylogenetic questions of various evolutionary depth (from species level to family level). In general, the newly developed nuclear markers are much easier to use and more phylogenetically informative than the "traditional markers", and show great potential to expedite resolution of many parts in the Beetle Tree of Life. This article is protected by copyright. All rights reserved.

  5. Arthropod Phylogenetics in Light of Three Novel Millipede (Myriapoda: Diplopoda) Mitochondrial Genomes with Comments on the Appropriateness of Mitochondrial Genome Sequence Data for Inferring Deep Level Relationships

    PubMed Central

    Brewer, Michael S.; Swafford, Lynn; Spruill, Chad L.; Bond, Jason E.

    2013-01-01

    Background Arthropods are the most diverse group of eukaryotic organisms, but their phylogenetic relationships are poorly understood. Herein, we describe three mitochondrial genomes representing orders of millipedes for which complete genomes had not been characterized. Newly sequenced genomes are combined with existing data to characterize the protein coding regions of myriapods and to attempt to reconstruct the evolutionary relationships within the Myriapoda and Arthropoda. Results The newly sequenced genomes are similar to previously characterized millipede sequences in terms of synteny and length. Unique translocations occurred within the newly sequenced taxa, including one half of the Appalachioria falcifera genome, which is inverted with respect to other millipede genomes. Across myriapods, amino acid conservation levels are highly dependent on the gene region. Additionally, individual loci varied in the level of amino acid conservation. Overall, most gene regions showed low levels of conservation at many sites. Attempts to reconstruct the evolutionary relationships suffered from questionable relationships and low support values. Analyses of phylogenetic informativeness show the lack of signal deep in the trees (i.e., genes evolve too quickly). As a result, the myriapod tree resembles previously published results but lacks convincing support, and, within the arthropod tree, well established groups were recovered as polyphyletic. Conclusions The novel genome sequences described herein provide useful genomic information concerning millipede groups that had not been investigated. Taken together with existing sequences, the variety of compositions and evolution of myriapod mitochondrial genomes are shown to be more complex than previously thought. Unfortunately, the use of mitochondrial protein-coding regions in deep arthropod phylogenetics appears problematic, a result consistent with previously published studies. Lack of phylogenetic signal renders the

  6. Phylogenetic relationships of Proboscoida Broch, 1910 (Cnidaria, Hydrozoa): Are traditional morphological diagnostic characters relevant for the delimitation of lineages at the species, genus, and family levels?

    PubMed

    Cunha, Amanda F; Collins, Allen G; Marques, Antonio C

    2017-01-01

    Overlapping variation of morphological characters can lead to misinterpretation in taxonomic diagnoses and the delimitation of different lineages. This is the case for hydrozoans that have traditionally been united in the family Campanulariidae, a group known for its wide morphological variation and complicated taxonomic history. In a recently proposed phylogenetic classification of leptothecate hydrozoans, this family was restricted to a more narrow sense while a larger clade containing most species traditionally classified in Campanulariidae, along with members of Bonneviellidae, was established as the suborder Proboscoida. We used molecular data to infer the phylogenetic relationships among campanulariids and assess the traditional classification of the family, as well as the new classification scheme for the group. The congruity and relevance of diagnostic characters were also evaluated. While mostly consistent with the new phylogenetic classification of Proboscoida, our increased taxon sampling resulted in some conflicts at the family level, specially regarding the monophyly of Clytiidae and Obeliidae. Considering the traditional classification, only Obeliidae is close to its original scope (as subfamily Obeliinae). At the genus level, Campanularia and Clytia are not monophyletic. Species with Obelia-like medusae do not form a monophyletic group, nor do species with fixed gonophores, indicating that these characters do not readily diagnose different genera. Finally, the species Orthopyxis integra, Clytia gracilis, and Obelia dichotoma are not monophyletic, suggesting that most of their current diagnostic characters are not informative for their delimitation. Several diagnostic characters in this group need to be reassessed, with emphasis on their variation, in order to have a consistent taxonomic and phylogenetic framework for the classification of campanulariid hydrozoans.

  7. Human ribosomes from cells with reduced dyskerin levels are intrinsically altered in translation.

    PubMed

    Penzo, Marianna; Rocchi, Laura; Brugiere, Sabine; Carnicelli, Domenica; Onofrillo, Carmine; Couté, Yohann; Brigotti, Maurizio; Montanaro, Lorenzo

    2015-08-01

    Dyskerin is a pseudouridine (ψ) synthase involved in fundamental cellular processes including uridine modification in rRNA and small nuclear RNA and telomere stabilization. Dyskerin functions are altered in X-linked dyskeratosis congenita (X-DC) and cancer. Dyskerin's role in rRNA pseudouridylation has been suggested to underlie the alterations in mRNA translation described in cells lacking dyskerin function, although relevant direct evidences are currently lacking. Our purpose was to establish definitely whether defective dyskerin function might determine an intrinsic ribosomal defect leading to an altered synthetic activity. Therefore, ribosomes from dyskerin-depleted human cells were purified and 1) added to a controlled reticulocyte cell-free system devoid of ribosomes to study mRNA translation; 2) analyzed for protein contamination and composition by mass spectrometry, 3) analyzed for global pseudouridylation levels. Ribosomes purified from dyskerin-depleted cells showed altered translational fidelity and internal ribosome entry site (IRES)-mediated translation. These ribosomes displayed reduced uridine modification, whereas they were not different in terms of protein contamination or ribosomal protein composition with respect to ribosomes from matched control cells with full dyskerin activity. In conclusion, lack of dyskerin function in human cells induces a defect in rRNA uridine modification, which is sufficient to alter ribosome activity.

  8. Multilocus phylogenetic analysis of true morels (Morchella) reveals high levels of endemics in Turkey relative to other regions of Europe.

    PubMed

    Taskin, Hatira; Büyükalaca, Saadet; Hansen, Karen; O'Donnell, Kerry

    2012-01-01

    The present study was conducted to better understand how the phylogenetic diversity of true morels (Morchella) in Turkey compares with species found in other regions of the world. The current research builds on our recently published surveys of 10 Turkish provinces and the northern hemisphere in which DNA sequence data from 247 and 562 collections respectively were analyzed phylogenetically. Herein we report on phylogenetic analyses of 243 additional collections made in spring 2009 and 2010 from eight additional provinces in the Aegean, Black Sea, central Anatolia, eastern Anatolia and Marmara regions of Turkey. Our analysis revealed that five species within the Esculenta clade (yellow morels) and 15 species within the Elata clade (black morels) were present in Turkey. Our preliminary results also indicate that M. anatolica, recently described from a collection in Muğla province in the Aegean region of Turkey, is a closely related sister of M. rufobrunnea; these two species comprise a separate evolutionary lineage from the Esculenta and Elata clades. Nine species of Morchella currently are known only from Turkey, four species were present in Turkey and other European countries and seven species might have been introduced to Turkey anthropogenically. Three of the putatively exotic species in Turkey appear to be endemic to western North America; they are nested within a clade of fire-adapted morels that dates to the late Oligocene, 25 000 000 y ago. Our results indicate that there are roughly twice as many Morchella species in Turkey compared with the other regions of Europe sampled. Knowledge of Morchella species diversity and their biogeographic distribution are crucial for formulating informed conservation policies directed at preventing species loss and ensuring that annual morel harvests are sustainable and ecologically sound.

  9. Age-associated alterations in the somatic mutation and DNA methylation levels in plants.

    PubMed

    Dubrovina, A S; Kiselev, K V

    2016-03-01

    Somatic mutations of the nuclear and mitochondrial DNA and alterations in DNA methylation levels in mammals are well known to play important roles in ageing and various diseases, yet their specific contributions await further investigation. For plants, it has also been proposed that unrepaired DNA damage and DNA polymerase errors accumulate in plant cells and lead to increased somatic mutation rate and alterations in transcription, which eventually contribute to plant ageing. A number of studies also show that DNA methylation levels vary depending on the age of plant tissue and chronological age of a whole plant. Recent studies reveal that prolonged cultivation of plant cells in vitro induces single nucleotide substitutions and increases global DNA methylation level in a time-dependent fashion. Changes in DNA methylation are known to influence DNA repair and can lead to altered mutation rates, and, therefore, it is interesting to investigate both the genetic and epigenetic integrity in relationship to ageing in plants. This review will summarise and discuss the current studies investigating somatic DNA mutation and DNA methylation levels in relation to plant ageing and senescence. The analysis has shown that there still remains a lack of clarity concerning plant biological ageing and the role of the genetic and epigenetic instabilities in this process.

  10. Alteration of prolactin serum levels during alcohol withdrawal correlates with craving in female patients.

    PubMed

    Hillemacher, Thomas; Bayerlein, Kristina; Wilhelm, Julia; Reulbach, Udo; Frieling, Helge; Bönsch, Dominikus; Kornhuber, Johannes; Bleich, Stefan

    2005-12-01

    Dopaminergic transmission has been suggested to be a main mechanism mediating reinforcement, withdrawal and craving in alcohol dependency. Dopamine is associated with prolactin secretion, acting as a prolactin inhibitor. The aim of the present study was to investigate whether there is an association between altered prolactin levels and craving during early and late alcohol withdrawal. Therefore, we examined 145 patients suffering from alcohol dependency after admission to the detoxification unit, assessing craving with the Obsessive Compulsive Drinking Scale (OCDS) and measuring prolactin serum levels during early withdrawal (-EW: day 0 or day 1) and late withdrawal (-LW: day 7-day 10). We observed a significant influence of the alteration of prolactin during withdrawal on craving in female patients (Spearman's rho, OCDS-EW: r=-0.607, p=0.001; OCDS-LW: r=-0.730, p<0.001; n=26). The association between prolactin alteration in percentage and craving in females was confirmed with general linear models (OCDS-EW: F=15.819, p=0.001, r(2)=0.530; OCDS-LW: F=17.091, p<0.001, r(2)=0.535). In male patients we did not find any significant results. Our findings support the previously described role of the hypothalamic-pituitary-adrenal (HPA) axis in the neurobiology of alcohol craving and show evidence of an association between increased prolactin serum levels and lower craving during alcohol withdrawal in female patients.

  11. Materials and methods for the alteration of enzyme and acetyl CoA levels in plants

    DOEpatents

    Nikolau, Basil J.; Wurtele, Eve S.; Oliver, David J.; Schnable, Patrick S.; Wen, Tsui-Jung

    2009-04-28

    The present invention provides nucleic acid and amino acid sequences of acetyl CoA synthetase (ACS), plastidic pyruvate dehydrogenase (pPDH), ATP citrate lyase (ACL), Arabidopsis pyruvate decarboxylase (PDC), and Arabidopsis aldehyde dehydrogenase (ALDH), specifically ALDH-2 and ALDH-4. The present invention also provides a recombinant vector comprising a nucleic acid sequence encoding one of the aforementioned enzymes, an antisense sequence thereto or a ribozyme therefor, a cell transformed with such a vector, antibodies to the enzymes, a plant cell, a plant tissue, a plant organ or a plant in which the level of an enzyme has been altered, and a method of producing such a plant cell, plant tissue, plant organ or plant. Desirably, alteration of the level of enzyme results in an alteration of the level of acetyl CoA in the plant cell, plant tissue, plant organ or plant. In addition, the present invention provides a recombinant vector comprising an antisense sequence of a nucleic acid sequence encoding pyruvate decarboxylase (PDC), the E1.alpha. subunit of pPDH, the E1.beta. subunit of pPDH, the E2 subunit of pPDH, mitochondrial pyruvate dehydrogenase (mtPDH) or aldehyde dehydrogenase (ALDH) or a ribozyme that can cleave an RNA molecule encoding PDC, E1.alpha. pPDH, E1.beta. pPDH, E2 pPDH, mtPDH or ALDH.

  12. Materials and methods for the alteration of enzyme and acetyl CoA levels in plants

    DOEpatents

    Nikolau, Basil J.; Wurtele, Eve S.; Oliver, David J.; Behal, Robert; Schnable, Patrick S.; Ke, Jinshan; Johnson, Jerry L.; Allred, Carolyn C.; Fatland, Beth; Lutziger, Isabelle; Wen, Tsui-Jung

    2005-09-13

    The present invention provides nucleic acid and amino acid sequences of acetyl CoA synthetase (ACS), plastidic pyruvate dehydrogenase (pPDH), ATP citrate lyase (ACL), Arabidopsis pyruvate decarboxylase (PDC), and Arabidopsis aldehyde dehydrogenase (ALDH), specifically ALDH-2 and ALDH-4. The present invention also provides a recombinant vector comprising a nucleic acid sequence encoding one of the aforementioned enzymes, an antisense sequence thereto or a ribozyme therefor, a cell transformed with such a vector, antibodies to the enzymes, a plant cell, a plant tissue, a plant organ or a plant in which the level of an enzyme has been altered, and a method of producing such a plant cell, plant tissue, plant organ or plant. Desirably, alteration of the level of enzyme results in an alteration of the level of acetyl CoA in the plant cell, plant tissue, plant organ or plant. In addition, the present invention provides a recombinant vector comprising an antisense sequence of a nucleic acid sequence encoding pyruvate decarboxylase (PDC), the E1.alpha. subunit of pPDH, the E1.beta. subunit of pPDH, the E2 subunit of pPDH, mitochondrial pyruvate dehydrogenase (mtPDH) or aldehyde dehydrogenase (ALDH) or a ribozyme that can cleave an RNA molecule encoding PDC, E1.alpha. pPDH, E1.beta. pPDH, E2 pPDH, mtPDH or ALDH.

  13. Materials and methods for the alteration of enzyme and acetyl CoA levels in plants

    DOEpatents

    Nikolau, Basil J.; Wurtele, Eve S.; Oliver, David J.; Behal, Robert; Schnable, Patrick S.; Ke, Jinshan; Johnson, Jerry L.; Allred, Carolyn C.; Fatland, Beth; Lutziger, Isabelle; Wen, Tsui-Jung

    2004-07-20

    The present invention provides nucleic acid and amino acid sequences of acetyl CoA synthetase (ACS), plastidic pyruvate dehydrogenase (pPDH), ATP citrate lyase (ACL), Arabidopsis pyruvate decarboxylase (PDC), and Arabidopsis aldehyde dehydrogenase (ALDH), specifically ALDH-2 and ALDH-4. The present invention also provides a recombinant vector comprising a nucleic acid sequence encoding one of the aforementioned enzymes, an antisense sequence thereto or a ribozyme therefor, a cell transformed with such a vector, antibodies to the enzymes, a plant cell, a plant tissue, a plant organ or a plant in which the level of an enzyme has been altered, and a method of producing such a plant cell, plant tissue, plant organ or plant. Desirably, alteration of the level of enzyme results in an alteration of the level of acetyl CoA in the plant cell, plant tissue, plant organ or plant. In addition, the present invention provides a recombinant vector comprising an antisense sequence of a nucleic acid sequence encoding pyruvate decarboxylase (PDC), the E1.sub..alpha. subunit of pPDH, the E1.sub..beta. subunit of pPDH, the E2 subunit of pPDH, mitochondrial pyurvate dehydrogenase (mtPDH) or aldehyde dehydrogenase (ALDH) or a ribozyme that can cleave an RNA molecule encoding PDC, E1.sub..alpha. pPDH, E1.sub..beta. pPDH, E2 pPDH, mtPDH or ALDH.

  14. Near-future carbon dioxide levels alter fish behaviour by interfering with neurotransmitter function

    NASA Astrophysics Data System (ADS)

    Nilsson, Göran E.; Dixson, Danielle L.; Domenici, Paolo; McCormick, Mark I.; Sørensen, Christina; Watson, Sue-Ann; Munday, Philip L.

    2012-03-01

    Predicted future CO2 levels have been found to alter sensory responses and behaviour of marine fishes. Changes include increased boldness and activity, loss of behavioural lateralization, altered auditory preferences and impaired olfactory function. Impaired olfactory function makes larval fish attracted to odours they normally avoid, including ones from predators and unfavourable habitats. These behavioural alterations have significant effects on mortality that may have far-reaching implications for population replenishment, community structure and ecosystem function. However, the underlying mechanism linking high CO2 to these diverse responses has been unknown. Here we show that abnormal olfactory preferences and loss of behavioural lateralization exhibited by two species of larval coral reef fish exposed to high CO2 can be rapidly and effectively reversed by treatment with an antagonist of the GABA-A receptor. GABA-A is a major neurotransmitter receptor in the vertebrate brain. Thus, our results indicate that high CO2 interferes with neurotransmitter function, a hitherto unrecognized threat to marine populations and ecosystems. Given the ubiquity and conserved function of GABA-A receptors, we predict that rising CO2 levels could cause sensory and behavioural impairment in a wide range of marine species, especially those that tightly control their acid-base balance through regulatory changes in HCO3- and Cl- levels.

  15. Alterations in the levels of plasma amino acids in polycystic ovary syndrome- A pilot study

    PubMed Central

    Unni, C. Sumithra N.; Lakshman, Lakshmi R.; Vaidyanathan, Kannan; Subhakumari, K.N.; Menon, N. Leela

    2015-01-01

    Background & objectives: Plasma amino acid levels are known to be altered in conditions like sepsis and burns which are situations of metabolic stress. Polycystic ovary syndrome (PCOS), a condition which affects a woman throughout her life, is said to be associated with metabolic stress. This study was undertaken to assess if there were significant alterations in the levels of plasma amino acids in women with PCOS. Methods: Sixty five women with PCOS along with the similar number of age matched normal controls were included in this study. Levels of 14 amino acids were determined using reverse phase high performance liquid chromatography. Results: The levels of methionine, cystine, isoleucine, phenylalanine, valine, tyrosine, proline, glycine, lysine and histidine were found to be significantly (P<0.001) lower in cases than in controls. Arginine and alanine levels were found to be significantly (P<0.001) higher in cases compared with controls. Interpretation & conclusions: Our findings showed significant derangement in the levels of plasma amino acids in women with PCOS which might be due to the oxidative and metabolic stress associated with it. Further studies need to be done to confirm the findings. PMID:26658589

  16. Fish oil supplementation alters levels of lipid mediators of inflammation in microenvironment of acute human wounds

    PubMed Central

    McDaniel, Jodi C.; Massey, Karen; Nicolaou, Anna

    2013-01-01

    Chronic wounds often result from prolonged inflammation involving excessive polymorphonuclear leukocyte activity. Studies show that the ω-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) found in fish oils generate bioactive lipid mediators that reduce inflammation and polymorphonuclear leukocyte recruitment in numerous inflammatory disease models. This study’s purpose was to test the hypotheses that boosting plasma levels of EPA and DHA with oral supplementation would alter lipid mediator levels in acute wound microenvironments and reduce polymorphonuclear leukocyte levels. Eighteen individuals were randomized to 28 days of either EPA + DHA supplementation (Active Group) or placebo. After 28 days, the Active Group had significantly higher plasma levels of EPA (p < 0.001) and DHA (p < 0.001) than the Placebo Group and significantly lower wound fluid levels of two 15-lipoxygenase products of ω-6 polyunsaturated fatty acids (9-hydroxyoctadecadienoic acid [p=0.033] and 15-hydroxyeicosatrienoic acid [p=0.006]), at 24 hours postwounding. The Active Group also had lower mean levels of myeloperoxidase, a leukocyte marker, at 12 hours and significantly more reepithelialization on Day 5 postwounding. We suggest that lipid mediator profiles can be manipulated by altering polyunsaturated fatty acid intake to create a wound microenvironment more conducive to healing. PMID:21362086

  17. Reproducibility of blood oxygen level-dependent signal changes with end-tidal carbon dioxide alterations.

    PubMed

    Dengel, Donald R; Evanoff, Nicholas G; Marlatt, Kara L; Geijer, Justin R; Mueller, Bryon A; Lim, Kelvin O

    2016-03-02

    Hypercapnia has been utilized as a stimulus to elicit changes in cerebral blood flow (CBF). However, in many instances it has been delivered in a non-controlled method that is often difficult to reproduce. The purpose of this study was to examine the within- and between-visit reproducibility of blood oxygen level-dependent (BOLD) signal changes to an iso-oxic square wave alteration in end-tidal carbon dioxide partial pressure (Pet CO2 ). Two 3-Tesla (3T) MRI scans were performed on the same visit, with two square wave alterations administered per scan. The protocol was repeated on a separate visit with minimum of 3 days between scanning sessions. Pet CO2 was altered to stimulate changes in cerebral vascular reactivity (CVR), while Pet O2 was held constant. Eleven subjects (six females; mean age 26·5 ± 5·7 years) completed the full testing protocol. Excellent within-visit square wave reproducibility (ICC > 0·75) was observed. Similarly, square waves were reproducible between scanning sessions (ICC > 0·7). This study demonstrates BOLD signal changes in response to alterations in Pet CO2 are reproducible both within- and between-visit MRI scans.

  18. High Pressure Germination of Bacillus subtilis Spores with Alterations in Levels and Types of Germination Proteins

    DTIC Science & Technology

    2014-01-01

    1ITLE AND SUBTITLE 5a CONTRACTNUMBER High pressure germination of Bacillus subtilis spores with W911NF-09-l-0286 alterations in levels and types of...A moderate high pressure (mHP) of 150 megaPascals (MPa) triggers germination of Bacillus subtilis spores via germinant receptors (GRs), while...germination by a very high pressure (vHP) of550 MPa is GR-independent. The mHP and vHP germination of Bacillus subtilis spores with different levels ofGRs

  19. Dimethylthiourea inhibition of B16 melanoma growth and induction of phenotypic alterations; relationship to ATP levels.

    PubMed Central

    Fux, A.; Sidi, Y.; Kessler-Icekson, G.; Wasserman, L.; Novogrodsky, A.; Nordenberg, J.

    1991-01-01

    1,3 Dimethylthiourea (DMTU) has previously been shown by us to inhibit the growth of melanoma cells and to induce phenotypic alterations in these cells, including ultrastructural alterations of mitochondria. These findings raised the possibility that impaired mitochondrial function might be involved in mediating the effect of DMTU on cell growth and phenotypic expression. The present study indicates that DMTU as well as another growth inhibitory methylurea derivative, tetramethylurea (TMU) significantly decrease ATP content in the B16 melanoma cell line. 1,3 Dimethylurea (1,3DMU) and 1,1 dimethylurea (1,1DMU) which are poor growth inhibitors, do not reduce ATP content significantly. Altered energy metabolism in the DMTU-treated cells is reflected by inhibition of the activity of cytochrome c oxidase and by increased lactate levels. A cell line selected for resistance to growth inhibition by DMTU was shown to be completely resistant to induction of phenotypic alterations by DMTU. These cells possess high lactate levels, high ATP content and a somewhat decreased Na/K ATPase activity as compared to wild type B16 F10 cells. 1,3 DMTU treatment of the resistant cells leads to a decrease in the activity of the mitochondrial enzyme cytochrome c oxidase, similar to its effect on the wild type B16 F10 cells. DMTU also reduces ATP content moderately in the resistant cells. However, the levels of ATP do not decrease beyond those found in untreated B16 F10 wild type cells. Taken together the results suggest that decreased ATP content might be involved, at least partially, in mediating the effects of DMTU on B16 melanoma cell growth and phenotypic expression. PMID:1850608

  20. The Volitional Nature of Nicotine Exposure Alters Anandamide and Oleoylethanolamide Levels in the Ventral Tegmental Area

    PubMed Central

    Buczynski, Matthew W; Polis, Ilham Y; Parsons, Loren H

    2013-01-01

    Cannabinoid-1 receptors (CB1) have an important role in nicotine reward and their function is disrupted by chronic nicotine exposure, suggesting nicotine-induced alterations in endocannabinoid (eCB) signaling. However, the effects of nicotine on brain eCB levels have not been rigorously evaluated. Volitional intake of nicotine produces physiological and behavioral effects distinct from forced drug administration, although the mechanisms underlying these effects are not known. This study compared the effects of volitional nicotine self-administration (SA) and forced nicotine exposure (yoked administration (YA)) on levels of eCBs and related neuroactive lipids in the ventral tegmental area (VTA) and other brain regions. Brain lipid levels were indexed both by in vivo microdialysis in the VTA and lipid extractions from brain tissues. Nicotine SA, but not YA, reduced baseline VTA dialysate oleoylethanolamide (OEA) levels relative to nicotine-naïve controls, and increased anandamide (AEA) release during nicotine intake. In contrast, all nicotine exposure paradigms increased VTA dialysate 2-arachidonoyl glycerol (2-AG) levels. Thus, nicotine differentially modulates brain lipid (2-AG, AEA, and OEA) signaling, and these modulations are influenced by the volitional nature of the drug exposure. Corresponding bulk tissue analysis failed to identify these lipid changes. Nicotine exposure had no effect on fatty acid amide hydrolase activity in the VTA, suggesting that changes in AEA and OEA signaling result from alterations in their nicotine-induced biosynthesis. Both CB1 (by AEA and 2-AG) and non-CB1 (by OEA) targets can alter the excitability and activity of the dopaminergic neurons in the VTA. Collectively, these findings implicate disrupted lipid signaling in the motivational effects of nicotine. PMID:23169348

  1. A new stress model, a scream sound, alters learning and monoamine levels in rat brain.

    PubMed

    Hu, Lili; Yang, Juan; Song, Tusheng; Hou, Ni; Liu, Yong; Zhao, Xiaoge; Zhang, Dianzeng; Wang, Lumin; Wang, Tao; Huang, Chen

    2014-01-17

    Most existing animal models for stress involve the simultaneous application of physical and psychological stress factors. In the current study, we described and used a novel psychological stress model (scream sound stress). To study the validity of it, we carried out acute and chronic scream sound stress. First, adult Sprague-Dawley (SD) rats were randomly divided into white noise, stress and background groups. The white noise group and stress group were treated with white noise and scream sound for 4h in the morning respectively. Compared with white noise and background groups, exposure to acute scream sound increased corticosterone (CORT) level and decreased latency in Morris water maze (MWM) test. The levels of noradrenaline (NE), dopamine (DA), 5-hydroxytryptamine (5-HT), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were altered in the striatum, hypothalamus and hippocampus of stress rats. Second, adult SD rats were randomly divided into background and stress groups, which were treated with scream sound for three weeks. Exposure to chronic scream sound suppressed body weight gain, increased corticosterone (CORT) level, influenced the morphology of adrenal gland, improved spleen and thymus indices, and decreased latency in MWM test. NE, DA, DOPAC, HVA and 5-HIAA levels were also altered in the brain of stress rats. Our results suggested that scream sound, as a novel stressor, facilitated learning ability, as well as altered monoamine levels in the rat brain. Moreover, scream sound is easy to apply and can be applied in more animals at the same time.

  2. The volitional nature of nicotine exposure alters anandamide and oleoylethanolamide levels in the ventral tegmental area.

    PubMed

    Buczynski, Matthew W; Polis, Ilham Y; Parsons, Loren H

    2013-03-01

    Cannabinoid-1 receptors (CB(1)) have an important role in nicotine reward and their function is disrupted by chronic nicotine exposure, suggesting nicotine-induced alterations in endocannabinoid (eCB) signaling. However, the effects of nicotine on brain eCB levels have not been rigorously evaluated. Volitional intake of nicotine produces physiological and behavioral effects distinct from forced drug administration, although the mechanisms underlying these effects are not known. This study compared the effects of volitional nicotine self-administration (SA) and forced nicotine exposure (yoked administration (YA)) on levels of eCBs and related neuroactive lipids in the ventral tegmental area (VTA) and other brain regions. Brain lipid levels were indexed both by in vivo microdialysis in the VTA and lipid extractions from brain tissues. Nicotine SA, but not YA, reduced baseline VTA dialysate oleoylethanolamide (OEA) levels relative to nicotine-naïve controls, and increased anandamide (AEA) release during nicotine intake. In contrast, all nicotine exposure paradigms increased VTA dialysate 2-arachidonoyl glycerol (2-AG) levels. Thus, nicotine differentially modulates brain lipid (2-AG, AEA, and OEA) signaling, and these modulations are influenced by the volitional nature of the drug exposure. Corresponding bulk tissue analysis failed to identify these lipid changes. Nicotine exposure had no effect on fatty acid amide hydrolase activity in the VTA, suggesting that changes in AEA and OEA signaling result from alterations in their nicotine-induced biosynthesis. Both CB(1) (by AEA and 2-AG) and non-CB(1) (by OEA) targets can alter the excitability and activity of the dopaminergic neurons in the VTA. Collectively, these findings implicate disrupted lipid signaling in the motivational effects of nicotine.

  3. Maternal folic acid supplementation to dams on marginal protein level alters brain fatty acid levels of their adult offspring.

    PubMed

    Rao, Shobha; Joshi, Sadhana; Kale, Anvita; Hegde, Mahabaleshwar; Mahadik, Sahebarao

    2006-05-01

    Studies on fetal programming of adult diseases have highlighted the importance of maternal nutrition during pregnancy. Folic acid and long-chain essential polyunsaturated fatty acids (LC-PUFAs) have independent effects on fetal growth. However, folic acid effects may also involve alteration of LC-PUFA metabolism. Because marginal deficiency of LC-PUFAs during critical periods of brain growth and development is associated with risks for adult diseases, it is highly relevant to investigate how maternal supplementation of such nutrients can alter brain fatty acid levels. We examined the impact of folic acid supplementation, conventionally used in maternal intervention, on brain essential fatty acid levels and plasma corticosterone concentrations in adult offspring at 11 months of age. Pregnant female rats from 4 groups (6 in each) were fed with casein diets either with 18 g protein/100 g diet (control diet) or treatment diets that were marginal in protein (MP), such as 12 g protein/100 g diet supplemented with 8 mg folic acid (FAS/MP), 12 g protein/100 g diet without folic acid (FAD/MP), or 12 g protein/100 g diet (MP) with 2 mg folic acid. Pups were weaned to a standard laboratory diet with 18 g protein/100 g diet. All male adult offspring in the FAS/MP group showed lower docosahexaenoic acid (P<.05) as compared with control adult offspring (6.04+/-2.28 vs 10.33+/-0.86 g/100 g fatty acids) and higher n-6/n-3 ratio (P<.05). Docosahexaenoic acid levels in FAS/MP adult offspring were also lower (P<.05) when compared with the MP group. Plasma corticosterone concentrations were higher (P<.05) in male adult offspring from the FAS/MP group compared with control as well as the MP adult offspring. Results suggest that maternal folic acid supplementation at MP intake decreased brain docosahexaenoic acid levels probably involving corticosterone increase.

  4. A Universal Phylogenetic Tree.

    ERIC Educational Resources Information Center

    Offner, Susan

    2001-01-01

    Presents a universal phylogenetic tree suitable for use in high school and college-level biology classrooms. Illustrates the antiquity of life and that all life is related, even if it dates back 3.5 billion years. Reflects important evolutionary relationships and provides an exciting way to learn about the history of life. (SAH)

  5. The effect of altered 5-hydroxytryptamine levels on beta-endorphin

    NASA Technical Reports Server (NTRS)

    Soliman, Karam F. A.; Mash, Deborah C.; Walker, Charles A.

    1986-01-01

    The purpose of the present study was to examine the effect of altering the concentration of 5-hydroxytryptamine (5-HT) on beta-endorphin (beta-Ep) content in the hypothalamus, thalamus, and periaqueductal gray (PAG)-rostral pons regions of the rat brain. The selective 5-HT reuptake inhibitor, fluoxetine (10 mg/kg), significantly lowered beta-Ep content in the hypothalamus and the PAG. Parachlorophenylalanine, which inhibits 5-HT synthesis, significantly elevated beta-Ep in all brain parts studied. Intracisternal injections of the neurotoxin 5-prime, 7-prime-dihydroxytryptamine with desmethylimipramine pretreatment significantly increased beta-Ep content in the hypothalamus and the PAG. In adrenalectomized rats, fluoxetine significantly decreased beta-Ep levels in the hypothalamus and increased the levels in the PAG. The results indicate that 5-HT may modulate the levels of brain beta-Ep.

  6. Modulation of ROS levels in fibroblasts by altering mitochondria regulates the process of wound healing.

    PubMed

    Janda, Jaroslav; Nfonsam, Valentine; Calienes, Fernanda; Sligh, James E; Jandova, Jana

    2016-05-01

    Mitochondria are the major source of reactive oxygen species (ROS) in fibroblasts which are thought to be crucial regulators of wound healing with a potential to affect the expression of nuclear genes involved in this process. ROS generated by mitochondria are involved in all stages of tissue repair process but the regulation of ROS-generating system in fibroblasts still remains poorly understood. The purpose of this study was to better understand molecular mechanisms of how the regulation of ROS levels generated by mitochondria may influence the process of wound repair. Cybrid model system of mtDNA variations was used to study the functional consequences of altered ROS levels on wound healing responses in a uniform nuclear background of cultured ρ(0) fibroblasts. Mitochondrial ROS in cybrids were modulated by antioxidants that quench ROS to examine their ability to close the wound. Real-time PCR arrays were used to investigate whether ROS generated by specific mtDNA variants have the ability to alter expression of some key nuclear-encoded genes central to the wound healing response and oxidative stress. Our data suggest levels of mitochondrial ROS affect expression of some nuclear encoded genes central to wound healing response and oxidative stress and modulation of mitochondrial ROS by antioxidants positively affects in vitro process of wound closure. Thus, regulation of mitochondrial ROS-generating system in fibroblasts can be used as effective natural redox-based strategy to help treat non-healing wounds.

  7. Detection of TTV in peripheral blood cells from patients with altered ALT and AST levels.

    PubMed

    de Oliveira, Jaqueline Carvalho; Nasser, Thiago Franco; Oda, Julie Massayo Maeda; Aoki, Mateus Nóbrega; Carneiro, Juliana Laino do Val; Barbosa, Décio Sabbatini; Reiche, Edna Maria Vissoci; Watanabe, Maria Angelica Ehara

    2008-04-01

    This work analyzes the prevalence of TTV DNA in peripheral blood cells from patients with hepatic alterations and healthy blood donors and measures levels of sodium, potassium, urea, creatinine, phosphatase alkaline, total and direct bilirubin, gamma glutamyl transferase (GGT), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in certain randomly selected patients. DNA samples from 111 individuals were evaluated. They were divided into two groups, "A" (study) and "B" (control), including 54 patients with liver enzyme alterations (ALT/AST) presenting non-B-non-C hepatitis and 57 blood donors, respectively. TTV DNA was determined by nested PCR. Certain products of the second-round PCR were sequenced. Serum biochemical assay was performed and disclosed TTV in 31.48% (17/54) of patients in group A and 5.26% (3/57) in the control group B. TTV prevalence was significantly higher in patients with liver disease than in healthy donors. In group A, sodium, potassium, urea, creatinine, phosphatase alkaline, total and direct bilirubin, gamma glutamyl transferase (GGT), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were analyzed in certain randomly selected patients and no significant difference in biochemical levels (p>0.05) was found when TTV infected and noninfected individuals were compared. Knowledge related to TTV has rapidly increased, but many fundamental aspects remain unclear. This led us to question the role of TTV and doubt remains as to whether or not it is just a commensal virus. Further studies are necessary to confirm and extend these findings.

  8. Methoxychlor reduces estradiol levels by altering steroidogenesis and metabolism in mouse antral follicles in vitro.

    PubMed

    Basavarajappa, Mallikarjuna S; Craig, Zelieann R; Hernández-Ochoa, Isabel; Paulose, Tessie; Leslie, Traci C; Flaws, Jodi A

    2011-06-15

    The organochlorine pesticide methoxychlor (MXC) is a known endocrine disruptor that affects adult rodent females by causing reduced fertility, persistent estrus, and ovarian atrophy. Since MXC is also known to target antral follicles, the major producer of sex steroids in the ovary, the present study was designed to test the hypothesis that MXC decreases estradiol (E₂) levels by altering steroidogenic and metabolic enzymes in the antral follicles. To test this hypothesis, antral follicles were isolated from CD-1 mouse ovaries and cultured with either dimethylsulfoxide (DMSO) or MXC. Follicle growth was measured every 24 h for 96 h. In addition, sex steroid hormone levels were measured using enzyme-linked immunosorbent assays (ELISA) and mRNA expression levels of steroidogenic enzymes as well as the E₂ metabolic enzyme Cyp1b1 were measured using qPCR. The results indicate that MXC decreased E₂, testosterone, androstenedione, and progesterone (P₄) levels compared to DMSO. In addition, MXC decreased expression of aromatase (Cyp19a1), 17β-hydroxysteroid dehydrogenase 1 (Hsd17b1), 17α-hydroxylase/17,20-lyase (Cyp17a1), 3β hydroxysteroid dehydrogenase 1 (Hsd3b1), cholesterol side-chain cleavage (Cyp11a1), steroid acute regulatory protein (Star), and increased expression of Cyp1b1 enzyme levels. Thus, these data suggest that MXC decreases steroidogenic enzyme levels, increases metabolic enzyme expression and this in turn leads to decreased sex steroid hormone levels.

  9. Alterations in serum immunoglobulin levels in workers occupationally exposed to trichloroethylene

    PubMed Central

    Zhang, Luoping; Bassig, Bryan A.; Huang, Hanlin; Tang, Xiaojiang; Rothman, Nathaniel; Lan, Qing

    2013-01-01

    Trichloroethylene (TCE) has been associated with a variety of immunotoxic effects and may be associated with an increased risk of non-Hodgkin lymphoma (NHL). Altered serum immunoglobulin (Ig) levels have been reported in NHL patients and in animals exposed to TCE. Recently, we reported that occupational exposure to TCE is associated with immunosuppressive effects and immune dysfunction, including suppression of B-cell counts and activation, even at relatively low levels. We hypothesized that TCE exposure would also affect Ig levels in humans. We measured serum levels of IgG, IgM and IgE, by enzyme-linked immunosorbent assay, in TCE-exposed workers (n = 80) and unexposed controls (n = 45), matched by age and gender, in a cross-sectional, molecular epidemiology study of occupational exposure to TCE in Guangdong, China. Exposed workers had about a 17.5% decline in serum levels of IgG compared with unexposed controls (P = 0.0002). Similarly, serum levels of IgM were reduced by about 38% in workers exposed to TCE compared with unexposed controls (P < 0.0001). Serum levels of both IgG and IgM were significantly decreased in workers exposed to TCE levels below 12 p.p.m., the median exposure level. Adjustment for B-cell counts had minimal impact on our findings. IgE levels were not significantly different between exposed and control subjects. These results provide further evidence that TCE is immunotoxic at relatively low exposure levels and provide additional biologic plausibility for the reported association of TCE with NHL. PMID:23276795

  10. Steroid levels in crinoid echinoderms are altered by exposure to model endocrine disruptors.

    PubMed

    Lavado, Ramón; Barbaglio, Alice; Carnevali, M Daniela Candia; Porte, Cinta

    2006-06-01

    Sexual steroids (testosterone and estradiol) were measured in the whole body of wild specimens of the crinoid Antedon mediterranea collected from the Tyrrhenian Sea (Italy). Testosterone levels (274-1,488 pg/g wet weight (w.w.)) were higher than those of estradiol (60-442 pg/g w.w.) and no significant differences between males and females were observed. No clear seasonal trend was either detected - individuals from February, June and October 2004 analyzed - apart from a peak of estradiol in males in autumn. Nonetheless, dramatic changes on tissue steroid levels were observed when individuals were exposed to model androgenic and anti-androgenic compounds for 2 and 4 weeks. The selected compounds were 17 alpha-methyltestosterone (17 alpha-MT), triphenyltin (TPT), fenarimol (FEN), cyproterone acetate (CPA), and p,p'-DDE. Endogenous testosterone levels were significantly increased after exposure to 17 alpha-MT, TPT and FEN, while different responses were observed for estradiol; 17 alpha-MT and FEN increased endogenous estradiol (up to seven-fold), and TPT lead to a significant decrease. Concerning the anti-androgenic compounds, CPA significantly reduced testosterone in a dose-dependent manner without altering estradiol levels, whereas specimens exposed to p,p'-DDE at a low dose (24 ng/L) for 4 weeks showed a four-fold increase in T levels. Overall, the data show the ability of the selected compounds to alter endogenous steroid concentrations in A. mediterranea, and suggest the existence in this echinoderm species of vertebrate-like mechanisms that can be affected by exposure to androgenic and anti-androgenic chemicals.

  11. Dihydrotestosterone alters cyclooxygenase-2 levels in human coronary artery smooth muscle cells

    PubMed Central

    Osterlund, Kristen L.; Handa, Robert J.

    2010-01-01

    Both protective and nonprotective effects of androgens on the cardiovascular system have been reported. Our previous studies show that the potent androgen receptor (AR) agonist dihydrotestosterone (DHT) increases levels of the vascular inflammatory mediator cyclooxygenase (COX)-2 in rodent cerebral arteries independent of an inflammatory stimulus. Little is known about the effects of androgens on inflammation in human vascular tissues. Therefore, we tested the hypothesis that DHT alters COX-2 levels in the absence and presence of induced inflammation in primary human coronary artery smooth muscle cells (HCASMC). Furthermore, we tested the ancillary hypothesis that DHT's effects on COX-2 levels are AR-dependent. Cells were treated with DHT (10 nM) or vehicle for 6 h in the presence or absence of LPS or IL-1β. Similar to previous observations in rodent arteries, in HCASMC, DHT alone increased COX-2 levels compared with vehicle. This effect of DHT was attenuated in the presence of the AR antagonist bicalutamide. Conversely, in the presence of LPS or IL-1β, increases in COX-2 were attenuated by cotreatment with DHT. Bicalutamide did not affect this response, suggesting that DHT-induced decreases in COX-2 levels occur independent of AR stimulation. Thus we conclude that DHT differentially influences COX-2 levels under physiological and pathophysiological conditions in HCASMC. This effect of DHT on COX-2 involves AR-dependent and- independent mechanisms, depending on the physiological state of the cell. PMID:20103743

  12. Influence of Altered Mass Loading on Testosterone Levels and Testicular Mass

    NASA Technical Reports Server (NTRS)

    Wang, Tommy J.; Ortiz, R. M.; Wade, C. E.; Hargens, Alan R. (Technical Monitor)

    1996-01-01

    Effects of altered load on testosterone levels and testicular mass in mammals are not well defined. Two separate studies (loading;centrifuged; +2G(sub z) and unloading;hindlimb suspension;HLS) were conducted to provide a better understanding of the effects of mass loading on testosterone levels and testicular mass. Daily urine samples were collected, and testicular mass measured at the end of the study. +2G(sub z): Sprague-Dawley rats (230-250 g) were centrifuged for 12 days at +2G(sub z): 8 centrifuged (EC) and 8 off centrifuge controls (OCC). EC had lower body mass, however relative testicular mass was greater. EC exhibited an increase in excreted testosterone levels between days 2 (T2) and 6 (T6), and returned to baseline at T9. HLS: To assess the effects of unloading Sprague-Dawley rats (125-150 g) were studied for 12 days: 10 suspended (Exp) and 10 ambulatory (Ctl). Exp had lower body mass during the study, with reduced absolute and relative testicular mass. Exp demonstrated lower excreted testosterone levels from T5-T12. Conclusions: Loading appears to stimulate anabolism, as opposed to unloading, as indicated by greater relative testicular mass and excreted testosterone levels. Reported changes in muscle mass during loading and unloading coincide with similar changes in excreted testosterone levels.

  13. Brain Injury Alters Ectonucleotidase Activities and Adenine Nucleotide Levels in Rat Serum

    PubMed Central

    Laketa, Danijela; Savić, Jasmina; Bjelobaba, Ivana; Lavrnja, Irena; Vasić, Vesna; Stojiljković, Mirjana; Nedeljković, Nadežda

    2015-01-01

    Summary Background Cortical stab injury (CSI) induces changes in the activity, expression and cellular distribution of specific ectonucleotidases at the injury site. Also, several experimentally induced neuropathologies are associated with changes in soluble ectonucleotidase activities in the plasma and serum, whilst various insults to the brain alter purine compounds levels in cerebrospinal fluid, but also in serum, indicating that insults to the brain may induce alterations in nucleotides release and rate of their hydrolysis in the vascular system. Since adenine nucleotides and adenosine regulate diverse cellular functions in the vascular system, including vascular tone, platelet aggregation and inflammatory responses of lymphocytes and macrophages, alterations of ectonucleotidase activities in the vascular system may be relevant for the clinical outcome of the primary insult. Methods We explored ectonucleotidase activities using specific enzyme assays and determined adenine nucleotides concentrations by the UPLC method in the rat serum after cortical stab injury. Results At 4-h post-injury, ATP and AMP hydrolysis increased by about 60% and 40%, respectively, while phosphodiesterase activity remained unchanged. Also, at 4-h post-injury a marked decrease in ATP concentration and more than 2-fold increase in AMP concentration were recorded. Conclusions CSI induces rapid up-regulation of nucleotide catabolizing soluble ectonucleotidases in rat serum, which leads to the observed shift in serum nucleotide levels. The results obtained imply that ectonucleotidases and adenine nucleotides participate in the communication between the brain and the vascular system in physiological and pathological conditions and thereby may be involved in the development of various human neuropathologies.

  14. Prenatal exposure to pesticides disrupts testicular histoarchitecture and alters testosterone levels in male Caiman latirostris.

    PubMed

    Rey, Florencia; González, Marianela; Zayas, Marcelo A; Stoker, Cora; Durando, Milena; Luque, Enrique H; Muñoz-de-Toro, Mónica

    2009-07-01

    The increased use of agrochemical pesticides, such as atrazine (ATZ) and endosulfan (END), may have a significant impact on ecosystem health and biodiversity. The aim of this study was to investigate the consequences of in ovum exposure to ATZ and END on Caiman latirostris gonadal histo-functional features. Caiman eggs were collected from environmentally pristine areas and incubated in controlled conditions at male producing temperature (33 degrees C). At stage 20 of embryonic development, the sensitive stage for gonadal sex determination, eggs were exposed to one dose of either END or ATZ. Gonadal histo-morphology was examined in caiman hatchlings and serum levels of testosterone were measured. Regardless of treatment condition, all eggs incubated at 33 degrees C resulted in male hatchlings. Tortuous seminiferous tubules with increased perimeter, disrupted distribution of peritubular myoid cells (desmin positive), and emptied tubular lumens characterized the testes of pesticide-exposed caiman. An imbalance between proliferative activity and cell death was observed in the testes of caiman exposed to the higher doses of END, mainly due to a high frequency of apoptosis in intratubular cells. This altered cell turnover was associated with decreased testosterone levels. Prenatal exposure to only one dose of END and ATZ disrupted neonatal male gonadal histo-functional features. Alterations described here could have detrimental effects on the sexual maturation of the caiman and, ultimately, on the success of male caiman reproduction.

  15. Marine mollusc predator-escape behaviour altered by near-future carbon dioxide levels.

    PubMed

    Watson, Sue-Ann; Lefevre, Sjannie; McCormick, Mark I; Domenici, Paolo; Nilsson, Göran E; Munday, Philip L

    2014-01-07

    Ocean acidification poses a range of threats to marine invertebrates; however, the potential effects of rising carbon dioxide (CO2) on marine invertebrate behaviour are largely unknown. Marine gastropod conch snails have a modified foot and operculum allowing them to leap backwards rapidly when faced with a predator, such as a venomous cone shell. Here, we show that projected near-future seawater CO2 levels (961 µatm) impair this escape behaviour during a predator-prey interaction. Elevated-CO2 halved the number of snails that jumped from the predator, increased their latency to jump and altered their escape trajectory. Physical ability to jump was not affected by elevated-CO2 indicating instead that decision-making was impaired. Antipredator behaviour was fully restored by treatment with gabazine, a GABA antagonist of some invertebrate nervous systems, indicating potential interference of neurotransmitter receptor function by elevated-CO2, as previously observed in marine fishes. Altered behaviour of marine invertebrates at projected future CO2 levels could have potentially far-reaching implications for marine ecosystems.

  16. Rat hippocampal alterations could underlie behavioral abnormalities induced by exposure to moderate noise levels.

    PubMed

    Uran, S L; Aon-Bertolino, M L; Caceres, L G; Capani, F; Guelman, L R

    2012-08-30

    Noise exposure is known to affect auditory structures in living organisms. However, it should not be ignored that many of the effects of noise are extra-auditory. Previous findings of our laboratory demonstrated that noise was able to induce behavioral alterations that are mainly related to the cerebellum (CE) and the hippocampus (HC). Therefore, the aim of this work was to reveal new data about the vulnerability of developing rat HC to moderate noise levels through the assessment of potential histological changes and hippocampal-related behavioral alterations. Male Wistar rats were exposed to noise (95-97 dB SPL, 2h daily) either for 1 day (acute noise exposure, ANE) or between postnatal days 15 and 30 (sub-acute noise exposure, SANE). Hippocampal histological evaluation as well as short (ST) and long term (LT) habituation and recognition memory assessments were performed. Results showed a mild disruption in the different hippocampal regions after ANE and SANE schemes, along with significant behavioral abnormalities. These data suggest that exposure of developing rats to noise levels of moderate intensity is able to trigger changes in the HC, an extra-auditory structure of the Central Nervous System (CNS), that could underlie the observed behavioral effects.

  17. Effect of altered reproductive function and lowered testosterone levels on bone density in male endurance athletes

    PubMed Central

    Bennell, Kim L; Brukner, Peter D; Malcolm, Susan A

    1996-01-01

    The effect of intense physical activity on female reproductive hormones is well recognised1–3 and there is evidence that menstrual disturbances associated with hypo-oestrogenism adversely affect bone density especially at the lumbar spine.4 5 Physical activity can also have a range of effects on male reproductive function depending upon the intensity and duration of the activity and the fitness of the individual.6 In particular, endurance training may be associated with reductions in circulating testosterone levels. Since testosterone has important anabolic roles, alterations in reproductive hormone profiles may have detrimental skeletal consequences similar to those seen in females with menstrual disturbances. The aim of this brief review is to present the limited literature on the relation between bone density and testosterone levels in male endurance athletes. PMID:8889111

  18. Altered protein levels in the isolated extracellular matrix of failing human hearts with dilated cardiomyopathy.

    PubMed

    DeAguero, Joshua L; McKown, Elizabeth N; Zhang, Liwen; Keirsey, Jeremy; Fischer, Edgar G; Samedi, Von G; Canan, Benjamin D; Kilic, Ahmet; Janssen, Paul M L; Delfín, Dawn A

    Dilated cardiomyopathy (DCM) is associated with extensive pathological cardiac remodeling and involves numerous changes in the protein expression profile of the extracellular matrix of the heart. We obtained seven human, end-stage, failing hearts with DCM (DCM-failing) and nine human, nonfailing donor hearts and compared their extracellular matrix protein profiles. We first showed that the DCM-failing hearts had indeed undergone extensive remodeling of the left ventricle myocardium relative to nonfailing hearts. We then isolated the extracellular matrix from a subset of these hearts and performed a proteomic analysis on the isolated matrices. We found that the levels of 26 structural proteins were altered in the DCM-failing isolated cardiac extracellular matrix compared to nonfailing isolated cardiac extracellular matrix. Overall, most of the extracellular matrix proteins showed reduced levels in the DCM-failing hearts, while all of the contractile proteins showed increased levels. There was a mixture of increased and decreased levels of cytoskeletal and nuclear transport proteins. Using immunoprobing, we verified that collagen IV (α2 and α6 isoforms), zyxin, and myomesin protein levels were reduced in the DCM-failing hearts. We expect that these data will add to the understanding of the pathology associated with heart failure with DCM.

  19. Endocannabinoid and ceramide levels are altered in patients with colorectal cancer.

    PubMed

    Chen, Ling; Chen, Huixia; Li, Yanting; Li, Lei; Qiu, Yan; Ren, Jie

    2015-07-01

    Endocannabinoids and ceramides have demonstrated growth inhibition, cell death induction and pro-apoptotic activity in cancer research. In the present study, we describe the profiles of two major endocannabinoids, ceramides, free fatty acids and relevant metabolic enzymes in 47 pairs of human colorectal cancer tissues and adjacent non-tumor tissues. Among them, anandamide (AEA) and its metabolite, arachidonic acid (AA), were markedly upregulated in cancer tissues particularly in those with lymphatic metastasis. The levels of C16 and C24 ceramides were significantly elevated in the colorectal tumor tissues, while levels of C18 and C20 ceramides showed opposite trends. Levels of two enzymes participating in the biosynthesis and degradation of AEA, N-acyl-phosphatidylethanolamine-hydrolyzing phospholipase D (NPLD) and fatty acid amide hydrolase (FAAH), together with the most abundant ceramide synthases (CerS1, CerS2, CerS5 and CerS6) in the colon were also determined. Quantitative-PCR analysis indicated that the mRNA levels of these enzymes were overexpressed in the tumor tissues. The activities of NPLD and FAAH were also upregulated. In addition, both gene and protein expression levels of cannabinoid receptor 1 (CB1) were elevated but not of CB2. Elevation of AEA and alteration of ceramides (C16, C24, C18, C20) may qualify as potential endogenous biomarkers and novel drug targets for colorectal cancer.

  20. Soluble Endoglin Level Increase Occurs Prior to Development of Subclinical Structural Vascular Alterations in Diabetic Adolescents

    PubMed Central

    Emeksiz, Hamdi Cihan; Bideci, Aysun; Damar, Çağrı; Derinkuyu, Betül; Çelik, Nurullah; Döğer, Esra; Yüce, Özge; Özmen, Mehmet Cüneyt; Çamurdan, Mahmut Orhun; Cinaz, Peyami

    2016-01-01

    Objective: Soluble endoglin (S-endoglin) has been implicated as a potential marker of endothelial dysfunction (ED) and was reported to be elevated in diabetic adults, correlating with the severity of diabetic vasculopathy. However, circulating S-endoglin and its association with other markers of ED have not been formerly analyzed in the first decade of diabetes onset in adolescents with type 1 diabetes mellitus (T1DM). Methods: Fifty-eight adolescents with moderately/poorly controlled T1DM were included in this study and twenty-nine healthy adolescents served as controls. The diabetic group was divided into two groups based on the presence of microalbuminuria, as the microalbuminuria group (n=15) and the normoalbuminuria group (n=43). Functional vascular alterations were evaluated by measuring serum S-endoglin and plasma nitric oxide (NO) concentrations, the flow-mediated dilatation (FMD) of the brachial artery. Carotid intima media thickness (CIMT) was measured for evaluation of structural vascular alterations. Results: The S-endoglin and NO levels of both microalbuminuria and normoalbuminuria groups were higher than those of the control group (for S-endoglin, p=0.047 and p<0.001; for NO, p=0.004 and p=0.006, respectively). The FMD percent was lower in the microalbuminuria group compared to the normoalbuminuria and control groups (p=0.036 and p=0.020, respectively). There were negative correlations between S-endoglin concentration and FMD percent (r=-0.213, p=0.051) and between serum S-endoglin concentration and albumin excretion rate (r=-0.361, p=0.005). No significant differences were found in CIMT among any of the groups (p=0.443). Conclusion: In adolescents with T1DM, S-endoglin concentrations might increase in parallel to the deterioration in endothelial function before subclinical structural vascular alterations become evident. PMID:27097763

  1. Altering footwear type influences gait during level walking and downhill transitions.

    PubMed

    Stern, Keith A; Gottschall, Jinger S

    2012-11-01

    The purpose of our study was to determine if altering the insoles within footwear or walking barefoot, as an attempt to increase or decrease cutaneous stimuli, would improve dynamic balance during a hill-walking task. We hypothesize that compared with foam insoles or iced bare feet, textured insoles or bare feet will result in greater speeds, longer step lengths, narrower step width, shorter stance time, and less tibialis anterior (TA), soleus (SOL), and lateral gastrocnemius (LG) activity during key gait cycle phases. Ten, healthy college students, 5 men and 5 women, completed the protocol that consisted of level walking and downhill transition walking in five different footwear insole or barefoot conditions. During level walking, conditions with the hypothesized greater cutaneous stimuli resulted in greater step length, which relates to a more stable gait. In detail, the texture insole condition average step length was 3% longer than the regular insole condition, which was 5% longer than the ice condition (p < .01). The same signals of increased stability were evident during the more challenging downhill transition stride. Step length during the barefoot condition was 8% longer than the ice condition (p < .05) and step width during the regular footwear condition was 5% narrower than the foam condition (p = .05). To add, during the preswing phase of level walking, TA activity of the textured insole condition was 30% less than the foam insole. Although our data show that footwear conditions alter gait patterns and lower leg muscle activity during walking, there is not enough evidence to support the hypothesis that textured insoles will improve dynamic balance as compared with other footwear types.

  2. Cognitive and cortical plasticity deficits correlate with altered amyloid-β CSF levels in multiple sclerosis.

    PubMed

    Mori, Francesco; Rossi, Silvia; Sancesario, Giulia; Codecà, Claudia; Mataluni, Giorgia; Monteleone, Fabrizia; Buttari, Fabio; Kusayanagi, Hajime; Castelli, Maura; Motta, Caterina; Studer, Valeria; Bernardi, Giorgio; Koch, Giacomo; Bernardini, Sergio; Centonze, Diego

    2011-02-01

    Cognitive dysfunction is of frequent observation in multiple sclerosis (MS). It is associated with gray matter pathology, brain atrophy, and altered connectivity, and recent evidence showed that acute inflammation can exacerbate mental deficits independently of the primary functional system involved. In this study, we measured cerebrospinal fluid (CSF) levels of amyloid-β(1-42) and τ protein in MS and in clinically isolated syndrome patients, as both proteins have been associated with cognitive decline in Alzheimer's disease (AD). In AD, amyloid-β(1-42) accumulates in the brain as insoluble extracellular plaques, possibly explaining why soluble amyloid-β(1-42) is reduced in the CSF of these patients. In our sample of MS patients, amyloid-β(1-42) levels were significantly lower in patients cognitively impaired (CI) and were inversely correlated with the number of Gadolinium-enhancing (Gd+) lesions at the magnetic resonance imaging (MRI). Positive correlations between amyloid-β(1-42) levels and measures of attention and concentration were also found. Furthermore, abnormal neuroplasticity of the cerebral cortex, explored with θ burst stimulation (TBS), was observed in CI patients, and a positive correlation was found between amyloid-β(1-42) CSF contents and the magnitude of long-term potentiation-like effects induced by TBS. No correlation was conversely found between τ protein concentrations and MRI findings, cognitive parameters, and TBS effects in these patients. Together, our results indicate that in MS, central inflammation is able to alter amyloid-β metabolism by reducing its concentration in the CSF and leading to impairment of synaptic plasticity and cognitive function.

  3. Reproductive experience alters corticosterone and CBG levels in the rat dam.

    PubMed

    Pawluski, Jodi L; Charlier, Thierry D; Lieblich, Stephanie E; Hammond, Geoffrey L; Galea, Liisa A M

    2009-01-08

    Reproductive experience has significant effects on the brain, behavior and hormone profiles of the mother. Recent work has demonstrated that primiparous rats exhibit decreased dendritic arborizations in the hippocampus, and enhanced hippocampus-dependent spatial memory performance at the time of weaning compared to nulliparous and, to a lesser degree, multiparous rats. Interestingly, enhanced spatial learning and reduced dendritic arbors are seen in nulliparous female rats exposed to chronic stress or repeated corticosterone administration. Based on these observations, we hypothesized that corticosterone may be altered in primiparous rats compared to multiparous and nulliparous rats. The present study investigated whether the levels of circulating corticosterone and its binding protein, corticosteroid binding globulin (CBG), are altered with reproductive experience and pup-exposure during late pregnancy and the postpartum. Total serum corticosterone and CBG were assayed from five groups; multiparous, primiparous, nulliparous, primip-no-pups, and sensitized rats during gestation (days 14 and 19) and the postpartum period (days 1, 5, 14, 21, and 35). Results show that primiparous rats had significantly elevated total corticosterone on postpartum day 1. In addition, primiparous and multiparous rats had significantly lower CBG throughout the postpartum period than all other groups, with primiparous rats exhibiting lower levels than multiparous rats during mid-lactation. These data suggest that free corticosterone is elevated in both primiparous and multiparous dams and is elevated to a greater degree in primiparous compared to multiparous dams during lactation. Corticosterone and CBG levels were positively correlated with specific maternal behaviors during the first week postpartum in parturient rats, but not in sensitized rats, suggesting a role for corticosterone in the modulation of maternal behavior in parturient rats alone.

  4. Pesticide Exposure Alters Follicle-Stimulating Hormone Levels in Mexican Agricultural Workers

    PubMed Central

    Recio, Rogelio; Ocampo-Gómez, Guadalupe; Morán-Martínez, Javier; Borja-Aburto, Victor; López-Cervantes, Malaquías; Uribe, Marisela; Torres-Sánchez, Luisa; Cebrián, Mariano E.

    2005-01-01

    Organophosphorous pesticides (OPs) are suspected of altering reproductive function by reducing brain acetylcholinesterase activity and monoamine levels, thus impairing hypothalamic and/or pituitary endocrine functions and gonadal processes. Our objective was to evaluate in a longitudinal study the association between OP exposure and serum levels of pituitary and sex hormones. Urinary OP metabolite levels were measured by gas–liquid chromatography, and serum pituitary and sex hormone levels by enzymatic immunoassay and radioimmunoassay in 64 men. A total of 147 urine and blood samples were analyzed for each parameter. More than 80% of the participants had at least one OP metabolite in their urine samples. The most frequent metabolite found was diethylthiophosphate (DETP; 55%), followed by diethylphosphate (DEP; 46%), dimethylthiophosphate (DMTP; 32%), and dimethyldithiophosphate (DMDTP; 31%). However, the metabolites detected at higher concentrations were DMTP, DEP, DMDTP, and dimethylphosphate. There was a high proportion of individuals with follicle-stimulating hormone (FSH) concentrations outside the range of normality (48%). The average FSH serum levels were higher during the heavy pesticide spraying season. However, a multivariate analysis of data collected in all periods showed that serum FSH levels were negatively associated with urinary concentrations of both DMTP and DMDTP, whereas luteinizing hormone (LH) was negatively associated with DMTP. We observed no significant associations between estradiol or testosterone serum levels with OP metabolites. The hormonal disruption in agricultural workers presented here, together with results from experimental animal studies, suggests that OP exposure disrupts the hypothalamic–pituitary endocrine function and also indicates that FSH and LH are the hormones most affected. PMID:16140621

  5. Methoxychlor reduces estradiol levels by altering steroidogenesis and metabolism in mouse antral follicles in vitro

    SciTech Connect

    Basavarajappa, Mallikarjuna S. Craig, Zelieann R. Hernandez-Ochoa, Isabel Paulose, Tessie Leslie, Traci C. Flaws, Jodi A.

    2011-06-15

    The organochlorine pesticide methoxychlor (MXC) is a known endocrine disruptor that affects adult rodent females by causing reduced fertility, persistent estrus, and ovarian atrophy. Since MXC is also known to target antral follicles, the major producer of sex steroids in the ovary, the present study was designed to test the hypothesis that MXC decreases estradiol (E{sub 2}) levels by altering steroidogenic and metabolic enzymes in the antral follicles. To test this hypothesis, antral follicles were isolated from CD-1 mouse ovaries and cultured with either dimethylsulfoxide (DMSO) or MXC. Follicle growth was measured every 24 h for 96 h. In addition, sex steroid hormone levels were measured using enzyme-linked immunosorbent assays (ELISA) and mRNA expression levels of steroidogenic enzymes as well as the E{sub 2} metabolic enzyme Cyp1b1 were measured using qPCR. The results indicate that MXC decreased E{sub 2}, testosterone, androstenedione, and progesterone (P{sub 4}) levels compared to DMSO. In addition, MXC decreased expression of aromatase (Cyp19a1), 17{beta}-hydroxysteroid dehydrogenase 1 (Hsd17b1), 17{alpha}-hydroxylase/17,20-lyase (Cyp17a1), 3{beta} hydroxysteroid dehydrogenase 1 (Hsd3b1), cholesterol side-chain cleavage (Cyp11a1), steroid acute regulatory protein (Star), and increased expression of Cyp1b1 enzyme levels. Thus, these data suggest that MXC decreases steroidogenic enzyme levels, increases metabolic enzyme expression and this in turn leads to decreased sex steroid hormone levels. - Highlights: > MXC inhibits steroidogenesis > MXC inhibits steroidogenic enzymes > MXC induces metabolic enzymes

  6. Altered MCM Protein Levels and Autophagic Flux in Aged and Systemic Sclerosis Dermal Fibroblasts

    PubMed Central

    Dumit, Verónica I.; Küttner, Victoria; Käppler, Jakob; Piera-Velazquez, Sonsoles; Jimenez, Sergio A.; Bruckner-Tuderman, Leena; Uitto, Jouni; Dengjel, Jörn

    2014-01-01

    Aging is a common risk factor of many disorders. With age, the level of insoluble extracellular matrix increases leading to increased stiffness of a number of tissues. Matrix accumulation can also be observed in fibrotic disorders, such as systemic sclerosis (SSc). Although the intrinsic aging process in skin is phenotypically distinct from SSc, here we demonstrate similar behavior of aged and SSc skin fibroblasts in culture. We have used quantitative proteomics to characterize the phenotype of dermal fibroblasts from healthy subjects of various ages and from patients with SSc. Our results demonstrate that proteins involved in DNA and RNA processing decrease with age and in SSc, while those involved in mitochondrial and other metabolic processes behave the opposite. Specifically, mini-chromosome maintenance (MCM) helicase proteins are less abundant with age and SSc, and they exhibit an altered subcellular distribution. We observed that lower levels of MCM7 correlate with reduced cell proliferation, lower autophagic capacity and higher intracellular protein expression phenotypes of aged and SSc cells. Additionally, we show that SSc fibroblasts exhibit higher levels of senescence than their healthy counterparts, suggesting further similarities between the fibrotic disorder and the aging process. Hence, at the molecular level, SSc fibroblasts exhibit intrinsic characteristics of fibroblasts from aged skin. PMID:24496236

  7. Saharan dust inputs and high UVR levels jointly alter the metabolic balance of marine oligotrophic ecosystems

    NASA Astrophysics Data System (ADS)

    Cabrerizo, Marco J.; Medina-Sánchez, Juan Manuel; González-Olalla, Juan Manuel; Villar-Argaiz, Manuel; Carrillo, Presentación

    2016-10-01

    The metabolic balance of the most extensive bioma on the Earth is a controversial topic of the global-change research. High ultraviolet radiation (UVR) levels by the shoaling of upper mixed layers and increasing atmospheric dust deposition from arid regions may unpredictably alter the metabolic state of marine oligotrophic ecosystems. We performed an observational study across the south-western (SW) Mediterranean Sea to assess the planktonic metabolic balance and a microcosm experiment in two contrasting areas, heterotrophic nearshore and autotrophic open sea, to test whether a combined UVR × dust impact could alter their metabolic balance at mid-term scales. We show that the metabolic state of oligotrophic areas geographically varies and that the joint impact of UVR and dust inputs prompted a strong change towards autotrophic metabolism. We propose that this metabolic response could be accentuated with the global change as remote-sensing evidence shows increasing intensities, frequencies and number of dust events together with variations in the surface UVR fluxes on SW Mediterranean Sea. Overall, these findings suggest that the enhancement of the net carbon budget under a combined UVR and dust inputs impact could contribute to boost the biological pump, reinforcing the role of the oligotrophic marine ecosystems as CO2 sinks.

  8. Saharan dust inputs and high UVR levels jointly alter the metabolic balance of marine oligotrophic ecosystems

    PubMed Central

    Cabrerizo, Marco J.; Medina-Sánchez, Juan Manuel; González-Olalla, Juan Manuel; Villar-Argaiz, Manuel; Carrillo, Presentación

    2016-01-01

    The metabolic balance of the most extensive bioma on the Earth is a controversial topic of the global-change research. High ultraviolet radiation (UVR) levels by the shoaling of upper mixed layers and increasing atmospheric dust deposition from arid regions may unpredictably alter the metabolic state of marine oligotrophic ecosystems. We performed an observational study across the south-western (SW) Mediterranean Sea to assess the planktonic metabolic balance and a microcosm experiment in two contrasting areas, heterotrophic nearshore and autotrophic open sea, to test whether a combined UVR × dust impact could alter their metabolic balance at mid-term scales. We show that the metabolic state of oligotrophic areas geographically varies and that the joint impact of UVR and dust inputs prompted a strong change towards autotrophic metabolism. We propose that this metabolic response could be accentuated with the global change as remote-sensing evidence shows increasing intensities, frequencies and number of dust events together with variations in the surface UVR fluxes on SW Mediterranean Sea. Overall, these findings suggest that the enhancement of the net carbon budget under a combined UVR and dust inputs impact could contribute to boost the biological pump, reinforcing the role of the oligotrophic marine ecosystems as CO2 sinks. PMID:27775100

  9. Community Phylogenetics: Assessing Tree Reconstruction Methods and the Utility of DNA Barcodes.

    PubMed

    Boyle, Elizabeth E; Adamowicz, Sarah J

    2015-01-01

    Studies examining phylogenetic community structure have become increasingly prevalent, yet little attention has been given to the influence of the input phylogeny on metrics that describe phylogenetic patterns of co-occurrence. Here, we examine the influence of branch length, tree reconstruction method, and amount of sequence data on measures of phylogenetic community structure, as well as the phylogenetic signal (Pagel's λ) in morphological traits, using Trichoptera larval communities from Churchill, Manitoba, Canada. We find that model-based tree reconstruction methods and the use of a backbone family-level phylogeny improve estimations of phylogenetic community structure. In addition, trees built using the barcode region of cytochrome c oxidase subunit I (COI) alone accurately predict metrics of phylogenetic community structure obtained from a multi-gene phylogeny. Input tree did not alter overall conclusions drawn for phylogenetic signal, as significant phylogenetic structure was detected in two body size traits across input trees. As the discipline of community phylogenetics continues to expand, it is important to investigate the best approaches to accurately estimate patterns. Our results suggest that emerging large datasets of DNA barcode sequences provide a vast resource for studying the structure of biological communities.

  10. Mice lacking Mrp1 have reduced testicular steroid hormone levels and alterations in steroid biosynthetic enzymes

    PubMed Central

    SIVILS, JEFFREY C.; GONZALEZ, IVEN; BAIN, LISA J.

    2010-01-01

    The multidrug resistance-associated protein 1 (MRP1/ABCC1) is a member of the ABC active transporter family that can transport several steroid hormone conjugates, including 17β-estradiol glucuronide, dehydroepiandrosterone sulfate (DHEAS), and estrone 3-sulfate. The present study investigated the role that MRP1 plays in maintaining proper hormone levels in the serum and testes. Serum and testicular steroid hormone levels were examined in both wild-type mice and Mrp1 null mice. Serum testosterone levels were reduced 5-fold in mice lacking Mrp1, while testicular androstenedione, testosterone, estradiol, and dehydroepiandrosterone (DHEA) were significantly reduced by 1.7- to 4.5-fold in Mrp1 knockout mice. Investigating the mechanisms responsible for the reduction in steroid hormones in Mrp1-/- mice revealed no differences in the expression or activity of enzymes that inactivate steroids, the sulfotransferases or glucuronosyltransferases. However, steroid biosynthetic enzyme levels in the testes were altered. Cyp17 protein levels were increased by 1.6-fold, while Cyp17 activity using progesterone as a substrate was also increased by 1.4-2.0-fold in mice lacking Mrp1. Additionally, the ratio of 17β-hydroxysteroid dehydrogenase to 3β-hydroxysteroid dehydrogenase, and steroidogenic factor 1 to 3βhydroxysteroid dehydrogenase were significantly increased in the testes of Mrp1-/- mice. These results indicate that Mrp1-/- mice have lowered steroid hormones levels, and suggests that upregulation of steroid biosynthetic enzymes may be an attempt to maintain proper steroid hormone homeostasis. PMID:20178799

  11. Altered negative priming in older subjects: first evidence from behavioral and neural level

    PubMed Central

    Bauer, Eva; Gebhardt, Helge; Gruppe, Harald; Gallhofer, Bernd; Sammer, Gebhard

    2012-01-01

    The impact of aging on the negative priming (NP) effect has been subject of many studies using behavioral measures. Results are inconsistent and corresponding neural data do not exist. We were interested in, whether or not processing of NP is altered in older in comparison to young adults (YA) on behavioral and neural level. Eighteen young and eighteen older healthy adults performed a location-based NP paradigm during fMRI. YA behaviorally showed a NP effect and NP associated fronto-striatal activation, which is in accordance with the inhibitory model of NP. In older subjects no significant behavioral NP effect and no NP-related activation in predefined brain regions could be found. This is discussed in context of the “loss of efficiency” hypothesis. One possible source for the lack of NP-related activation is a reduction of gray matter (GM) volume in older subjects as shown using voxel based morphometry (VBM). PMID:23060774

  12. A large-scale, higher-level, molecular phylogenetic study of the insect order Lepidoptera (moths and butterflies)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Higher-level relationships within the Lepidoptera, and particularly within the species-rich subclade Ditrysia, are generally not well understood, although recent studies have yielded progress. 483 taxa spanning 115 of 124 families were sampled for 19 protein-coding nuclear genes. Their aligned nucle...

  13. Diabetic retinopathy alters light-induced clock gene expression and dopamine levels in the mouse retina

    PubMed Central

    Lahouaoui, Hasna; Coutanson, Christine; Cooper, Howard M.; Bennis, Mohamed

    2016-01-01

    Purpose Diabetic retinopathy is one of the most common consequences of diabetes that affects millions of working-age adults worldwide and leads to progressive degeneration of the retina, visual loss, and blindness. Diabetes is associated with circadian disruption of the central and peripheral circadian clocks, but the mechanisms responsible for such alterations are unknown. Using a streptozotocin (STZ)-induced model of diabetes, we investigated whether diabetes alters 1) the circadian regulation of clock genes in the retina and in the central clocks, 2) the light response of clock genes in the retina, and/or 3) light-driven retinal dopamine (DA), a major output marker of the retinal clock. Methods To quantify circadian expression of clock and clock-controlled genes, retinas and suprachiasmatic nucleus (SCN) from the same animals were collected every 4 h in circadian conditions, 12 weeks post-diabetes. Induction of Per1, Per2, and c-fos mRNAs was quantified in the retina after the administration of a pulse of monochromatic light (480 nm, 1.17×1014 photons/cm2/s, 15 min) at circadian time 16. Gene expression was assessed with real-time reverse transcription PCR (RT–PCR). Pooled retinas from the control and STZ-diabetic mice were collected 2 h after light ON and light OFF (Zeitgeber time (ZT)2 and ZT14), and DA and its metabolite were analyzed with high-performance liquid chromatography (HPLC). Results We found variable effects of diabetes on the expression of clock genes in the retina and only slight differences in phase and/or amplitude in the SCN. c-fos and Per1 induction by a 480 nm light pulse was abolished in diabetic animals at 12 weeks post-induction of diabetes in comparison with the control mice, suggesting a deficit in light-induced neuronal activation of the retinal clock. Finally, we quantified a 56% reduction in the total number of tyrosine hydroxylase (TH) immunopositive cells, associated with a decrease in DA levels during the subjective day (ZT2

  14. Neurotensin receptor binding levels in basal ganglia are not altered in Huntington's chorea or schizophrenia

    SciTech Connect

    Palacios, J.M.; Chinaglia, G.; Rigo, M.; Ulrich, J.; Probst, A. )

    1991-02-01

    Autoradiographic techniques were used to examine the distribution and levels of neurotensin receptor binding sites in the basal ganglia and related regions of the human brain. Monoiodo ({sup 125}I-Tyr3)neurotensin was used as a ligand. High amounts of neurotensin receptor binding sites were found in the substantia nigra pars compacta. Lower but significant quantities of neurotensin receptor binding sites characterized the caudate, putamen, and nucleus accumbens, while very low quantities were seen in both medial and lateral segments of the globus pallidus. In Huntington's chorea, the levels of neurotensin receptor binding sites were found to be comparable to those of control cases. Only slight but not statistically significant decreases in amounts of receptor binding sites were detected in the dorsal part of the head and in the body of caudate nucleus. No alterations in the levels of neurotensin receptor binding sites were observed in the substantia nigra pars compacta and reticulata. These results suggest that a large proportion of neurotensin receptor binding sites in the basal ganglia are located on intrinsic neurons and on extrinsic afferent fibers that do not degenerate in Huntington's disease.

  15. Ambient CO2, fish behaviour and altered GABAergic neurotransmission: exploring the mechanism of CO2-altered behaviour by taking a hypercapnia dweller down to low CO2 levels.

    PubMed

    Regan, Matthew D; Turko, Andy J; Heras, Joseph; Andersen, Mads Kuhlmann; Lefevre, Sjannie; Wang, Tobias; Bayley, Mark; Brauner, Colin J; Huong, Do Thi Thanh; Phuong, Nguyen Thanh; Nilsson, Göran E

    2016-01-01

    Recent studies suggest that projected rises of aquatic CO2 levels cause acid-base regulatory responses in fishes that lead to altered GABAergic neurotransmission and disrupted behaviour, threatening fitness and population survival. It is thought that changes in Cl(-) and HCO3 (-) gradients across neural membranes interfere with the function of GABA-gated anion channels (GABAA receptors). So far, such alterations have been revealed experimentally by exposing species living in low-CO2 environments, like many oceanic habitats, to high levels of CO2 (hypercapnia). To examine the generality of this phenomenon, we set out to study the opposite situation, hypothesizing that fishes living in typically hypercapnic environments also display behavioural alterations if exposed to low CO2 levels. This would indicate that ion regulation in the fish brain is fine-tuned to the prevailing CO2 conditions. We quantified pH regulatory variables and behavioural responses of Pangasianodon hypophthalmus, a fish native to the hypercapnic Mekong River, acclimated to high-CO2 (3.1 kPa) or low-CO2 (0.04 kPa) water. We found that brain and blood pH was actively regulated and that the low-CO2 fish displayed significantly higher activity levels, which were reduced after treatment with gabazine, a GABAA receptor blocker. This indicates an involvement of the GABAA receptor and altered Cl(-) and HCO3 (-) ion gradients. Indeed, Goldman calculations suggest that low levels of environmental CO2 may cause significant changes in neural ion gradients in P. hypophthalmus. Taken together, the results suggest that brain ion regulation in fishes is fine-tuned to the prevailing ambient CO2 conditions and is prone to disruption if these conditions change.

  16. Below-ambient levels of UV induce chloroplast structural change and alter starch metabolism.

    PubMed

    Fagerberg, W R

    2007-01-01

    Electromagnetic radiation (EMR) in the 400-700 nm bandwidth of photosynthetically active radiation (PAR) has been established as an important source of energy for photosynthesis and environmental signals regulating many aspects of green-plant life. Above-ambient levels of UV-B radiation (290-320 nm) under high-PAR conditions have been shown to elicit responses in chloroplasts of Brassica napus similar to those of chloroplasts at low-PAR exposure (W. Fagerberg and J. Bornman, Physiol. Plant. 101: 833-844, 1997). The question arises as to whether UV at normal levels can also evoke similar responses. Here we provide evidence that even below-ambient levels of UV-B (1/28 ambient; Durham, N.H., U.S.A., 1200 hours, March) were capable of inducing an increase in thylakoid surface area relative to the chloroplast volume typical of a low-PAR response (shade response) in sunflowers. This response occurred even though leaves were concurrently exposed to PAR levels that normally induce a "sun" or high-PAR response in the absence of UV-B. Subambient levels of UV-B were also associated with a decrease in chloroplast and starch volume. Exposure to levels of UV-A 1/10 of ambient appeared to enhance the high-PAR response of the chloroplast, characterized by an increase in the amounts of stored starch, an increase in chloroplast volume density ratio values, and a decrease in thylakoid surface area density ratios relative to the high-light controls. These effects were opposite to those seen in UV-B-exposed tissue. In a general sense, subambient levels of UV-B evoked a response similar to that elicited by low-PAR irradiance, while subambient UV-A elicited responses similar to those typical of high-PAR irradiance. The fact that below-ambient levels of UV altered a normal chloroplast structural response to PAR provides evidence that UV may be an important environmental signal for plants.

  17. Prenatal Hyperandrogenization Induces Metabolic and Endocrine Alterations Which Depend on the Levels of Testosterone Exposure

    PubMed Central

    Amalfi, Sabrina; Velez, Leandro Martín; Heber, María Florencia; Vighi, Susana; Ferreira, Silvana Rocío; Orozco, Adriana Vega; Pignataro, Omar; Motta, Alicia Beatriz

    2012-01-01

    Prenatal hyperandrogenism is able to induce polycystic ovary syndrome (PCOS) in rats. The aim of the present study was to establish if the levels of prenatal testosterone may determine the extent of metabolic and endocrine alterations during the adult life. Pregnant Sprague Dawley rats were prenatally injected with either 2 or 5 mg free testosterone (groups T2 and T5 respectively) from day 16 to day 19 day of gestation. Female offspring from T2 and T5 displayed different phenotype of PCOS during adult life. Offspring from T2 showed hyperandrogenism, ovarian cysts and ovulatory cycles whereas those from T5 displayed hyperandrogenism, ovarian cysts and anovulatory cycles. Both group showed increased circulating glucose levels after the intraperitoneal glucose tolerance test (IPGTT; an evaluation of insulin resistance). IPGTT was higher in T5 rats and directly correlated with body weight at prepubertal age. However, the decrease in the body weight at prepubertal age was compensated during adult life. Although both groups showed enhanced ovarian steroidogenesis, it appears that the molecular mechanisms involved were different. The higher dose of testosterone enhanced the expression of both the protein that regulates cholesterol availability (the steroidogenic acute regulatory protein (StAR)) and the protein expression of the transcriptional factor: peroxisome proliferator-activated receptor gamma (PPAR gamma). Prenatal hyperandrogenization induced an anti-oxidant response that prevented a possible pro-oxidant status. The higher dose of testosterone induced a pro-inflammatory state in ovarian tissue mediated by increased levels of prostaglandin E (PG) and the protein expression of cyclooxygenase 2 (COX2, the limiting enzyme of PGs synthesis). In summary, our data show that the levels of testosterone prenatally injected modulate the uterine environment and that this, in turn, would be responsible for the endocrine and metabolic abnormalities and the phenotype of PCOS

  18. Tooth Movement Alterations by Different Low Level Laser Protocols: A Literature Review

    PubMed Central

    Seifi, Massoud; Vahid-Dastjerdi, Elahe

    2015-01-01

    Low-Level Laser Therapy (LLLT) provides several benefits for patients receiving orthodontic treatment. According to some literatures, Orthodontic Tooth Movement (OTM) can be enhanced but some investigators have reported contradictory results. This article reviews the literature regarding the different aspects of the use of LLLT on OTM and its alterations. The general data regarding the study design, sample size, wavelength (nm), power (mW), and duration were extracted and recorded independently. Electronic databases of PubMed and ScienceDirect from January 2009 to August 2014 were searched. Also Google Scholar and grey literature was searched for relevant references. Some investigators found that the amount of tooth movement in the Low-Energy Laser Irradiation (LELI) group was significantly greater than in the nonirradiation group by the end of the experimental period. Low-level laser irradiation accelerates the bone remodeling process by stimulating osteoblastic and osteoclastic cell proliferation and function during orthodontic tooth movement. But some researchers have reported that no statistical differences in the mean rate of tooth movement were noted between low energy and high energy experimental sides and their controls. Some evidence shows that low-level laser irradiation accelerates the bone remodeling process and some evidence shows that LLLT has not effect on OTM. In some investigations no statistical differences in the mean rate of tooth movement can be seen between low energy and high energy experimental sides and their controls. It has been shown by authors that laser irradiation can reduce the amount of OTM and a clinical usage for the inhibitory role of low level laser irradiation is enforcing the anchorage unit. PMID:25699160

  19. Lamotrigine, carbamazepine and phenytoin differentially alter extracellular levels of 5-hydroxytryptamine, dopamine and amino acids.

    PubMed

    Ahmad, Shagufta; Fowler, Leslie J; Whitton, Peter S

    2005-02-01

    We have studied the effects of treatment with the anticonvulsants lamotrigine (LTG), phenytoin (PHN) and carbamazepine (CBZ) on basal and stimulated extracellular aspartate (ASP), glutamate (GLU), taurine (TAU), GABA, 5-hydroxytryptamine (5-HT) and dopamine (DA) in the hippocampus of freely moving rats using microdialysis. All of the drugs investigated have had inhibition of Na(+) channel activity implicated as their principal mechanism of action. Neither LTG (10-20 mg/kg), PHN (20-40 mg/kg) or CBZ (10-20 mg/kg) had an effect on the basal extracellular concentrations of any of the amino acids studied with the exception of glutamate, which was decreased at the highest LTG dose. However, when amino acid transmitter levels were increased with 50 microM veratridine, LTG was found to cause a dose-dependent decrease in dialysate levels of all four amino acids, with the effect being most pronounced for glutamate. In contrast, PHN decreased extracellular aspartate levels but had no effect on evoked-extracellular GLU, TAU or GABA. Somewhat unexpectedly, CBZ did not alter the stimulated increase in the excitatory amino acids, GLU and ASP, but, rather surprisingly for an antiepileptic drug, markedly decreased that of the inhibitory substances TAU and GABA. The three drugs had differing effects on basal extracellular 5-HT and DA. LTG caused a dose-dependent decrease in both, while CBZ and PHN both increased extracellular 5-HT and DA. When extracellular 5-HT and DA was evoked by veratridine LTG had no significant effect on this, while PHN but not CBZ increased stimulated extracellular 5-HT and both PHN and CBZ augmented DA. Thus, the effects of the three drugs studied seemed to depend on whether extracellular transmitter levels are evoked or basal and the particular transmitter in question. This suggests that there are marked differences in the neurochemical mechanisms of antiepileptic drug action of the three compounds studied.

  20. Alteration of T Cell Subtypes in Beta-Thalassaemia Major: Impact of Ferritin Level

    PubMed Central

    Karimi, Leila; Beshkar, Pezhman

    2016-01-01

    Introduction Oxidative damage and regular antigenic stimulation are main factors in accelerating immunosenescence. The present study was conducted to investigate new concepts of early immunosenescence in thalassaemia patients. Materials and Methods Twenty seven beta-thalassaemia major patients and a group of matched healthy volunteers aged 10-30 years in Shahrekord, Iran were recruited into the study. Ferritin level was determined and CD4 or CD8 T cells were analysed versus phenotyping markers, CD27, CD28, CD57 and CCR7, by flowcytometry. Data were analysed by Mann-Whitney and Spearman’s correlation coefficient test in SPSS 11.5. Results Absolute lymphocytosis and partial decrease in T cells were observed in the patients. CD4+CD57+ and CD4+CCR7- T cells were significantly higher, whereas CD8+CD27+ and CD8+CCR7+ T cells were partially higher in patients. A negative correlation was observed between ferritin level and number of CD8+CD27+ and CD8+CCR7+ T cells, whereas the correlation was positive between ferritin level and number of CD57+ T cells. Conclusion Moderate alteration of T cell repertoire and increase in CCR27-, CCR7-, and CD57+ T cells could reflect antigenic stimulation, decline in naïve T cells, and being closer to terminally differentiated cells. Effect of iron overload is potentially explained by positive correlation of blood transfusion and ferritin level with frequency of CD3+CD27- and that of ferritin with frequency of CD57+ T cells. PMID:27042462

  1. Acute exposure to 2,4-dinitrophenol alters zebrafish swimming performance and whole body triglyceride levels.

    PubMed

    Marit, Jordan S; Weber, Lynn P

    2011-06-01

    While swimming endurance (critical swimming speed or U(crit)) and lipid stores have both been reported to acutely decrease after exposure to a variety of toxicants, the relationship between these endpoints has not been clearly established. In order to examine these relationships, adult zebrafish (Danio rerio) were aqueously exposed to solvent control (ethanol) or two nominal concentrations of 2,4-dinitrophenol (DNP), a mitochondrial electron transport chain uncoupler, for a 24-h period. Following exposure, fish were placed in a swim tunnel in clean water for swimming testing or euthanized immediately without testing, followed by analysis of whole body triglyceride levels. U(crit) decreased in both the 6 mg/L and 12 mg/L DNP groups, with 12 mg/L approaching the LC₅₀. A decrease in tail beat frequency was observed without a significant change in tail beat amplitude. In contrast, triglyceride levels were elevated in a concentration-dependent manner in the DNP exposure groups, but only in fish subjected to swimming tests. This increase in triglyceride stores may be due to a direct interference of DNP on lipid catabolism as well as increased triglyceride production when zebrafish were subjected to the co-stressors of swimming and toxicant exposure. Future studies should be directed at determining how acute DNP exposure combines with swimming to cause alterations in triglyceride accumulation.

  2. Smoking, alcoholism and genetic polymorphisms alter CYP2B6 levels in human brain.

    PubMed

    Miksys, Sharon; Lerman, Caryn; Shields, Peter G; Mash, Deborah C; Tyndale, Rachel F

    2003-07-01

    CYP2B6 metabolizes drugs such as nicotine and bupropion, and many toxins and carcinogens. Nicotine induces CYP2B1 in rat brain and in humans polymorphic variation in CYP2B6 affects smoking cessation rates. The aim of this study was to compare CYP2B6 expression in brains of human smokers and non-smokers and alcoholics and non-alcoholics (n=26). CYP2B6 expression was brain region-specific, and was observed in both neurons and astrocytes. CYP2B6 levels were higher in brains of smokers and alcoholics, particularly in cerebellar Purkinje cells and hippocampal pyramidal neurons, cells known to be damaged in alcoholics. Significantly more (p<0.05) CYP2B6 protein was seen in four brain regions of smoking alcoholics compared to non-smoking non-alcoholics: hippocampus (5.8-fold), caudate nucleus (3.3-fold), putamen (3.0-fold) and cerebellar hemisphere (1.6-fold). The genetic variant C1459T (R487C) has been associated with reduced hepatic enzyme levels, stability and activity. Preliminary genotyping of this small sample (n=24) suggested that individuals with the CC genotype had higher brain CYP2B6 than those with the CT or TT genotype. Higher brain CYP2B6 activity in smokers and alcoholics may cause altered sensitivity to centrally acting drugs, increased susceptibility to neurotoxins and carcinogenic xenobiotics and contribute to central tolerance to nicotine.

  3. Exposure to caregiver maltreatment alters expression levels of epigenetic regulators in the medial prefrontal cortex

    PubMed Central

    Blaze, Jennifer; Roth, Tania L

    2013-01-01

    Quality of maternal care experienced during infancy is a key factor that can confer vulnerability or resilience to psychiatric disorders later in life. Research continues to indicate that early-life experiences can affect developmental trajectories through epigenetic alterations capable of affecting gene regulation and neural plasticity. Previously, our lab has shown that experiences within an adverse caregiving environment (i.e. maltreatment) produce aberrant DNA methylation patterns at various gene loci in the medial prefrontal cortex (mPFC) of developing and adult rats. This study aimed to determine whether caregiver maltreatment likewise affects expression levels of several genes important in regulating DNA methylation patterns (Dnmt1, Dnmt3a, MeCP2, Gadd45b, and Hdac1). While we observed minimal changes in gene expression within the mPFC of developing rats, we observed expression changes for all genes in adult animals. Specifically, exposure to maltreatment produced a significant decrease in mRNA levels of all epigenetic regulators in adult males and a significant decrease in Gadd45b in adult females. Our results here provide further empirical support for the long-term and sex-specific epigenetic consequences of caregiver maltreatment on the mPFC. PMID:24120634

  4. Fetal rat metabonome alteration by prenatal caffeine ingestion probably due to the increased circulatory glucocorticoid level and altered peripheral glucose and lipid metabolic pathways

    SciTech Connect

    Liu, Yansong; Xu, Dan; Feng, Jianghua; Kou, Hao; Liang, Gai; Yu, Hong; He, Xiaohua; Zhang, Baifang; Chen, Liaobin; Magdalou, Jacques; Wang, Hui

    2012-07-15

    The aims of this study were to clarify the metabonome alteration in fetal rats after prenatal caffeine ingestion and to explore the underlying mechanism pertaining to the increased fetal circulatory glucocorticoid (GC). Pregnant Wistar rats were daily intragastrically administered with different doses of caffeine (0, 20, 60 and 180 mg/kg) from gestational days (GD) 11 to 20. Metabonome of fetal plasma and amniotic fluid on GD20 were analyzed by {sup 1}H nuclear magnetic resonance-based metabonomics. Gene and protein expressions involved in the GC metabolism, glucose and lipid metabolic pathways in fetal liver and gastrocnemius were measured by real-time RT-PCR and immunohistochemistry. Fetal plasma metabonome were significantly altered by caffeine, which presents as the elevated α- and β‐glucose, reduced multiple lipid contents, varied apolipoprotein contents and increased levels of a number of amino acids. The metabonome of amniotic fluids showed a similar change as that in fetal plasma. Furthermore, the expressions of 11β-hydroxysteroid dehydrogenase 2 (11β-HSD-2) were decreased, while the level of blood GC and the expressions of 11β-HSD-1 and glucocorticoid receptor (GR) were increased in fetal liver and gastrocnemius. Meanwhile, the expressions of insulin-like growth factor 1 (IGF-1), IGF-1 receptor and insulin receptor were decreased, while the expressions of adiponectin receptor 2, leptin receptors and AMP-activated protein kinase α2 were increased after caffeine treatment. Prenatal caffeine ingestion characteristically change the fetal metabonome, which is probably attributed to the alterations of glucose and lipid metabolic pathways induced by increased circulatory GC, activated GC metabolism and enhanced GR expression in peripheral metabolic tissues. -- Highlights: ► Prenatal caffeine ingestion altered the metabonome of IUGR fetal rats. ► Caffeine altered the glucose and lipid metabolic pathways of IUGR fetal rats. ► Prenatal caffeine

  5. The Human Gut Chip “HuGChip”, an Explorative Phylogenetic Microarray for Determining Gut Microbiome Diversity at Family Level

    PubMed Central

    Tottey, William; Denonfoux, Jeremie; Jaziri, Faouzi; Parisot, Nicolas; Missaoui, Mohiedine; Hill, David; Borrel, Guillaume; Peyretaillade, Eric; Alric, Monique; Harris, Hugh M. B.; Jeffery, Ian B.; Claesson, Marcus J.; O'Toole, Paul W.; Peyret, Pierre; Brugère, Jean-François

    2013-01-01

    Evaluating the composition of the human gut microbiota greatly facilitates studies on its role in human pathophysiology, and is heavily reliant on culture-independent molecular methods. A microarray designated the Human Gut Chip (HuGChip) was developed to analyze and compare human gut microbiota samples. The PhylArray software was used to design specific and sensitive probes. The DNA chip was composed of 4,441 probes (2,442 specific and 1,919 explorative probes) targeting 66 bacterial families. A mock community composed of 16S rRNA gene sequences from intestinal species was used to define the threshold criteria to be used to analyze complex samples. This was then experimentally verified with three human faecal samples and results were compared (i) with pyrosequencing of the V4 hypervariable region of the 16S rRNA gene, (ii) metagenomic data, and (iii) qPCR analysis of three phyla. When compared at both the phylum and the family level, high Pearson's correlation coefficients were obtained between data from all methods. The HuGChip development and validation showed that it is not only able to assess the known human gut microbiota but could also detect unknown species with the explorative probes to reveal the large number of bacterial sequences not yet described in the human gut microbiota, overcoming the main inconvenience encountered when developing microarrays. PMID:23690942

  6. Effects of Altered Levels of Extracellular Superoxide Dismutase and Irradiation on Hippocampal Neurogenesis in Female Mice

    SciTech Connect

    Zou, Yani; Leu, David; Chui, Jennifer; Fike, John R.; Huang, Ting-Ting

    2013-11-15

    Purpose: Altered levels of extracellular superoxide dismutase (EC-SOD) and cranial irradiation have been shown to affect hippocampal neurogenesis. However, previous studies were only conducted in male mice, and it was not clear if there was a difference between males and females. Therefore, female mice were studied and the results compared with those generated in male mice from an earlier study. Methods and Materials: Female wild-type, EC-SOD-null (KO), and EC-SOD bigenic mice with neuronal-specific expression of EC-SOD (OE) were subjected to a single dose of 5-Gy gamma rays to the head at 8 weeks of age. Progenitor cell proliferation, differentiation, and long-term survival of newborn neurons were determined. Results: Similar to results from male mice, EC-SOD deficiency and irradiation both resulted in significant reductions in mature newborn neurons in female mice. EC-SOD deficiency reduced long-term survival of newborn neurons whereas irradiation reduced progenitor cell proliferation. Overexpression of EC-SOD corrected the negative impacts from EC-SOD deficiency and irradiation and normalized the production of newborn neurons in OE mice. Expression of neurotrophic factors brain-derived neurotrophic factor and neurotrophin-3 were significantly reduced by irradiation in wild-type mice, but the levels were not changed in KO and OE mice even though both cohorts started out with a lower baseline level. Conclusion: In terms of hippocampal neurogenesis, EC-SOD deficiency and irradiation have the same overall effects in males and females at the age the studies were conducted.

  7. A Large-Scale, Higher-Level, Molecular Phylogenetic Study of the Insect Order Lepidoptera (Moths and Butterflies)

    PubMed Central

    Regier, Jerome C.; Mitter, Charles; Zwick, Andreas; Bazinet, Adam L.; Cummings, Michael P.; Kawahara, Akito Y.; Sohn, Jae-Cheon; Zwickl, Derrick J.; Cho, Soowon; Davis, Donald R.; Baixeras, Joaquin; Brown, John; Parr, Cynthia; Weller, Susan; Lees, David C.; Mitter, Kim T.

    2013-01-01

    Background Higher-level relationships within the Lepidoptera, and particularly within the species-rich subclade Ditrysia, are generally not well understood, although recent studies have yielded progress. We present the most comprehensive molecular analysis of lepidopteran phylogeny to date, focusing on relationships among superfamilies. Methodology / Principal Findings 483 taxa spanning 115 of 124 families were sampled for 19 protein-coding nuclear genes, from which maximum likelihood tree estimates and bootstrap percentages were obtained using GARLI. Assessment of heuristic search effectiveness showed that better trees and higher bootstrap percentages probably remain to be discovered even after 1000 or more search replicates, but further search proved impractical even with grid computing. Other analyses explored the effects of sampling nonsynonymous change only versus partitioned and unpartitioned total nucleotide change; deletion of rogue taxa; and compositional heterogeneity. Relationships among the non-ditrysian lineages previously inferred from morphology were largely confirmed, plus some new ones, with strong support. Robust support was also found for divergences among non-apoditrysian lineages of Ditrysia, but only rarely so within Apoditrysia. Paraphyly for Tineoidea is strongly supported by analysis of nonsynonymous-only signal; conflicting, strong support for tineoid monophyly when synonymous signal was added back is shown to result from compositional heterogeneity. Conclusions / Significance Support for among-superfamily relationships outside the Apoditrysia is now generally strong. Comparable support is mostly lacking within Apoditrysia, but dramatically increased bootstrap percentages for some nodes after rogue taxon removal, and concordance with other evidence, strongly suggest that our picture of apoditrysian phylogeny is approximately correct. This study highlights the challenge of finding optimal topologies when analyzing hundreds of taxa. It also

  8. The transcriptome and proteome are altered in marine polychaetes (Annelida) exposed to elevated metal levels.

    PubMed

    Neave, Matthew J; Streten-Joyce, Claire; Nouwens, Amanda S; Glasby, Chris J; McGuinness, Keith A; Parry, David L; Gibb, Karen S

    2012-05-17

    Polychaetes are often used in toxicological studies to understand mechanisms of resistance and for biomarker detection, however, we know of only a few genetic pathways involved in resistance. We found the marine polychaete Ophelina sp.1 (Opheliidae) in sediment containing high copper levels and investigated this phenomenon by measuring metal accumulation in the worms and changes in gene and protein expression. We sequenced the transcriptome of Ophelina sp.1 from both the impacted and reference sediments using 454-sequencing and analysed their proteomes using differential in gel electrophoresis (DIGE). We used the sequenced transcriptome to guide protein identification. Transcripts coding for the copper chaperone, Atox1, were up-regulated in the worms inhabiting the high copper sediment. In addition, genes coding for respiratory proteins, detoxification proteins and cytoskeletal proteins were significantly altered in metal-exposed worms; many of these changes were also detected in the proteome. This dual approach has provided a better understanding of heavy metal resistance in polychaetes and we now have a wider range of suitable indicator genes and proteins for future biomarker development.

  9. Alterations in plant growth and in root hormone levels of lodgepole pines inoculated with rhizobacteria.

    PubMed

    Bent, E; Tuzun, S; Chanway, C P; Enebak, S

    2001-09-01

    The presence of other soil microorganisms might influence the ability of rhizobacterial inoculants to promote plant growth either by reducing contact between the inoculant and the plant root or by interfering with the mechanism(s) involved in rhizobacterially mediated growth promotion. We conducted the following experiments to determine whether reductions in the extent of growth promotion of lodgepole pine mediated by Paenibacillus polymyxa occur in the presence of a forest soil isolate (Pseudomonas fluorescens M20) and whether changes in plant growth promotion mediated by P. polymyxa (i) are related to changes in P. polymyxa density in the rhizosphere or (ii) result from alterations in root hormone levels. The extent of plant growth, P. polymyxa rhizosphere density, and root hormone concentrations were determined for lodgepole pine treated with (i) a single growth-promoting rhizobacterial strain (P. polymyxa L6 or Pw-2) or (ii) a combination of bacteria: strain L6 + strain M20 or strain Pw-2 + strain M20. There was no difference in the growth of pines inoculated with strain L6 and those inoculated with strain L6 + strain M20. However, seedlings inoculated with strain Pw-2 had more lateral roots and greater root mass at 12 weeks after inoculation than plants inoculated with strain Pw-2 + strain M20. The extent of growth promotion mediated by P. polymyxa L6 and Pw-2 in each treatment was not correlated to the average population density of each strain in the rhizosphere. Bacterial species-specific effects were observed in root hormone levels: indole-3-acetic acid concentration was elevated in roots inoculated with P. polymyxa L6 or Pw-2, while dihydrozeatin riboside concentration was elevated in roots inoculated with P. fluorescens M20.

  10. Altered Carbon Isotope Discrimination of C3 Plants Under Very High pCO2 Levels

    NASA Astrophysics Data System (ADS)

    Panetta, R. J.; Schubert, B.; Jahren, H.

    2009-12-01

    Various modeling and proxy-based reconstructions of atmospheric pCO2 levels for the last 120 Ma have estimated RCO2 as high as 12x for the Early Cretaceous, generally decreasing into the Cenozoic, and decreasing further into the Quaternary. Multiple ecological studies to assess the effect of elevated CO2 on plant biomass and δ13C value have been spurred on by recent increases in greenhouse gases, however these studies typically grow plants under only slightly elevated CO2 levels (i.e., the twenty foremost studies published since 1990 involved 550 to 750 ppm pCO2, which equals RCO2 = 1.4 to 1.9x). In order to recreate the highest pCO2 environments of the last 120 Ma, we grew radish (Raphanus sativus L.) in growth chambers that maintained controlled environmental conditions and pCO2 levels ranging from ~5 to 11x that of today’s atmosphere (1791 to 4200 ppm); upon harvest we measured total biomass and stable carbon isotope ratio (δ13Cplant) in both above and below ground plant tissue. Unlike the 1:1 relationship between stable isotopes of atmospheric CO2 (δ13Catm) and δ13Cplant observed at lower pCO2 levels (i.e., RCO2 = 1x to 3x; Jahren et al., 2008), the δ13Cplant of biomass grown at more elevated RCO2 was dependent upon δ13Catm according to the linear relationship: δ13Cplant = 1.9(δ13Cplant) - 12.2 ‰ (r2 = 0.71). Concomitantly, we see a highly significant (p < 0.001) positive correlation between net carbon isotope discrimination in plant tissue and pCO2 level, with a change in the average Δδ13Cplant-atm in R. sativus L. from -27.0 to -28.0 ‰ at RCO2 = 5x to 11x, respectively. We will discuss possible mechanisms for changing isotope discrimination at very high pCO2 levels that may not be operative at lower concentrations. For example, we noted a striking reduction in the variability of biomass between plants grown at the same (very high) level of pCO2. This variability (calculated as the standard deviation of the log-transformed biomass data after

  11. Altered Refractive Development in Mice With Reduced Levels of Retinal Dopamine

    PubMed Central

    Bergen, Michael A.; Park, Han na; Chakraborty, Ranjay; Landis, Erica G.; Sidhu, Curran; He, Li; Iuvone, P. Michael; Pardue, Machelle T.

    2016-01-01

    Purpose The neuromodulator dopamine (DA) has been implicated in the prevention of excessive ocular elongation and myopia in various animal models. This study used retina-specific DA knockout mice to investigate the role of retinal DA in refractive development and susceptibility to experimental myopia. Methods Measurements of refractive error, corneal curvature, and ocular biometrics were obtained as a function of age for both untreated and form-deprived (FD) groups of retina-specific tyrosine hydroxylase knockout (rTHKO) and control (Ctrl) mice. Retinas from each group were analyzed by HPLC for levels of DA and its primary metabolite (DOPAC). Results Under normal visual conditions, rTHKO mice showed significantly myopic refractions (F(1,188) = 7.602, P < 0.001) and steeper corneas (main effect of genotype F(1,180) = 5.1, P < 0.01) at 4 and 6 weeks of age compared with Ctrl mice. Retina-specific THKO mice also had thinner corneas (main effect of genotype F(1,181) = 37.17, P < 0.001), thinner retinas (F(6,181) = 6.07, P < 0.001), and shorter axial lengths (F(6,181) = 3.78, P < 0.01) than Ctrl mice. Retina-specific THKO retinas contained less than 15% of DA and DOPAC compared with Ctrl retinas, and the remaining DA had a significantly higher turnover, as indicated by DOPAC/DA ratios (Student's t-test, P < 0.05). Retina-specific THKO mice showed similar, yet more variable, responses to 6 weeks of FD compared with Ctrl mice. Conclusions Diminished retinal DA induced spontaneous myopia in mice raised under laboratory conditions without form deprivation. The relative myopic shift in rTHKO mice may be explained by steeper corneas, an unexpected finding. The chronic loss of DA did not significantly alter the FD myopia response in rTHKO mice. PMID:27750284

  12. [Foundations of the new phylogenetics].

    PubMed

    Pavlinov, I Ia

    2004-01-01

    Evolutionary idea is the core of the modern biology. Due to this, phylogenetics dealing with historical reconstructions in biology takes a priority position among biological disciplines. The second half of the 20th century witnessed growth of a great interest to phylogenetic reconstructions at macrotaxonomic level which replaced microevolutionary studies dominating during the 30s-60s. This meant shift from population thinking to phylogenetic one but it was not revival of the classical phylogenetics; rather, a new approach emerged that was baptized The New Phylogenetics. It arose as a result of merging of three disciplines which were developing independently during 60s-70s, namely cladistics, numerical phyletics, and molecular phylogenetics (now basically genophyletics). Thus, the new phylogenetics could be defined as a branch of evolutionary biology aimed at elaboration of "parsimonious" cladistic hypotheses by means of numerical methods on the basis of mostly molecular data. Classical phylogenetics, as a historical predecessor of the new one, emerged on the basis of the naturphilosophical worldview which included a superorganismal idea of biota. Accordingly to that view, historical development (the phylogeny) was thought an analogy of individual one (the ontogeny) so its most basical features were progressive parallel developments of "parts" (taxa), supplemented with Darwinian concept of monophyly. Two predominating traditions were diverged within classical phylogenetics according to a particular interpretation of relation between these concepts. One of them (Cope, Severtzow) belittled monophyly and paid most attention to progressive parallel developments of morphological traits. Such an attitude turned this kind of phylogenetics to be rather the semogenetics dealing primarily with evolution of structures and not of taxa. Another tradition (Haeckel) considered both monophyletic and parallel origins of taxa jointly: in the middle of 20th century it was split into

  13. Kidney Function Alters the Relationship between Postoperative Troponin T Level and Death

    PubMed Central

    Wang, Chew-Yin; Ong, Gracie S.Y.; Tan, Alvin S.B.; Mansor, Marzida; Shariffuddin, Ina I.; Hashim, Noorjahan H.M.; Lai, Hou Yee; Undok, A. Wahab; Kolandaivel, Ushananthini N.; Vajiravelu, Vasanthan; Garg, Amit X.; Cuerden, Meaghan; Guyatt, Gordon; Thabane, Lehana; Mooney, John; Lee, Vincent; Chow, Clara; Devereaux, Phillip J.

    2015-01-01

    Cardiac troponin T (cTnT), even at low concentrations, is a risk factor for 30-day mortality in patients undergoing noncardiac surgery, but it is uncertain whether that risk is generalizable to patients with poor kidney function. We, therefore, evaluated the relationship between cTnT concentration and kidney function on the outcome of 30-day mortality in a post hoc analysis of a prospective cohort study of patients undergoing noncardiac surgery. cTnT was measured for 3 days after surgery and considered abnormal if the peak was ≥0.02 ng/ml. Of the included 14,037 patients, 267 (1.9%) patients died within 30 days of surgery. The adjusted hazard ratios for death with an abnormal cTnT concentration were 4.37 (95% confidence intervals [95% CI], 3.21 to 6.22), 6.15 (95% CI, 2.95 to 140.9), 6.30 (95% CI, 3.12 to 21.23), 1.33 (95% CI, 0.56 to 4.85), and 1.46 (95% CI, 0.46 to 9.21) for eGFR≥60, 45 to <60, 30 to <45, 15 to <30, and <15 ml/min per 1.73 m2 or on dialysis, respectively. Compared with patients with eGFR≥60 ml/min per 1.73 m2, the adjusted hazard ratio was significantly lower for patients with eGFR=15 to <30 ml/min per 1.73 m2 (interaction P value=0.02). Redefining abnormal cTnT concentration as ≥0.03 ng/ml or a change of ≥0.02 ng/ml did not alter results. Because the risk associated with postoperative cTnT levels may be different for patients with eGFR<30 ml/min per 1.73 m2, additional research is required to determine how to interpret perioperative cTnT values for patients with low kidney function. PMID:25711126

  14. A reassessment of the phylogenetic utility of genus-level morphological characters in the family Bogidiellidae (Crustacea, Amphipoda), with description of a new species of Eobogidiella Karaman, 1981

    PubMed Central

    Sidorov, Dmitry A.; Katz, Aron D.; Taylor, Steven J.; Chertoprud, Mikhail V.

    2016-01-01

    Abstract Bogidiellidae is the most diverse and cosmopolitan family of stygobiotic amphipods, and inhabits a variety of subterranean biotopes, especially interstitial habitats. While the family is characterized by considerable sexual dimorphism, this dimorphism has adversely affected our understanding of the systematics of the group. Most species have restricted geographic ranges and occur in difficult to sample habitats, so it is common for individual species descriptions to be based on a single sex. In this work we revisit an analysis of morphological characters in an attempt to clarify their phylogenetic utility in resolving taxonomic relationships among genera by introducing a new species, two additional characters, and phylogenetic statistical support values. Eobogidiella venkataramani sp. n., from a spring fed brook in the Shirawati River basin along the escarpment of the Western Ghats (Karnataka, India) differs from the only known congener, Eobogidiella purmamarcensis, from Argentina, in the structure of mouthparts, the shape and ornamentation on gnathopods and characters of the telson. Our phylogenetic analyses indicate that the available morphological characters are not sufficient to resolve phylogenetic relationships within Bogidiellidae, thus these characters alone cannot be used to determine the phylogenetic placement of Eobogidiella venkataramani sp. n. within the family. Nevertheless, Eobogidiella venkataramani sp. n. shares diagnostic characters with Eobogidiella, supporting placement of the new species in this genus. Our findings point towards a critical need to resolve relationships within the family using molecular approaches, along with the development of a suite of additional morphological characters for Bogidiellidae. This is the third species of Bogidiellidae from southern India. PMID:27587976

  15. Microbial Communities on Seafloor Basalts at Dorado Outcrop Reflect Level of Alteration and Highlight Global Lithic Clades

    PubMed Central

    Lee, Michael D.; Walworth, Nathan G.; Sylvan, Jason B.; Edwards, Katrina J.; Orcutt, Beth N.

    2015-01-01

    Areas of exposed basalt along mid-ocean ridges and at seafloor outcrops serve as conduits of fluid flux into and out of a subsurface ocean, and microbe–mineral interactions can influence alteration reactions at the rock–water interface. Located on the eastern flank of the East Pacific Rise, Dorado Outcrop is a site of low-temperature (<20°C) hydrothermal venting and represents a new end-member in the current survey of seafloor basalt biomes. Consistent with prior studies, a survey of 16S rRNA gene sequence diversity using universal primers targeting the V4 hypervariable region revealed much greater richness and diversity on the seafloor rocks than in surrounding seawater. Overall, Gamma-, Alpha-, and Deltaproteobacteria, and Thaumarchaeota dominated the sequenced communities, together making up over half of the observed diversity, though bacterial sequences were more abundant than archaeal in all samples. The most abundant bacterial reads were closely related to the obligate chemolithoautotrophic, sulfur-oxidizing Thioprofundum lithotrophicum, suggesting carbon and sulfur cycling as dominant metabolic pathways in this system. Representatives of Thaumarchaeota were detected in relatively high abundance on the basalts in comparison to bottom water, possibly indicating ammonia oxidation. In comparison to other sequence datasets from globally distributed seafloor basalts, this study reveals many overlapping and cosmopolitan phylogenetic groups and also suggests that substrate age correlates with community structure. PMID:26779122

  16. Microbial Communities on Seafloor Basalts at Dorado Outcrop Reflect Level of Alteration and Highlight Global Lithic Clades.

    PubMed

    Lee, Michael D; Walworth, Nathan G; Sylvan, Jason B; Edwards, Katrina J; Orcutt, Beth N

    2015-01-01

    Areas of exposed basalt along mid-ocean ridges and at seafloor outcrops serve as conduits of fluid flux into and out of a subsurface ocean, and microbe-mineral interactions can influence alteration reactions at the rock-water interface. Located on the eastern flank of the East Pacific Rise, Dorado Outcrop is a site of low-temperature (<20°C) hydrothermal venting and represents a new end-member in the current survey of seafloor basalt biomes. Consistent with prior studies, a survey of 16S rRNA gene sequence diversity using universal primers targeting the V4 hypervariable region revealed much greater richness and diversity on the seafloor rocks than in surrounding seawater. Overall, Gamma-, Alpha-, and Deltaproteobacteria, and Thaumarchaeota dominated the sequenced communities, together making up over half of the observed diversity, though bacterial sequences were more abundant than archaeal in all samples. The most abundant bacterial reads were closely related to the obligate chemolithoautotrophic, sulfur-oxidizing Thioprofundum lithotrophicum, suggesting carbon and sulfur cycling as dominant metabolic pathways in this system. Representatives of Thaumarchaeota were detected in relatively high abundance on the basalts in comparison to bottom water, possibly indicating ammonia oxidation. In comparison to other sequence datasets from globally distributed seafloor basalts, this study reveals many overlapping and cosmopolitan phylogenetic groups and also suggests that substrate age correlates with community structure.

  17. ALTERATION IN COMMUNITY-DWELLING OLDER ADULTS’ LEVEL WALKING FOLLOWING PERTURBATION TRAINING

    PubMed Central

    Yang, Feng; Pai, Yi-Chung

    2013-01-01

    While perturbation training is promising in reducing fall-risk among older adults, its impact on altering their spontaneous gait pattern has not been investigated. The purpose of this study was to determine to what extent older adults’ gait pattern would be affected by exposure to 24 repeated slips. Seventy-three community-dwelling older adults (age: 72.6 ± 5.4 years) underwent 24 repeated-slip exposure induced by unannounced unlocking and relocking of low-friction sections of a 7-m pathway upon which they walked. Full body kinematics and kinetics were recorded during the training. The gait parameters and the center of mass (COM) stability against backward balance loss were compared before and after the training. The results revealed that the training reduced fall incidence from 43.8% upon the novel slip to 0 at the end of training. After the training, subjects significantly improved gait stability by forward positioning of their COM relative to the base of support without altering gait speed. This forward COM shift resulted from a shortened step at the end of single stance and forward trunk leaning during double stance. They also adopted flat foot landing with knee flexed at touchdown (with an average change of 6.9 and 4.1 degrees, respectively). The perturbation training did alter community-dwelling older adults’ spontaneous gait pattern. These changes enabled them to improve their volitional control of stability and their resistance to unpredictable and unpreventable slip-related postural disturbance. PMID:23978691

  18. L-4F Differentially Alters Plasma Levels of Oxidized Fatty Acids Resulting in more Anti-Inflammatory HDL in Mice

    PubMed Central

    Imaizumi, Satoshi; Grijalva, Victor; Navab, Mohamad; Van Lenten, Brian J.; Wagner, Alan C.; Anantharamaiah, G.M.; Fogelman, Alan M.; Reddy, Srinivasa T.

    2011-01-01

    To determine in vivo if L-4F differentially alters plasma levels of oxidized fatty acids resulting in more anti-inflammatory HDL. Injecting L-4F into apoE null mice resulted in a significant reduction in plasma levels of 15-HETE, 5-HETE, 13-HODE and 9-HODE. In contrast, plasma levels of 20-HETE were not reduced and plasma levels of 14,15-EET, which are derived from the cytochrome P450 pathway, were elevated after injection of L-4F. Injection of 13(S)-HPODE into wild-type C57BL/6J mice caused an increase in plasma levels of 13-HODE and 9-HODE and was accompanied by a significant loss in the anti-inflammatory properties of HDL. The response of atherosclerosis resistant C3H/HeJ mice to injection of 13(S)-HPODE was similar but much more blunted. Injection of L-4F at a site different from that at which the 13(S)-HPODE was injected resulted in significantly lower plasma levels of 13-HODE and 9-HODE and significantly less loss of HDL anti-inflammatory properties in both strains. i) L-4F differentially alters plasma levels of oxidized fatty acids in vivo. ii) The resistance of the C3H/HeJ strain to atherosclerosis may in part be mediated by a reduced reaction of this strain to these potent lipid oxidants. L-4F differentially alters plasma levels of oxidized fatty acids in mice and the resistance of C3H/HeJ mice to atherosclerosis may be mediated by a reduced reaction of this strain to these potent lipid oxidants. PMID:20642447

  19. Alteration in the cytokine levels and histopathological damage in common carp induced by glyphosate.

    PubMed

    Ma, Junguo; Li, Xiaoyu

    2015-06-01

    Glyphosate is one of the most frequently used herbicides, and it has been demonstrated to generate a series of toxicological problems in animals and humans. However, relatively little is known about the effects of glyphosate on the immune system of fish. In the present study, the acute toxicity of glyphosate on common carp was first determined; then, the contents of interferon-γ (IFN-γ), interleukin-1β (IL-1β), and tumor necrosis factor -α (TNF-α) and histopathological alterations in the liver, kidneys, and spleen of common carp exposed to 52.08 or 104.15 mg L(-1) of glyphosate for 168 h were also determined and evaluated. The results of the acute toxicity tests showed that the 96 h LC50 of glyphosate for common carp was 520.77 mg L(-1). Moreover, sub-acute exposure of glyphosate altered the contents of IFN-γ, IL-1β, and TNF-α in fish immune organs. For example, there was a remarkable increase in the IFN-γ content in the kidneys, while there was a decrease in the liver and spleen. The IL-1β content increased in liver and kidneys, but it decreased in the spleen, and TNF-α mainly increased in the fish liver, kidneys, and spleen. In addition, glyphosate-exposure also caused remarkable histopathological damage in the fish liver, kidneys, and spleen. These results suggest that glyphosate-caused cytokine alterations may result in an immune suppression or excessive activation in the treated common carp as well as may cause immune dysfunction or reduced immunity. In conclusion, glyphosate has immunotoxic effects on common carp.

  20. Growth of Streptococcus mutans in Biofilms Alters Peptide Signaling at the Sub-population Level

    PubMed Central

    Shields, Robert C.; Burne, Robert A.

    2016-01-01

    Streptococcus mutans activates multiple cellular processes in response to the formation of a complex between comX-inducing peptide (XIP) and the ComR transcriptional regulator. Bulk phase and microfluidic experiments previously revealed that ComR-dependent activation of comX is altered by pH and by carbohydrate source. Biofilm formation is a major factor in bacterial survival and virulence in the oral cavity. Here, we sought to determine the response of S. mutans biofilm cells to XIP during different stages of biofilm maturation. Using flow cytometry and confocal microscopy, we showed that exogenous addition of XIP to early biofilms resulted in robust comX activation. However, as the biofilms matured, increasing amounts of XIP were required to activate comX expression. Single-cell analysis demonstrated that the entire population was responding to XIP with activation of comX in early biofilms, but only a sub-population was responding in mature biofilms. The sub-population response of mature biofilms was retained when the cells were dispersed and then treated with XIP. The proportion and intensity of the bi-modal response of mature biofilm cells was altered in mutants lacking the Type II toxins MazF and RelE, or in a strain lacking the (p)ppGpp synthase/hydrolase RelA. Thus, competence signaling is markedly altered in cells growing in mature biofilms, and pathways that control cell death and growth/survival decisions modulate activation of comX expression in these sessile populations. PMID:27471495

  1. Environmental prenatal stress eliminates brain and maternal behavioral sex differences and alters hormone levels in female rats.

    PubMed

    Del Cerro, M C R; Ortega, E; Gómez, F; Segovia, S; Pérez-Laso, C

    2015-07-01

    Environmental prenatal stress (EPS) has effects on fetuses that are long-lasting, altering their hormone levels, brain morphology and behavior when they reach maturity. In previous research, we demonstrated that EPS affects the expression of induced maternal behavior (MB), the neuroendocrine system, and morphology of the sexually dimorphic accessory olfactory bulb (AOB) involved in reproductive behavior patterns. The bed nucleus of the accessory olfactory tract (BAOT) is another vomeronasal (VN) structure that plays an inhibitory role in rats in the expression of induced maternal behavior in female and male virgins. In the present study, we have ascertained whether the behavioral, neuroendocrine, and neuromorphological alterations of the AOB found after EPS also appear in the BAOT. After applying EPS to pregnant rats during the late gestational period, in their female offspring at maturity we tested induced maternal behavior, BAOT morphology and plasma levels of testosterone (T), estradiol (E2), progesterone (P), adrenocorticotropic hormone (ACTH) and corticosterone (Cpd B). EPS: a) affected the induction of MB, showed a male-like pattern of care for pups, b) elevated plasma levels of Cpd B and reduced E2 in comparison with the controls, and c) significantly increased the number of BAOT neurons compared to the control females and comparable to the control male group. These findings provide further evidence that stress applied to pregnant rats produces long-lasting behavioral, endocrine and neuroanatomical alterations in the female offspring that are evident when they become mature.

  2. Alteration of the kidney membrane proteome of Mizuhopecten yessoensis induced by low-level methyl parathion exposure.

    PubMed

    Huang, Xiang; Huang, He-Qing

    2012-06-15

    Methyl parathion (MP) is a widely used organophosphorus pesticide that causes severe health and environmental effects. We investigated the alteration of the proteomic profile in the membrane enriched fraction of the kidneys of the scallop Mizuhopecten yessoensis exposed to low-level MP. Gas chromatography analysis showed that MP residues were significantly accumulated in the kidneys and the digestive glands of the scallops. According to two-dimensional electrophoresis, 17 proteins were differentially modulated under MP exposure. The mRNA expressions of 12 differential proteins were analyzed using quantitative PCR, and 10 showed consistent alteration of mRNA level with that of protein expression level. Altered expressions of two proteins (mitochondrial processing peptidase and α-tubulin) were also examined using Western blotting, showing that the mitochondrial processing peptidase was down-regulated but α-tubulin remained unchanged in response to MP exposure. Subcellular locations of all the identified proteins that were predicted using bioinformatics tools indicate that few of them are permanently located in the membrane. The differentially expressed proteins are involved in several critical biological processes, and their relevance to human health has been illuminated. These data taken together have provided some novel insights into the chronic toxicity mechanism of MP and have suggested mitochondrial processing peptidase as a potential biomarker for human health and environmental monitoring.

  3. Altered metabolism of copper, zinc, and magnesium is associated with increased levels of glycated hemoglobin in patients with diabetes mellitus.

    PubMed

    Viktorínová, Alena; Toserová, Eva; Krizko, Marián; Duracková, Zdenka

    2009-10-01

    Diabetes mellitus (DM) is associated with the alterations in the metabolism of copper (Cu), zinc (Zn), and magnesium (Mg). The aim of the present study was to investigate plasma levels of these elements in patients with DM and in healthy subjects. Association between glycated hemoglobin and levels of metals was also evaluated. We studied 36 subjects with DM (type 1, 11; type 2, 25) and 34 healthy subjects matched for age, sex, and duration of diabetes. Plasma concentrations of Cu, Zn, and Mg were measured by atomic absorption spectrometry. An imbalance in the levels of studied metals was observed in both type 1 and type 2 DM. We found higher levels of Cu (P < .001) and Cu/Zn ratio (P < .0001) and decreased levels of Zn (P < .01) and Mg (P < .0001) in patients with DM when compared with controls. Negative correlation between Cu and Zn (r = -0.626, P < .0001) was found in patients with DM. Glycated hemoglobin levels were positively correlated with Cu (r = 0.709, P < .001) and Cu/Zn ratio (r = 0.777, P < .001) and inversely correlated with Zn (r = - 0.684, P < .001) and Mg (r = -0.646, P < .001). In conclusion, patients with DM had altered metabolism of Cu, Zn, and Mg; and this may be related to increased values of glycated hemoglobin. We concluded that impaired metabolism of these elements may contribute to the progression of DM and diabetic complications.

  4. Prenatal exposure to low levels of carbon monoxide alters sciatic nerve myelination in rat offspring.

    PubMed

    Carratù, M R; Cagiano, R; Desantis, S; Labate, M; Tattoli, M; Trabace, L; Cuomo, V

    2000-08-25

    Prenatal exposure to low concentrations of carbon monoxide (CO, 75 and 150 ppm from day 0 to day 20 of gestation), resulting in maternal blood HbCO concentrations equivalent to those maintained by human cigarette smokers, leads to subtle myelin alterations in the sciatic nerve of male rat offspring. The rapid growth spurt in pup body weight was related to the period of maximal increase in myelin sheath thickness in both control and CO-exposed animals. A significant reduction in myelin sheath thickness of sciatic nerve fibers, paralleled by changes in the frequency distribution, occurred in both 40- and 90-day-old rats exposed in utero to CO (75 and 150 ppm). Myelin deficit observed in 75 and 150 ppm CO-exposed animals showed up only after the major spurt in myelination but not early during development. The subtle myelin alterations observed in CO-exposed offspring were not accompanied by changes in developmental pattern of axon diameters and did not result in a gross impairment of motor activity. These results suggest that the myelination process is selectively targeted by a prenatal exposure model simulating the CO exposure observed in human cigarette smokers.

  5. Alterations in Lipid Levels of Mitochondrial Membranes Induced by Amyloid-β: A Protective Role of Melatonin

    PubMed Central

    Rosales-Corral, Sergio A.; Lopez-Armas, Gabriela; Cruz-Ramos, Jose; Melnikov, Valery G.; Tan, Dun-Xian; Manchester, Lucien C.; Munoz, Ruben; Reiter, Russel J.

    2012-01-01

    Alzheimer pathogenesis involves mitochondrial dysfunction, which is closely related to amyloid-β (Aβ) generation, abnormal tau phosphorylation, oxidative stress, and apoptosis. Alterations in membranal components, including cholesterol and fatty acids, their characteristics, disposition, and distribution along the membranes, have been studied as evidence of cell membrane alterations in AD brain. The majority of these studies have been focused on the cytoplasmic membrane; meanwhile the mitochondrial membranes have been less explored. In this work, we studied lipids and mitochondrial membranes in vivo, following intracerebral injection of fibrillar amyloid-β (Aβ). The purpose was to determine how Aβ may be responsible for beginning of a vicious cycle where oxidative stress and alterations in cholesterol, lipids and fatty acids, feed back on each other to cause mitochondrial dysfunction. We observed changes in mitochondrial membrane lipids, and fatty acids, following intracerebral injection of fibrillar Aβ in aged Wistar rats. Melatonin, a well-known antioxidant and neuroimmunomodulator indoleamine, reversed some of these alterations and protected mitochondrial membranes from obvious damage. Additionally, melatonin increased the levels of linolenic and n-3 eicosapentaenoic acid, in the same site where amyloid β was injected, favoring an endogenous anti-inflammatory pathway. PMID:22666620

  6. Lead (Pb) exposure reduces global DNA methylation level by non-competitive inhibition and alteration of dnmt expression.

    PubMed

    Sanchez, Oscar F; Lee, Jinyoung; Yu King Hing, Nathaphon; Kim, Seong-Eun; Freeman, Jennifer L; Yuan, Chongli

    2017-02-22

    Low-dose exposure to lead (Pb) is connected to developmental neurological alterations by inducing molecular changes, such as aberrant gene expression patterns. The attributing molecular mechanism, however, is not well-elucidated. In this study, we revealed epigenetic features and mechanisms that can alter gene expression patterns by identifying changes in DNA methyltransferase (DNMT) activity, expression pattern and DNA methylation level using moelcular studies and a zebrafish animal model. We characterized the effects of Pb on the activities of various DNMTs in vitro and determined the molecular role of Pb in modulating DNMT activity via kinetic experiments. An exposure of 100 or 500 ppb of Pb was found to significantly lower the activity of maintenance DNMTs. The inhibition mechanism can be described using non-competitive Michaelis-Menten kinetics. A zebrafish animal model was then used to assess the biological significance of our findings. An embryonic exposure to 100 or 500 ppb Pb resulted in a significant change in global methylation levels consistent with previous studies using human and rodent model. Our study also suggests that Pb exposure in zebrafish alters the expression patterns of dnmt3 and dnmt4 which are human DNMT3b orthologs. The knowledge from this study suggests that Pb exposure can affect the activity of maintenance DNMTs via non-competitive inhibition, which has not been reported previously. Meanwhile, the expression pattern of de novo methyltransferases can also be altered. Collectively, they result in a reduction in global DNA methylation level in Pb-exposed zebrafish model, which can be compared to findings in human and rodent studies.

  7. Alterations in plasma vascular endothelial growth factor levels in patients with schizophrenia before and after treatment.

    PubMed

    Lee, Bun-Hee; Hong, Jin-Pyo; Hwang, Jung-A; Ham, Byung-Joo; Na, Kyoung-Sae; Kim, Won-Joong; Trigo, Jose; Kim, Yong-Ku

    2015-07-30

    Vascular endothelial growth factor (VEGF), a potent angiogenetic factor, is a known neurotrophic factor. In this study, we examined plasma levels of VEGF in 50 patients with schizophrenia (SPR) and 50 healthy control subjects. We also explored any changes in plasma VEGF levels after 6-week treatment with antipsychotic agents in patients with schizophrenia. All subjects with schizophrenia were either medication-naïve or medication-free for at least 4 weeks before assessment. Plasma VEGF levels in all subjects were significantly correlated with smoking duration, which was considered to be a significant covariate. Pre-treatment plasma VEGF levels in patients with schizophrenia were significantly lower than those in healthy controls. Post-treatment VEGF levels were significantly increased in patients with schizophrenia. Plasma VEGF levels in patients with schizophrenia did not exhibit significant correlation with the total or subscale scores of the Positive and Negative Syndrome Scale (PANSS) either at baseline or at the end of the 6-week treatment. In conclusion, our findings reveal that plasma VEGF levels before treatment were lower in patients with schizophrenia and that their VEGF levels increased after treatment. Thus, VEGF may have a neuroprotective role in the improvement of schizophrenia or in the treatment effects of antipsychotics.

  8. Long-term variation in above and belowground plant inputs alters soil organic matter biogeochemistry at the molecular-level

    NASA Astrophysics Data System (ADS)

    Simpson, M. J.; Pisani, O.; Lin, L.; Lun, O.; Simpson, A.; Lajtha, K.; Nadelhoffer, K. J.

    2015-12-01

    The long-term fate of soil carbon reserves with global environmental change remains uncertain. Shifts in moisture, altered nutrient cycles, species composition, or rising temperatures may alter the proportions of above and belowground biomass entering soil. However, it is unclear how long-term changes in plant inputs may alter the composition of soil organic matter (SOM) and soil carbon storage. Advanced molecular techniques were used to assess SOM composition in mineral soil horizons (0-10 cm) after 20 years of Detrital Input and Removal Treatment (DIRT) at the Harvard Forest. SOM biomarkers (solvent extraction, base hydrolysis and cupric (II) oxide oxidation) and both solid-state and solution-state nuclear magnetic resonance (NMR) spectroscopy were used to identify changes in SOM composition and stage of degradation. Microbial activity and community composition were assessed using phospholipid fatty acid (PLFA) analysis. Doubling aboveground litter inputs decreased soil carbon content, increased the degradation of labile SOM and enhanced the sequestration of aliphatic compounds in soil. The exclusion of belowground inputs (No roots and No inputs) resulted in a decrease in root-derived components and enhanced the degradation of leaf-derived aliphatic structures (cutin). Cutin-derived SOM has been hypothesized to be recalcitrant but our results show that even this complex biopolymer is susceptible to degradation when inputs entering soil are altered. The PLFA data indicate that changes in soil microbial community structure favored the accelerated processing of specific SOM components with littler manipulation. These results collectively reveal that the quantity and quality of plant litter inputs alters the molecular-level composition of SOM and in some cases, enhances the degradation of recalcitrant SOM. Our study also suggests that increased litterfall is unlikely to enhance soil carbon storage over the long-term in temperate forests.

  9. Phylogenetic fields of species: cross-species patterns of phylogenetic structure and geographical coexistence.

    PubMed

    Villalobos, Fabricio; Rangel, Thiago F; Diniz-Filho, José Alexandre F

    2013-04-07

    Differential coexistence among species underlies geographical patterns of biodiversity. Understanding such patterns has relied either on ecological or historical approaches applied separately. Recently, macroecology and community phylogenetics have tried to integrate both ecological and historical approaches. However, macroecology is mostly non-phylogenetic, whereas community phylogenetics is largely focused on local scales. Here, we propose a conceptual framework to link macroecology and community phylogenetics by exploring the evolutionary context of large-scale species coexistence, introducing the phylogenetic field concept. This is defined as the phylogenetic structure of species co-occurrence within a focal species' geographical range. We developed concepts and methods for analysing phylogenetic fields and applied them to study coexistence patterns of the bat family Phyllostomidae. Our analyses showed that phyllostomid bats coexist mostly with closely related species, revealing a north-south gradient from overdispersed to clustered phylogenetic fields. Patterns at different phylogenetic levels (i.e. all species versus close relatives only) presented the same gradient. Results support the tropical niche conservatism hypothesis, potentially mediated by higher speciation rates in the region of origin coupled with shared environmental preferences among species. The phylogenetic field approach enables species-based community phylogenetics, instead of those that are site-based, allowing the description of historical processes at more appropriate macroecological and biogeographic scales.

  10. Plasma homocysteine levels are independently associated with alterations of large artery stiffness in men but not in women

    PubMed Central

    Sheng, Li; Wu, Cai; Bai, Yong-Yi; Xiao, Wen-Kai; Feng, Dan; Ye, Ping

    2015-01-01

    Objectives To investigate the associations of the plasma homocysteine levels with the alterations in arterial stiffness in a community-based cohort. The gender differences in these associations were examined. Methods We evaluated the relationship between plasma homocysteine levels to three measures of vascular function [carotid-femoral pulse wave velocity (CF-PWV), carotid-ankle PWV (CA-PWV) and heart rate corrected augmentation index (AI)] in 1680 participants (mean age: 61.5 years; 709 men, 971 women) from communities of Beijing, China. Results In univariate analysis, plasma homocysteine levels was positively related to the CF-PWV (r = 0.211, P < 0.0001) and CA-PWV (r = 0.148, P < 0.0001), whereas inversely associated with AI (r = −0.052, P = 0.016). In multiple linear regression models adjusting for covariants, plasma homocysteine remained positively related to the CF-PWV (standardized β = 0.065, P = 0.007) in total cases. When the groups of men and women were examined separately, plasma homocysteine remained positively associated with the CF-PWV (standardized β = 0.082, P = 0.023) in men, whereas the relations between homocysteine and any of the arterial stiffness indices were not further present in women. Conclusions In Chinese population, plasma homocysteine levels are independently associated with alterations of large artery stiffness in men but not in women. PMID:26089849

  11. Altered levels of brain neurotransmitter from new born rabbits with intrauterine restriction.

    PubMed

    Hernández-Andrade, E; Cortés-Camberos, A J; Díaz, N F; Flores-Herrera, H; García-López, G; González-Jiménez, M; Santamaría, A; Molina-Hernández, A

    2015-01-01

    Fetal intrauterine growth restriction generates chronic hypoxia due to placental insufficiency. Despite the hemodynamic process of blood flow, redistributions are taking place in key organs such as the fetal brain during intrauterine growth restriction, in order to maintain oxygen and nutrients supply. The risk of short- and long-term neurological effects are still present in hypoxic offspring. Most studies previously reported the effect of hypoxia on the levels of a single neurotransmitter, making it difficult to have a better understanding of the relationship among neurotransmitter levels and the defects reported in products that suffer intrauterine growth restriction, such as motor development, coordination and execution of movement, and the learning-memory process. The aim of this study was to evaluate the levels of gamma-aminobutyric acid, glutamate, dopamine and serotonin in three structures of the brain related to the above-mentioned function such as the cerebral cortex, the striatum, and the hippocampus in the chronic hypoxic newborn rabbit model. Our results showed a significant increase in glutamate and dopamine levels in all studied brain structures and a significant decrease in gamma-aminobutyric acid levels but only in the striatum, suggesting that the imbalance on the levels of several neurotransmitters could be involved in new born brain damage due to perinatal hypoxia.

  12. Association of Type 2 Diabetes Mellitus related SNP genotypes with altered serum adipokine levels and metabolic syndrome phenotypes

    PubMed Central

    Al-Daghri, Nasser M; Al-Attas, Omar S; Krishnaswamy, Soundararajan; Mohammed, Abdul Khader; Alenad, Amal M; Chrousos, George P; Alokail, Majed S

    2015-01-01

    The pathogenesis of T2DM involves secretion of several pro-inflammatory molecules by the dramatically increased adipocytes, both by number and size, and associated macrophages of adipose tissue. Since T2DM is usually preceded by obesity and chronic systemic inflammation, the objective of this study was to explore for any association between genetic variants of previously established 36 T2DM-associated SNPs and altered serum adipocytokine levels and metabolic syndrome phenotypes. Study consisted of 566 subjects (284 males and 282 females) of whom 147 were T2DM patients and 419 healthy controls. Study subjects were genotyped for 36 T2DM-linked single nucleotide polymorphisms (SNPs) using the KASPar SNP Genotyping System and grouped into different genotypes for each SNP. Various anthropometric and biochemical parameters were measured following standard procedures. The mean values of serum levels of individual adipocytokines and the presence/absence of metabolic syndrome phenotypes corresponding to various genotypes were compared by determining the odds ratios. Genotypic variants of five and seven of the 36 T2DM-related SNPs were significantly associated with altered serum levels of adiponectin and aPAI, respectively. Six variants of the 36 SNPs were associated with metabolic syndrome manifestations. This study identified positive associations between genotypic variants of five and seven of the 36 T2DM related SNPs and altered serum levels of adiponectin and aPAI, respectively. Six of 36 SNPs were also associated with metabolic syndrome in the studied population. The relation between specific SNPs and individual phenotypic traits may be useful in explaining the causal mechanisms of hereditary component of T2DM. PMID:26064370

  13. Systems-level metabolism of the altered Schaedler flora, a complete gut microbiota.

    PubMed

    Biggs, Matthew B; Medlock, Gregory L; Moutinho, Thomas J; Lees, Hannah J; Swann, Jonathan R; Kolling, Glynis L; Papin, Jason A

    2017-02-01

    The altered Schaedler flora (ASF) is a model microbial community with both in vivo and in vitro relevance. Here we provide the first characterization of the ASF community in vitro, independent of a murine host. We compared the functional genetic content of the ASF to wild murine metagenomes and found that the ASF functionally represents wild microbiomes better than random consortia of similar taxonomic composition. We developed a chemically defined medium that supported growth of seven of the eight ASF members. To elucidate the metabolic capabilities of these ASF species-including potential for interactions such as cross-feeding-we performed a spent media screen and analyzed the results through dynamic growth measurements and non-targeted metabolic profiling. We found that cross-feeding is relatively rare (32 of 3570 possible cases), but is enriched between Clostridium ASF356 and Parabacteroides ASF519. We identified many cases of emergent metabolism (856 of 3570 possible cases). These data will inform efforts to understand ASF dynamics and spatial distribution in vivo, to design pre- and probiotics that modulate relative abundances of ASF members, and will be essential for validating computational models of ASF metabolism. Well-characterized, experimentally tractable microbial communities enable research that can translate into more effective microbiome-targeted therapies to improve human health.

  14. Systems-level metabolism of the altered Schaedler flora, a complete gut microbiota

    PubMed Central

    Biggs, Matthew B; Medlock, Gregory L; Moutinho, Thomas J; Lees, Hannah J; Swann, Jonathan R; Kolling, Glynis L; Papin, Jason A

    2017-01-01

    The altered Schaedler flora (ASF) is a model microbial community with both in vivo and in vitro relevance. Here we provide the first characterization of the ASF community in vitro, independent of a murine host. We compared the functional genetic content of the ASF to wild murine metagenomes and found that the ASF functionally represents wild microbiomes better than random consortia of similar taxonomic composition. We developed a chemically defined medium that supported growth of seven of the eight ASF members. To elucidate the metabolic capabilities of these ASF species—including potential for interactions such as cross-feeding—we performed a spent media screen and analyzed the results through dynamic growth measurements and non-targeted metabolic profiling. We found that cross-feeding is relatively rare (32 of 3570 possible cases), but is enriched between Clostridium ASF356 and Parabacteroides ASF519. We identified many cases of emergent metabolism (856 of 3570 possible cases). These data will inform efforts to understand ASF dynamics and spatial distribution in vivo, to design pre- and probiotics that modulate relative abundances of ASF members, and will be essential for validating computational models of ASF metabolism. Well-characterized, experimentally tractable microbial communities enable research that can translate into more effective microbiome-targeted therapies to improve human health. PMID:27824342

  15. The TOC159 mutant of Arabidopsis thaliana accumulates altered levels of saturated and polyunsaturated fatty acids.

    PubMed

    Afitlhile, Meshack; Fry, Morgan; Workman, Samantha

    2015-02-01

    We evaluated whether the TOC159 mutant of Arabidopsis called plastid protein import 2-2 (ppi2-2) accumulates normal levels of fatty acids, and transcripts of fatty acid desaturases and galactolipid synthesis enzymes. The ppi2-2 mutant accumulates decreased pigments and total fatty acid content. The MGD1 gene was downregulated and the mutant accumulates decreased levels of monogalactosyldiacylglycerol (MGDG) and 16:3, which suggests that the prokaryotic pathway was impaired in the mutant. The HY5 gene, which encodes long hypocotyl5 transcription factor, was upregulated in the mutant. The DGD1 gene, an HY5 target was marginally increased and the mutant accumulates digalactosyldiacylglycerol at the control level. The mutant had increased expression of 3-ketoacyl-ACP synthase II gene, which encodes a plastid enzyme that elongates 16:0 to 18:0. Interestingly, glycerolipids in the mutant accumulate increased levels of 18:0. A gene that encodes stearoyl-ACP desaturase (SAD) was expressed at the control level and 18:1 was increased, which suggest that SAD may be strongly regulated at the posttranscriptional level. The molar ratio of MGDG to bilayer forming plastid lipids was decreased in the cold-acclimated wild type but not in the ppi2-2 mutant. This indicates that the mutant was unresponsive to cold-stress, and is consistent with increased levels of 18:0, and decreased 16:3 and 18:3 in the ppi2-2 mutant. Overall, these data indicate that a defective Toc159 receptor impaired the synthesis of MGDG, and affected desaturation of 16 and 18-carbon fatty acids. We conclude that expression of the MGD1 gene and synthesis of MGDG are tightly linked to plastid biogenesis.

  16. Biochemical and Structural Characterizations of Two Dictyostelium Cellobiohydrolases from the Amoebozoa Kingdom Reveal a High Level of Conservation between Distant Phylogenetic Trees of Life

    PubMed Central

    Hobdey, Sarah E.; Knott, Brandon C.; Haddad Momeni, Majid; Taylor, Larry E.; Borisova, Anna S.; Podkaminer, Kara K.; VanderWall, Todd A.; Himmel, Michael E.; Decker, Stephen R.

    2016-01-01

    ABSTRACT Glycoside hydrolase family 7 (GH7) cellobiohydrolases (CBHs) are enzymes commonly employed in plant cell wall degradation across eukaryotic kingdoms of life, as they provide significant hydrolytic potential in cellulose turnover. To date, many fungal GH7 CBHs have been examined, yet many questions regarding structure-activity relationships in these important natural and commercial enzymes remain. Here, we present the crystal structures and a biochemical analysis of two GH7 CBHs from social amoeba: Dictyostelium discoideum Cel7A (DdiCel7A) and Dictyostelium purpureum Cel7A (DpuCel7A). DdiCel7A and DpuCel7A natively consist of a catalytic domain and do not exhibit a carbohydrate-binding module (CBM). The structures of DdiCel7A and DpuCel7A, resolved to 2.1 Å and 2.7 Å, respectively, are homologous to those of other GH7 CBHs with an enclosed active-site tunnel. Two primary differences between the Dictyostelium CBHs and the archetypal model GH7 CBH, Trichoderma reesei Cel7A (TreCel7A), occur near the hydrolytic active site and the product-binding sites. To compare the activities of these enzymes with the activity of TreCel7A, the family 1 TreCel7A CBM and linker were added to the C terminus of each of the Dictyostelium enzymes, creating DdiCel7ACBM and DpuCel7ACBM, which were recombinantly expressed in T. reesei. DdiCel7ACBM and DpuCel7ACBM hydrolyzed Avicel, pretreated corn stover, and phosphoric acid-swollen cellulose as efficiently as TreCel7A when hydrolysis was compared at their temperature optima. The Ki of cellobiose was significantly higher for DdiCel7ACBM and DpuCel7ACBM than for TreCel7A: 205, 130, and 29 μM, respectively. Taken together, the present study highlights the remarkable degree of conservation of the activity of these key natural and industrial enzymes across quite distant phylogenetic trees of life. IMPORTANCE GH7 CBHs are among the most important cellulolytic enzymes both in nature and for emerging industrial applications for

  17. Habitat fragmentation differentially affects trophic levels and alters behavior in a multi-trophic marine system.

    PubMed

    Rielly-Carroll, Elizabeth; Freestone, Amy L

    2017-03-01

    Seagrass, an important subtidal marine ecosystem, is being lost at a rate of 110 km(2) year(-1), leading to fragmented seagrass seascapes. Habitat fragmentation is predicted to affect trophic levels differently, with higher trophic levels being more sensitive, stressing the importance of a multi-trophic perspective. Utilizing the trophic relationship between the blue crab (Callinectes sapidus) and hard clam (Mercenaria mercenaria), where adult blue crabs prey on juvenile blue crabs, and juvenile blue crabs prey on small hard clams, we examined whether predation rates, abundance, and behavior of predators and prey differed between continuous and fragmented seagrass in a multi-trophic context at two sites in Barnegat Bay, NJ. We tested the hypothesis that fragmented habitats would differentially affect trophic levels within a tri-trophic system, and our results supported this hypothesis. Densities of adult blue crabs were higher in fragmented than continuous habitats. Densities of juvenile blue crabs, the primary predator of hard clams, were lower in fragmented habitats than continuous, potentially due to increased predation by adult blue crabs. Clams experienced lower predation and burrowed to a shallower depth in fragmented habitats than in continuous habitat, likely due in part to the low densities of juvenile blue crabs, their primary predator. Our results suggest that while trophic levels are differentially affected, the impact of habitat fragmentation may be stronger on intermediate rather than top trophic levels in some marine systems.

  18. Neonatal manipulation of oxytocin alters oxytocin levels in the pituitary of adult rats.

    PubMed

    Young, E; Carter, C S; Cushing, B S; Caldwell, J D

    2005-07-01

    The neuropeptide oxytocin (OT) and its OT antagonists (OTA) in infant rats affect their behavior as adults. In this study we attempted to determine whether treating rats on the day of birth (postnatal day 1) with OT or OTA would affect brain OT levels of these rats as adults. Rat pups were injected with OT (3 microg), OTA (0.3 microg) or saline vehicle ip on postnatal day 1. As 60-day-old adults, treated rats were killed, and the OT content in their medial preoptic areas (MPOAs), medial hypothalami (MH) and pituitaries were assayed. In females, treatment with OTA on postnatal day 1 significantly decreased pituitary OT levels as adults. In males, by contrast, treatment with OTA on postnatal day 1 resulted in increased pituitary OT levels when they become adults compared to male rats treated with OT on postnatal day 1. There were no significant effects of neonatal treatment on OT levels in either the MH or MPOA. Day 1 postnatal treatment with OT or OTA had a long-term sexually dimorphic effect on OT levels in the pituitary.

  19. CrBPF1 overexpression alters transcript levels of terpenoid indole alkaloid biosynthetic and regulatory genes

    PubMed Central

    Li, Chun Yao; Leopold, Alex L.; Sander, Guy W.; Shanks, Jacqueline V.; Zhao, Le; Gibson, Susan I.

    2015-01-01

    Terpenoid indole alkaloid (TIA) biosynthesis in Catharanthus roseus is a complex and highly regulated process. Understanding the biochemistry and regulation of the TIA pathway is of particular interest as it may allow the engineering of plants to accumulate higher levels of pharmaceutically important alkaloids. Toward this end, we generated a transgenic C. roseus hairy root line that overexpresses the CrBPF1 transcriptional activator under the control of a β-estradiol inducible promoter. CrBPF1 is a MYB-like protein that was previously postulated to help regulate the expression of the TIA biosynthetic gene STR. However, the role of CrBPF1 in regulation of the TIA and related pathways had not been previously characterized. In this study, transcriptional profiling revealed that overexpression of CrBPF1 results in increased transcript levels for genes from both the indole and terpenoid biosynthetic pathways that provide precursors for TIA biosynthesis, as well as for genes in the TIA biosynthetic pathway. In addition, overexpression of CrBPF1 causes increases in the transcript levels for 11 out of 13 genes postulated to act as transcriptional regulators of genes from the TIA and TIA feeder pathways. Interestingly, overexpression of CrBPF1 causes increased transcript levels for both TIA transcriptional activators and repressors. Despite the fact that CrBPF1 overexpression affects transcript levels of a large percentage of TIA biosynthetic and regulatory genes, CrBPF1 overexpression has only very modest effects on the levels of the TIA metabolites analyzed. This finding may be due, at least in part, to the up-regulation of both transcriptional activators and repressors in response to CrBPF1 overexpression, suggesting that CrBPF1 may serve as a “fine-tune” regulator for TIA biosynthesis, acting to help regulate the timing and amplitude of TIA gene expression. PMID:26483828

  20. Low-level red laser therapy alters effects of ultraviolet C radiation on Escherichia coli cells.

    PubMed

    Canuto, K S; Sergio, L P S; Guimarães, O R; Geller, M; Paoli, F; Fonseca, A S

    2015-07-10

    Low-level lasers are used at low power densities and doses according to clinical protocols supplied with laser devices or based on professional practice. Although use of these lasers is increasing in many countries, the molecular mechanisms involved in effects of low-level lasers, mainly on DNA, are controversial. In this study, we evaluated the effects of low-level red lasers on survival, filamentation, and morphology of Escherichia coli cells that were exposed to ultraviolet C (UVC) radiation. Exponential and stationary wild-type and uvrA-deficient E. coli cells were exposed to a low-level red laser and in sequence to UVC radiation. Bacterial survival was evaluated to determine the laser protection factor (ratio between the number of viable cells after exposure to the red laser and UVC and the number of viable cells after exposure to UVC). Bacterial filaments were counted to obtain the percentage of filamentation. Area-perimeter ratios were calculated for evaluation of cellular morphology. Experiments were carried out in duplicate and the results are reported as the means of three independent assays. Pre-exposure to a red laser protected wild-type and uvrA-deficient E. coli cells against the lethal effect of UVC radiation, and increased the percentage of filamentation and the area-perimeter ratio, depending on UVC fluence and physiological conditions in the cells. Therapeutic, low-level red laser radiation can induce DNA lesions at a sub-lethal level. Consequences to cells and tissues should be considered when clinical protocols based on this laser are carried out.

  1. Low-level red laser therapy alters effects of ultraviolet C radiation on Escherichia coli cells.

    PubMed

    Canuto, K S; Sergio, L P S; Guimarães, O R; Geller, M; Paoli, F; Fonseca, A S

    2015-10-01

    Low-level lasers are used at low power densities and doses according to clinical protocols supplied with laser devices or based on professional practice. Although use of these lasers is increasing in many countries, the molecular mechanisms involved in effects of low-level lasers, mainly on DNA, are controversial. In this study, we evaluated the effects of low-level red lasers on survival, filamentation, and morphology of Escherichia colicells that were exposed to ultraviolet C (UVC) radiation. Exponential and stationary wild-type and uvrA-deficientE. coli cells were exposed to a low-level red laser and in sequence to UVC radiation. Bacterial survival was evaluated to determine the laser protection factor (ratio between the number of viable cells after exposure to the red laser and UVC and the number of viable cells after exposure to UVC). Bacterial filaments were counted to obtain the percentage of filamentation. Area-perimeter ratios were calculated for evaluation of cellular morphology. Experiments were carried out in duplicate and the results are reported as the means of three independent assays. Pre-exposure to a red laser protected wild-type and uvrA-deficient E. coli cells against the lethal effect of UVC radiation, and increased the percentage of filamentation and the area-perimeter ratio, depending on UVC fluence and physiological conditions in the cells. Therapeutic, low-level red laser radiation can induce DNA lesions at a sub-lethal level. Consequences to cells and tissues should be considered when clinical protocols based on this laser are carried out.

  2. The Effects of Altered Membrane Cholesterol Levels on Sodium Pump Activity in Subclinical Hypothyroidism

    PubMed Central

    2017-01-01

    Background Metabolic dysfunctions characteristic of overt hypothyroidism (OH) start at the early stage of subclinical hypothyroidism (SCH). Na+/K+-ATPase (the sodium pump) is a transmembrane enzyme that plays a vital role in cellular activities in combination with membrane lipids. We evaluated the effects of early changes in thyroid hormone and membrane cholesterol on sodium pump activity in SCH and OH patients. Methods In 32 SCH patients, 35 OH patients, and 34 euthyroid patients, sodium pump activity and cholesterol levels in red blood cell membranes were measured. Serum thyroxine (T4) and thyroid stimulating hormone (TSH) levels were measured using enzyme-linked immunosorbent assays. Differences in their mean values were analysed using post hoc analysis of variance. We assessed the dependence of the sodium pump on other metabolites by multiple regression analysis. Results Sodium pump activity and membrane cholesterol were lower in both hypothyroid groups than in control group, OH group exhibiting lower values than SCH group. In SCH group, sodium pump activity showed a significant direct dependence on membrane cholesterol with an inverse relationship with serum TSH levels. In OH group, sodium pump activity depended directly on membrane cholesterol and serum T4 levels. No dependence on serum cholesterol was observed in either case. Conclusion Despite the presence of elevated serum cholesterol in hypothyroidism, membrane cholesterol contributed significantly to maintain sodium pump activity in the cells. A critical reduction in membrane cholesterol levels heralds compromised enzyme activity, even in the early stage of hypothyroidism, and this can be predicted by elevated TSH levels alone, without any evident clinical manifestations. PMID:28256112

  3. Low-level red laser therapy alters effects of ultraviolet C radiation on Escherichia coli cells

    PubMed Central

    Canuto, K.S.; Sergio, L.P.S.; Guimarães, O.R.; Geller, M.; Paoli, F.; Fonseca, A.S.

    2015-01-01

    Low-level lasers are used at low power densities and doses according to clinical protocols supplied with laser devices or based on professional practice. Although use of these lasers is increasing in many countries, the molecular mechanisms involved in effects of low-level lasers, mainly on DNA, are controversial. In this study, we evaluated the effects of low-level red lasers on survival, filamentation, and morphology of Escherichia colicells that were exposed to ultraviolet C (UVC) radiation. Exponential and stationary wild-type and uvrA-deficientE. coli cells were exposed to a low-level red laser and in sequence to UVC radiation. Bacterial survival was evaluated to determine the laser protection factor (ratio between the number of viable cells after exposure to the red laser and UVC and the number of viable cells after exposure to UVC). Bacterial filaments were counted to obtain the percentage of filamentation. Area-perimeter ratios were calculated for evaluation of cellular morphology. Experiments were carried out in duplicate and the results are reported as the means of three independent assays. Pre-exposure to a red laser protected wild-type and uvrA-deficient E. coli cells against the lethal effect of UVC radiation, and increased the percentage of filamentation and the area-perimeter ratio, depending on UVC fluence and physiological conditions in the cells. Therapeutic, low-level red laser radiation can induce DNA lesions at a sub-lethal level. Consequences to cells and tissues should be considered when clinical protocols based on this laser are carried out. PMID:26445338

  4. Alterations in Hormone Levels After Adjuvant Chemoradiation in Male Rectal Cancer Patients

    SciTech Connect

    Yoon, Frederick H.; Perera, Francisco Fisher, Barbara; Stitt, Larry

    2009-07-15

    Purpose: To evaluate follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels after postoperative chemoradiation in men with rectal cancer. Methods and Materials: Forty-three men with rectal cancer had baseline and postchemoradiation FSH, LH, and testosterone measured. Adjuvant chemoradiation consisted of two 5-day cycles of bolus 5-fluorouracil (5-FU) every 4 weeks at a dose of 500 mg/m{sup 2}/d followed by concurrent chemoradiation followed by two additional 5-day cycles of 5-FU at a dose of 450 mg/m{sup 2}/d. Continuous-infusion 5-FU at 225 mg/m{sup 2}/d was given during radiation. Pelvic radiation consisted of a three- or four-field technique with a median dose of 54.0 Gy in 30 fractions. Results: Median follow-up was 6.1 years. Mean baseline FSH levels increased from 5.3 to a peak of 23.9 IU/L (p < 0.001) 13-24 months after chemoradiation. Mean baseline LH levels increased from 4.3 to a peak of 8.5 IU/L (p < 0.001) within 6 months after chemoradiation. Mean testosterone levels decreased from 15.4 nmol/L at baseline to 8.0 nmol/L more than 4 years after chemoradiation. Mean testosterone to mean LH ratio decreased from 4.4 at baseline to 1.1 after 48 months posttreatment, suggesting a continued decrease in Leydig cell function with time. Testicular dose was measured in 5 patients. Median dose was 4 Gy (range, 1.5-8.9 Gy). Conclusions: Chemoradiation in men with rectal cancer causes persistent increases in FSH and LH levels and decreases in testosterone levels.

  5. Sulforaphane reduces the alterations induced by quinolinic acid: modulation of glutathione levels.

    PubMed

    Santana-Martínez, R A; Galván-Arzáte, S; Hernández-Pando, R; Chánez-Cárdenas, M E; Avila-Chávez, E; López-Acosta, G; Pedraza-Chaverrí, J; Santamaría, A; Maldonado, P D

    2014-07-11

    Glutamate-induced excitotoxicity involves a state of acute oxidative stress, which is a crucial event during neuronal degeneration and is part of the physiopathology of neurodegenerative diseases. In this work, we evaluated the ability of sulforaphane (SULF), a natural dietary isothiocyanate, to induce the activation of transcription factor Nrf2 (a master regulator of redox state in the cell) in a model of striatal degeneration in rats infused with quinolinic acid (QUIN). Male Wistar rats received SULF (5mg/kg, i.p.) 24h and 5min before the intrastriatal infusion of QUIN. SULF increased the reduced glutathione (GSH) levels 4h after QUIN infusion, which was associated with its ability to increase the activity of glutathione reductase (GR), an antioxidant enzyme capable to regenerate GSH levels at 24h. Moreover, SULF treatment increased glutathione peroxidase (GPx) activity, while no changes were observed in γ-glutamyl cysteine ligase (GCL) activity. SULF treatment also prevented QUIN-induced oxidative stress (measured by oxidized proteins levels), the histological damage and the circling behavior. These results suggest that the protective effect of SULF could be related to its ability to preserve GSH levels and increase GPx and GR activities.

  6. CSF beta-amyloid levels are altered in narcolepsy: a link with the inflammatory hypothesis?

    PubMed

    Liguori, Claudio; Placidi, Fabio; Albanese, Maria; Nuccetelli, Marzia; Izzi, Francesca; Marciani, Maria Grazia; Mercuri, Nicola Biagio; Bernardini, Sergio; Romigi, Andrea

    2014-08-01

    Narcolepsy is characterized by hypocretin deficiency due to the loss of hypothalamic orexinergic neurons, and is associated with both the human leucocyte antigen DQB1*06:02 and the T cell receptor polymorphism. The above relationship suggests autoimmune/inflammatory processes underlying the loss of orexinergic neurons in narcolepsy. To test the autoimmune/inflammatory hypothesis by means of cerebrospinal fluid (CSF) levels of beta-amyloid1-42 and/or total tau proteins in a sample of narcoleptic patients, we analysed 16 narcoleptic patients and 16 healthy controls. Beta-amyloid1-42 CSF levels were significantly lower in narcoleptic patients compared with healthy controls. We also documented pathologically low levels of CSF beta-amyloid1-42 (<500 pg mL(-1) ) in six of 16 narcoleptic patients (37.5%). We hypothesize that the significant decrease of the CSF beta-amyloid1-42 levels in narcoleptic patients may support both the inflammatory/autoimmune hypothesis as the basis of the pathogenesis of narcolepsy and the prevalence of an 'amyloidogenic' pathway caused by the deficiency of the alpha-secretases enzymes.

  7. Acute gastric pH changes alter intraluminal but not plasma peptide levels.

    PubMed

    Mueller, C R; Ure, T; O'Dorisio, T M; Barrie, R J; Woltering, E A

    1991-12-01

    Gastric acidity is influenced by systemic and local peptide effects. Previous work by others has shown that intraluminally secreted peptides may have a role in local control of gastric acidity; however, the response of these peptides to acute changes in gastric pH is unknown. To determine the effects of acute changes in pH on systemic and intraluminal peptide levels, 14 normal volunteers underwent placement of a nasogastric tube after an overnight fast. Blood and gastric fluid were analyzed on a control day, 2 hours after completion of 24 hours of aluminum-magnesium antacid therapy and after 24 hours of H2 blockade. Plasma and acid-alcohol-extracted gastric peptide levels were measured with specific radioimmunoassays. Specimens were subdivided into two groups: 28 gastric fluid specimens with a pH less than 4 and 10 specimens with a pH greater than 4. In the patients with a pH greater than 4, the luminal peptides, motilin, neurotensin, pancreatic polypeptide, somatostatin, substance P, and gastrin, were decreased by 50% to 90% and gastrin-releasing peptide was decreased by 36% compared with specimens with a pH less than 4. Conversely, intraluminal vasoactive intestinal polypeptide and calcitonin levels were elevated by 60% and 27%, respectively, in the samples with a pH greater than 4. Intraluminal peptide concentrations are responsive to changes in intragastric pH; however, this response was not seen in plasma peptide levels.

  8. Changes in Voice Level Caused by Several Forms of Altered Feedback in Fluent Speakers and Stutterers.

    ERIC Educational Resources Information Center

    Howell, Peter

    1990-01-01

    Fluent speakers and stutterer's increased voice level were analyzed in response to voice-delayed auditory feedback, an Edinburgh masker, and white noise. These results are used to assess auditory feedback monitoring accounts of speech behavior of fluent speakers and stutterers with some implications for the treatment of stuttering. (37 references)…

  9. Imipramine reverses alterations in cytokines and BDNF levels induced by maternal deprivation in adult rats.

    PubMed

    Réus, Gislaine Z; Dos Santos, Maria Augusta B; Abelaira, Helena M; Ribeiro, Karine F; Petronilho, Fabrícia; Vuolo, Francieli; Colpo, Gabriela D; Pfaffenseller, Bianca; Kapczinski, Flávio; Dal-Pizzol, Felipe; Quevedo, João

    2013-04-01

    A growing body of evidence is pointing toward an association between immune molecules, as well brain-derived neurotrophic factor (BDNF) and the depression. The present study was aimed to evaluate the behavioral and molecular effects of the antidepressant imipramine in maternally deprived adult rats. To this aim, maternally deprived and non-deprived (control group) male rats were treated with imipramine (30mg/kg) once a day for 14 days during their adult phase. Their behavior was then assessed using the forced swimming test. In addition to this, IL-10, TNF-α and IL-1β cytokines were assessed in the serum and cerebrospinal fluid (CSF). In addition, BDNF protein levels were assessed in the prefrontal cortex, hippocampus and amygdala. In deprived rats treated with saline was observed an increase on immobility time, compared with non-deprived rats treated with imipramine (p<0.05). Deprived rats treated with saline presented a decrease on BDNF levels in the amygdala (p<0.05), compared with all other groups. The IL-10 levels were decreased in the serum (p<0.05). TNF-α and IL-1β levels were increased in the serum and CSF of deprived rats treated with saline (p<0.05). Interestingly, imipramine treatment reversed the effects of maternal deprivation on BDNF and cytokines levels (p<0.05). Finally, these findings further support a relationship between immune activation, neurotrophins and the depression, and considering the action of imipramine, it is suggested that classic antidepressants could exert their effects by modulating the immune system.

  10. High levels of psychopathic traits alters moral choice but not moral judgment

    PubMed Central

    Tassy, Sébastien; Deruelle, Christine; Mancini, Julien; Leistedt, Samuel; Wicker, Bruno

    2013-01-01

    Psychopathy is a personality disorder frequently associated with immoral behaviors. Previous behavioral studies on the influence of psychopathy on moral decision have yielded contradictory results, possibly because they focused either on judgment (abstract evaluation) or on choice of hypothetical action, two processes that may rely on different mechanisms. In this study, we explored the influence of the level of psychopathic traits on judgment and choice of hypothetical action during moral dilemma evaluation. A population of 102 students completed a questionnaire with ten moral dilemmas and nine non-moral dilemmas. The task included questions targeting both judgment (“Is it acceptable to … in order to …?”) and choice of hypothetical action (“Would you … in order to …?”). The level of psychopathic traits of each participant was evaluated with the Levenson Self-Report Psychopathy (LSRP) scale. Logistic regression fitted with the generalized estimating equations method analyses were conducted using responses to the judgment and choice tasks as the dependent variables and psychopathy scores as predictor. Results show that a high level of psychopathic traits, and more specifically those related to affective deficit, predicted a greater proportion of utilitarian responses for the choice but not for the judgment question. There was no first-order interaction between the level of psychopathic traits and other potential predictors. The relation between a high level of psychopathic traits and increased utilitarianism in choice of action but not in moral judgment may explain the contradictory results of previous studies where these two processes were not contrasted. It also gives further support to the hypothesis that choice of action endorsement and abstract judgment during moral dilemma evaluation are partially distinct neural and psychological processes. We propose that this distinction should be better taken into account in the evaluation of psychopathic

  11. Iron Supplementation Alters Heme and Heme Oxygenase 1 (HO-1) Levels In Pregnant Women in Ghana

    PubMed Central

    Salifu, Hassana; Wilson, Nana O.; Liu, Mingli; Dickinson-Copeland, Carmen; Yatich, Nelly; Keenan, John; Turpin, Cornelius; Jolly, Pauline; Gyasi, Richard; Adjei, Andrew A.; Stiles, Jonathan K.

    2016-01-01

    Background Iron supplementation is recommended for pregnant women to meet their iron requirement for a healthy pregnancy. The benefits and risks of universal iron supplementation during pregnancy in malaria endemic countries are currently being debated. As part of a broader study that focused on the effect of heme/HO-1 on pregnancy outcomes in malaria in pregnancy, we determined the association between iron supplementation and free heme levels in blood of pregnant women with and without malaria in Ghana. We hypothesized that pregnant women with malaria who took iron supplements will have higher levels of Heme/HO-1 than those who did not take iron supplements. Methods A total of 337 women were recruited for this study. Blood samples were collected for malaria diagnosis and heme/HO-1 measurement. Quantification of heme was done using a heme colorimetric assay kit and HO-1 levels were performed using Enzyme-Linked Immunosorbent Assay (ELISA) on plasma samples. Results Malaria positive iron supplemented women, in their third trimester, had significantly higher median levels of heme 59.3(43.1 – 60.4) than non-malaria iron supplemented women 35.7(33.0 – 62.2), p = 0.026. Also, malaria positive iron supplemented women had significant higher median levels of HO-16.2(IQR 4.9 – 8.1) than pregnant women who did not take iron supplements 2.9 (IQR 2.1 – 3.8), p = <0.001 Conclusion Although iron supplementation may be highly beneficial and improve pregnancy outcomes for iron deficient or anemic mothers, it is also likely that iron supplementation for pregnant women who are not iron deficient may put this group of women at risk for adverse pregnancy outcomes. Findings from this study sheds light on the effect of iron supplementation on malaria derived heme in pregnancy, which may inform how iron supplementation is recommended for pregnant women who are not iron deficient. PMID:28124024

  12. High homocysteine levels prevent via H2 S the CoCl2 -induced alteration of lymphocyte viability.

    PubMed

    Bruzzese, Laurie; Fenouillet, Emmanuel; Fromonot, Julien; Durand-Gorde, Josée-Martine; Condo, Jocelyne; Kipson, Nathalie; Mottola, Giovanna; Deharo, Pierre; Guieu, Régis; Ruf, Jean

    2016-08-01

    High homocysteine (HCy) levels are associated with lymphocyte-mediated inflammatory responses that are sometimes in turn related to hypoxia. Because adenosine is a potent lymphocyte suppressor produced in hypoxic conditions and shares metabolic pathways with HCy, we addressed the influence of high HCy levels on the hypoxia-induced, adenosine-mediated, alteration of lymphocyte viability. We treated mitogen-stimulated human lymphocytes isolated from healthy individuals and the human lymphoma T-cell line CEM with cobalt chloride (CoCl2 )to reproduce hypoxia. We found that CoCl2 -altered cell viability was dose-dependently reversed using HCy. In turn, the HCy effect was inhibited using DL-propargylglycine, a specific inhibitor of the hydrogen sulphide (H2 S)-synthesizing enzyme cystathionine-γ-lyase involved in HCy catabolism. We then addressed the intracellular metabolic pathway of adenosine and HCy, and the role of the adenosine A2A receptor (A2 A R). We observed that: (i) hypoxic conditions lowered the intracellular concentration of HCy by increasing adenosine production, which resulted in high A2 A R expression and 3', 5'-cyclic adenosine monophosphate production; (ii) increasing intracellular HCy concentration reversed the hypoxia-induced adenosinergic signalling despite high adenosine concentration by promoting both S-adenosylhomocysteine and H2 S production; (iii) DL-propargylglycine that inhibits H2 S production abolished the HCy effect. Together, these data suggest that high HCy levels prevent, via H2 S production and the resulting down-regulation of A2 A R expression, the hypoxia-induced adenosinergic alteration of lymphocyte viability. We point out the relevance of these mechanisms in the pathophysiology of cardiovascular diseases.

  13. Environmental acidification is not associated with altered plasma corticosterone levels in the stream-side salamander, Desmognathus ochrophaeus.

    PubMed

    Woodley, Sarah K; Freeman, Peter; Ricciardella, Lauren F

    2014-05-15

    As environments become increasingly altered due to anthropogenic factors, interest is growing in how endocrine systems respond to pollution and environmental degradation. Glucocorticoid hormones (GCs) are a type of stress hormones that are released upon activation of the hypothalamic-pituitary-adrenal axis and have widespread effects throughout the body. We tested the hypothesis that exposure to environmental acidification is associated with altered levels of plasma GCs in adult, stream-side Allegheny Mountain dusky salamanders (Desmognathus ochrophaeus). We compared plasma corticosterone (CORT) in salamanders living in 9 streams that differed in pH. Although capture and handling induced a robust increase in plasma CORT in all populations of salamanders, we discerned no significant effect of environmental pH on baseline CORT or handling-induced CORT levels. In a laboratory study, low pH decreased salamander locomotory activity compared to acid-neutral controls, but there was no effect of pH on plasma CORT. Decreased locomotory activity is a common amphibian response to stress, indicating that low pH has adverse effects on Allegheny Mountain dusky salamanders. Overall, we conclude that the effects of environmental pH on salamander behavior and other potential responses are not mediated by changes in plasma CORT levels. We discuss alternative explanations for our results and describe difficulties involved in searching for relationships between plasma GCs and environmental degradation.

  14. Serum level of scorpion toxins, electrolytes and electrocardiogram alterations in Mexican children envenomed by scorpion sting.

    PubMed

    Osnaya-Romero, N; Acosta-Saavedra, L C; Goytia-Acevedo, R; Lares-Asseff, I; Basurto-Celaya, G; Perez-Guille, G; Possani, L D; Calderón-Aranda, E S

    2016-11-01

    The scorpion Centruroides limpidus limpidus (C.l.l.) is endemic in México, producing hundreds of accidents in humans; children being one of the most susceptible targets. Few studies reported that severe envenoming by scorpion venom induces cardiac damage and electrolytes abnormalities in children, but the relationship of envenoming severity and toxic blood levels is unknown. The aim of this study was to determine the relationship among clinical status of envenoming, serum electrolyte, electrocardiographic abnormalities, and serum toxin levels in 44 children stung by scorpion over a period of 6 months in the State of Morelos, Mexico. The patients were said to be asymptomatic, when they presented just local symptoms, and were said to be symptomatic when showing local symptoms and at least one systemic symptom. The clinical status was evaluated at the admission at the emergency room of the Hospital, and 30 min after the administration of polyspecific F(ab')2 anti-scorpion therapy to symptomatic children. Forty-one percent of the children were asymptomatic and 59% symptomatic. Potassium and sodium imbalance and an elongation of the QT interval were detected; the rate of hypokalemia was higher in symptomatic than on asymptomatic children (50% and 6%, respectively). Hypokalemia persisted in 19% in symptomatic patients, whereas sodium reached normal levels 30 min after anti-venom therapy. The hypokalemia statistically correlated with elongation of the QT interval. The concentration of the toxic components of C.l.l in serum was significantly higher in symptomatic than asymptomatic children, and the serum levels of the toxic component significantly decreased to undetectable levels after the application of anti-venom therapy. Despite the small size of the sample, this study establishes that severity of envenoming was statistically related to potassium imbalance in serum, QT interval and the concentration of toxic components in serum, which decreased at undetectable levels

  15. Dysregulation of Autonomic Nervous System in Chagas’ Heart Disease Is Associated with Altered Adipocytokines Levels

    PubMed Central

    Barbosa-Ferreira, João Marcos; Mady, Charles; Ianni, Barbara Maria; Lopes, Heno Ferreira; Ramires, Felix José Alvarez; Salemi, Vera Maria Cury; Grupi, Cesar José; Hachul, Denise Tessariol; Fernandes, Fábio

    2015-01-01

    Background Chagas disease (CD) induces autonomic dysfunction and inflammatory activity, which may promote metabolic abnormalities. We studied metabolism and his correlation with Autonomic Nervous System (ANS) and inflammation in CD. Methods and Results Sixty subjects were divided into 4 groups: control group (CG), IF (indeterminate form) group; ECG group (ECG abnormalities and normal left ventricular systolic function), and LVD group (left ventricular sistolic dysfunction). Levels of adiponectin, leptin, insulin, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) were assayed in serum samples by ELISA. ANS was assessed by heart rate variability in frequency domain in 24-hour Holter and postural tilt test (rest and orthostatic position). High frequency (HFr) component values were used to estimate parasympathetic activity and low frequency (LFr) component, sympathetic activity. Analyzes were made of the correlations of each of the metabolic parameters (leptin and adiponectin) with the inflammatory cytokines (interleukin-6 and TNF- alpha) and with the ANS assessment measurements. No significant differences were observed in leptin and insulin levels. Adiponectin was higher in ECG and LVD groups: [CG = 4766.5 (5529.5), IF = 4003.5 (2482.5), ECG = 8376.5 (8388.5), LVD = 8798 (4188.0) ng/mL, p<0.001)]. IL-6 and TNF-alpha were higher in LVD group: [IL-6: CG = 1.85 (6.41); IF = 1.58 (1.91); ECG = 1.0 (1.57); LVD= 31.44 (72.19) pg/ml; p = 0.001. TNF-alpha: CG = 22.57 (88.2); IF = 19.31 (33.16); ECG = 12.45 (3.07); LVD = 75.15 (278.57) pg/ml; p = 0.04]. Adiponectin levels had a positive association with the HFr component (r = 0.539; p = 0.038) and an inverse association with the LFr component (r = - 0.539; p = 0.038) in ECG group. Leptin levels had a negative association with the HFr component (r= - 0.632; p = 0.011) and a positive association with the LFr component (r = 0.632; p = 0.011) in LVD group. Conclusions We found increased adiponectin levels in

  16. Longitudinal studies showing alterations in the levels and functional response of T and B lymphocytes in human pregnancy.

    PubMed Central

    Strelkauskas, A J; Davies, I J; Dray, S

    1978-01-01

    Altered blood levels of T and B lymphocytes were found in the first half of human pregnancy. A total of twenty-two women were tested, using direct or indirect rosetting assays or the fluorescence-activated cell sorter, to determine the levels of peripheral blood T and B cells. In all cases, an inversion of T- and B-cell levels was observed, i.e. T-cell levels were decreased and B-cell levels (as measured by the presence of surface immunoglobulin or the presence of B-cell surface antigens) were increased. This inversion was exhibited as early as 1 week post-implantation. Lymphocytes from two fo the women were also examined for stimulation with phytohaemagglutinin (PHA) and pokeweed mitogen (PWM) at intervals during gestation, and the amount of [3H]thymidine uptake was compared to that of two non-pregnant women tested at each interval. The values obtained for the pregnant women with PHA were markedly lower, and with pokeweed mitogen slightly lower, than those of non-pregnant controls. However, the PHA and PWM values in the pregnant women returned to levels similar to those of the nonpregnant women shortly after the T- and B-cell levels returned to normal. Thus the decrease in the response of the lymphocytes to mitogens during early pregnancy appears to parallel the numerical deficiency of T cells. PMID:308426

  17. Levels of estradiol and testosterone are altered in Chinese men with sexual dysfunction.

    PubMed

    Wu, F; Chen, T; Mao, S; Jiang, H; Ding, Q; Xu, G

    2016-09-01

    An estimated 20-30% of adult men have at least one manifestation of sexual dysfunction, the most common of which are premature ejaculation (PE) and erectile dysfunction (ED). Emerging evidence has suggested an association between the regulation of hormones with the processes of erection and ejaculation. In this study, we aim to investigate the relationship between sexual dysfunction, namely, PE and ED, and the levels and ratios of estradiol to testosterone in Chinese men. A retrospective case-control study was performed involving 878 male patients aged from 18 to 74 years (mean: 36 years). The ratio of estradiol to testosterone was significantly higher for subjects with ED (7.45 ± 3.09 × 10(-3) ; p < 0.001), and combined PE and ED (6.66 ± 3.05 × 10(-3) ; p = 0.032) compared with that of the control group (6.01 ± 2.61 × 10(-3) ). The ratio was also significantly higher for ED patients when compared with PE patients (5.26 ± 2.18 × 10(-3) ; p < 0.001). Furthermore, compared with the control group, subjects with PE had similar levels of estradiol (95.47 ± 37.86 pmol/L vs. 94.12 ± 32.32 pmol/L; p = 0.678) but significantly higher levels of testosterone (18.66 ± 6.03 nmol/L vs. 16.82 ± 4.93 nmol/L; p < 0.001). This contrasted with the ED group, which showed similar levels of testosterone (16.96 ± 5.86 nmol/L vs. 16.82 ± 4.93 nmol/L; p = 0.773) and significantly higher levels of estradiol (116.88 ± 40.81 pmol/L vs. 94.12 ± 32.32 pmol/L; p < 0.001) compared with control. Subjects with combined ED and PE also had a significantly higher level of estradiol (104.98 ± 43.99 pmol/L vs. 94.12 ± 32.32 pmol/L; p = 0.014) and similar levels of testosterone (17.30 ± 7.23 nmol/L vs. 16.82 ± 4.93 nmol/L; p = 0.503) compared with control. In conclusion, this study involving Chinese males with sexual dysfunction reports, for the first time, that there is an association between sexual dysfunction

  18. High-fat diet transition reduces brain DHA levels associated with altered brain plasticity and behaviour.

    PubMed

    Sharma, Sandeep; Zhuang, Yumei; Gomez-Pinilla, Fernando

    2012-01-01

    To assess how the shift from a healthy diet rich in omega-3 fatty acids to a diet rich in saturated fatty acid affects the substrates for brain plasticity and function, we used pregnant rats fed with omega-3 supplemented diet from their 2nd day of gestation period as well as their male pups for 12 weeks. Afterwards, the animals were randomly assigned to either a group fed on the same diet or a group fed on a high-fat diet (HFD) rich in saturated fats for 3 weeks. We found that the HFD increased vulnerability for anxiety-like behavior, and that these modifications harmonized with changes in the anxiety-related NPY1 receptor and the reduced levels of BDNF, and its signalling receptor pTrkB, as well as the CREB protein. Brain DHA contents were significantly associated with the levels of anxiety-like behavior in these rats.

  19. Estrogen alters baseline and inflammatory-induced cytokine levels independent from hypothalamic-pituitary-adrenal axis activity.

    PubMed

    Shivers, Kai-Yvonne; Amador, Nicole; Abrams, Lisa; Hunter, Deirtra; Jenab, Shirzad; Quiñones-Jenab, Vanya

    2015-04-01

    Although estrogen reduces inflammatory-mediated pain responses, the mechanisms behind its effects are unclear. This study investigated if estrogen modulates inflammatory signaling by reducing baseline or inflammation-induced cytokine levels in the injury-site, serum, dorsal root ganglia (DRG) and/or spinal cord. We further tested whether estrogen effects on cytokine levels are in part mediated through hypothalamic-pituitary-adrenal (HPA) axis activation. Lumbar DRG, spinal cord, serum, and hind paw tissue were analyzed for cytokine levels in 17β-estradiol-(20%) or vehicle-(100% cholesterol) treated female rats following ovariectomy/sham adrenalectomy (OVX), adrenalectomy/sham ovariectomy (ADX) or ADX+OVX operation at baseline and post formalin injection. Formalin significantly increased pro-inflammatory interleukin (IL)-6 levels in the paw, as well as pro- and anti-inflammatory cytokine levels in the DRG, spinal cord and serum in comparison to naïve conditions. Estrogen replacement significantly increased anti-inflammatory IL-10 levels in the DRG. Centrally, estradiol significantly decreased pro-inflammatory tumor necrosis factor (TNF)-α and IL-1β levels, as well as IL-10 levels, in the spinal cord in comparison to cholesterol treatment. At both sites, most estradiol modulatory effects occurred irrespective of pain or surgical condition. Estradiol alone had no influence on cytokine release in the paw or serum, indicating that estrogen effects were site-specific. Although cytokine levels were altered between surgical conditions at baseline and following formalin administration, ADX operation did not significantly reverse estradiol's modulation of cytokine levels. These results suggest that estrogen directly regulates cytokines independent of HPA axis activity in vivo, in part by reducing cytokine levels in the spinal cord.

  20. Alteration in plasma testosterone levels in male mice lacking soluble epoxide hydrolase.

    PubMed

    Luria, Ayala; Morisseau, Christophe; Tsai, Hsing-Ju; Yang, Jun; Inceoglu, Bora; De Taeye, Bart; Watkins, Steven M; Wiest, Michelle M; German, J Bruce; Hammock, Bruce D

    2009-08-01

    Soluble epoxide hydrolase (Ephx2, sEH) is a bifunctional enzyme with COOH-terminal hydrolase and NH(2)-terminal phosphatase activities. sEH converts epoxyeicosatrienoic acids (EETs) to dihydroxyeicosatrienoic acids (DHETs), and the phosphatase activity is suggested to be involved in cholesterol metabolism. EETs participate in a wide range of biological functions, including regulation of vascular tone, renal tubular transport, cardiac contractility, and inflammation. Inhibition of sEH is a potential approach for enhancing the biological activity of EETs. Therefore, disruption of sEH activity is becoming an attractive therapeutic target for both cardiovascular and inflammatory diseases. To define the physiological role of sEH, we characterized a knockout mouse colony lacking expression of the Ephx2 gene. Lack of sEH enzyme is characterized by elevation of EET to DHET ratios in both the linoleate and arachidonate series in plasma and tissues of both female and male mice. In male mice, this lack of expression was also associated with decreased plasma testosterone levels, sperm count, and testicular size. However, this genotype was still able to sire litters. Plasma cholesterol levels also declined in this genotype. Behavior tests such as anxiety-like behavior and hedonic response were also examined in Ephx2-null and WT mice, as all can be related to hormonal changes. Null mice showed a level of anxiety with a decreased hedonic response. In conclusion, this study provides a broad biochemical, physiological, and behavioral characterization of the Ephx2-null mouse colony and suggests a mechanism by which sEH and its substrates may regulate circulating levels of testosterone through cholesterol biosynthesis and metabolism.

  1. Imatinib alters cell viability but not growth factors levels in TM4 Sertoli cells

    PubMed Central

    Hashemnia, Seyyed Mohammad Reza; Atari-Hajipirloo, Somayeh; Roshan-Milani, Shiva; Valizadeh, Nasim; Mahabadi, Sonya; Kheradmand, Fatemeh

    2016-01-01

    Background: The anticancer agent imatinib (IM) is a small molecular analog of ATP that inhibits tyrosine kinase activity of platelet derived growth factors (PDGFs) and stem cell factor (SCF) receptor in cancer cells. However these factors have a key role in regulating growth and development of normal Sertoli, Leydig and germ cells. Objective: The aim of this study was to determine cell viability, PDGF and SCF levels in mouse normal Sertoli cells exposed to IM. Materials and Methods: In this experimental study, the mouse TM4 Sertoli cells were treated with 0, 2.5, 5, 10 and 20 μM IM for 2, 4 or 6 days. The cell viability and growth factors levels were assessed by MTT and ELISA methods, respectively. For statistical analysis, One-Way ANOVA was performed. Results: IM showed significant decrease in Sertoli cell viability compared to control group (p=0.001). However, IM increased PDGF and SCF level insignificantly (p>0.05). Conclusion: Results suggested that IM treatment induced a dose dependent reduction of cell viability in Sertoli cells. It seems that treatment with this anticancer drug is involved in the fertility process. Further studies are needed to evaluate the role of PDGF and SCF in this cell. PMID:27738659

  2. Chronic stress alters the expression levels of longevity-related genes in the rat hippocampus.

    PubMed

    Sánchez-Hidalgo, Ana C; Muñoz, Mario F; Herrera, Antonio J; Espinosa-Oliva, Ana M; Stowell, Rianne; Ayala, Antonio; Machado, Alberto; Venero, José L; de Pablos, Rocío M

    2016-07-01

    The molecular mechanisms underlying the negative effects of psychological stress on cellular stress during aging and neurodegenerative diseases are poorly understood. The main objective of this study was to test the effect of chronic psychological stress, and the consequent increase of circulating glucocorticoids, on several hippocampal genes involved in longevity. Sirtuin-1, p53, thioredoxin-interacting protein, and heat shock protein 70 were studied at the mRNA and protein levels in stressed and non-stressed animals. Stress treatment for 10 days decreased sirtuin-1 and heat shock protein 70 levels, but increased levels of p53, thioredoxin-interacting protein and the NADPH oxidase enzyme. Examination of protein expression following two months of stress treatment indicated that sirtuin-1 remained depressed. In contrast, an increase was observed for thioredoxin-interacting protein, heat shock protein 70, p53 and the NADPH oxidase enzyme. The effect of stress was reversed by mifepristone, a glucocorticoid receptor antagonist. These data suggest that chronic stress could contribute to aging in the hippocampus.

  3. Levels of sparganum infections and phylogenetic analysis of the tapeworm Spirometra erinaceieuropaei sparganum in wild frogs from Henan Province in central China.

    PubMed

    Wei, T; Zhang, X; Cui, J; Liu, L N; Jiang, P; Wang, Z Q

    2015-07-01

    Sparganosis is a serious food-borne parasitic zoonosis caused by infection with Spirometra spargana. The prevalence of sparganum infection in wild frogs (Rana nigromaculata, R. limmochari, R. temporaria and Bufo gargarizans) was investigated in Henan Province of central China during 2008-2012. Of 3482 caught wild frogs, 565 (16.23%) were found to be infected with plerocercoids (spargana) of the genus Spirometra. Spargana were found in 14.85% (320/2155) of R. nigromaculata, 20.82% (233/1119) of R. limmochari and 10.91% (12/110) of R. temporaria frogs. However, no sparganum was found in B. gargarizans. To investigate the phylogenetic position of collected spargana, three mitochondrial DNA (mtDNA) regions, namely cytochrome c oxidase subunits 1 and 3 (cox1 and cox3), and NADH dehydrogenase subunit 4 (nad4), were amplified, sequenced and analysed. Sequences of cox1, cox3 and pnad4 were 417, 390 and 578 bp in length, respectively. The base composition of cox1, cox3 and pnad4 were generally AT rich with a mean of 63.5%, 68.3% and 67% AT, respectively. Phylogenetic analysis showed that all the sparganum isolates in Henan Province represented Spirometra erinaceieuropaei and were a well-supported clade. These findings demonstrated clearly the usefulness of the three mtDNA sequences for molecular identification and population genetics studies of S. erinaceieuropaei spargana of human and animal health significance.

  4. Alteration in plasma corticosterone levels following long term oral administration of lead produces depression like symptoms in rats.

    PubMed

    Haider, Saida; Saleem, Sadia; Tabassum, Saiqa; Khaliq, Saima; Shamim, Saima; Batool, Zehra; Parveen, Tahira; Inam, Qurat-ul-ain; Haleem, Darakhshan J

    2013-03-01

    Lead toxicity is known to induce a broad range of physiological, biochemical and behavioral dysfunctions that may result in adverse effects on several organs, including the central nervous system. Long-term exposure to low levels of lead (Pb(2+)) has been shown to produce behavioral deficits in rodents and humans by affecting hypothalamic-pituitary-adrenal (HPA) axis. These deficits are thought to be associated with altered brain monoamine neurotransmission and due to changes in glucocorticoids levels. This study was designed to investigate the effects of Pb(2+)exposure on growth rate, locomotor activity, anxiety, depression, plasma corticosterone and brain serotonin (5-HT) levels in rats. Rats were exposed to lead in drinking water (500 ppm; lead acetate) for 5 weeks. The assessment of depression was done using the forced swimming test (FST). Estimation of brain 5-HT was determined by high-performance liquid chromatography with electrochemical detection. Plasma corticosterone was determined by spectrofluorimetric method. The present study showed that long term exposure to Pb(2+) significantly decreased the food intake followed by the decrease in growth rate in Pb(2+)exposed rats as compared to control group. No significant changes in open field activity were observed following Pb(2+)exposure while significant increase in anxiogenic effect was observed. Increased plasma corticosterone and decreased 5-HT levels were exhibited by Pb(2+)exposed rats as compared to controls. A significant increase in depressive like symptoms was exhibited by Pb(2+)exposed rats as compared to control rats. The results are discussed in the context of Pb(2+) inducing a stress-like response in rats leading to changes in plasma corticosterone and brain 5-HT levels via altering tryptophan pyrrolase activity.

  5. CSF levels of heart fatty acid binding protein are altered during early phases of Alzheimer's disease.

    PubMed

    Chiasserini, Davide; Parnetti, Lucilla; Andreasson, Ulf; Zetterberg, Henrik; Giannandrea, David; Calabresi, Paolo; Blennow, Kaj

    2010-01-01

    Heart fatty acid binding protein (HFABP) has been proposed as a putative marker for dementia disorders. To evaluate the value of this protein as an early marker of Alzheimer's disease (AD), we analyzed HFABP level and the classical biomarkers amyloid-β (Aβ)1-42, total tau (t-tau), and phosphorylated tau (p-tau) in cerebrospinal fluid (CSF) of patients with mild cognitive impairment (MCI) followed up for four years (n=41), AD (n=32), and subjects with other neurological diseases without dementia (OND, n=25). HFABP levels were higher in AD patients and in MCI converting to AD (MCI-AD) with respect to OND and to cognitively stable MCI patients (MCI-MCI). The receiver operator characteristics analysis for HFABP alone showed a sensitivity of 87% and a specificity of 81% for AD versus OND (area under the curve, AUC=0.83); sensitivity and specificity were 46% and 94%, respectively, when comparing MCI-MCI versus MCI-AD. CSF HFABP levels showed a strong positive correlation with both t-tau and p-tau. Interestingly, the ratio between HFABP and Aβ1-42 improved the performance in distinguishing AD from OND (sensitivity: 90%; specificity 82%, AUC=0.89), and gave the best accuracy in discriminating MCI-AD from MCI-MCI (sensitivity: 80%; specificity 100%, AUC=0.90). Survival analysis by means of Kaplan-Meier curve showed a significantly higher proportion of MCI patients converting to AD in the group with higher values of HFABP/Aβ1-42 ratio (cut-off=0.7). A significant correlation between HFABP/Aβ1-42 ratio and MMSE annual decrease rate was also documented (p<0.0001). HFABP /Aβ1-42 ratio might be a useful predictor of conversion in MCI patients.

  6. Changing climate and sea level alter Hg mobility at Lake Tulane, Florida, U.S.

    PubMed

    Jacobson, G L; Norton, S A; Grimm, E C; Edgar, T

    2012-11-06

    Between 45,000 cal years BP and the beginning of the Holocene, the accumulation rate for Hg in sediments of Lake Tulane, Florida ranged from ≈2 to 10 μg m(-2) yr(-1), compared with 53 μg Hg m(-2) yr(-1) in the 1985-1990 period of anthropogenic input. The locality experienced regional draw-down of the water table during the Wisconsinan glaciation, which lowered global sea level by nearly 130 m. Natural atmospheric deposition of Hg to the surrounding area resulted in long-term (ca. 100,000 years) sequestration of this atmospheric flux of Hg, primarily by adsorption in the oxic Al- and Fe-hydroxide-rich sandy subsoil. Global sea level rise during deglaciation led to a rising regional water table, flooding the oxidized soils surrounding Tulane. Iron and adsorbed Hg were mobilized by reductive dissolution and transported by groundwater flow to Lake Tulane and ultimately to the accumulating sediment. The accumulation rate of Hg (and Fe) increased rapidly about 16,000 cal years BP, peaked at nearly 60 μg Hg m(-2) yr(-1) ca. 13,000-14,000 cal years BP, declined sharply during the Younger Dryas, and then increased sharply to a second 60 μg Hg m(-2) yr(-1) peak about 5000 cal years BP. Thereafter, it declined nearly to background by 900 cal years BP. In similar geologic situations, rapid modern sea level rise will initiate this process globally, and may mobilize large accumulations of Hg and lesser amounts of As, and other redox sensitive metals to groundwater and surface water.

  7. F-cell levels are altered with erythrocyte density in sickle cell disease.

    PubMed

    Basu, Sumanta; Dash, Bisnu Prasad; Patel, Dilip Kumar; Chakravarty, Sudipa; Chakravarty, Amit; Banerjee, Debashis; Chakrabarti, Abhijit

    2011-08-15

    Lighter cells from density fractionated erythrocytes of sickle cell disease (SCD) patients carry higher amount of externalized phosphatidylserine (PS) and cell surface glycophorins compared to the denser counterparts. Further analysis also revealed that the denser cells contained higher levels of fetal hemoglobin (HbF) compared to the lighter cells, supported by the presence of larger number of F-cells in these populations. In this report, we have found direct evidence on the higher survival of the HbF rich erythrocytes in SCD.

  8. Fungal phyllosphere communities are altered by indirect interactions among trophic levels.

    PubMed

    Perez, Jose L; French, J Victor; Summy, Kenneth R; Baines, Anita Davelos; Little, Christopher R

    2009-05-01

    Trophic interactions involving predators, herbivores, and plants have been described in terrestrial systems. However, there is almost no information on the effect of trophic interactions on microbial phyllosphere community abundance, diversity, or structure. In this study, the interaction between a parasitoid, an insect herbivore, and the fungal phyllosphere community is examined. Parasitoid wasps have an indirect negative impact on fungal community diversity. On the citrus phyllosphere, the exotic wasp species, Amitus hesperidum and Encarsia opulenta, may parasitize the citrus blackfly (Aleurocanthus woglumi). If parasitism levels are low, the blackfly may produce significant amounts of honeydew secretions on the surface of the leaf. Honeydew deposition provides a carbon-rich substrate for the development of fungal growth persisting as sooty mold on the leaves. Leaves from sooty mold-infested grapefruit (Citrus paradisi) trees were collected from multiple orchards in south Texas. The effect of different levels of exotic parasite activity, citrus blackfly, and sooty mold infestation on phyllosphere mycobiota community structure and diversity was examined. Our results suggest the presence of the parasitoid may lead to a top-down trophic cascade affecting phyllosphere fungal community diversity and structure. Additionally, persistent sooty mold deposits that have classically been referred to as Capnodium citri (and related asexual morphological forms) actually comprise a myriad of fungal species including many saprophytes and potential fruit and foliar pathogens of citrus.

  9. Alterative LEU designs for the FRM-II with power levels of 20-22 MW.

    SciTech Connect

    Hanan, N. A.; Smith, R. S.; Matos, J. E.

    1999-09-27

    Alternative LEU Designs for the FRM-II have been developed by the RERTR Program at Argonne National Laboratory (ANL) at the request of an FRM-II Expert Group established by the German Federal Government in January 1999 to evaluate the options for using LEU fuel instead of HEU fuel in cores with power levels of 20 MW. The ANL designs would use the same building structure and maintain as many of the HEU design features as practical. The range of potential LEU fuels was expanded from previous studies to include already-tested silicide fuels with uranium densities up to 6.7 g/cm{sup 3} and the new U-Mo fuels that show excellent prospects for achieving uranium densities in the 8-9 g/cm{sup 3} range. For each of the LEU cores; the design parameters were chosen to match the 50 day cycle length of the HEU core and to maximize the thermal neutron flux in the Cold Neutron Source and beam tubes. The studies concluded that an LEU core with a diameter of about 29 cm instead of 24 cm in HEU design and operating at a power level of 20 MW would have thermal neutron fluxes that are 0.85 times that of the HEU design at the center of the Cold Neutron Source. With a potential future upgrade to a power of 22 MW, this ratio would increase to 0.93.

  10. Alterations in osmoregulation, antioxidant enzymes and indole alkaloid levels in Catharanthus roseus exposed to water deficit.

    PubMed

    Jaleel, C Abdul; Manivannan, P; Kishorekumar, A; Sankar, B; Gopi, R; Somasundaram, R; Panneerselvam, R

    2007-10-01

    Catharanthus roseus (L.) G. Don plants were grown in different water regimes in order to study the drought induced osmotic stress and proline (PRO) metabolism, antioxidative enzyme activities and indole alkaloid accumulation. The plants under pot culture were subjected to 10, 15 and 20 days interval drought (DID) stress from 30 days after sowing (DAS) and regular irrigation was kept as control. The plants were uprooted on 41DAS (10DID), 46DAS (15DID) and 51DAS (20DID). The drought stressed plants showed increased aminoacid (AA), glycine betaine (GB) and PRO contents and decreased proline oxidase (PROX) and increased gamma-glutamyl kinase (gamma-GK) activities when compared to control. The antioxidative enzymes like peroxidase (POX) and polyphenol oxidase (PPO) increased to a significant level in drought stressed plants when compared to control. The drought stressed C. roseus plants showed an increase in total indole alkaloid content in shoots and roots when compared to well-watered control plants. Our results suggest that the cultivation of medicinal plants like C. roseus in water deficit areas would increase its PRO metabolism, osmoregulation, defense system and the level of active principles.

  11. Forest loss increases insect herbivory levels in human-altered landscapes

    NASA Astrophysics Data System (ADS)

    Dodonov, Pavel; Morante-Filho, José Carlos; Mariano-Neto, Eduardo; Cazetta, Eliana; Andrade, Edyla Ribeiro de; Rocha-Santos, Larissa; Inforzato, Igor; Gomes, Francisco Sanches; Faria, Deborah

    2016-11-01

    Insect herbivory has been observed to be affected by habitat loss and fragmentation, although the mechanisms by which these anthropogenic disturbances affect this process are not well understood. To aid in clarifying this issue, we assessed the relation between forest cover and leaf damage caused by herbivorous insects on a representative tropical forest understory plant family, the Rubiaceae. We measured leaf area loss of Rubiaceae plants in 20 forest sites located in the Brazilian Atlantic forest, and also tested whether variation in forest cover, abundance of insectivorous birds (predators) and of Rubiaceae plants (resources) could explain the observed variation in leaf damage. Herbivory levels varied between 2.6 and 12.5 percent leaf area lost and increased with decreasing forest cover, whereas the other explanatory variables did not provide additional explanatory power. Therefore, forest loss appears to be the main driver of changes in local herbivory, and ecological processes such as top-down and bottom-up control may not account for the deforestation-related increase in herbivory levels. Other mechanisms, for example leaf quality and/or the influence of the adjoining land uses, have to be explored in future studies.

  12. Task alters category representations in prefrontal but not high-level visual cortex.

    PubMed

    Bugatus, Lior; Weiner, Kevin S; Grill-Spector, Kalanit

    2017-04-04

    A central question in neuroscience is how cognitive tasks affect category representations across the human brain. Regions in lateral occipito-temporal cortex (LOTC), ventral temporal cortex (VTC), and ventro-lateral prefrontal cortex (VLFPC) constitute the extended "what" pathway, which is considered instrumental for visual category processing. However, it is unknown (1) whether distributed responses across LOTC, VTC, and VLPC explicitly represent category, task, or some combination of both, and (2) in what way representations across these subdivisions of the extended 'what' pathway may differ. To fill these gaps in knowledge, we scanned 12 participants using fMRI to test the effect of category and task on distributed responses across LOTC, VTC, and VLPFC. Results reveal that task and category modulate responses in both high-level visual regions, as well as prefrontal cortex. However, we found fundamentally different types of representations across the brain. Distributed responses in high-level visual regions are more strongly driven by category than task, and exhibit task-independent category representations. In contrast, distributed responses in prefrontal cortex are more strongly driven by task than category, and contain task-dependent category representations. Together, these findings of differential representations across the brain support a new idea that LOTC and VTC maintain stable and separable category representations allowing efficient processing of visual information, while prefrontal cortex contains flexible representations in which separable category information may emerge only when relevant to the task.

  13. Chemoreception of hunger levels alters the following behaviour of a freshwater snail.

    PubMed

    Larcher, Marie; Crane, Adam L

    2015-12-01

    Chemically-mediated orientation is essential for many animals that must locate sites containing resources such as mates or food. One way to find these areas is by using publically-available information from other individuals. We tested a freshwater snail, Physa gyrina, for chemoreception of conspecific cues and predicted they could discriminate between cues based on information regarding hunger levels. We placed 'tracker' snails into a 2-arm arena where they could either follow or avoid an area previously used by a 'marker' snail. The hunger levels of both trackers and markers was manipulated, being either starved or fed. Starved and fed trackers did not differ in their following response when markers were hungry, but starved trackers were significantly more likely to follow fed markers, compared to fed trackers that tended to avoid areas used by fed markers. This outcome suggests that P. gyrina uses conspecific chemical cues to find food and potentially in some situations to avoid intra-specific food competition.

  14. Lack of Platelet-Activating Factor Receptor Attenuates Experimental Food Allergy but Not Its Metabolic Alterations regarding Adipokine Levels

    PubMed Central

    Batista, Nathália Vieira; Fonseca, Roberta Cristelli; Perez, Denise; Pereira, Rafaela Vaz Sousa; de Lima Alves, Juliana; Pinho, Vanessa; Faria, Ana Maria Caetano; Cara, Denise Carmona

    2016-01-01

    Platelet-activating factor (PAF) is known to be an important mediator of anaphylaxis. However, there is a lack of information in the literature about the role of PAF in food allergy. The aim of this work was to elucidate the participation of PAF during food allergy development and the consequent adipose tissue inflammation along with its alterations. Our data demonstrated that, both before oral challenge and after 7 days receiving ovalbumin (OVA) diet, OVA-sensitized mice lacking the PAF receptor (PAFR) showed a decreased level of anti-OVA IgE associated with attenuated allergic markers in comparison to wild type (WT) mice. Moreover, there was less body weight and adipose tissue loss in PAFR-deficient mice. However, some features of inflamed adipose tissue presented by sensitized PAFR-deficient and WT mice after oral challenge were similar, such as a higher rate of rolling leukocytes in this tissue and lower circulating levels of adipokines (resistin and adiponectin) in comparison to nonsensitized mice. Therefore, PAF signaling through PAFR is important for the allergic response to OVA but not for the adipokine alterations caused by this inflammatory process. Our work clarifies some effects of PAF during food allergy along with its role on the metabolic consequences of this inflammatory process. PMID:27314042

  15. Altering cAMP levels within a central pattern generator modifies or disrupts rhythmic motor output.

    PubMed

    Clemens, Stefan; Calin-Jageman, Robert; Sakurai, Akira; Katz, Paul S

    2007-12-01

    Cyclic AMP is a second messenger that has been implicated in the neuromodulation of rhythmically active motor patterns. Here, we tested whether manipulating cAMP affects swim motor pattern generation in the mollusc, Tritonia diomedea. Inhibiting adenylyl cyclase (AC) with 9-cyclopentyladenine (9-CPA) slowed or stopped the swim motor pattern. Inhibiting phosphodiesterase with 3-isobutyl-1-methylxanthine (IBMX) or applying dibutyryl-cAMP (dB-cAMP) disrupted the swim motor pattern, as did iontophoresing cAMP into the central pattern generator neuron C2. Additionally, during wash-in, IBMX sometimes temporarily produced extended or spontaneous swim motor patterns. Photolysis of caged cAMP in C2 after initiation of the swim motor pattern inhibited subsequent bursting. These results suggest that cAMP levels can dynamically modulate swim motor pattern generation, possibly shaping the output of the central pattern generator on a cycle-by-cycle basis.

  16. Newer therapeutic strategies to alter high-density lipoprotein level and function.

    PubMed

    Bosch, Nicholas; Frishman, William H

    2014-01-01

    Measurements of low levels of high-density lipoprotein (HDL) cholesterol have been identified as a risk factor for premature coronary artery disease, however, to date, current pharmacologic approaches for raising HDL have provided little benefit, if at all, in reducing cardiovascular outcomes. It has been shown that HDL can modify many aspects of plaque pathogenesis. Its most established role is in reverse cholesterol transportation, but HDL can also affect oxidation, inflammation, cellular adhesion, and vasodilatation. Considering these potential benefits of HDL, newer treatments have been developed to modify HDL activity, which include the use of oral cholesteryl ester transfer protein inhibitors, apolipoprotein (apo)A-I infusions, apoA-I mimetics, drugs to increase apoA-I synthesis, and agonists of the liver X receptor. These new therapies are reviewed in this article.

  17. Supraphysiological Levels of Quercetin Glycosides are Required to Alter Mineralization in Saos2 Cells

    PubMed Central

    Nash, Leslie A.; Peters, Sandra J.; Sullivan, Philip J.; Ward, Wendy E.

    2016-01-01

    Flavonoid intake is positively correlated to bone mineral density (BMD) in women. Flavonoids such as quercetin exhibit strong anti-oxidant and anti-inflammatory activity that may be beneficial for bone health. Quercetin, previously shown to positively influence osteoblasts, is metabolized into glycosides including rutin and hyperoside. We compared the effects of these glycosides on mineralization in human osteoblast (Saos2) cells. Administration of rutin (≥25 µM) and hyperoside (≥5 µM) resulted in higher mineral content, determined using the alizarin red assay. This was accompanied by higher alkaline phosphatase activity with no cell toxicity. The expression of osteopontin, sclerostin, TNFα and IL6, known stimuli for decreasing osteoblast activity, were reduced with the addition of rutin or hyperoside. In summary, rutin and hyperoside require supraphysiological levels, when administered individually, to positively influence osteoblast activity. This information may be useful in developing nutraceuticals to support bone health. PMID:27136576

  18. Unexpected rates of chromosomal instabilities and alterations of hormone levels in Namibian uranium miners

    SciTech Connect

    Zaire, R.; Notter, M.; Thiel, E.

    1997-05-01

    A common problem in determining the health consequences of radiation exposure is factoring out other carcinogenic influences. The conditions in Namibia provide a test case for distinguishing the effects of long-term low-dose exposure to uranium from the other environmental factors because of good air quality and the lack of other industries with negative health effects. Present records indicate a much higher prevalence of cancer among male workers in the open-pit uranium mine in Namibia compared with the general population. The objective of the present study was to determine whether long-term exposure to low doses of uranium increases the risk of a biological radiation damage which would lead to malignant diseases and to derive a dose-response model for these miners. To investigate this risk, we measured uranium excretion in urine, neutrophil counts and the serum level of FSH, LH and testosterone and analyzed chromosome aberrations in whole blood cells using fluorescence in situ hybridization. A representative cohort of 75 non-smoking, HIV-negative miners was compared to a control group of 31 individuals with no occupational history in mining. A sixfold increase in uranium excretion among the miners compared to the controls was recorded (P < 0.001). Furthermore, we determined a significant reduction in testosterone levels (P < 0.008) and neutrophil count (P < 0.0001). Most remarkably, cells with multiple aberrations such as {open_quotes}rogue{close_quotes} cells were observed for the first time in miners; these cells had previously been found only after short-term high-dose radiation exposure, e.g. from the Hiroshima atomic bomb or the Chernobyl accident. 19 refs., 1 fig., 3 tabs.

  19. Low-level neonatal thimerosal exposure: further evaluation of altered neurotoxic potential in SJL mice.

    PubMed

    Berman, Robert F; Pessah, Isaac N; Mouton, Peter R; Mav, Deepak; Harry, Jean

    2008-02-01

    Ethylmercury in thimerosal-preserved childhood vaccines has been suggested to be neurotoxic and to contribute to the etiology of neurodevelopmental disorders, including autism. Immune system function may be an important factor influencing vulnerability of the developing nervous system to thimerosal. This possibility is based in part on a report by Hornig et al. (2004, Mol. Psychiatry 9, 833-845) of neurodevelomental toxicity in SJL/J mice that develop autoantibodies when exposed to organic mercury. The present study reexamined this possibility by injecting neonatal SJL/J mice with thimerosal, with and without combined HiB and DTP vaccines. Injections modeled childhood vaccination schedules, with mice injected on postnatal days 7, 9, 11, and 15 with 14.2, 10.8, 9.2, and 5.6 mug/kg mercury from thimerosal, respectively, or vehicle. Additional groups received vaccine only or a 10 times higher thimerosal + vaccine dose. Low levels of mercury were found in blood, brain, and kidneys 24 h following the last thimerosal injection. Survival, body weight, indices of early development (negative geotaxis, righting) and hippocampal morphology were not affected. Performance was unaffected in behavioral tests selected to assess behavioral domains relevant to core deficits in neurodevelopmental disorders such as autism (i.e., social interaction, sensory gating, anxiety). In an open-field test the majority of behaviors were unaffected by thimerosal injection, although thimerosal-injected female mice showed increased time in the margin of an open field at 4 weeks of age. Considered together the present results do not indicate pervasive developmental neurotoxicity following vaccine-level thimerosal injections in SJL mice, and provide little if any support for the hypothesis that thimerosal exposure contributes to the etiology of neurodevelopmental disorders.

  20. Epigenetic Alterations in Human Liver From Subjects With Type 2 Diabetes in Parallel With Reduced Folate Levels

    PubMed Central

    Matte, Ashok; Perfilyev, Alexander; de Mello, Vanessa D.; Käkelä, Pirjo; Pihlajamäki, Jussi

    2015-01-01

    Objective: Epigenetic variation may contribute to the development of complex metabolic diseases such as type 2 diabetes (T2D). Hepatic insulin resistance is a hallmark of T2D. However, it remains unknown whether epigenetic alterations take place in the liver from diabetic subjects. Therefore, we investigated the genome-wide DNA methylation pattern in the liver from subjects with T2D and nondiabetic controls and related epigenetic alterations to gene expression and circulating folate levels. Research Design and Methods: Liver biopsies were obtained from 35 diabetic and 60 nondiabetic subjects, which are part of the Kuopio Obesity Surgery Study. The genome-wide DNA methylation pattern was analyzed in the liver using the HumanMethylation450 BeadChip. RNA expression was analyzed from a subset of subjects using the HumanHT-12 Expression BeadChip. Results: After correction for multiple testing, we identified 251 individual CpG sites that exhibit differential DNA methylation in liver obtained from T2D compared with nondiabetic subjects (Q < .05). These include CpG sites annotated to genes that are biologically relevant to the development of T2D such as GRB10, ABCC3, MOGAT1, and PRDM16. The vast majority of the significant CpG sites (94%) displayed decreased DNA methylation in liver from subjects with T2D. The hypomethylation found in liver from diabetic subjects may be explained by reduced folate levels. Indeed, subjects with T2D had significantly reduced erythrocyte folate levels compared with nondiabetic subjects. We further identified 29 genes that displayed both differential DNA methylation and gene expression in human T2D liver including the imprinted gene H19. Conclusions: Our study highlights the importance of epigenetic and transcriptional changes in the liver from subjects with T2D. Reduced circulating folate levels may provide an explanation for hypomethylation in the human diabetic liver. PMID:26418287

  1. Minocycline treatment inhibits microglial activation and alters spinal levels of endocannabinoids in a rat model of neuropathic pain

    PubMed Central

    Guasti, Leonardo; Richardson, Denise; Jhaveri, Maulik; Eldeeb, Khalil; Barrett, David; Elphick, Maurice R; Alexander, Stephen PH; Kendall, David; Michael, Gregory J; Chapman, Victoria

    2009-01-01

    Activation of spinal microglia contributes to aberrant pain responses associated with neuropathic pain states. Endocannabinoids (ECs) are present in the spinal cord, and inhibit nociceptive processing; levels of ECs may be altered by microglia which modulate the turnover of endocannabinoids in vitro. Here, we investigate the effect of minocycline, an inhibitor of activated microglia, on levels of the endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG), and the related compound N-palmitoylethanolamine (PEA), in neuropathic spinal cord. Selective spinal nerve ligation (SNL) in rats resulted in mechanical allodynia and the presence of activated microglia in the ipsilateral spinal cord. Chronic daily treatment with minocycline (30 mg/kg, ip for 14 days) significantly reduced the development of mechanical allodynia at days 5, 10 and 14 post-SNL surgery, compared to vehicle-treated SNL rats (P < 0.001). Minocycline treatment also significantly attenuated OX-42 immunoreactivity, a marker of activated microglia, in the ipsilateral (P < 0.001) and contralateral (P < 0.01) spinal cord of SNL rats, compared to vehicle controls. Minocycline treatment significantly (P < 0.01) decreased levels of 2-AG and significantly (P < 0.01) increased levels of PEA in the ipsilateral spinal cord of SNL rats, compared to the contralateral spinal cord. Thus, activation of microglia affects spinal levels of endocannabinoids and related compounds in neuropathic pain states. PMID:19570201

  2. Activation of vagus nerve by semapimod alters substance P levels and decreases breast cancer metastasis.

    PubMed

    Erin, Nuray; Duymuş, Ozlem; Oztürk, Saffet; Demir, Necdet

    2012-11-10

    Chronic inflammation is involved in initiation as well as in progression of cancer. Semapimod, a tetravalent guanylhydrazon and formerly known as CNI-1493, inhibits the release of inflammatory cytokines from activated macrophages and this effect is partly mediated by the vagus nerve. Our previous findings demonstrated that inactivation of vagus nerve activity as well sensory neurons enhanced visceral metastasis of 4THM breast carcinoma. Hence semapimod by activating vagus nerve may inhibit breast cancer metastasis. Here, effects of semapimod on breast cancer metastasis, the role of vagal sensory neurons on this effect and changes in mediators of the neuroimmune connection, such as substance P (SP) as well as neprilysin-like activity, were examined. Vagotomy was performed on half of the control animals that were treated with semapimod following orthotopic injection of 4THM breast carcinoma cells. Semapimod decreased lung and liver metastases in control but not in vagotomized animals with an associated increased SP levels in sensory nerve endings. Semapimod also increased neprilysin-like activity in lung tissue of control animals but not in tumor-bearing animals. This is the first report demonstrating that semapimod enhances vagal sensory nerve activity and may have anti-tumoral effects under in-vivo conditions. Further studies, however, are required to elucidate the conditions and the mechanisms involved in anti-tumoral effects of semapimod.

  3. Disease variants alter transcription factor levels and methylation of their binding sites.

    PubMed

    Bonder, Marc Jan; Luijk, René; Zhernakova, Daria V; Moed, Matthijs; Deelen, Patrick; Vermaat, Martijn; van Iterson, Maarten; van Dijk, Freerk; van Galen, Michiel; Bot, Jan; Slieker, Roderick C; Jhamai, P Mila; Verbiest, Michael; Suchiman, H Eka D; Verkerk, Marijn; van der Breggen, Ruud; van Rooij, Jeroen; Lakenberg, Nico; Arindrarto, Wibowo; Kielbasa, Szymon M; Jonkers, Iris; van 't Hof, Peter; Nooren, Irene; Beekman, Marian; Deelen, Joris; van Heemst, Diana; Zhernakova, Alexandra; Tigchelaar, Ettje F; Swertz, Morris A; Hofman, Albert; Uitterlinden, André G; Pool, René; van Dongen, Jenny; Hottenga, Jouke J; Stehouwer, Coen D A; van der Kallen, Carla J H; Schalkwijk, Casper G; van den Berg, Leonard H; van Zwet, Erik W; Mei, Hailiang; Li, Yang; Lemire, Mathieu; Hudson, Thomas J; Slagboom, P Eline; Wijmenga, Cisca; Veldink, Jan H; van Greevenbroek, Marleen M J; van Duijn, Cornelia M; Boomsma, Dorret I; Isaacs, Aaron; Jansen, Rick; van Meurs, Joyce B J; 't Hoen, Peter A C; Franke, Lude; Heijmans, Bastiaan T

    2017-01-01

    Most disease-associated genetic variants are noncoding, making it challenging to design experiments to understand their functional consequences. Identification of expression quantitative trait loci (eQTLs) has been a powerful approach to infer the downstream effects of disease-associated variants, but most of these variants remain unexplained. The analysis of DNA methylation, a key component of the epigenome, offers highly complementary data on the regulatory potential of genomic regions. Here we show that disease-associated variants have widespread effects on DNA methylation in trans that likely reflect differential occupancy of trans binding sites by cis-regulated transcription factors. Using multiple omics data sets from 3,841 Dutch individuals, we identified 1,907 established trait-associated SNPs that affect the methylation levels of 10,141 different CpG sites in trans (false discovery rate (FDR) < 0.05). These included SNPs that affect both the expression of a nearby transcription factor (such as NFKB1, CTCF and NKX2-3) and methylation of its respective binding site across the genome. Trans methylation QTLs effectively expose the downstream effects of disease-associated variants.

  4. A new genus of speleophriid copepod (Copepoda: Misophrioida) from a cenote in the Yucatan, Mexico with a phylogenetic analysis at the species level.

    PubMed

    Boxshall, Geoff A; Zylinski, Sarah; Jaume, Damià; Iliffe, Thomas M; Suárez-Morales, Eduardo

    2014-06-23

    A new genus and species of speleophriid copepod, Mexicophria cenoticola gen. et sp. nov., is described based on material collected from a cenote in the Yucatan Peninsula of Mexico. It is characterised by relatively reduced fifth legs that are located adjacent to the ventral midline in both sexes, by the possession of a bulbous swelling on the first antennulary segment in both sexes, and by the reduced setation of the swimming legs. The presence of just one inner margin seta on the second endopodal segment of legs 2 to 4 is a unique feature for the family. A phylogenetic analysis places the new genus on a basal lineage of the family together with its sister taxon, Boxshallia Huys, 1988, from Lanzarote in the Canary Islands, and recovers the existing genera as monophyletic units. The zoogeography is discussed at local, regional, ocean basin  and global scales.

  5. Profiling phylogenetic informativeness.

    PubMed

    Townsend, Jeffrey P

    2007-04-01

    The resolution of four controversial topics in phylogenetic experimental design hinges upon the informativeness of characters about the historical relationships among taxa. These controversies regard the power of different classes of phylogenetic character, the relative utility of increased taxonomic versus character sampling, the differentiation between lack of phylogenetic signal and a historical rapid radiation, and the design of taxonomically broad phylogenetic studies optimized by taxonomically sparse genome-scale data. Quantification of the informativeness of characters for resolution of phylogenetic hypotheses during specified historical epochs is key to the resolution of these controversies. Here, such a measure of phylogenetic informativeness is formulated. The optimal rate of evolution of a character to resolve a dated four-taxon polytomy is derived. By scaling the asymptotic informativeness of a character evolving at a nonoptimal rate by the derived asymptotic optimum, and by normalizing so that net phylogenetic informativeness is equivalent for all rates when integrated across all of history, an informativeness profile across history is derived. Calculation of the informativeness per base pair allows estimation of the cost-effectiveness of character sampling. Calculation of the informativeness per million years allows comparison across historical radiations of the utility of a gene for the inference of rapid adaptive radiation. The theory is applied to profile the phylogenetic informativeness of the genes BRCA1, RAG1, GHR, and c-myc from a muroid rodent sequence data set. Bounded integrations of the phylogenetic profile of these genes over four epochs comprising the diversifications of the muroid rodents, the mammals, the lobe-limbed vertebrates, and the early metazoans demonstrate the differential power of these genes to resolve the branching order among ancestral lineages. This measure of phylogenetic informativeness yields a new kind of information

  6. Time Course of Behavioral Alteration and mRNA Levels of Neurotrophic Factor Following Stress Exposure in Mouse.

    PubMed

    Hashikawa, Naoya; Ogawa, Takumi; Sakamoto, Yusuke; Ogawa, Mami; Matsuo, Yumi; Zamami, Yoshito; Hashikawa-Hobara, Narumi

    2015-08-01

    Stress is known to affect neurotrophic factor expression, which induces depression-like behavior. However, whether there are time-dependent changes in neurotrophic factor mRNA expression following stress remains unclear. In the present study, we tested whether chronic stress exposure induces long-term changes in depression-related behavior, serum corticosterone, and hippocampal proliferation as well as neurotrophic factor family mRNA levels, such as brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin-3 (NT-3), and ciliary neurotrophic factor (CNTF), in the mouse hippocampus. The mRNA level of neurotrophic factors (BDNF, NGF, NT-3, and CNTF) was measured using the real-time PCR. The serum corticosterone level was evaluated by enzyme-linked immunosorbent assay, and, for each subject, the hippocampal proliferation was examined by 5-bromo-2-deoxyuridine immunostaining. Mice exhibited depression-like behavior in the forced-swim test (FST) and decreased BDNF mRNA and hippocampal proliferation in the middle of the stress exposure. After 15 days of stress exposure, we observed increased immobility in the FST, serum corticosterone levels, and BDNF mRNA levels and degenerated hippocampal proliferation, maintained for at least 2 weeks. Anhedonia-like behavior in the sucrose preference test and NGF mRNA levels were decreased following 15 days of stress. NGF mRNA levels were significantly higher 1 week after stress exposure. The current data demonstrate that chronic stress exposure induces prolonged BDNF and NGF mRNA changes and increases corticosterone levels and depression-like behavior in the FST, but does not alter other neurotrophic factors or performance in the sucrose preference test.

  7. Proteasome Inhibitors Alter Levels of Intracellular Peptides in HEK293T and SH-SY5Y Cells

    PubMed Central

    Dasgupta, Sayani; Castro, Leandro M.; Dulman, Russell; Yang, Ciyu; Schmidt, Marion; Ferro, Emer S.; Fricker, Lloyd D.

    2014-01-01

    The proteasome cleaves intracellular proteins into peptides. Earlier studies found that treatment of human embryonic kidney 293T (HEK293T) cells with epoxomicin (an irreversible proteasome inhibitor) generally caused a decrease in levels of intracellular peptides. However, bortezomib (an antitumor drug and proteasome inhibitor) caused an unexpected increase in the levels of most intracellular peptides in HEK293T and SH-SY5Y cells. To address this apparent paradox, quantitative peptidomics was used to study the effect of a variety of other proteasome inhibitors on peptide levels in HEK293T and SH-SY5Y cells. Inhibitors tested included carfilzomib, MG132, MG262, MLN2238, AM114, and clasto-Lactacystin β-lactone. Only MG262 caused a substantial elevation in peptide levels that was comparable to the effect of bortezomib, although carfilzomib and MLN2238 elevated the levels of some peptides. To explore off-target effects, the proteosome inhibitors were tested with various cellular peptidases. Bortezomib did not inhibit tripeptidyl peptidase 2 and only weakly inhibited cellular aminopeptidase activity, as did some of the other proteasome inhibitors. However, potent inhibitors of tripeptidyl peptidase 2 (butabindide) and cellular aminopeptidases (bestatin) did not substantially alter the peptidome, indicating that the increase in peptide levels due to proteasome inhibitors is not a result of peptidase inhibition. Although we cannot exclude other possibilities, we presume that the paradoxical increase in peptide levels upon treatment with bortezomib and other inhibitors is the result of allosteric effects of these compounds on the proteasome. Because intracellular peptides are likely to be functional, it is possible that some of the physiologic effects of bortezomib and carfilzomib arise from the perturbation of peptide levels inside the cell. PMID:25079948

  8. Wastewater treatment plant effluent alters pituitary gland gonadotropin mRNA levels in juvenile coho salmon (Oncorhynchus kisutch).

    PubMed

    Harding, Louisa B; Schultz, Irvin R; da Silva, Denis A M; Ylitalo, Gina M; Ragsdale, Dave; Harris, Stephanie I; Bailey, Stephanie; Pepich, Barry V; Swanson, Penny

    2016-09-01

    It is well known that endocrine disrupting compounds (EDCs) present in wastewater treatment plant (WWTP) effluents interfere with reproduction in fish, including altered gonad development and induction of vitellogenin (Vtg), a female-specific egg yolk protein precursor produced in the liver. As a result, studies have focused on the effects of EDC exposure on the gonad and liver. However, impacts of environmental EDC exposure at higher levels of the hypothalamic-pituitary-gonad axis are less well understood. The pituitary gonadotropins, follicle-stimulating hormone (Fsh) and luteinizing hormone (Lh) are involved in all aspects of gonad development and are subject to feedback from gonadal steroids making them a likely target of endocrine disruption. In this study, the effects of WWTP effluent exposure on pituitary gonadotropin mRNA expression were investigated to assess the utility of Lh beta-subunit (lhb) as a biomarker of estrogen exposure in juvenile coho salmon (Oncorhynchus kisutch). First, a controlled 72-h exposure to 17α-ethynylestradiol (EE2) and 17β-trenbolone (TREN) was performed to evaluate the response of juvenile coho salmon to EDC exposure. Second, juvenile coho salmon were exposed to 0, 20 or 100% effluent from eight WWTPs from the Puget Sound, WA region for 72h. Juvenile coho salmon exposed to 2 and 10ng EE2L(-1) had 17-fold and 215-fold higher lhb mRNA levels relative to control fish. Hepatic vtg mRNA levels were dramatically increased 6670-fold, but only in response to 10ng EE2L(-1) and Fsh beta-subunit (fshb) mRNA levels were not altered by any of the treatments. In the WWTP effluent exposures, lhb mRNA levels were significantly elevated in fish exposed to five of the WWTP effluents. In contrast, transcript levels of vtg were not affected by any of the WWTP effluent exposures. Mean levels of natural and synthetic estrogens in fish bile were consistent with pituitary lhb expression, suggesting that the observed lhb induction may be due to

  9. Altered Brain Network in Amyotrophic Lateral Sclerosis: A Resting Graph Theory-Based Network Study at Voxel-Wise Level.

    PubMed

    Zhou, Chaoyang; Hu, Xiaofei; Hu, Jun; Liang, Minglong; Yin, Xuntao; Chen, Lin; Zhang, Jiuquan; Wang, Jian

    2016-01-01

    Amyotrophic lateral sclerosis (ALS) is a rare degenerative disorder characterized by loss of upper and lower motor neurons. Neuroimaging has provided noticeable evidence that ALS is a complex disease, and shown that anatomical and functional lesions extend beyond precentral cortices and corticospinal tracts, to include the corpus callosum; frontal, sensory, and premotor cortices; thalamus; and midbrain. The aim of this study is to investigate graph theory-based functional network abnormalities at voxel-wise level in ALS patients on a whole brain scale. Forty-three ALS patients and 44 age- and sex-matched healthy volunteers were enrolled. The voxel-wise network degree centrality (DC), a commonly employed graph-based measure of network organization, was used to characterize the alteration of whole brain functional network. Compared with the controls, the ALS patients showed significant increase of DC in the left cerebellum posterior lobes, bilateral cerebellum crus, bilateral occipital poles, right orbital frontal lobe, and bilateral prefrontal lobes; significant decrease of DC in the bilateral primary motor cortex, bilateral sensory motor region, right prefrontal lobe, left bilateral precuneus, bilateral lateral temporal lobes, left cingulate cortex, and bilateral visual processing cortex. The DC's z-scores of right inferior occipital gyrus were significant negative correlated with the ALSFRS-r scores. Our findings confirm that the regions with abnormal network DC in ALS patients were located in multiple brain regions including primary motor, somatosensory and extra-motor areas, supporting the concept that ALS is a multisystem disorder. Specifically, our study found that DC in the visual areas was altered and ALS patients with higher DC in right inferior occipital gyrus have more severity of disease. The result demonstrated that the altered DC value in this region can probably be used to assess severity of ALS.

  10. Ultra-fast alterations in mRNA levels uncover multiple players in light stress acclimation in plants.

    PubMed

    Suzuki, Nobuhiro; Devireddy, Amith R; Inupakutika, Madhuri A; Baxter, Aaron; Miller, Gad; Song, Luhua; Shulaev, Elena; Azad, Rajeev K; Shulaev, Vladimir; Mittler, Ron

    2015-11-01

    The acclimation of plants to changes in light intensity requires rapid responses at several different levels. These include biochemical and biophysical responses as well as alterations in the steady-state level of different transcripts and proteins. Recent studies utilizing promoter::reporter constructs suggested that transcriptional responses to changes in light intensity could occur within seconds, rates for which changes in mRNA expression are not routinely measured or functionally studied. To identify and characterize rapid changes in the steady-state level of different transcripts in response to light stress we performed RNA sequencing analysis of Arabidopsis thaliana plants subjected to light stress. Here we report that mRNA accumulation of 731 transcripts occurs as early as 20-60 sec following light stress application, and that at least five of these early response transcripts play an important biological role in the acclimation of plants to light stress. More than 20% of transcripts accumulating in plants within 20-60 sec of initiation of light stress are H2 O2 - and ABA-response transcripts, and the accumulation of several of these transcripts is inhibited by transcriptional inhibitors. In accordance with the association of rapid response transcripts with H2 O2 and ABA signaling, a mutant impaired in ABA sensing (abi-1) was found to be more tolerant to light stress, and the response of several of the rapid response transcripts was altered in mutants impaired in reactive oxygen metabolism. Our findings reveal that transcriptome reprogramming in plants could occur within seconds of initiation of abiotic stress and that this response could invoke known as well as unknown proteins and pathways.

  11. Teaching Molecular Phylogenetics through Investigating a Real-World Phylogenetic Problem

    ERIC Educational Resources Information Center

    Zhang, Xiaorong

    2012-01-01

    A phylogenetics exercise is incorporated into the "Introduction to biocomputing" course, a junior-level course at Savannah State University. This exercise is designed to help students learn important concepts and practical skills in molecular phylogenetics through solving a real-world problem. In this application, students are required to identify…

  12. Is a low level of free thyroxine in the maternal circulation associated with altered endothelial function in gestational diabetes?

    PubMed Central

    Guzmán-Gutiérrez, Enrique; Veas, Carlos; Leiva, Andrea; Escudero, Carlos; Sobrevia, Luis

    2014-01-01

    Synthesis of thyroid hormones, thyroxine (T4) and tri-iodothyronine (T3), in the human fetus starts from 17 to 19th weeks of gestation. Despite the majority of normal pregnant women reaching adequate levels of circulating thyroid hormones, in some cases, women with normal pregnancies have low level of free T4 during first trimester of pregnancy, suggesting that T4 action may be compromised in those women and their fetuses. In addition, pathological low levels of thyroid hormones are detected in isolated maternal hypothyroxemia (IMH) and clinical hypothyroidism. Nevertheless, human placenta regulates T3/T4 concentration in the fetal circulation by modulating the expression and activity of both thyroid hormone transporters (THT) and deiodinases. Then, placenta can control the availability of T3/T4 in the feto-placental circulation, and therefore may generate an adaptive response in cases where the mother courses with low levels of T4. In addition, T3/T4 might control vascular response in the placenta, in particularly endothelial cells may induce the synthesis and release of vasodilators such as nitric oxide (NO) or vasoconstrictors such as endothelin-1 mediated by these hormones. On the other hand, low levels of T4 have been associated with increase in gestational diabetes (GD) markers. Since GD is associated with impaired placental vascular function characterized by increased NO synthesis in placental arteries and veins, as well as elevated placental angiogenesis, it is unknown whether reduced T4 level at the maternal circulation could result in an altered placental endothelial function during GD. In this review, we analyze available information regarding thyroid hormones and endothelial dysfunction in GD; and propose that low maternal levels of T4 observed in GD may be compensated by increased placental availability of T3/T4 via elevation in the activity of THT and/or reduction in deiodinases in the feto-placental circulation. PMID:24936187

  13. Phylogenetic Trees From Sequences

    NASA Astrophysics Data System (ADS)

    Ryvkin, Paul; Wang, Li-San

    In this chapter, we review important concepts and approaches for phylogeny reconstruction from sequence data.We first cover some basic definitions and properties of phylogenetics, and briefly explain how scientists model sequence evolution and measure sequence divergence. We then discuss three major approaches for phylogenetic reconstruction: distance-based phylogenetic reconstruction, maximum parsimony, and maximum likelihood. In the third part of the chapter, we review how multiple phylogenies are compared by consensus methods and how to assess confidence using bootstrapping. At the end of the chapter are two sections that list popular software packages and additional reading.

  14. Alterations of GABA and glutamate-glutamine levels in premenstrual dysphoric disorder: a 3T proton magnetic resonance spectroscopy study.

    PubMed

    Liu, Bo; Wang, Guangbin; Gao, Dongmei; Gao, Fei; Zhao, Bin; Qiao, Mingqi; Yang, Huan; Yu, Yanhong; Ren, Fuxin; Yang, Ping; Chen, Weibo; Rae, Caroline D

    2015-01-30

    Increasing evidence has suggested that the GABAergic neurotransmitter system is involved in the pathogenesis of premenstrual dysphoric disorder (PMDD). We used proton magnetic resonance spectroscopy ((1)H MRS) to investigate whether PMDD is associated with alterations in brain GABA levels. Levels of glutamate-glutamine (Glx) were also explored. Participants comprised 22 women with PMDD and 22 age-matched healthy controls who underwent 3T (1)H MRS during the late luteal phase of the menstrual cycle. GABA+ and Glx levels were quantified in the anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC) and the left basal ganglia (ltBG). Water-scaled GABA+ concentrations and GABA+/tCr ratios were significantly lower in both the ACC/mPFC and ltBG regions of PMDD women than in healthy controls. Glx/tCr ratios were significantly higher in the ACC/mPFC region of PMDD women than healthy controls. Our preliminary findings provide the first report of abnormal levels of GABA+ and Glx in mood-related brain regions of women with PMDD, indicating that dysregulation of the amino acid neurotransmitter system may be an important neurobiological mechanism in the pathogenesis of PMDD.

  15. Master's level in primary health care education - students' and preceptors' perceptions and experiences of the alteration in the clinical areas

    PubMed Central

    2010-01-01

    Background Many Western European countries are undergoing reforms with changes in higher education according to the Bologna declaration for Higher European Education Area. In accordance with these changes, the Master's degree was introduced in specialist nurse education in Sweden in 2007, and as a result changed the curriculum and modified theoretical and clinical areas. The aim of this study was to investigate students' and preceptors' perceptions and experiences of Master's level education in primary health care with a focus on the clinical area. Methods A descriptive design and qualitative approach was used. Interviews with ten students and ten preceptors were performed twice, before and after the clinical practice period. Interviews were audio-recorded, transcribed verbatim and themes formulated. Results Students perceived alteration in the content of the education at the Master's level such as more independence and additional assignments. The preceptors perceived benefits with the Master's level but were unsure of how to transform theoretical and abstract knowledge into practice. Writing the Master's thesis was seen by students to take time away from clinical practice. For some students and preceptors the content of the Master's level clinical practice area was experienced as vague and indistinct. The students had not expected supervision to be different from earlier experiences, while preceptors felt higher demands and requested more knowledge. Both students and preceptors perceived that education at the Master's level might lead to a higher status for the nurses' profession in primary health care. Conclusions Students and preceptors experienced both advantages and disadvantages concerning the change in specialist nurse education in primary health care at the Master's level. The altered educational content was experienced as a step forward, but they also questioned how the new knowledge could be used in practice. The relevance of the Master's thesis was

  16. Association of Urinary Metal Profiles with Altered Glucose Levels and Diabetes Risk: A Population-Based Study in China

    PubMed Central

    Feng, Wei; Cui, Xiuqing; Liu, Bing; Liu, Chuanyao; Xiao, Yang; Lu, Wei; Guo, Huan; He, Meian; Zhang, Xiaomin; Yuan, Jing; Chen, Weihong; Wu, Tangchun

    2015-01-01

    Background Elevated heavy metals and fasting plasma glucose (FPG) levels were both associated with increased risk of cardiovascular diseases. However, studies on the associations of heavy metals and essential elements with altered FPG and diabetes risk were limited or conflicting. The objective of this study was to evaluate the potential associations of heavy metals and essential trace elements with FPG and diabetes risk among general Chinese population. Methods We conducted a cross-sectional study to investigate the associations of urinary concentrations of 23 metals with FPG, impaired fasting glucose (IFG) and diabetes among 2242 community-based Chinese adults in Wuhan. We used the false discovery rate (FDR) method to correct for multiple hypothesis tests. Results After adjusting for potential confounders, urinary aluminum, titanium, cobalt, nickel, copper, zinc, selenium, rubidium, strontium, molybdenum, cadmium, antimony, barium, tungsten and lead were associated with altered FPG, IFG or diabetes risk (all P< 0.05); arsenic was only dose-dependently related to diabetes (P< 0.05). After additional adjustment for multiple testing, titanium, copper, zinc, selenium, rubidium, tungsten and lead were still significantly associated with one or more outcomes (all FDR-adjusted P< 0.05). Conclusions Our results suggest that multiple metals in urine are associated with FPG, IFG or diabetes risk. Because the cross-sectional design precludes inferences about causality, further prospective studies are warranted to validate our findings. PMID:25874871

  17. A single exposure to bisphenol A alters the levels of important neuroproteins in adult male and female mice.

    PubMed

    Viberg, Henrik; Lee, Iwa

    2012-10-01

    Bisphenol A (BPA) is widely used in polymer products in food and beverage containers, baby bottles, dental sealants and fillings, adhesives, protective coatings, flame retardants, water supply pipes, and compact discs, and is found in the environment and in placental tissue, fetuses and breast milk. We have recently reported that a single neonatal exposure to bisphenol A can induce persistent aberrations in spontaneous behavior, in a dose-dependent manner, and affect the adult response to the cholinergic agent nicotine. Furthermore, other recent reports indicate that pre- and perinatal exposure to bisphenol A can induce neurotoxic effects. The present study indicates that a single neonatal exposure to bisphenol A, on postnatal day 10, during the peak of the brain growth spurt, can alter the adult levels of proteins important for normal brain development (CaMKII and synaptophysin). These alterations are induced in both male and female mice and effects are seen in both hippocampus and cerebral cortex. These results further support our recent study showing that neonatal exposure to bisphenol A can act as a developmental neurotoxicant and the effects are similar to effects seen after a single postnatal exposure to other POPs, such as PBDEs, PCBs and PFCs.

  18. Drospirenone intake alters plasmatic steroid levels and cyp17a1 expression in gonads of juvenile sea bass.

    PubMed

    Blanco, Maria; Fernandes, Denise; Medina, Paula; Blázquez, Mercedes; Porte, Cinta

    2016-06-01

    Drospirenone (DRO) is one of the most widely used progestins in contraceptive treatments and hormone replacement therapies. The pharmacokinetics and potential toxicological effects of DRO were investigated in juvenile sea bass (Dicentrarchus labrax) exposed through the diet (0.01-10 μg DRO/g) for up to 31 days. DRO was detected in the blood (4-27 ng/mL) of fish exposed to the highest concentration, with no significant bioaccumulation over time and no alteration of hepatic metabolizing enzymes, namely, CYP1A and CYP3A-catalysed activities and UDP-glucuronyltransferase (UGT). Pregnenolone (P5), progesterone (P4), 17α-hydroxyprogesterone (17P4), 17α-hydroxypregnenolone (17P5), androstenedione (AD) and testosterone (T) were determined in plasma and gene expression of cyp17a1, cyp19a1a and cyp11β analysed by qRT-PCR in gonads. The significant increase in plasmatic levels of 17P5, 17P4 and AD detected after 31 days exposure to 10 ng DRO/g together with the increased expression of cyp17a1 in females evidence the ability of DRO to alter steroid synthesis at low intake concentrations (7 ng DRO/day). However, the potential consequences of this steroid shift for female reproduction remain to be investigated.

  19. Periodontitis increases rheumatic factor serum levels and citrullinated proteins in gingival tissues and alter cytokine balance in arthritic rats

    PubMed Central

    Corrêa, Mônica G.; Sacchetti, Silvana B.; Ribeiro, Fernanda Vieira; Pimentel, Suzana Peres; Casarin, Renato Corrêa Viana; Cirano, Fabiano Ribeiro; Casati, Marcio Z.

    2017-01-01

    This study investigated some immunological features by experimental periodontitis (EP) and rheumatoid arthritis (RA) disease interact in destructive processes in arthritic rats. Rats were assigned to the following groups: EP +RA; RA; EP; and Negative Control. RA was induced by immunizations with type-II collagen and a local immunization with Complete Freund’s adjuvant in the paw. Periodontitis was induced by ligating the right first molars. The serum level of rheumatoid factor (RF) and anti-citrullinated protein antibody (ACCPA) were measured before the induction of EP (T1) and at 28 days after (T2) by ELISA assay. ACCPA levels were also measured in the gingival tissue at T2. The specimens were processed for morphometric analysis of bone loss, and the gingival tissue surrounding the first molar was collected for the quantification of interleukin IL-1β, IL-4, IL-6, IL-17 and TNF-α using a Luminex/MAGpix assay. Paw edema was analyzed using a plethysmometer. Periodontitis increased the RF and ACCPA levels in the serum and in the gingival tissue, respectively. Besides, the level of paw swelling was increased by EP and remained in progress until the end of the experiment, when EP was associated with RA. Greater values of IL-17 were observed only when RA was present, in spite of PE. It can be concluded that periodontitis increases rheumatic factor serum levels and citrullinated proteins level in gingival tissues and alter cytokine balance in arthritic rats; at the same time, arthritis increases periodontal destruction, confirming the bidirectional interaction between diseases. PMID:28358812

  20. Phylogenetic lineages in Entomophthoromycota

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Entomophthoromycota Humber is one of five major phylogenetic lineages among the former phylum Zygomycota. These early terrestrial fungi share evolutionarily ancestral characters such as coenocytic mycelium and gametangiogamy as a sexual process resulting in zygospore formation. Previous molecular st...

  1. Altering dietary levels of protein or vitamins and minerals does not modify morphine-induced analgesia in male rats.

    PubMed

    Kanarek, R B; D'Anci, K E; Przypek, J M; Mathes, W F

    1999-02-01

    Previous research has demonstrated that chronic intake of nutritive sweet solutions, but not nonnutritive sweet solutions, enhances morphine's analgesic potency. To separate out the effects of sweet taste from other changes in dietary intake, which result when rats consume a sucrose solution, the effects of altering dietary levels of protein, or vitamins and minerals on morphine-induced analgesia were examined. In Experiment 1, 40 male Long-Evans rats were fed standard chow or a semipurified diet containing either 10, 20, or 40% protein. Three weeks later, antinociceptive responses to morphine were examined using the tail flick procedure. Tail flick latencies were measured immediately prior to and 30, 60, and 90 min after the administration of morphine sulfate (0.0, 1.25, 2.5, and 5.0 mg/kg, SC). At all three measurement times, antinociceptive responses increased directly as a function of the dose of morphine, but did not differ as a function of diet. In Experiment 2, 24 rats were maintained on either standard laboratory chow or semipurified diets containing 20% protein and either 100% or 25% of the recommended levels of vitamins and minerals for 3 weeks. Tail flick latencies were measured immediately prior to and 30 min after injections (SC) of 2.5 mg/kg morphine sulfate. This procedure was repeated until a cumulative dose of 10.0 mg/kg was obtained. Tail flick latencies increased significantly as a function of drug dose, but did not differ across dietary conditions. These results demonstrate that the increase in morphine-induced analgesia seen in rats consuming a sucrose solution is not due to alterations in either protein or micronutrient intake.

  2. Quantifying phylogenetic beta diversity: distinguishing between 'true' turnover of lineages and phylogenetic diversity gradients.

    PubMed

    Leprieur, Fabien; Albouy, Camille; De Bortoli, Julien; Cowman, Peter F; Bellwood, David R; Mouillot, David

    2012-01-01

    The evolutionary dissimilarity between communities (phylogenetic beta diversity PBD) has been increasingly explored by ecologists and biogeographers to assess the relative roles of ecological and evolutionary processes in structuring natural communities. Among PBD measures, the PhyloSor and UniFrac indices have been widely used to assess the level of turnover of lineages over geographical and environmental gradients. However, these indices can be considered as 'broad-sense' measures of phylogenetic turnover as they incorporate different aspects of differences in evolutionary history between communities that may be attributable to phylogenetic diversity gradients. In the present study, we extend an additive partitioning framework proposed for compositional beta diversity to PBD. Specifically, we decomposed the PhyloSor and UniFrac indices into two separate components accounting for 'true' phylogenetic turnover and phylogenetic diversity gradients, respectively. We illustrated the relevance of this framework using simple theoretical and archetypal examples, as well as an empirical study based on coral reef fish communities. Overall, our results suggest that using PhyloSor and UniFrac may greatly over-estimate the level of spatial turnover of lineages if the two compared communities show contrasting levels of phylogenetic diversity. We therefore recommend that future studies use the 'true' phylogenetic turnover component of these indices when the studied communities encompass a large phylogenetic diversity gradient.

  3. Manganese exposure alters extracellular GABA, GABA receptor and transporter protein and mRNA levels in the developing rat brain.

    PubMed

    Anderson, Joel G; Fordahl, Steve C; Cooney, Paula T; Weaver, Tara L; Colyer, Christa L; Erikson, Keith M

    2008-11-01

    Unlike other essential trace elements (e.g., zinc and iron) it is the toxicity of manganese (Mn) that is more common in human populations than its deficiency. Data suggest alterations in dopamine biology may drive the effects associated with Mn neurotoxicity, though recently gamma-aminobutyric acid (GABA) has been implicated. In addition, iron deficiency (ID), a common nutritional problem, may cause disturbances in neurochemistry by facilitating accumulation of Mn in the brain. Previous data from our lab have shown decreased brain tissue levels of GABA as well as decreased (3)H-GABA uptake in synaptosomes as a result of Mn exposure and ID. These results indicate a possible increase in the concentration of extracellular GABA due to alterations in expression of GABA transport and receptor proteins. In this study weanling-male Sprague-Dawley rats were randomly placed into one of four dietary treatment groups: control (CN; 35mg Fe/kg diet), iron-deficient (ID; 6mg Fe/kg diet), CN with Mn supplementation (via the drinking water; 1g Mn/l) (CNMn), and ID with Mn supplementation (IDMn). Using in vivo microdialysis, an increase in extracellular GABA concentrations in the striatum was observed in response to Mn exposure and ID although correlational analysis reveals that extracellular GABA is related more to extracellular iron levels and not Mn. A diverse effect of Mn exposure and ID was observed in the regions examined via Western blot and RT-PCR analysis, with effects on mRNA and protein expression of GAT-1, GABA(A), and GABA(B) differing between and within the regions examined. For example, Mn exposure reduced GAT-1 protein expression by approximately 50% in the substantia nigra, while increasing mRNA expression approximately four-fold, while in the caudate putamen mRNA expression was decreased with no effect on protein expression. These data suggest that Mn exposure results in an increase in extracellular GABA concentrations via altered expression of transport and

  4. Using chromosomal data in the phylogenetic and molecular dating framework: karyotype evolution and diversification in Nierembergia (Solanaceae) influenced by historical changes in sea level.

    PubMed

    Acosta, M C; Moscone, E A; Cocucci, A A

    2016-05-01

    Karyotype data within a phylogenetic framework and molecular dating were used to examine chromosome evolution in Nierembergia and to infer how geological or climatic processes have influenced in the diversification of this solanaceous genus native to South America and Mexico. Despite the numerous studies comparing karyotype features across species, including the use of molecular phylogenies, to date relatively few studies have used formal comparative methods to elucidate chromosomal evolution, especially to reconstruct the whole ancestral karyotypes. Here, we mapped on the Nierembergia phylogeny one complete set of chromosomal data obtained by conventional staining, AgNOR-, C- and fluorescent chromosome banding, and fluorescent in situ hybridisation. In addition, we used a Bayesian molecular relaxed clock to estimate divergence times between species. Nierembergia showed two major divergent clades: a mountainous species group with symmetrical karyotypes, large chromosomes, only one nucleolar organising region (NOR) and without centromeric heterochromatin, and a lowland species group with asymmetrical karyotypes, small chromosomes, two chromosomes pairs with NORs and centromeric heterochromatin bands. Molecular dating on the DNA phylogeny revealed that both groups diverged during Late Miocene, when Atlantic marine ingressions, called the 'Paranense Sea', probably forced the ancestors of these species to find refuge in unflooded areas for about 2 Myr. This split agrees with an increased asymmetry and heterochromatin amount, and decrease in karyotype length and chromosome size. Thus, when the two Nierembergia ancestral lineages were isolated, major divergences occurred in chromosomal evolution, and then each lineage underwent speciation separately, with relatively minor changes in chromosomal characteristics.

  5. Alterations in vitamin A and E levels in liver and testis of wild ungulates from a lead mining area.

    PubMed

    Rodríguez-Estival, Jaime; Taggart, Mark A; Mateo, Rafael

    2011-02-01

    In animals, exposure to metal pollution can induce oxidative stress via several mechanisms. This stress might then cause adverse effects on functions such as male reproductive capacity. Antioxidant vitamins A and E play an important role in maintaining organism functions under stressed conditions. This study assessed the effect of different metals and metalloids on levels of vitamins A and E in livers and testis (n = 67 and 36) of red deer and in livers (n = 22) of wild boar. The study compared animals residing within and outside a polluted mining area. Red deer from mined areas showed significant reductions in liver retinyl docosahexaenoate and retinyl docosapentaenoate. Free retinol, α-tocopherol, and retinyl palmitate in the testis were also lower. This might indicate that increased internal usage of these antioxidants is occurring as deer try to maintain the integrity and function of reproductive tissue. Wild boar from mined areas also showed significant reductions in liver retinyl stearate but increased free retinol levels. This might suggest that vitamin A is being mobilized to a greater degree to cope with the induced oxidative stress caused by exposure to metal pollution. Additionally, a significant negative relationship between liver α-tocopherol and bone lead (Pb) in boar might indicate some long-term effects of Pb on antioxidant levels. Results suggest that vitamin A and E status can be altered as a consequence of exposure to Pb pollution and that complex differences in this response probably exist between species.

  6. Phylogenetic analysis of adenovirus sequences.

    PubMed

    Harrach, Balázs; Benko, Mária

    2007-01-01

    Members of the family Adenoviridae have been isolated from a large variety of hosts, including representatives from every major vertebrate class from fish to mammals. The high prevalence, together with the fairly conserved organization of the central part of their genomes, make the adenoviruses one of (if not the) best models for studying viral evolution on a larger time scale. Phylogenetic calculation can infer the evolutionary distance among adenovirus strains on serotype, species, and genus levels, thus helping the establishment of a correct taxonomy on the one hand, and speeding up the process of typing new isolates on the other. Initially, four major lineages corresponding to four genera were recognized. Later, the demarcation criteria of lower taxon levels, such as species or types, could also be defined with phylogenetic calculations. A limited number of possible host switches have been hypothesized and convincingly supported. Application of the web-based BLAST and MultAlin programs and the freely available PHYLIP package, along with the TreeView program, enables everyone to make correct calculations. In addition to step-by-step instruction on how to perform phylogenetic analysis, critical points where typical mistakes or misinterpretation of the results might occur will be identified and hints for their avoidance will be provided.

  7. Changes in vasotocin levels in relation to ovarian development in the catfish Heteropneustes fossilis exposed to altered photoperiod and temperature.

    PubMed

    Chaube, Radha; Singh, Rahul Kumar; Joy, Keerikattil P

    2015-10-01

    Photoperiod and temperature are the major proximate factors that activate the brain-pituitary-gonadal-endocrine axis stimulating gonadal recrudescence. Vasotocin (VT), the basic nonapeptide hormone, is secreted by the nucleus preopticus in the hypothalamus and released from the pituitary into circulation as a neurohormone for physiological actions. Additionally, VT is secreted de novo in the ovary of the catfish and has been implicated in ovarian functions. In the present study, we evaluated the changes in VT secretion during altered photoperiod and temperature exposure. The ovarian changes were monitored over gonadosomatic index (GSI) and plasma steroid hormone levels. Exposure of the catfish to long photoperiod (LP, 16L:08D) daily, alone or in combination with high temperature (HT, 28 ± 2 °C), for 14 or 28 days resulted in a decrease in brain-pituitary VT level with a concomitant increase in plasma and ovarian VT levels. The changes were greater in the LP + HT group on day 28. Concurrently, the treatments stimulated the GSI and plasma estradiol-17β (E2), testosterone (T) and progesterone (P4) levels with higher more responses in the LP + HT group. Exposure of the catfish to short photoperiod (SP, 08L:16D) daily or total darkness (TD, 24L:00D) daily, with or without changing the ambient temperature, for 14 or 28 days produced a depressing effect on VT, GSI and steroid hormone levels, the range of the response varied with the temperature. The brain VT level was low except in the TD + NT group. Plasma and ovarian VT levels decreased more in the SP and TD groups under ambient temperature than in the groups at the raised temperature. The GSI and plasma steroid hormones (E2, T and P4) responded in a similar manner. Plasma cortisol level registered a significant increase in all the groups compared to the initial control groups, and the increase was significantly higher on day 28. The simultaneous activation of VT secretion and ovarian recrudescence by

  8. Chronic low-level domoic acid exposure alters gene transcription and impairs mitochondrial function in the CNS

    PubMed Central

    Hiolski, Emma M; Kendrick, Preston S; Frame, Elizabeth R; Myers, Mark S; Bammler, Theo K; Beyer, Richard P; Farin, Federico M; Wilkerson, Hui-wen; Smith, Donald R; Marcinek, David J; Lefebvre, Kathi A

    2014-01-01

    Domoic acid is an algal-derived seafood toxin that functions as a glutamate agonist and exerts excitotoxicity via overstimulation of glutamate receptors (AMPA, NMDA) in the central nervous system (CNS). At high (symptomatic) doses, domoic acid is well-known to cause seizures, brain lesions and memory loss; however, a significant knowledge gap exists regarding the health impacts of repeated low-level (asymptomatic) exposure. Here, we investigated the impacts of low-level repetitive domoic acid exposure on gene transcription and mitochondrial function in the vertebrate CNS using a zebrafish model in order to: 1) identify transcriptional biomarkers of exposure; and 2) examine potential pathophysiology that may occur in the absence of overt excitotoxic symptoms. We found that transcription of genes related to neurological function and development were significantly altered, and that asymptomatic exposure impaired mitochondrial function. Interestingly, the transcriptome response was highly-variable across the exposure duration (36 weeks), with little to no overlap of specific genes across the six exposure time points (2, 6, 12, 18, 24, and 36 weeks). Moreover, there were no apparent similarities at any time point with the gene transcriptome profile exhibited by the glud1 mouse model of chronic moderate excess glutamate release. These results suggest that although the fundamental mechanisms of toxicity may be similar, gene transcriptome responses to domoic acid exposure do not extrapolate well between different exposure durations. However, the observed impairment of mitochondrial function based on respiration rates and mitochondrial protein content suggests that repetitive low-level exposure does have fundamental cellular level impacts that could contribute to chronic health consequences. PMID:25033243

  9. Maximizing the phylogenetic diversity of seed banks.

    PubMed

    Griffiths, Kate E; Balding, Sharon T; Dickie, John B; Lewis, Gwilym P; Pearce, Tim R; Grenyer, Richard

    2015-04-01

    Ex situ conservation efforts such as those of zoos, botanical gardens, and seed banks will form a vital complement to in situ conservation actions over the coming decades. It is therefore necessary to pay the same attention to the biological diversity represented in ex situ conservation facilities as is often paid to protected-area networks. Building the phylogenetic diversity of ex situ collections will strengthen our capacity to respond to biodiversity loss. Since 2000, the Millennium Seed Bank Partnership has banked seed from 14% of the world's plant species. We assessed the taxonomic, geographic, and phylogenetic diversity of the Millennium Seed Bank collection of legumes (Leguminosae). We compared the collection with all known legume genera, their known geographic range (at country and regional levels), and a genus-level phylogeny of the legume family constructed for this study. Over half the phylogenetic diversity of legumes at the genus level was represented in the Millennium Seed Bank. However, pragmatic prioritization of species of economic importance and endangerment has led to the banking of a less-than-optimal phylogenetic diversity and prioritization of range-restricted species risks an underdispersed collection. The current state of the phylogenetic diversity of legumes in the Millennium Seed Bank could be substantially improved through the strategic banking of relatively few additional taxa. Our method draws on tools that are widely applied to in situ conservation planning, and it can be used to evaluate and improve the phylogenetic diversity of ex situ collections.

  10. ToF–SIMS imaging of molecular-level alteration mechanisms in Le Bonheur de vivre by Henri Matisse

    PubMed Central

    deGhetaldi, Kristin; Wiggins, Marcie B.; Buckley, Barbara; Baade, Brian; Mass, Jennifer L.; Beebe, Thomas P.

    2016-01-01

    Time-of-flight secondary ion mass spectrometry (ToF–SIMS) has recently been shown to be a valuable tool for cultural heritage studies, especially when used in conjunction with established analytical techniques in the field. The ability of ToF–SIMS to simultaneously image inorganic and organic species within a paint cross section at micrometer-level spatial resolution makes it a uniquely qualified analytical technique to aid in further understanding the processes of pigment and binder alteration, as well as pigment–binder interactions. In this study, ToF–SIMS was used to detect and image both molecular and elemental species related to CdS pigment and binding medium alteration on the painting Le Bonheur de vivre (1905–1906, The Barnes Foundation) by Henri Matisse. Three categories of inorganic and organic components were found throughout Le Bonheur de vivre and co-localized in cross-sectional samples using high spatial resolution ToF–SIMS analysis: (1) species relating to the preparation and photo-induced oxidation of CdS yellow pigments (2) varying amounts of long-chain fatty acids present in both the paint and primary ground layer and (3) specific amino acid fragments, possibly relating to the painting’s complex restoration history. ToF–SIMS’s ability to discern both organic and inorganic species via cross-sectional imaging was used to compare samples collected from Le Bonheur de vivre to artificially aged reference paints in an effort to gather mechanistic information relating to alteration processes that have been previously explored using μXANES, SR-μXRF, SEM–EDX, and SR-FTIR. The relatively high sensitivity offered by ToF–SIMS imaging coupled to the high spatial resolution allowed for the positive identification of degradation products (such as cadmium oxalate) in specific paint regions that have before been unobserved. The imaging of organic materials has provided an insight into the extent of destruction of the original binding medium

  11. ToF-SIMS imaging of molecular-level alteration mechanisms in Le Bonheur de vivre by Henri Matisse

    NASA Astrophysics Data System (ADS)

    Voras, Zachary E.; deGhetaldi, Kristin; Wiggins, Marcie B.; Buckley, Barbara; Baade, Brian; Mass, Jennifer L.; Beebe, Thomas P.

    2015-11-01

    Time-of-flight secondary ion mass spectrometry (ToF-SIMS) has recently been shown to be a valuable tool for cultural heritage studies, especially when used in conjunction with established analytical techniques in the field. The ability of ToF-SIMS to simultaneously image inorganic and organic species within a paint cross section at micrometer-level spatial resolution makes it a uniquely qualified analytical technique to aid in further understanding the processes of pigment and binder alteration, as well as pigment-binder interactions. In this study, ToF-SIMS was used to detect and image both molecular and elemental species related to CdS pigment and binding medium alteration on the painting Le Bonheur de vivre (1905-1906, The Barnes Foundation) by Henri Matisse. Three categories of inorganic and organic components were found throughout Le Bonheur de vivre and co-localized in cross-sectional samples using high spatial resolution ToF-SIMS analysis: (1) species relating to the preparation and photo-induced oxidation of CdS yellow pigments (2) varying amounts of long-chain fatty acids present in both the paint and primary ground layer and (3) specific amino acid fragments, possibly relating to the painting's complex restoration history. ToF-SIMS's ability to discern both organic and inorganic species via cross-sectional imaging was used to compare samples collected from Le Bonheur de vivre to artificially aged reference paints in an effort to gather mechanistic information relating to alteration processes that have been previously explored using μXANES, SR-μXRF, SEM-EDX, and SR-FTIR. The relatively high sensitivity offered by ToF-SIMS imaging coupled to the high spatial resolution allowed for the positive identification of degradation products (such as cadmium oxalate) in specific paint regions that have before been unobserved. The imaging of organic materials has provided an insight into the extent of destruction of the original binding medium, as well as

  12. Altered blood oxygen level-dependent signal variability in chronic post-traumatic stress disorder during symptom provocation

    PubMed Central

    Ke, Jun; Zhang, Li; Qi, Rongfeng; Xu, Qiang; Li, Weihui; Hou, Cailan; Zhong, Yuan; Zhang, Zhiqiang; He, Zhong; Li, Lingjiang; Lu, Guangming

    2015-01-01

    Background Recent research suggests that variability in brain signal provides important information about brain function in health and disease. However, it is unknown whether blood oxygen level-dependent (BOLD) signal variability is altered in post-traumatic stress disorder (PTSD). We aimed to identify the BOLD signal variability changes of PTSD patients during symptom provocation and compare the brain patterns of BOLD signal variability with those of brain activation. Methods Twelve PTSD patients and 14 age-matched controls, who all experienced a mining accident, underwent clinical assessment as well as fMRI scanning while viewing trauma-related and neutral pictures. BOLD signal variability and brain activation were respectively examined with standard deviation (SD) and general linear model analysis, and compared between the PTSD and control groups. Multiple regression analyses were conducted to explore the association between PTSD symptom severity and these two brain measures across all subjects as well as in the PTSD group. Results PTSD patients showed increased activation in the middle occipital gyrus compared with controls, and an inverse correlation was found between PTSD symptom severity and brain activation in the hippocampus and anterior cingulate cortex/medial prefrontal cortex. Brain variability analysis revealed increased SD in the insula, anterior cingulate cortex/medial prefrontal cortex, and vermis, and decreased SD in the parahippocapal gyrus, dorsolateral prefrontal cortex, somatosensory cortex, and striatum. Importantly, SD alterations in several regions were found in both traumatic and neutral conditions and were stratified by PTSD symptom severity. Conclusion BOLD signal variability may be a reliable and sensitive biomarker of PTSD, and combining brain activation and brain variability analysis may provide complementary insight into the neural basis of this disorder. PMID:26229476

  13. Altered gravitropic response, amyloplast sedimentation and circumnutation in the Arabidopsis shoot gravitropism 5 mutant are associated with reduced starch levels.

    PubMed

    Tanimoto, Mimi; Tremblay, Reynald; Colasanti, Joseph

    2008-05-01

    Plants have developed sophisticated gravity sensing mechanisms to interpret environmental signals that are vital for optimum plant growth. Loss of SHOOT GRAVITROPISM 5 (SGR5) gene function has been shown to affect the gravitropic response of Arabidopsis inflorescence stems. SGR5 is a member of the INDETERMINATE DOMAIN (IDD) zinc finger protein family of putative transcription factors. As part of an ongoing functional analysis of Arabidopsis IDD genes (AtIDD) we have extended the characterisation of SGR5, and show that gravity sensing amyloplasts in the shoot endodermis of sgr5 mutants sediment more slowly than wild type, suggesting a defect in gravity perception. This is correlated with lower amyloplast starch levels, which may account for the reduced gravitropic sensitivity in sgr5. Further, we find that sgr5 mutants have a severely attenuated stem circumnutation movement typified by a reduced amplitude and an decreased periodicity. adg1-1 and sex1-1 mutants, which contain no starch or increased starch, respectively, also show alterations in the amplitude and period of circumnutation. Together these results suggest that plant growth movement may depend on starch levels and/or gravity sensing. Overall, we propose that loss of SGR5 regulatory activity affects starch accumulation in Arabidopsis shoot tissues and causes decreased sensitivity to gravity and diminished circumnutational movements.

  14. Increased levels of adenosine and ecto 5'-nucleotidase (CD73) activity precede renal alterations in experimental diabetic rats.

    PubMed

    Oyarzún, C; Salinas, C; Gómez, D; Jaramillo, K; Pérez, G; Alarcón, S; Podestá, L; Flores, C; Quezada, C; San Martín, R

    The pathogenesis of diabetic nephropathy (DN) has not been clearly established, making diagnosis and patient management difficult. Recent studies using experimental diabetic models have implicated adenosine signaling with renal cells dysfunction. Therefore, the study of the biochemical mechanisms that regulate extracellular adenosine availability during DN is of emerging interest. Using streptozotocin-induced diabetic rats we demonstrated that urinary levels of adenosine were early increased. Further analyses showed an increased expression of the ecto 5'-nucleotidase (CD73), which hydrolyzes AMP to adenosine, at the renal proximal tubules and a higher enzymatic activity in tubule extracts. These changes precede the signs of diabetic kidney injury recognized by significant proteinuria, morphological alterations and the presence of the renal fibrosis markers alpha smooth muscle actin and fibronectin, collagen deposits and thickening of the glomerular basement membrane. In the proximal tubule cell line HK2 we identified TGF-β as a key modulator of CD73 activity. Importantly, the increased activity of CD73 could be screened in urinary sediments from diabetic rats. In conclusion, the increase of CD73 activity is a key component in the production of high levels of adenosine and emerges as a new tool for the early diagnosis of tubular injury in diabetic kidney disease.

  15. Projected near-future CO2 levels increase activity and alter defensive behaviours in the tropical squid Idiosepius pygmaeus

    PubMed Central

    Spady, Blake L.; Watson, Sue-Ann; Chase, Tory J.; Munday, Philip L.

    2014-01-01

    ABSTRACT Carbon dioxide (CO2) levels projected to occur in the oceans by the end of this century cause a range of behavioural effects in fish, but whether other highly active marine organisms, such as cephalopods, are similarly affected is unknown. We tested the effects of projected future CO2 levels (626 and 956 µatm) on the behaviour of male two-toned pygmy squid, Idiosepius pygmaeus. Exposure to elevated CO2 increased the number of active individuals by 19–25% and increased movement (number of line-crosses) by nearly 3 times compared to squid at present-day CO2. Squid vigilance and defensive behaviours were also altered by elevated CO2 with >80% of individuals choosing jet escape responses over defensive arm postures in response to a visual startle stimulus, compared with 50% choosing jet escape responses at control CO2. In addition, more escape responses were chosen over threat behaviours in body pattern displays at elevated CO2 and individuals were more than twice as likely to use ink as a defence strategy at 956 µatm CO2, compared with controls. Increased activity could lead to adverse effects on energy budgets as well as increasing visibility to predators. A tendency to respond to a stimulus with escape behaviours could increase survival, but may also be energetically costly and could potentially lead to more chases by predators compared with individuals that use defensive postures. These results demonstrate that projected future ocean acidification affects the behaviours of a tropical squid species. PMID:25326517

  16. Phylogenetically resolving epidemiologic linkage

    PubMed Central

    Romero-Severson, Ethan O.; Bulla, Ingo; Leitner, Thomas

    2016-01-01

    Although the use of phylogenetic trees in epidemiological investigations has become commonplace, their epidemiological interpretation has not been systematically evaluated. Here, we use an HIV-1 within-host coalescent model to probabilistically evaluate transmission histories of two epidemiologically linked hosts. Previous critique of phylogenetic reconstruction has claimed that direction of transmission is difficult to infer, and that the existence of unsampled intermediary links or common sources can never be excluded. The phylogenetic relationship between the HIV populations of epidemiologically linked hosts can be classified into six types of trees, based on cladistic relationships and whether the reconstruction is consistent with the true transmission history or not. We show that the direction of transmission and whether unsampled intermediary links or common sources existed make very different predictions about expected phylogenetic relationships: (i) Direction of transmission can often be established when paraphyly exists, (ii) intermediary links can be excluded when multiple lineages were transmitted, and (iii) when the sampled individuals’ HIV populations both are monophyletic a common source was likely the origin. Inconsistent results, suggesting the wrong transmission direction, were generally rare. In addition, the expected tree topology also depends on the number of transmitted lineages, the sample size, the time of the sample relative to transmission, and how fast the diversity increases after infection. Typically, 20 or more sequences per subject give robust results. We confirm our theoretical evaluations with analyses of real transmission histories and discuss how our findings should aid in interpreting phylogenetic results. PMID:26903617

  17. The phylogenetic likelihood library.

    PubMed

    Flouri, T; Izquierdo-Carrasco, F; Darriba, D; Aberer, A J; Nguyen, L-T; Minh, B Q; Von Haeseler, A; Stamatakis, A

    2015-03-01

    We introduce the Phylogenetic Likelihood Library (PLL), a highly optimized application programming interface for developing likelihood-based phylogenetic inference and postanalysis software. The PLL implements appropriate data structures and functions that allow users to quickly implement common, error-prone, and labor-intensive tasks, such as likelihood calculations, model parameter as well as branch length optimization, and tree space exploration. The highly optimized and parallelized implementation of the phylogenetic likelihood function and a thorough documentation provide a framework for rapid development of scalable parallel phylogenetic software. By example of two likelihood-based phylogenetic codes we show that the PLL improves the sequential performance of current software by a factor of 2-10 while requiring only 1 month of programming time for integration. We show that, when numerical scaling for preventing floating point underflow is enabled, the double precision likelihood calculations in the PLL are up to 1.9 times faster than those in BEAGLE. On an empirical DNA dataset with 2000 taxa the AVX version of PLL is 4 times faster than BEAGLE (scaling enabled and required). The PLL is available at http://www.libpll.org under the GNU General Public License (GPL).

  18. Phylogenetically resolving epidemiologic linkage

    SciTech Connect

    Romero-Severson, Ethan O.; Bulla, Ingo; Leitner, Thomas

    2016-02-22

    The use of phylogenetic trees in epidemiological investigations has become commonplace, but their epidemiological interpretation has not been systematically evaluated. Here, we use an HIV-1 within-host coalescent model to probabilistically evaluate transmission histories of two epidemiologically linked hosts. Previous critique of phylogenetic reconstruction has claimed that direction of transmission is difficult to infer, and that the existence of unsampled intermediary links or common sources can never be excluded. The phylogenetic relationship between the HIV populations of epidemiologically linked hosts can be classified into six types of trees, based on cladistic relationships and whether the reconstruction is consistent with the true transmission history or not. We show that the direction of transmission and whether unsampled intermediary links or common sources existed make very different predictions about expected phylogenetic relationships: (i) Direction of transmission can often be established when paraphyly exists, (ii) intermediary links can be excluded when multiple lineages were transmitted, and (iii) when the sampled individuals’ HIV populations both are monophyletic a common source was likely the origin. Inconsistent results, suggesting the wrong transmission direction, were generally rare. In addition, the expected tree topology also depends on the number of transmitted lineages, the sample size, the time of the sample relative to transmission, and how fast the diversity increases after infection. Typically, 20 or more sequences per subject give robust results. Moreover, we confirm our theoretical evaluations with analyses of real transmission histories and discuss how our findings should aid in interpreting phylogenetic results.

  19. Phylogenetically resolving epidemiologic linkage

    DOE PAGES

    Romero-Severson, Ethan O.; Bulla, Ingo; Leitner, Thomas

    2016-02-22

    The use of phylogenetic trees in epidemiological investigations has become commonplace, but their epidemiological interpretation has not been systematically evaluated. Here, we use an HIV-1 within-host coalescent model to probabilistically evaluate transmission histories of two epidemiologically linked hosts. Previous critique of phylogenetic reconstruction has claimed that direction of transmission is difficult to infer, and that the existence of unsampled intermediary links or common sources can never be excluded. The phylogenetic relationship between the HIV populations of epidemiologically linked hosts can be classified into six types of trees, based on cladistic relationships and whether the reconstruction is consistent with the truemore » transmission history or not. We show that the direction of transmission and whether unsampled intermediary links or common sources existed make very different predictions about expected phylogenetic relationships: (i) Direction of transmission can often be established when paraphyly exists, (ii) intermediary links can be excluded when multiple lineages were transmitted, and (iii) when the sampled individuals’ HIV populations both are monophyletic a common source was likely the origin. Inconsistent results, suggesting the wrong transmission direction, were generally rare. In addition, the expected tree topology also depends on the number of transmitted lineages, the sample size, the time of the sample relative to transmission, and how fast the diversity increases after infection. Typically, 20 or more sequences per subject give robust results. Moreover, we confirm our theoretical evaluations with analyses of real transmission histories and discuss how our findings should aid in interpreting phylogenetic results.« less

  20. Alteration of Hemostatic Parameters in Patients with Different Levels of Subclinical Hypothyroidism and the Effect of L-thyroxine Treatment.

    PubMed

    Gao, Fang; Wang, Guangya; Xu, Jinxiu

    2017-01-01

    Subclinical hypothyroidism (SH) is associated with hypercoagulability and hypofibrinolysis. The objective of this study was to assess the effect of L-thyroxine (L-T4) treatment and to evaluate changes in the hemostatic abnormalities of patients with varying severities of SH. We measured tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), D-dimer (DDI), fibrinogen (FIB), platelet counts (PLT), mean platelet volume (MPV), platelet distribution width (PDW), activated partial thromboplastin time (APTT), and prothrombin time (PT) in 149 female subjects. The prospective study included 54 patients in the control group, 53 patients with 4.2 μIU/mLlevels. There were significant differences in the triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), and serum uric acid (UA) levels, and in the MPV, PDW, APTT, FIB, PAI-1, t-PA, and DDI (P<0.05) measurements among three groups. These data were further tested using the least significant difference method for multiple comparisons. Patients in the severe SH group showed higher FIB, PAI-1 and t-PA levels, lower DDI levels and shorter APTT compared with the control group, whereas the hemostatic parameters in the mild SH patients were not different compared with those of the control group. After 6 months of L-T4 treatment, a significant decrease in FIB, PAI-1 and t-PA levels and an increase in APTT and DDI were observed in the severe SH group. In conclusion, SH patients displayed a distinct pattern of alteration of hemostatic parameters that was dependent on the severity of the disease. Patients with TSH levels ≥10 μIU/mL displayed hypercoagulability, which was reversed by 6 months of L-T4 treatment.

  1. Biochemical and structural characterizations of two Dictyostelium cellobiohydrolases from the amoebozoa kingdom reveal a high level of conservation between distant phylogenetic trees of life

    SciTech Connect

    Hobdey, Sarah E.; Knott, Brandon C.; Momeni, Majid Haddad; Taylor, II, Larry E.; Borisova, Anna S.; Podkaminer, Kara K.; VanderWall, Todd A.; Himmel, Michael E.; Decker, Stephen R.; Beckham, Gregg T.; Stahlberg, Jerry

    2016-04-01

    Glycoside hydrolase family 7 (GH7) cellobiohydrolases (CBHs) are enzymes often employed in plant cell wall degradation across eukaryotic kingdoms of life, as they provide significant hydrolytic potential in cellulose turnover. To date, many fungal GH7 CBHs have been examined, yet many questions regarding structure-activity relationships in these important natural and commercial enzymes remain. Here, we present the crystal structures and a biochemical analysis of two GH7 CBHs from social amoeba: Dictyostelium discoideum Cel7A (DdiCel7A) and Dictyostelium purpureum Cel7A (DpuCel7A). DdiCel7A and DpuCel7A natively consist of a catalytic domain and do not exhibit a carbohydrate-binding module (CBM). The structures of DdiCel7A and DpuCel7A, resolved to 2.1 Å and 2.7 Å, respectively, are homologous to those of other GH7 CBHs with an enclosed active-site tunnel. Two primary differences between the Dictyostelium CBHs and the archetypal model GH7 CBH, Trichoderma reesei Cel7A (TreCel7A), occur near the hydrolytic active site and the product-binding sites. To compare the activities of these enzymes with the activity of TreCel7A, the family 1 TreCel7A CBM and linker were added to the C terminus of each of the Dictyostelium enzymes, creating DdiCel7ACBM and DpuCel7ACBM, which were recombinantly expressed in T. reesei. DdiCel7ACBM and DpuCel7ACBM hydrolyzed Avicel, pretreated corn stover, and phosphoric acid-swollen cellulose as efficiently as TreCel7A when hydrolysis was compared at their temperature optima. The Ki of cellobiose was significantly higher for DdiCel7ACBM and DpuCel7ACBM than for TreCel7A: 205, 130, and 29 μM, respectively. Finally, taken together, the present study highlights the remarkable degree of conservation of the activity of these key natural and industrial enzymes across quite distant phylogenetic trees of life.

  2. Biochemical and structural characterizations of two Dictyostelium cellobiohydrolases from the amoebozoa kingdom reveal a high level of conservation between distant phylogenetic trees of life

    DOE PAGES

    Hobdey, Sarah E.; Knott, Brandon C.; Momeni, Majid Haddad; ...

    2016-04-01

    Glycoside hydrolase family 7 (GH7) cellobiohydrolases (CBHs) are enzymes often employed in plant cell wall degradation across eukaryotic kingdoms of life, as they provide significant hydrolytic potential in cellulose turnover. To date, many fungal GH7 CBHs have been examined, yet many questions regarding structure-activity relationships in these important natural and commercial enzymes remain. Here, we present the crystal structures and a biochemical analysis of two GH7 CBHs from social amoeba: Dictyostelium discoideum Cel7A (DdiCel7A) and Dictyostelium purpureum Cel7A (DpuCel7A). DdiCel7A and DpuCel7A natively consist of a catalytic domain and do not exhibit a carbohydrate-binding module (CBM). The structures of DdiCel7Amore » and DpuCel7A, resolved to 2.1 Å and 2.7 Å, respectively, are homologous to those of other GH7 CBHs with an enclosed active-site tunnel. Two primary differences between the Dictyostelium CBHs and the archetypal model GH7 CBH, Trichoderma reesei Cel7A (TreCel7A), occur near the hydrolytic active site and the product-binding sites. To compare the activities of these enzymes with the activity of TreCel7A, the family 1 TreCel7A CBM and linker were added to the C terminus of each of the Dictyostelium enzymes, creating DdiCel7ACBM and DpuCel7ACBM, which were recombinantly expressed in T. reesei. DdiCel7ACBM and DpuCel7ACBM hydrolyzed Avicel, pretreated corn stover, and phosphoric acid-swollen cellulose as efficiently as TreCel7A when hydrolysis was compared at their temperature optima. The Ki of cellobiose was significantly higher for DdiCel7ACBM and DpuCel7ACBM than for TreCel7A: 205, 130, and 29 μM, respectively. Finally, taken together, the present study highlights the remarkable degree of conservation of the activity of these key natural and industrial enzymes across quite distant phylogenetic trees of life.« less

  3. Rice Stripe Virus Infection Alters mRNA Levels of Sphingolipid-Metabolizing Enzymes and Sphingolipids Content in Laodelphax striatellus

    PubMed Central

    Li, Fei-Qiang; Bai, Yue-Liang; Shi, Xiao-Xiao; Zhu, Mu-Fei; Zhang, Min-Jing; Mao, Cun-Gui; Zhu, Zeng-Rong

    2017-01-01

    Sphingolipids and their metabolites have been implicated in viral infection and replication in mammal cells but how their metabolizing enzymes in the host are regulated by viruses remains largely unknown. Here we report the identification of 12 sphingolipid genes and their regulation by Rice stripe virus in the small brown planthopper (Laodelphax striatellus Fallén), a serious pest of rice throughout eastern Asia. According to protein sequence similarity, we identified 12 sphingolipid enzyme genes in L. striatellus. By comparing their mRNA levels in viruliferous versus nonviruliferous L. striatellus at different life stages by qPCR, we found that RSV infection upregulated six genes (LsCGT1, LsNAGA1, LsSGPP, LsSMPD4, LsSMS, and LsSPT) in most stages of L. striatellus. Especially, four genes (LsCGT1, LsSMPD2, LsNAGA1, and LsSMS) and another three genes (LsNAGA1, LsSGPP, and LsSMS) were significantly upregulated in viruliferous third-instar and fourth-instar nymphs, respectively. HPLC-MS/MS results showed that RSV infection increased the levels of various ceramides, such as Cer18:0, Cer20:0, and Cer22:0 species, in third and fourth instar L. striatellus nymphs. Together, these results demonstrate that RSV infection alters the transcript levels of various sphingolipid enzymes and the contents of sphingolipids in L. striatellus, indicating that sphingolipids may be important for RSV infection or replication in L. striatellus. PMID:28130458

  4. Adrenergic drugs modify the level of noradrenaline in the insular cortex and alter extinction of conditioned taste aversion in rats.

    PubMed

    Fresquet, Nadine; Angst, Marie-Josée; Schleef, Carmen; Gobaille, Serge; Sandner, Guy

    2007-03-12

    We compared the effect of conditioned taste aversion in rats by measuring the amount of sucrose that they drunk after conditioning, which differed according to whether rats had drunk the sucrose freely (SD: self drinking) during the conditioning session, or had been forced to drink it (IO: intra-oral administration through a chronically implanted cannula). The SD procedure delayed the extinction of conditioned taste aversion. Enhanced arousal, alertness, awareness or attention in the SD condition may have strengthened the memory of the taste. Brain noradrenergic networks are involved in such processes. We administered two noradrenergic drugs that produce opposite effects on noradrenaline release in the brain, methoxy-idazoxan, RX821002 (1mg/kg, i.p.), and guanfacine (0.12mg/kg, i.p.). We evaluated their effect (i) on the level of noradrenaline in the gustatory cortex using microdialysis, (ii) on glycaemia that is an essential factor of taste learning and (iii) on the comparative SD versus IO conditioned taste aversion protocol mentioned above. Injecting RX821001 increased the level of noradrenaline in the gustatory cortex up to two-fold of the baseline. This effect lasted 1h. The same dose of RX821002 did not elicit any alteration of glycaemia. It enhanced extinction of conditioned taste aversion in the SD group of rats. Injecting 0.12mg/kg of guanfacine produced the opposite effect. The noradrenaline level of the gustatory cortex decreased, but only down to 20% of the baseline. This decrease lasted 2h. Guanfacine increased glycaemia. Extinction of conditioned taste aversion was only marginally decreased by guanfacine in the SD group of rats. These results fit with Aston-Jones' point of view that the role of the noradrenergic coeruleo-cortical system may be to enhance arousal, alertness, awareness or attention to an event by a transient increase of cortical noradrenaline.

  5. Genetic alterations of IL-1 receptor antagonist in mice affect plasma cholesterol level and foam cell lesion size.

    PubMed

    Devlin, Cecilia M; Kuriakose, George; Hirsch, Emmet; Tabas, Ira

    2002-04-30

    Inflammatory cytokines have been linked to atherosclerosis by using cell culture models and acute inflammation in animals. The goal of this study was to examine lipoprotein levels and early atherosclerosis in chronic animal models of altered IL-1 physiology by using mice with deficient or excess IL-1 receptor antagonist (IL-1ra). IL-1ra knockout C57BL/6J mice fed a cholesterol/cholate diet for 3 mo had a 3-fold decrease in non-high-density lipoprotein cholesterol and a trend toward increased foam-cell lesion area compared to wild-type littermate controls. IL-1ra transgenic/low-density lipoprotein receptor (LDLR) knockout mice fed a cholesterol-saturated fat diet for 10 wk showed a 40% increase in non-high-density lipoprotein cholesterol, consistent with the IL-1ra knockout data, although there was no change in lesion size. When these IL1-ra overexpressing transgenic mice on the LDLR knockout background were fed a high-cholesterol/high-fat diet containing cholate, however, a statistically significant 40% decrease in lesion area was observed compared to LDLR knockout mice lacking the transgene. By immunohistochemistry, IL-1ra was present in C57BL/6J and LDLR knockout aortae, absent in IL-1ra knockout aortae, and present at high levels in LDLR knockout/IL-1ra transgene aortae. In summary, IL-1ra tended to increase plasma lipoprotein levels and, when fed a cholate-containing diet, decrease foam-cell lesion size. These data demonstrate that in selected models of murine atherosclerosis, chronic IL-1ra depletion or overexpression has potentially important effects on lipoprotein metabolism and foam-cell lesion development.

  6. Neonatal pain-related stress and NFKBIA genotype are associated with altered cortisol levels in preterm boys at school age.

    PubMed

    Grunau, Ruth E; Cepeda, Ivan L; Chau, Cecil M Y; Brummelte, Susanne; Weinberg, Joanne; Lavoie, Pascal M; Ladd, Mihoko; Hirschfeld, Aaron F; Russell, Evan; Koren, Gideon; Van Uum, Stan; Brant, Rollin; Turvey, Stuart E

    2013-01-01

    Neonatal pain-related stress is associated with elevated salivary cortisol levels to age 18 months in children born very preterm, compared to full-term, suggesting early programming effects. Importantly, interactions between immune/inflammatory and neuroendocrine systems may underlie programming effects. We examined whether cortisol changes persist to school age, and if common genetic variants in the promoter region of the NFKBIA gene involved in regulation of immune and inflammatory responses, modify the association between early experience and later life stress as indexed by hair cortisol levels, which provide an integrated index of endogenous HPA axis activity. Cortisol was assayed in hair samples from 128 children (83 born preterm ≤ 32 weeks gestation and 45 born full-term) without major sensory, motor or cognitive impairments at age 7 years. We found that hair cortisol levels were lower in preterm compared to term-born children. Downregulation of the HPA axis in preterm children without major impairment, seen years after neonatal stress terminated, suggests persistent alteration of stress system programming. Importantly, the etiology was gender-specific such that in preterm boys but not girls, specifically those with the minor allele for NFKBIA rs2233409, lower hair cortisol was associated with greater neonatal pain (number of skin-breaking procedures from birth to term), independent of medical confounders. Moreover, the minor allele (CT or TT) of NFKBIA rs2233409 was associated with higher secretion of inflammatory cytokines, supporting the hypothesis that neonatal pain-related stress may act as a proinflammatory stimulus that induces long-term immune cell activation. These findings are the first evidence that a long-term association between early pain-related stress and cortisol may be mediated by a genetic variants that regulate the activity of NF-κB, suggesting possible involvement of stress/inflammatory mechanisms in HPA programming in boys born very

  7. Estrogenic Exposure Alters the Spermatogonial Stem Cells in the Developing Testis, Permanently Reducing Crossover Levels in the Adult

    PubMed Central

    Vrooman, Lisa A.; Oatley, Jon M.; Griswold, Jodi E.; Hassold, Terry J.; Hunt, Patricia A.

    2015-01-01

    Bisphenol A (BPA) and other endocrine disrupting chemicals have been reported to induce negative effects on a wide range of physiological processes, including reproduction. In the female, BPA exposure increases meiotic errors, resulting in the production of chromosomally abnormal eggs. Although numerous studies have reported that estrogenic exposures negatively impact spermatogenesis, a direct link between exposures and meiotic errors in males has not been evaluated. To test the effect of estrogenic chemicals on meiotic chromosome dynamics, we exposed male mice to either BPA or to the strong synthetic estrogen, ethinyl estradiol during neonatal development when the first cells initiate meiosis. Although chromosome pairing and synapsis were unperturbed, exposed outbred CD-1 and inbred C3H/HeJ males had significantly reduced levels of crossovers, or meiotic recombination (as defined by the number of MLH1 foci in pachytene cells) by comparison with placebo. Unexpectedly, the effect was not limited to cells exposed at the time of meiotic entry but was evident in all subsequent waves of meiosis. To determine if the meiotic effects induced by estrogen result from changes to the soma or germline of the testis, we transplanted spermatogonial stem cells from exposed males into the testes of unexposed males. Reduced recombination was evident in meiocytes derived from colonies of transplanted cells. Taken together, our results suggest that brief exogenous estrogenic exposure causes subtle changes to the stem cell pool that result in permanent alterations in spermatogenesis (i.e., reduced recombination in descendent meiocytes) in the adult male. PMID:25615633

  8. Reproductive experience reduces circulating 17beta-estradiol and prolactin levels during proestrus and alters estrogen sensitivity in female rats.

    PubMed

    Bridges, Robert S; Byrnes, Elizabeth M

    2006-05-01

    The reproductive experiences of pregnancy, parturition, and lactation affect a range of neural and endocrine processes after the end of lactation. In women, previous parity results in reduced circulating prolactin (PRL) and androgen levels years after giving birth. Reductions in PRL secretion also occur in reproductively experienced, female rats. In the present study we examined the status and regulation of estradiol (E(2)) and PRL during the reproductive cycle after reproductive experience. These hormones regulate one another and have been implicated in a number of disease and aging processes. Using a rat model, the patterns of E(2) and PRL secretion, pituitary PRL content, and estrogen receptor alpha expression were characterized from 1200-1800 h on proestrus in age-matched, primiparous and nulliparous animals. The possible effect of parity on estrogen sensitivity was then examined by challenging nonlactating, ovariectomized, age-matched, multiparous and nulliparous rats with estradiol benzoate (EB; 0, 1, 5, 25, and 125 microg/kg) and measuring PRL responses 24 and 48 h later. Previous parity resulted in modest, yet significant, reductions in E(2) and PRL levels on proestrus, a limited increase in pituitary estrogen receptor alpha expression, and a significant shift in estrogen sensitivity, as measured by EB-induced PRL secretion. Nulliparous animals were more sensitive than multiparous rats to the two lower doses of EB, whereas multiparous animals were more responsive to the highest EB dose. These unique parity-induced alterations in the female's endocrine state that persist beyond lactation may impact a multitude of estrogen-mediated processes over the female's adult life span.

  9. Effects of a low-level semiconductor gallium arsenide laser on local pathological alterations induced by Bothrops moojeni snake venom.

    PubMed

    Aranha de Sousa, Elziliam; Bittencourt, José Adolfo Homobono Machado; Seabra de Oliveira, Nayana Keyla; Correia Henriques, Shayanne Vanessa; dos Santos Picanço, Leide Caroline; Lobato, Camila Pena; Ribeiro, José Renato; Pereira, Washington Luiz Assunção; Carvalho, José Carlos Tavares; da Silva, Jocivânia Oliveira

    2013-10-01

    Antivenom therapy has been ineffective in neutralizing the tissue damage caused by snakebites. Among therapeutic strategies to minimize effects after envenoming, it was hypothesized that a low level laser would reduce complications and reduce the severity of local snake venom effects. In the current study, the effect of a low-level semiconductor gallium arsenide (GaAs) laser on the local pathological alterations induced by B. moojeni snake venom was investigated. The experimental groups consisted of five male mice, each administered either B. moojeni venom (VB), B. moojeni venom + antivenom (VAV), B. moojeni venom + laser (VL), B. moojeni venom + antivenom + laser (VAVL), or sterile saline solution (SSS) alone. Paw oedema was induced by intradermal administration of 0.05 mg kg(-1) of B. moojeni venom and was expressed in mm of directly induced oedema. Mice received by subcutaneous route 0.20 mg kg(-1) of venom for evaluating nociceptive activity and the time (in seconds) spent in licking and biting the injected paw was taken as an indicator of pain response. Inflammatory infiltration was determined by counting the number of leukocytes present in the gastrocnemius muscle after venom injection (0.10 mg kg(-1)). For histological examination of myonecrosis, venom (0.10 mg kg(-1)) was administered intramuscularly. The site of venom injection was irradiated by the GaAs laser and some animals received antivenom intraperitoneally. The results indicated that GaAs laser irradiation can help in reducing some local effects produced by the B. moojeni venom in mice, stimulating phagocytosis, proliferation of myoblasts and the regeneration of muscle fibers.

  10. Phylogenetic character mapping of proteomic diversity shows high correlation with subspecific phylogenetic diversity in Trypanosoma cruzi

    PubMed Central

    Telleria, Jenny; Biron, David G.; Brizard, Jean-Paul; Demettre, Edith; Séveno, Martial; Barnabé, Christian; Ayala, Francisco J.; Tibayrenc, Michel

    2010-01-01

    We performed a phylogenetic character mapping on 26 stocks of Trypanosoma cruzi, the parasite responsible for Chagas disease, and 2 stocks of the sister taxon T. cruzi marinkellei to test for possible associations between T. cruzi–subspecific phylogenetic diversity and levels of protein expression, as examined by proteomic analysis and mass spectrometry. We observed a high level of correlation (P < 10−4) between genetic distance, as established by multilocus enzyme electrophoresis, and proteomic dissimilarities estimated by proteomic Euclidian distances. Several proteins were found to be specifically associated to T. cruzi phylogenetic subdivisions (discrete typing units). This study explores the previously uncharacterized links between infraspecific phylogenetic diversity and gene expression in a human pathogen. It opens the way to searching for new vaccine and drug targets and for identification of specific biomarkers at the subspecific level of pathogens. PMID:21059959

  11. Molecular phylogenetics before sequences

    PubMed Central

    Ragan, Mark A; Bernard, Guillaume; Chan, Cheong Xin

    2014-01-01

    From 1971 to 1985, Carl Woese and colleagues generated oligonucleotide catalogs of 16S/18S rRNAs from more than 400 organisms. Using these incomplete and imperfect data, Carl and his colleagues developed unprecedented insights into the structure, function, and evolution of the large RNA components of the translational apparatus. They recognized a third domain of life, revealed the phylogenetic backbone of bacteria (and its limitations), delineated taxa, and explored the tempo and mode of microbial evolution. For these discoveries to have stood the test of time, oligonucleotide catalogs must carry significant phylogenetic signal; they thus bear re-examination in view of the current interest in alignment-free phylogenetics based on k-mers. Here we consider the aims, successes, and limitations of this early phase of molecular phylogenetics. We computationally generate oligonucleotide sets (e-catalogs) from 16S/18S rRNA sequences, calculate pairwise distances between them based on D2 statistics, compute distance trees, and compare their performance against alignment-based and k-mer trees. Although the catalogs themselves were superseded by full-length sequences, this stage in the development of computational molecular biology remains instructive for us today. PMID:24572375

  12. Change in Auxin and Cytokinin Levels Coincides with Altered Expression of Branching Genes during Axillary Bud Outgrowth in Chrysanthemum

    PubMed Central

    Dierck, Robrecht; De Keyser, Ellen; De Riek, Jan; Dhooghe, Emmy; Van Huylenbroeck, Johan; Prinsen, Els; Van Der Straeten, Dominique

    2016-01-01

    In the production and breeding of Chrysanthemum sp., shoot branching is an important quality aspect as the outgrowth of axillary buds determines the final plant shape. Bud outgrowth is mainly controlled by apical dominance and the crosstalk between the plant hormones auxin, cytokinin and strigolactone. In this work the hormonal and genetic regulation of axillary bud outgrowth was studied in two differently branching cut flower Chrysanthemum morifolium (Ramat) genotypes. C17 is a split-type which forms an inflorescence meristem after a certain vegetative period, while C18 remains vegetative under long day conditions. Plant growth of both genotypes was monitored during 5 subsequent weeks starting one week before flower initiation occurred in C17. Axillary bud outgrowth was measured weekly and samples of shoot apex, stem and axillary buds were taken during the first two weeks. We combined auxin and cytokinin measurements by UPLC-MS/MS with RT-qPCR expression analysis of genes involved in shoot branching regulation pathways in chrysanthemum. These included bud development genes (CmBRC1, CmDRM1, CmSTM, CmLsL), auxin pathway genes (CmPIN1, CmTIR3, CmTIR1, CmAXR1, CmAXR6, CmAXR2, CmIAA16, CmIAA12), cytokinin pathway genes (CmIPT3, CmHK3, CmRR1) and strigolactone genes (CmMAX1 and CmMAX2). Genotype C17 showed a release from apical dominance after floral transition coinciding with decreased auxin and increased cytokinin levels in the subapical axillary buds. As opposed to C17, C18 maintained strong apical dominance with vegetative growth throughout the experiment. Here high auxin levels and decreasing cytokinin levels in axillary buds and stem were measured. A differential expression of several branching genes accompanied the different hormonal change and bud outgrowth in C17 and C18. This was clear for the strigolactone biosynthesis gene CmMAX1, the transcription factor CmBRC1 and the dormancy associated gene CmDRM1, that all showed a decreased expression in C17 at floral

  13. The role of natural glasses as analogues in projecting the long-term alteration of high-level nuclear waste glasses: Part 1

    SciTech Connect

    Mazer, J.J.

    1993-12-31

    The common observation of glasses persisting in natural environments for long periods of time (up to tens of millions of years) provides compelling evidence that these materials can be kinetically stable in a variety of subsurface environments. This paper reviews how natural and historical synthesized glasses can be employed as natural analogues for understanding and projecting the long-term alteration of high-level nuclear waste glasses. The corrosion of basaltic glass results in many of the same alteration features found in laboratory testing of the corrosion of high-level radioactive waste glasses. Evidence has also been found indicating similarities in the rate controlling processes, such as the effects of silica concentration on corrosion in groundwater and in laboratory leachates. Naturally altered rhyolitic glasses and tektites provide additional evidence that can be used to constrain estimates of long-term waste glass alteration. When reacted under conditions where water is plentiful, the corrosion for these glasses is dominated by network hydrolysis, while the corrosion is dominated by molecular water diffusion and secondary mineral formation under conditions where water contact is intermittent or where water is relatively scarce. Synthesized glasses that have been naturally altered result in alkali-depleted alteration features that are similar to those found for natural glasses and for nuclear waste glasses. The characteristics of these alteration features appear to be dependent on the alteration conditions which affect the dominant reaction processes during weathering. In all cases, care must be taken to ensure that the information being provided by natural analogues is related to nuclear waste glass corrosion in a clear and meaningful way.

  14. Mono-hydroxy methoxychlor alters levels of key sex steroids and steroidogenic enzymes in cultured mouse antral follicles

    SciTech Connect

    Craig, Zelieann R.; Leslie, Traci C.; Hatfield, Kimberly P.; Gupta, Rupesh K.; Flaws, Jodi A.

    2010-12-01

    Methoxychlor (MXC) is an organochlorine pesticide that reduces fertility in female rodents by decreasing antral follicle numbers and increasing follicular death. MXC is metabolized in the body to mono-hydroxy MXC (mono-OH). Little is known about the effects of mono-OH on the ovary. Thus, this work tested the hypothesis that mono-OH exposure decreases production of 17{beta}-estradiol (E{sub 2}) by cultured mouse antral follicles. Antral follicles were isolated from CD-1 mice (age 35-39 days) and exposed to dimethylsulfoxide (DMSO), or mono-OH (0.1-10 {mu}g/mL) for 96 h. Media and follicles were collected for analysis of sex steroid levels and mRNA expression, respectively. Mono-OH treatment (10 {mu}g/mL) decreased E{sub 2} (DMSO: 3009.72 {+-} 744.99 ng/mL; mono-OH 0.1 {mu}g/mL: 1679.66 {+-} 461.99 ng/mL; 1 {mu}g/mL: 1752.72 {+-} 532.41 ng/mL; 10 {mu}g/mL: 45.89 {+-} 33.83 ng/mL), testosterone (DMSO: 15.43 {+-} 2.86 ng/mL; mono-OH 0.1 {mu}g/mL: 17.17 {+-} 4.71 ng/mL; 1 {mu}g/mL: 13.64 {+-} 3.53 ng/mL; 10 {mu}g/mL: 1.29 {+-} 0.23 ng/mL), androstenedione (DMSO: 1.92 {+-} 0.34 ng/mL; mono-OH 0.1 {mu}g/mL: 1.49 {+-} 0.43 ng/mL; 1 {mu}g/mL: 0.64 {+-} 0.31 ng/mL; 10 {mu}g/mL: 0.12 {+-} 0.06 ng/mL) and progesterone (DMSO: 24.11 {+-} 4.21 ng/mL; mono-OH 0.1 {mu}g/mL: 26.77 {+-} 4.41 ng/mL; 1 {mu}g/mL: 20.90 {+-} 3.75 ng/mL; 10 {mu}g/mL: 9.44 {+-} 2.97 ng/mL) levels. Mono-OH did not alter expression of Star, Hsd3b1, Hsd17b1 and Cyp1b1, but it did reduce levels of Cyp11a1, Cyp17a1 and Cyp19a1 mRNA. Collectively, these data suggest that mono-OH significantly decreases levels of key sex steroid hormones and the expression of enzymes required for steroidogenesis.

  15. GidB mutation as a phylogenetic marker for Q1 cluster Mycobacterium tuberculosis isolates and intermediate-level streptomycin resistance determinant in Lisbon, Portugal.

    PubMed

    Perdigão, J; Macedo, R; Machado, D; Silva, C; Jordão, L; Couto, I; Viveiros, M; Portugal, I

    2014-05-01

    Development of streptomycin resistance in Mycobacterium tuberculosis is usually associated with mutations in rpsL and rrs genes, although up to 50% of clinical streptomycin-resistant isolates may present no mutation in either of these genes. In the present report we investigate the role of gidB gene mutations in streptomycin resistance. We have analyzed 52 streptomycin-resistant and 30 streptomycin-susceptible Mycobacterium tuberculosis clinical isolates by sequencing and endonuclease analysis of the gidB and rpsL genes. All clinical isolates were genotyped by 12-loci MIRU-VNTR. The gidB gene of 18 streptomycin-resistant isolates was sequenced and four missense mutations were found: F12L (1/18), L16R (18/18), A80P (4/18) and S100F (18/18). The remaining isolates were screened by endonuclease analysis for mutations A80P in the gidB gene and K43R in the rpsL gene. Overall, mutation A80P in the gidB gene was found in eight streptomycin-resistant isolates and 11 streptomycin-susceptible multidrug-resistant isolates. Also noteworthy, is the fact that gidB mutations were only present in isolates without rpsL and rrs mutations, all from genetic cluster Q1. Streptomycin quantitative drug susceptibility testing showed that isolates carrying the gidB A80P mutation were streptomycin intermediate-level resistant and that standard drug susceptibility testing yielded inconsistent results, probably due to borderline resistance. We conclude that gidB mutations may explain the high number of streptomycin-resistant strains with no mutation in rpsL or rrs. These mutations might occasionally confer low-level streptomycin resistance that will go undetected in standard susceptibility testing.

  16. Refuting phylogenetic relationships

    PubMed Central

    Bucknam, James; Boucher, Yan; Bapteste, Eric

    2006-01-01

    Background Phylogenetic methods are philosophically grounded, and so can be philosophically biased in ways that limit explanatory power. This constitutes an important methodologic dimension not often taken into account. Here we address this dimension in the context of concatenation approaches to phylogeny. Results We discuss some of the limits of a methodology restricted to verificationism, the philosophy on which gene concatenation practices generally rely. As an alternative, we describe a software which identifies and focuses on impossible or refuted relationships, through a simple analysis of bootstrap bipartitions, followed by multivariate statistical analyses. We show how refuting phylogenetic relationships could in principle facilitate systematics. We also apply our method to the study of two complex phylogenies: the phylogeny of the archaea and the phylogeny of the core of genes shared by all life forms. While many groups are rejected, our results left open a possible proximity of N. equitans and the Methanopyrales, of the Archaea and the Cyanobacteria, and as well the possible grouping of the Methanobacteriales/Methanoccocales and Thermosplasmatales, of the Spirochaetes and the Actinobacteria and of the Proteobacteria and firmicutes. Conclusion It is sometimes easier (and preferable) to decide which species do not group together than which ones do. When possible topologies are limited, identifying local relationships that are rejected may be a useful alternative to classical concatenation approaches aiming to find a globally resolved tree on the basis of weak phylogenetic markers. Reviewers This article was reviewed by Mark Ragan, Eugene V Koonin and J Peter Gogarten. PMID:16956399

  17. Prioritizing Populations for Conservation Using Phylogenetic Networks

    PubMed Central

    Volkmann, Logan; Martyn, Iain; Moulton, Vincent; Spillner, Andreas; Mooers, Arne O.

    2014-01-01

    In the face of inevitable future losses to biodiversity, ranking species by conservation priority seems more than prudent. Setting conservation priorities within species (i.e., at the population level) may be critical as species ranges become fragmented and connectivity declines. However, existing approaches to prioritization (e.g., scoring organisms by their expected genetic contribution) are based on phylogenetic trees, which may be poor representations of differentiation below the species level. In this paper we extend evolutionary isolation indices used in conservation planning from phylogenetic trees to phylogenetic networks. Such networks better represent population differentiation, and our extension allows populations to be ranked in order of their expected contribution to the set. We illustrate the approach using data from two imperiled species: the spotted owl Strix occidentalis in North America and the mountain pygmy-possum Burramys parvus in Australia. Using previously published mitochondrial and microsatellite data, we construct phylogenetic networks and score each population by its relative genetic distinctiveness. In both cases, our phylogenetic networks capture the geographic structure of each species: geographically peripheral populations harbor less-redundant genetic information, increasing their conservation rankings. We note that our approach can be used with all conservation-relevant distances (e.g., those based on whole-genome, ecological, or adaptive variation) and suggest it be added to the assortment of tools available to wildlife managers for allocating effort among threatened populations. PMID:24586451

  18. Disentangling the responses of boreal stream assemblages to low stressor levels of diffuse pollution and altered channel morphology.

    PubMed

    Turunen, Jarno; Muotka, Timo; Vuori, Kari-Matti; Karjalainen, Satu Maaria; Rääpysjärvi, Jaana; Sutela, Tapio; Aroviita, Jukka

    2016-02-15

    Non-point diffuse pollution from land use and alteration of hydromorphology are among the most detrimental stressors to stream ecosystems. We explored the independent and interactive effects of morphological channel alteration (channelization for water transport of timber) and diffuse pollution on species richness and community structure of four organism groups in boreal streams: diatoms, macrophytes, macroinvertebrates, and fish. Furthermore, the effect of these stressors on stream condition was evaluated by Ecological Quality Ratios (EQR) from the national Water Framework Directive (WFD) assessment system. We grouped 91 study sites into four groups that were impacted by either diffuse pollution or hydromorphological alteration, by both stressors, or by neither one. Macroinvertebrate richness was reduced by diffuse pollution, whereas other biological groups were unaltered. Hydromorphological modification had no effect on taxon richness of any of the assemblages. Community structure of all groups was significantly affected by diffuse pollution but not by hydromorphology. Similarly, EQRs indicated negative response by diatoms, macroinvertebrates and fish to diffuse pollution, but not to hydromorphological alteration. Agricultural diffuse pollution thus affected species identities and abundances rather than taxonomic richness. Our results suggest that channelization of boreal streams for timber transport has not altered hydromorphological conditions sufficiently to have a strong impact on stream biota, whereas even moderate nutrient enrichment may be ecologically harmful. Controlling diffuse pollution and associated land use stressors should be prioritized over restoration of in-stream habitat structure to improve the ecological condition of boreal streams.

  19. Alu elements and hominid phylogenetics.

    PubMed

    Salem, Abdel-Halim; Ray, David A; Xing, Jinchuan; Callinan, Pauline A; Myers, Jeremy S; Hedges, Dale J; Garber, Randall K; Witherspoon, David J; Jorde, Lynn B; Batzer, Mark A

    2003-10-28

    Alu elements have inserted in primate genomes throughout the evolution of the order. One particular Alu lineage (Ye) began amplifying relatively early in hominid evolution and continued propagating at a low level as many of its members are found in a variety of hominid genomes. This study represents the first conclusive application of short interspersed elements, which are considered nearly homoplasy-free, to elucidate the phylogeny of hominids. Phylogenetic analysis of Alu Ye5 elements and elements from several other subfamilies reveals high levels of support for monophyly of Hominidae, tribe Hominini and subtribe Hominina. Here we present the strongest evidence reported to date for a sister relationship between humans and chimpanzees while clearly distinguishing the chimpanzee and human lineages.

  20. Brain transcription factor gene expression, neurotransmitter levels, and novelty response behaviors: alterations during rat amphetamine withdrawal and following chronic injection stress.

    PubMed

    Persico, A M; Schindler, C W; Zaczek, R; Brannock, M T; Uhl, G R

    1995-03-01

    Transcription factors are known to act as gene expression regulators, possibly linking extracellular stimuli to long-term modifications at the neuronal level. Such modifications may potentially underlie chronic psychostimulant- and stress-induced behavioral alterations. This study illustrates how a 2 week, twice daily 7.5 mg/kg d-amphetamine or saline regimen alters rat brain regional expression of transcription factor genes, including c-fos, fos-B, jun-B, c-jun, and zif 268, and seeks potential correlations between those changes and alterations in neurotransmitter levels and behavioral novelty responses. Amphetamine withdrawal-induced decreases in transcription factor mRNA levels, assessed using Northern blot analysis, appear most prominent in prefrontal cortex, begin approximately 12 h after the last injection, and largely recover to control levels by 54 h. Prefrontal cortical and striatal dopamine content, assessed using HPLC, decrease and recover over a similar time course. Behavioral "stereotypy time" manifest by animals exposed to a novel environment, a measure sensitive to psychostimulant withdrawal, also decreases beginning 12 h after the last injection, is still significantly reduced at 54 h, and recovers at 72 h. Chronic saline injections are followed by a consistent decrease in transcription factor gene expression, observed 6 h after the last injection, followed by a "rebound" increase at 12 h. These changes are accompanied by dramatic, mostly biphasic alterations in prefrontal cortical biogenic amines and by a short-lived increase in striatal dopamine turnover. At the same time, rats display much longer-lasting decreases in locomotor responses when exposed to a novel environment, with recovery occurring only 54 h after the last injection. The delayed recovery of behavioral responses to novelty is consistent with potential involvement of changes in transcription factor-mediated gene expression in neurochemical mechanisms underlying psychostimulant

  1. Primate molecular phylogenetics in a genomic era.

    PubMed

    Ting, Nelson; Sterner, Kirstin N

    2013-02-01

    A primary objective of molecular phylogenetics is to use molecular data to elucidate the evolutionary history of living organisms. Dr. Morris Goodman founded the journal Molecular Phylogenetics and Evolution as a forum where scientists could further our knowledge about the tree of life, and he recognized that the inference of species trees is a first and fundamental step to addressing many important evolutionary questions. In particular, Dr. Goodman was interested in obtaining a complete picture of the primate species tree in order to provide an evolutionary context for the study of human adaptations. A number of recent studies use multi-locus datasets to infer well-resolved and well-supported primate phylogenetic trees using consensus approaches (e.g., supermatrices). It is therefore tempting to assume that we have a complete picture of the primate tree, especially above the species level. However, recent theoretical and empirical work in the field of molecular phylogenetics demonstrates that consensus methods might provide a false sense of support at certain nodes. In this brief review we discuss the current state of primate molecular phylogenetics and highlight the importance of exploring the use of coalescent-based analyses that have the potential to better utilize information contained in multi-locus data.

  2. Genomic Repeat Abundances Contain Phylogenetic Signal

    PubMed Central

    Dodsworth, Steven; Chase, Mark W.; Kelly, Laura J.; Leitch, Ilia J.; Macas, Jiří; Novák, Petr; Piednoël, Mathieu; Weiss-Schneeweiss, Hanna; Leitch, Andrew R.

    2015-01-01

    A large proportion of genomic information, particularly repetitive elements, is usually ignored when researchers are using next-generation sequencing. Here we demonstrate the usefulness of this repetitive fraction in phylogenetic analyses, utilizing comparative graph-based clustering of next-generation sequence reads, which results in abundance estimates of different classes of genomic repeats. Phylogenetic trees are then inferred based on the genome-wide abundance of different repeat types treated as continuously varying characters; such repeats are scattered across chromosomes and in angiosperms can constitute a majority of nuclear genomic DNA. In six diverse examples, five angiosperms and one insect, this method provides generally well-supported relationships at interspecific and intergeneric levels that agree with results from more standard phylogenetic analyses of commonly used markers. We propose that this methodology may prove especially useful in groups where there is little genetic differentiation in standard phylogenetic markers. At the same time as providing data for phylogenetic inference, this method additionally yields a wealth of data for comparative studies of genome evolution. PMID:25261464

  3. Phylogenetic tree shapes resolve disease transmission patterns

    PubMed Central

    Colijn, Caroline; Gardy, Jennifer

    2014-01-01

    Background and Objectives: Whole-genome sequencing is becoming popular as a tool for understanding outbreaks of communicable diseases, with phylogenetic trees being used to identify individual transmission events or to characterize outbreak-level overall transmission dynamics. Existing methods to infer transmission dynamics from sequence data rely on well-characterized infectious periods, epidemiological and clinical metadata which may not always be available, and typically require computationally intensive analysis focusing on the branch lengths in phylogenetic trees. We sought to determine whether the topological structures of phylogenetic trees contain signatures of the transmission patterns underlying an outbreak. Methodology: We use simulated outbreaks to train and then test computational classifiers. We test the method on data from two real-world outbreaks. Results: We show that different transmission patterns result in quantitatively different phylogenetic tree shapes. We describe topological features that summarize a phylogeny’s structure and find that computational classifiers based on these are capable of predicting an outbreak’s transmission dynamics. The method is robust to variations in the transmission parameters and network types, and recapitulates known epidemiology of previously characterized real-world outbreaks. Conclusions and implications: There are simple structural properties of phylogenetic trees which, when combined, can distinguish communicable disease outbreaks with a super-spreader, homogeneous transmission and chains of transmission. This is possible using genome data alone, and can be done during an outbreak. We discuss the implications for management of outbreaks. PMID:24916411

  4. Morphological, molecular and phylogenetic analyses of the spirurid nematode Stegophorus macronectes (Johnston & Mawson, 1942).

    PubMed

    Vidal, V; Ortiz, J; Diaz, J I; Zafrilla, B; Bonete, M J; Ruiz De Ybañez, M R; Palacios, M J; Benzal, J; Valera, F; De La Cruz, C; Motas, M; Bautista, V; Machordom, A; Barbosa, A

    2016-03-01

    Stegophorus macronectes (Johnston & Mawson, 1942) is a gastrointestinal parasite found in Antarctic seabirds. The original description of the species, which was based only on females, is poor and fragmented with some unclear diagnostic characters. This study provides new morphometric and molecular data on this previously poorly described parasite. Nuclear rDNA sequences (18S, 5.8S, 28S and internal transcribed spacer (ITS) regions) were isolated from S. macronectes specimens collected from the chinstrap penguin Pygoscelis antarctica Forster on Deception Island, Antarctica. Using 18S rDNA sequences, phylogenetic analyses (maximum likelihood, maximum parsimony and Bayesian inference) of the order Spirurida were performed to determine the phylogenetic location of this species. Primer pairs of the ITS regions were designed for genus-level identification of specimens, regardless of their cycle, as an alternative to coprological methods. The utility of this molecular method for identification of morphologically altered specimens is also discussed.

  5. Phylogenetic conservatism of extinctions in marine bivalves.

    PubMed

    Roy, Kaustuv; Hunt, Gene; Jablonski, David

    2009-08-07

    Evolutionary histories of species and lineages can influence their vulnerabilities to extinction, but the importance of this effect remains poorly explored for extinctions in the geologic past. When analyzed using a standardized taxonomy within a phylogenetic framework, extinction rates of marine bivalves estimated from the fossil record for the last approximately 200 million years show conservatism at multiple levels of evolutionary divergence, both within individual families and among related families. The strength of such phylogenetic clustering varies over time and is influenced by earlier extinction history, especially by the demise of volatile taxa in the end-Cretaceous mass extinction. Analyses of the evolutionary roles of ancient extinctions and predictive models of vulnerability of taxa to future natural and anthropogenic stressors should take phylogenetic relationships and extinction history into account.

  6. Molecular phylogenetics of the hummingbird genus Coeligena.

    PubMed

    Parra, Juan Luis; Remsen, J V; Alvarez-Rebolledo, Mauricio; McGuire, Jimmy A

    2009-11-01

    Advances in the understanding of biological radiations along tropical mountains depend on the knowledge of phylogenetic relationships among species. Here we present a species-level molecular phylogeny based on a multilocus dataset for the Andean hummingbird genus Coeligena. We compare this phylogeny to previous hypotheses of evolutionary relationships and use it as a framework to understand patterns in the evolution of sexual dichromatism and in the biogeography of speciation within the Andes. Previous phylogenetic hypotheses based mostly on similarities in coloration conflicted with our molecular phylogeny, emphasizing the unreliability of color characters for phylogenetic inference. Two major clades, one monochromatic and the other dichromatic, were found in Coeligena. Closely related species were either allopatric or parapatric on opposite mountain slopes. No sister lineages replaced each other along an elevational gradient. Our results indicate the importance of geographic isolation for speciation in this group and the potential interaction between isolation and sexual selection to promote diversification.

  7. Phylogenetic Comparative Assembly

    NASA Astrophysics Data System (ADS)

    Husemann, Peter; Stoye, Jens

    Recent high throughput sequencing technologies are capable of generating a huge amount of data for bacterial genome sequencing projects. Although current sequence assemblers successfully merge the overlapping reads, often several contigs remain which cannot be assembled any further. It is still costly and time consuming to close all the gaps in order to acquire the whole genomic sequence. Here we propose an algorithm that takes several related genomes and their phylogenetic relationships into account to create a contig adjacency graph. From this a layout graph can be computed which indicates putative adjacencies of the contigs in order to aid biologists in finishing the complete genomic sequence.

  8. Lung Adenocarcinoma of Never Smokers and Smokers Harbor Differential Regions of Genetic Alteration and Exhibit Different Levels of Genomic Instability

    PubMed Central

    Thu, Kelsie L.; Vucic, Emily A.; Chari, Raj; Zhang, Wei; Lockwood, William W.; English, John C.; Fu, Rong; Wang, Pei; Feng, Ziding; MacAulay, Calum E.; Gazdar, Adi F.; Lam, Stephen; Lam, Wan L.

    2012-01-01

    Recent evidence suggests that the observed clinical distinctions between lung tumors in smokers and never smokers (NS) extend beyond specific gene mutations, such as EGFR, EML4-ALK, and KRAS, some of which have been translated into targeted therapies. However, the molecular alterations identified thus far cannot explain all of the clinical and biological disparities observed in lung tumors of NS and smokers. To this end, we performed an unbiased genome-wide, comparative study to identify novel genomic aberrations that differ between smokers and NS. High resolution whole genome DNA copy number profiling of 69 lung adenocarcinomas from smokers (n = 39) and NS (n = 30) revealed both global and regional disparities in the tumor genomes of these two groups. We found that NS lung tumors had a greater proportion of their genomes altered than those of smokers. Moreover, copy number gains on chromosomes 5q, 7p, and 16p occurred more frequently in NS. We validated our findings in two independently generated public datasets. Our findings provide a novel line of evidence distinguishing genetic differences between smoker and NS lung tumors, namely, that the extent of segmental genomic alterations is greater in NS tumors. Collectively, our findings provide evidence that these lung tumors are globally and genetically different, which implies they are likely driven by distinct molecular mechanisms. PMID:22412972

  9. A modest glucokinase overexpression in the liver promotes fed expression levels of glycolytic and lipogenic enzyme genes in the fasted state without altering SREBP-1c expression.

    PubMed

    Scott, D K; Collier, J J; Doan, T T T; Bunnell, A S; Daniels, M C; Eckert, D T; O'Doherty, R M

    2003-12-01

    Hepatic genes crucial for carbohydrate and lipid homeostasis are regulated by insulin and glucose metabolism. However, the relative contributions of insulin and glucose to the regulation of metabolic gene expression are poorly defined in vivo. To address this issue, adenovirus-mediated hepatic overexpression of glucokinase was used to determine the effects of increased hepatic glucose metabolism on gene expression in fasted or ad libitum fed rats. In the fasted state, a 3 fold glucokinase overexpression was sufficient to mimic feeding-induced increases in pyruvate kinase and acetyl CoA carboxylase mRNA levels, demonstrating a primary role for glucose metabolism in the regulation of these genes in vivo. Conversely, glucokinase overexpression was unable to mimic feeding-induced alterations of fatty acid synthase, glucose-6-phosphate dehydrogenase, carnitine palmitoyl transferase I or PEPCK mRNAs, indicating insulin as the primary regulator of these genes. Interestingly, glucose-6-phosphatase mRNA was increased by glucokinase overexpression in both the fasted and fed states, providing evidence, under these conditions, for the dominance of glucose over insulin signaling for this gene in vivo. Importantly, glucokinase overexpression did not alter sterol regulatory element binding protein 1-c mRNA levels in vivo and glucose signaling did not alter the expression of this gene in primary hepatocytes. We conclude that a modest hepatic overexpression of glucokinase is sufficient to alter expression of metabolic genes without changing the expression of SREBP-1c.

  10. Increased taxon sampling greatly reduces phylogenetic error.

    PubMed

    Zwickl, Derrick J; Hillis, David M

    2002-08-01

    Several authors have argued recently that extensive taxon sampling has a positive and important effect on the accuracy of phylogenetic estimates. However, other authors have argued that there is little benefit of extensive taxon sampling, and so phylogenetic problems can or should be reduced to a few exemplar taxa as a means of reducing the computational complexity of the phylogenetic analysis. In this paper we examined five aspects of study design that may have led to these different perspectives. First, we considered the measurement of phylogenetic error across a wide range of taxon sample sizes, and conclude that the expected error based on randomly selecting trees (which varies by taxon sample size) must be considered in evaluating error in studies of the effects of taxon sampling. Second, we addressed the scope of the phylogenetic problems defined by different samples of taxa, and argue that phylogenetic scope needs to be considered in evaluating the importance of taxon-sampling strategies. Third, we examined the claim that fast and simple tree searches are as effective as more thorough searches at finding near-optimal trees that minimize error. We show that a more complete search of tree space reduces phylogenetic error, especially as the taxon sample size increases. Fourth, we examined the effects of simple versus complex simulation models on taxonomic sampling studies. Although benefits of taxon sampling are apparent for all models, data generated under more complex models of evolution produce higher overall levels of error and show greater positive effects of increased taxon sampling. Fifth, we asked if different phylogenetic optimality criteria show different effects of taxon sampling. Although we found strong differences in effectiveness of different optimality criteria as a function of taxon sample size, increased taxon sampling improved the results from all the common optimality criteria. Nonetheless, the method that showed the lowest overall

  11. Entanglement, Invariants, and Phylogenetics

    NASA Astrophysics Data System (ADS)

    Sumner, J. G.

    2007-10-01

    This thesis develops and expands upon known techniques of mathematical physics relevant to the analysis of the popular Markov model of phylogenetic trees required in biology to reconstruct the evolutionary relationships of taxonomic units from biomolecular sequence data. The techniques of mathematical physics are plethora and have been developed for some time. The Markov model of phylogenetics and its analysis is a relatively new technique where most progress to date has been achieved by using discrete mathematics. This thesis takes a group theoretical approach to the problem by beginning with a remarkable mathematical parallel to the process of scattering in particle physics. This is shown to equate to branching events in the evolutionary history of molecular units. The major technical result of this thesis is the derivation of existence proofs and computational techniques for calculating polynomial group invariant functions on a multi-linear space where the group action is that relevant to a Markovian time evolution. The practical results of this thesis are an extended analysis of the use of invariant functions in distance based methods and the presentation of a new reconstruction technique for quartet trees which is consistent with the most general Markov model of sequence evolution.

  12. Phylogenetic trees in bioinformatics

    SciTech Connect

    Burr, Tom L

    2008-01-01

    Genetic data is often used to infer evolutionary relationships among a collection of viruses, bacteria, animal or plant species, or other operational taxonomic units (OTU). A phylogenetic tree depicts such relationships and provides a visual representation of the estimated branching order of the OTUs. Tree estimation is unique for several reasons, including: the types of data used to represent each OTU; the use ofprobabilistic nucleotide substitution models; the inference goals involving both tree topology and branch length, and the huge number of possible trees for a given sample of a very modest number of OTUs, which implies that fmding the best tree(s) to describe the genetic data for each OTU is computationally demanding. Bioinformatics is too large a field to review here. We focus on that aspect of bioinformatics that includes study of similarities in genetic data from multiple OTUs. Although research questions are diverse, a common underlying challenge is to estimate the evolutionary history of the OTUs. Therefore, this paper reviews the role of phylogenetic tree estimation in bioinformatics, available methods and software, and identifies areas for additional research and development.

  13. Melanogenesis stimulation in B16-F10 melanoma cells induces cell cycle alterations, increased ROS levels and a differential expression of proteins as revealed by proteomic analysis

    SciTech Connect

    Cunha, Elizabeth S.; Kawahara, Rebeca; Kadowaki, Marina K.; Amstalden, Hudson G.; Noleto, Guilhermina R.; Cadena, Silvia Maria S.C.; Winnischofer, Sheila M.B.; Martinez, Glaucia R.

    2012-09-10

    Considering that stimulation of melanogenesis may lead to alterations of cellular responses, besides melanin production, our main goal was to study the cellular effects of melanogenesis stimulation of B16-F10 melanoma cells. Our results show increased levels of the reactive oxygen species after 15 h of melanogenesis stimulation. Following 48 h of melanogenesis stimulation, proliferation was inhibited (by induction of cell cycle arrest in the G1 phase) and the expression levels of p21 mRNA were increased. In addition, melanogenesis stimulation did not induce cellular senescence. Proteomic analysis demonstrated the involvement of proteins from other pathways besides those related to the cell cycle, including protein disulfide isomerase A3, heat-shock protein 70, and fructose biphosphate aldolase A (all up-regulated), and lactate dehydrogenase (down-regulated). In RT-qPCR experiments, the levels of pyruvate kinase M2 mRNA dropped, whereas the levels of ATP synthase (beta-F1) mRNA increased. These data indicate that melanogenesis stimulation of B16-F10 cells leads to alterations in metabolism and cell cycle progression that may contribute to an induction of cell quiescence, which may provide a mechanism of resistance against cellular injury promoted by melanin synthesis. -- Highlights: Black-Right-Pointing-Pointer Melanogenesis stimulation by L-tyrosine+NH{sub 4}Cl in B16-F10 melanoma cells increases ROS levels. Black-Right-Pointing-Pointer Melanogenesis inhibits cell proliferation, and induced cell cycle arrest in the G1 phase. Black-Right-Pointing-Pointer Proteomic analysis showed alterations in proteins of the cell cycle and glucose metabolism. Black-Right-Pointing-Pointer RT-qPCR analysis confirmed alterations of metabolic targets after melanogenesis stimulation.

  14. Functional and phylogenetic diversity of woody plants drive herbivory in a highly diverse forest.

    PubMed

    Schuldt, Andreas; Assmann, Thorsten; Bruelheide, Helge; Durka, Walter; Eichenberg, David; Härdtle, Werner; Kröber, Wenzel; Michalski, Stefan G; Purschke, Oliver

    2014-05-01

    Biodiversity loss may alter ecosystem processes, such as herbivory, a key driver of ecological functions in species-rich (sub)tropical forests. However, the mechanisms underlying such biodiversity effects remain poorly explored, as mostly effects of species richness - a very basic biodiversity measure - have been studied. Here, we analyze to what extent the functional and phylogenetic diversity of woody plant communities affect herbivory along a diversity gradient in a subtropical forest. We assessed the relative effects of morphological and chemical leaf traits and of plant phylogenetic diversity on individual-level variation in herbivory of dominant woody plant species across 27 forest stands in south-east China. Individual-level variation in herbivory was best explained by multivariate, community-level diversity of leaf chemical traits, in combination with community-weighted means of single traits and species-specific phylodiversity measures. These findings deviate from those based solely on trait variation within individual species. Our results indicate a strong impact of generalist herbivores and highlight the need to assess food-web specialization to determine the direction of biodiversity effects. With increasing plant species loss, but particularly with the concomitant loss of functional and phylogenetic diversity in these forests, the impact of herbivores will probably decrease - with consequences for the herbivore-mediated regulation of ecosystem functions.

  15. Functional and phylogenetic diversity of woody plants drive herbivory in a highly diverse forest

    PubMed Central

    Schuldt, Andreas; Assmann, Thorsten; Bruelheide, Helge; Durka, Walter; Eichenberg, David; Härdtle, Werner; Kröber, Wenzel; Michalski, Stefan G; Purschke, Oliver

    2014-01-01

    Biodiversity loss may alter ecosystem processes, such as herbivory, a key driver of ecological functions in species-rich (sub)tropical forests. However, the mechanisms underlying such biodiversity effects remain poorly explored, as mostly effects of species richness – a very basic biodiversity measure – have been studied. Here, we analyze to what extent the functional and phylogenetic diversity of woody plant communities affect herbivory along a diversity gradient in a subtropical forest.We assessed the relative effects of morphological and chemical leaf traits and of plant phylogenetic diversity on individual-level variation in herbivory of dominant woody plant species across 27 forest stands in south-east China.Individual-level variation in herbivory was best explained by multivariate, community-level diversity of leaf chemical traits, in combination with community-weighted means of single traits and species-specific phylodiversity measures. These findings deviate from those based solely on trait variation within individual species.Our results indicate a strong impact of generalist herbivores and highlight the need to assess food-web specialization to determine the direction of biodiversity effects. With increasing plant species loss, but particularly with the concomitant loss of functional and phylogenetic diversity in these forests, the impact of herbivores will probably decrease – with consequences for the herbivore-mediated regulation of ecosystem functions. PMID:24460549

  16. The phylogenetic diversity of metagenomes.

    PubMed

    Kembel, Steven W; Eisen, Jonathan A; Pollard, Katherine S; Green, Jessica L

    2011-01-01

    Phylogenetic diversity--patterns of phylogenetic relatedness among organisms in ecological communities--provides important insights into the mechanisms underlying community assembly. Studies that measure phylogenetic diversity in microbial communities have primarily been limited to a single marker gene approach, using the small subunit of the rRNA gene (SSU-rRNA) to quantify phylogenetic relationships among microbial taxa. In this study, we present an approach for inferring phylogenetic relationships among microorganisms based on the random metagenomic sequencing of DNA fragments. To overcome challenges caused by the fragmentary nature of metagenomic data, we leveraged fully sequenced bacterial genomes as a scaffold to enable inference of phylogenetic relationships among metagenomic sequences from multiple phylogenetic marker gene families. The resulting metagenomic phylogeny can be used to quantify the phylogenetic diversity of microbial communities based on metagenomic data sets. We applied this method to understand patterns of microbial phylogenetic diversity and community assembly along an oceanic depth gradient, and compared our findings to previous studies of this gradient using SSU-rRNA gene and metagenomic analyses. Bacterial phylogenetic diversity was highest at intermediate depths beneath the ocean surface, whereas taxonomic diversity (diversity measured by binning sequences into taxonomically similar groups) showed no relationship with depth. Phylogenetic diversity estimates based on the SSU-rRNA gene and the multi-gene metagenomic phylogeny were broadly concordant, suggesting that our approach will be applicable to other metagenomic data sets for which corresponding SSU-rRNA gene sequences are unavailable. Our approach opens up the possibility of using metagenomic data to study microbial diversity in a phylogenetic context.

  17. Network-Level Dysconnectivity in Drug-Naïve First-Episode Psychosis: Dissociating Transdiagnostic and Diagnosis-Specific Alterations

    PubMed Central

    Gong, Qiyong; Hu, Xinyu; Pettersson-Yeo, William; Xu, Xin; Lui, Su; Crossley, Nicolas; Wu, Min; Zhu, Hongyan; Mechelli, Andrea

    2017-01-01

    The neuroimaging literature provides compelling evidence for functional dysconnectivity in people with psychosis. However, it is likely that at least some of the observed alterations represent secondary effects of illness chronicity and/or antipsychotic medication. In addition, the extent to which these alterations are specific to psychosis or represent a transdiagnostic feature of psychiatric illness remains unclear. The aim of this study was therefore to examine the diagnostic specificity of functional dysconnectivity in drug-naïve first-episode psychosis (FEP). We used resting-state functional magnetic resonance imaging and functional connectivity analysis to estimate network-level connectivity in 50 patients with FEP, 50 patients with major depressive disorder (MDD), 50 patients with post-traumatic stress disorder (PTSD), and 122 healthy controls (HCs). The FEP, MDD, and PTSD groups showed reductions in intranetwork connectivity of the default mode network relative to the HC group (p<0.05 corrected); therefore, intranetwork alterations were expressed across the three diagnostic groups. In addition, the FEP group showed heightened internetwork connectivity between the default mode network, particularly the anterior cingulate cortex, and the central executive network relative to the MDD, PTSD, and HC groups (p<0.05 corrected); therefore, internetwork alterations were specific to the FEP. These findings suggest that network-level alterations are present in individuals with a first episode of psychosis who have not been exposed to antipsychotic medication. In addition, they suggest a dissociation between aberrant internetwork connectivity as a distinctive feature of psychosis and aberrant intranetwork connectivity as a transdiagnostic feature of psychiatric illness. PMID:27782128

  18. Conservation biology of Malagasy strepsirhines: a phylogenetic approach.

    PubMed

    Lehman, Shawn M

    2006-06-01

    The phylogenetic diversity of extant lemurs represents one of the most important but least studied aspects of the conservation biology of primates. The phylogenetic diversity of a species is inversely proportional to the relative number and closeness of its phylogenetic relatives. Phylogenetic diversity can then be used to determine conservation priorities for specific biogeographic regions. Although Malagasy strepsirhines represent the highest phylogenetic diversity among primates at the global level, there are few phylogenetic data on species-specific and regional conservation plans for lemurs in Madagascar. Therefore, in this paper the following questions are addressed for extant lemurs: 1) how does the measure of taxonomic uniqueness used by Mittermeier et al. (1992 Lemurs of Madagascar; Gland, Switzerland: IUCN) equate with an index of phylogenetic diversity, 2) what are the regional conservation priorities based on analyses of phylogenetic diversity in extant lemurs, and 3) what conservation recommendations can be made based on analyses of phylogenetic diversity in lemurs? Taxonomic endemicity standardized weight (TESW) indices of phylogenetic diversity were used to determine the evolutionary component of biodiversity and to prioritize regions for conserving lemur taxa. TESW refers to the standardization of phylogenetic diversity indices for widespread taxa and endemicity of species. The phylogenetic data came from recent genetic studies of Malagasy strepsirhines at the species level. Lemur species were assigned as being either present or absent in six biogeographic regions. TESW indices were combined with data on lemur complementarity and protected areas to assign conservation priorities at the regional level. Although there were no overall differences between taxonomic ranks and phylogenetic rankings, there were significant differences for the top-ranked taxa. The phylogenetic component of lemur diversity is greatest for Daubentonia madagascariensis

  19. Ovarian stimulation using human chorionic gonadotrophin impairs blastocyst implantation and decidualization by altering ovarian hormone levels and downstream signaling in mice.

    PubMed

    Ezoe, Kenji; Daikoku, Takiko; Yabuuchi, Akiko; Murata, Nana; Kawano, Hiroomi; Abe, Takashi; Okuno, Takashi; Kobayashi, Tamotsu; Kato, Keiichi

    2014-11-01

    Ovarian stimulation induced by follicle-stimulating hormone and human chorionic gonadotrophin (hCG) is commonly used in assisted reproductive technology to increase embryo production. However, recent clinical and animal studies have shown that ovarian stimulation disrupts endometrial function and embryo development and adversely affects pregnancy outcomes. How ovarian stimulation impairs pregnancy establishment and the precise mechanisms by which this stimulation reduces the chances of conception remain unclear. In this study, we first demonstrated that ovarian stimulation using hCG alone impairs implantation, decidualization and fetal development of mice by generating abnormal ovarian hormone levels. We also showed that ovarian hormone levels were altered because of changes in the levels of the enzymes involved in their synthesis in the follicles and corpora lutea. Furthermore, we determined that anomalous ovarian hormone secretion induced by ovarian stimulation alters the spatiotemporal expression of progesterone receptors and their downstream genes, especially in the uterine epithelium. Epithelial estrogenic signaling and cell proliferation were promoted on the day of implantation in stimulated mice and these changes led to the failure of uterine transition from the prereceptive to the receptive state. Collectively, our findings indicate that ovarian stimulation using hCG induces an imbalance in steroid hormone secretion, which causes a failure of the development of uterine receptivity and subsequent implantation and decidualization by altering the expression of steroid receptors and their downstream signaling associated with embryo implantation.

  20. Incompletely resolved phylogenetic trees inflate estimates of phylogenetic conservatism.

    PubMed

    Davies, T Jonathan; Kraft, Nathan J B; Salamin, Nicolas; Wolkovich, Elizabeth M

    2012-02-01

    The tendency for more closely related species to share similar traits and ecological strategies can be explained by their longer shared evolutionary histories and represents phylogenetic conservatism. How strongly species traits co-vary with phylogeny can significantly impact how we analyze cross-species data and can influence our interpretation of assembly rules in the rapidly expanding field of community phylogenetics. Phylogenetic conservatism is typically quantified by analyzing the distribution of species values on the phylogenetic tree that connects them. Many phylogenetic approaches, however, assume a completely sampled phylogeny: while we have good estimates of deeper phylogenetic relationships for many species-rich groups, such as birds and flowering plants, we often lack information on more recent interspecific relationships (i.e., within a genus). A common solution has been to represent these relationships as polytomies on trees using taxonomy as a guide. Here we show that such trees can dramatically inflate estimates of phylogenetic conservatism quantified using S. P. Blomberg et al.'s K statistic. Using simulations, we show that even randomly generated traits can appear to be phylogenetically conserved on poorly resolved trees. We provide a simple rarefaction-based solution that can reliably retrieve unbiased estimates of K, and we illustrate our method using data on first flowering times from Thoreau's woods (Concord, Massachusetts, USA).

  1. Altered serum levels of interleukin-3 in first-episode drug-naive and chronic medicated schizophrenia.

    PubMed

    Fu, Yin Yang; Zhang, Tong; Xiu, Mei Hong; Tang, Wei; Han, Mei; Yun, Long Tan; Chen, Da Chun; Chen, Song; Tan, Shu Ping; Soares, Jair C; Tang, Wen Jie; Zhang, Xiang Yang

    2016-10-01

    Elevated serum levels of Interleukin-3 (IL-3), a major component of the cytokines, have been observed in chronic and medicated patients with schizophrenia, but this elevation may reflect either or both medication and illness chronicity effects. Thus, we compared serum IL-3 levels in first-episode drug-naive (FEDN) to chronic medicated patients with schizophrenia and examined the association of IL-3 with their psychopathological symptoms. Serum IL-3 levels were assessed in 55 FEDN patients, 52 chronic medicated patients and 43 healthy controls. Schizophrenia symptomatology was assessed with the Positive and Negative Syndrome Scale (PANSS). Serum IL-3 levels were measured by sandwich enzyme-linked immunosorbent assay (ELISA). We found significantly lower IL-3 levels in FEDN patients than both chronic patients and healthy controls (both p<0.001), while IL-3 levels in chronic patients were markedly higher than in healthy controls. No significant association was observed between IL-3 and any clinical psychopathology in FEDN patients; however, we found a significant correlation between serum IL-3 levels and the PANSS general psychopathology subscore in chronic medicated patients (p<0.05). Decreased IL-3 levels in FEDN patients suggest that suppressed immune function may be associated with developing schizophrenia, but as the disease progresses IL-3 levels increase perhaps related to medication treatment or other factors that occur during chronic illness.

  2. Porin alterations present in non-carbapenemase-producing Enterobacteriaceae with high and intermediate levels of carbapenem resistance in Chile.

    PubMed

    Wozniak, Aniela; Villagra, Nicolás A; Undabarrena, Agustina; Gallardo, Natalia; Keller, Nicole; Moraga, Marcela; Román, Juan C; Mora, Guido C; García, Patricia

    2012-09-01

    The main goal of this work was to identify the mechanisms responsible for carbapenem resistance in 61 Chilean clinical isolates of Enterobacteriaceae (Enterobacter spp., Serratia marcescens, Morganella morganii, Escherichia coli and Klebsiella pneumoniae) with reduced susceptibility to at least one carbapenem (ertapenem, imipenem or meropenem). All of the isolates were analysed for the presence of carbapenemases, extended spectrum β-lactamases (ESBLs), AmpC enzymes and outer-membrane proteins. None of the isolates exhibited carbapenemase activity nor did they have any of the carbapenemase genes that were screened for. Most of the 61 strains produced at least one ESBL and/or one AmpC enzyme and either lost their porins or had altered porins according to sequence analysis. The distribution of ESBLs and AmpC enzymes was different among the species studied. Resistance in K. pneumoniae and E. coli isolates was associated with ESBLs; in M. morganii isolates, resistance was attributed to overexpression of an AmpC enzyme; and in Enterobacter spp. isolates, resistance was associated with both types of enzymes. In K. pneumoniae isolates, porin integrity was more a determinant of carbapenem resistance than the presence of ESBLs, whereas in isolates of Enterobacter spp., M. morganii and S. marcescens, the presence of an overexpressed AmpC enzyme was associated with higher imipenem and meropenem MIC values. Therefore, carbapenem resistance in Chilean isolates is not due to true carbapenemases but rather to a combination of porin loss/alteration and β-lactamase activity. The fact that carbapenemases were not detected in this study is unique, given that many countries in the region have already reported the presence of these enzymes.

  3. Antidepressant Effects of Electroconvulsive Therapy Unrelated to the Brain's Functional Network Connectivity alterations at an Individual Level

    PubMed Central

    Chen, Guang-Dong; Ji, Feng; Li, Gong-Ying; Lyu, Bo-Xuan; Hu, Wei; Zhuo, Chuan-Jun

    2017-01-01

    Background: Electroconvulsive therapy (ECT) can alleviate the symptoms of treatment-resistant depression (TRD). Functional network connectivity (FNC) is a newly developed method to investigate the brain's functional connectivity patterns. The first aim of this study was to investigate FNC alterations between TRD patients and healthy controls. The second aim was to explore the relationship between the ECT treatment response and pre-ECT treatment FNC alterations in individual TRD patients. Methods: This study included 82 TRD patients and 41 controls. Patients were screened at baseline and after 2 weeks of treatment with a combination of ECT and antidepressants. Group information guided-independent component analysis (GIG-ICA) was used to compute subject-specific functional networks (FNs). Grassmann manifold and step-wise forward component selection using support vector machines were adopted to perform the FNC measure and extract the functional networks' connectivity patterns (FCP). Pearson's correlation analysis was used to calculate the correlations between the FCP and ECT response. Results: A total of 82 TRD patients in the ECT group were successfully treated. On an average, 8.50 ± 2.00 ECT sessions were conducted. After ECT treatment, only 42 TRD patients had an improved response to ECT (the Hamilton scores reduction rate was more than 50%), response rate 51%. 8 FNs (anterior and posterior default mode network, bilateral frontoparietal network, audio network, visual network, dorsal attention network, and sensorimotor network) were obtained using GIG-ICA. We did not found that FCPs were significantly different between TRD patients and healthy controls. Moreover, the baseline FCP was unrelated to the ECT treatment response. Conclusions: The FNC was not significantly different between the TRD patients and healthy controls, and the baseline FCP was unrelated to the ECT treatment response. These findings will necessitate that we modify the experimental scheme to

  4. Reductions in frontocortical cytokine levels are associated with long-lasting alterations in reward valuation after methamphetamine.

    PubMed

    Stolyarova, Alexandra; Thompson, Andrew B; Barrientos, Ruth M; Izquierdo, Alicia

    2015-03-13

    Alterations in reward valuation are thought to have a central role at all stages of the addiction process. We previously reported work aversion in an effortful T-maze task following a binge exposure to methamphetamine, and no such changes in effort following escalating doses. Limitations of the T-maze task include its two available options, with an effort requirement, in the form of increasing barrier height, varying incrementally as a function of time, and reward magnitudes held constant. Reward preferences and choices, however, are likely affected by the number of options available and the manner in which alternatives are presented. In the present experiment, we investigated the long-lasting, off-drug effects of methamphetamine on reward choices in a novel effortful maze task with three possible courses of action, each associated with different effort requirements and reward magnitudes. Neuroinflammatory responses associated with drug exposure, proposed as one of the mechanisms contributing to suboptimal choices on effort-based tasks, were also examined. We investigated region-specific changes in pro- and anti-inflammatory markers in the mesocorticolimbic pathway after methamphetamine, and their relationship with animals' reward choices. We observed long-lasting, increased sensitivity to differences in reward magnitude in the methamphetamine group: animals were more likely to overcome greater effort costs to obtain larger rewards on our novel effortful maze task. These behavioral changes were strongly predicted by pronounced decreases in frontocortical cytokines, but not amygdalar or striatal markers. The present results provide the first evidence that neuroinflammatory processes are associated with alterations in reward valuation during protracted drug withdrawal.

  5. Associations of plasma natriuretic peptide, adrenomedullin, and homocysteine levels with alterations in arterial stiffness: The Framingham Heart Study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Experimental studies suggest that the natriuretic peptides influence lipid and fatty acid metabolism. Although it has been shown that obese individuals have reduced natriuretic peptide levels, conflicting data exist on the relation of natriuretic peptide levels to other metabolic risk factors. We ex...

  6. Epigallocatechin gallate induces a hepatospecific decrease in the CYP3A expression level by altering intestinal flora.

    PubMed

    Ikarashi, Nobutomo; Ogawa, Sosuke; Hirobe, Ryuta; Kon, Risako; Kusunoki, Yoshiki; Yamashita, Marin; Mizukami, Nanaho; Kaneko, Miho; Wakui, Nobuyuki; Machida, Yoshiaki; Sugiyama, Kiyoshi

    2017-03-30

    In previous studies, we showed that a high-dose intake of green tea polyphenol (GP) induced a hepatospecific decrease in the expression and activity of the drug-metabolizing enzyme cytochrome P450 3A (CYP3A). In this study, we examined whether this decrease in CYP3A expression is induced by epigallocatechin gallate (EGCG), which is the main component of GP. After a diet containing 1.5% EGCG was given to mice, the hepatic CYP3A expression was measured. The level of intestinal bacteria of Clostridium spp., the concentration of lithocholic acid (LCA) in the feces, and the level of the translocation of pregnane X receptor (PXR) to the nucleus in the liver were examined. A decrease in the CYP3A expression level was observed beginning on the second day of the treatment with EGCG. The level of translocation of PXR to the nucleus was significantly lower in the EGCG group. The fecal level of LCA was clearly decreased by the EGCG treatment. The level of intestinal bacteria of Clostridium spp. was also decreased by the EGCG treatment. It is clear that the hepatospecific decrease in the CYP3A expression level observed after a high-dose intake of GP was caused by EGCG. Because EGCG, which is not absorbed from the intestine, causes a decrease in the level of LCA-producing bacteria in the colon, the level of LCA in the liver decreases, resulting in a decrease in the nuclear translocation of PXR, which in turn leads to the observed decrease in the expression level of CYP3A.

  7. An oxidative fluctuation hypothesis of aging generated by imaging H₂O₂ levels in live Caenorhabditis elegans with altered lifespans.

    PubMed

    Fu, Xinmiao; Tang, Yan; Dickinson, Bryan C; Chang, Christopher J; Chang, Zengyi

    2015-03-20

    Reactive oxygen species (ROS) are important factors mediating aging according to the free radical theory of aging. Few studies have systematically measured ROS levels in relationship to aging, partly due to the lack of tools for detection of specific ROS in live animals. By using the H₂O₂-specific fluorescence probe Peroxy Orange 1, we assayed the H₂O₂ levels of live Caenorhabditis elegans with 41 aging-related genes being individually knocked down by RNAi. Knockdown of 14 genes extends the lifespan but increases H₂O₂ level or shortens the lifespan but decreases H₂O₂ level, contradicting the free radical theory of aging. Strikingly, a significant inverse correlation between lifespan and the normalized standard deviation of H₂O₂ levels was observed (p < 0.0001). Such inverse correlation was also observed in worms cultured under heat shock conditions. An oxidative fluctuation hypothesis of aging is thus proposed and suggests that the ability of animals to homeostatically maintain the ROS levels within a narrow range is more important for lifespan extension than just minimizing the ROS levels though the latter still being crucial.

  8. Two Independent Regions of Simian Virus 40 T Antigen Increase CBP/p300 Levels, Alter Patterns of Cellular Histone Acetylation, and Immortalize Primary Cells

    PubMed Central

    Sáenz Robles, Maria Teresa; Shivalila, Chikdu; Wano, Jeremy; Sorrells, Shelly; Roos, Alison

    2013-01-01

    Simian virus 40 (SV40) large T antigen (SVT) interferes with normal cell regulation and thus has been used to identify cellular components controlling proliferation and homeostasis. We have previously shown that SVT-mediated transformation requires interaction with the histone acetyltransferases (HATs) CBP/p300 and now report that the ectopic expression of SVT in several cell types in vivo and in vitro results in a significant increase in the steady-state levels of CBP/p300. Furthermore, SVT-expressing cells contain higher levels of acetylated CBP/p300, a modification that has been linked to increased HAT activity. Concomitantly, the acetylation levels of histone residues H3K56 and H4K12 are markedly increased in SVT-expressing cells. Other polyomavirus-encoded large T antigens also increase the levels of CBP/p300 and sustain a rise in the acetylation levels of H3K56 and H4K12. SVT does not affect the transcription of CBP/p300, but rather, alters their overall levels through increasing the loading of CBP/p300 mRNAs onto polysomes. Two distinct regions within SVT, one located in the amino terminus and one in the carboxy terminus, can independently alter both the levels of CBP/p300 and the loading of CBP/p300 transcripts onto polysomes. Within the amino-terminal fragment, a functional J domain is necessary for increasing CBP/p300 and specific histone acetylation levels, as well as for immortalizing primary cells. These studies uncover the action of polyomavirus T antigens on cellular CBP/p300 and suggest that additional mechanisms are used by T antigens to induce cell immortalization and transformation. PMID:24089570

  9. Phylogenetic constraints on ecosystem functioning.

    PubMed

    Gravel, Dominique; Bell, Thomas; Barbera, Claire; Combe, Marine; Pommier, Thomas; Mouquet, Nicolas

    2012-01-01

    There is consensus that biodiversity losses will result in declining ecosystem functioning if species have different functional traits. Phylogenetic diversity has recently been suggested as a predictor of ecosystem functioning because it could approximate the functional complementarity among species. Here we describe an experiment that takes advantage of the rapid evolutionary response of bacteria to disentangle the role of phylogenetic and species diversity. We impose a strong selection regime on marine bacterial lineages and assemble the ancestral and evolved lines in microcosms of varying lineage and phylogenetic diversity. We find that the relationship between phylogenetic diversity and productivity is strong for the ancestral lineages but brakes down for the evolved lineages. Our results not only emphasize the potential of using phylogeny to evaluate ecosystem functioning, but also they warn against using phylogenetics as a proxy for functional diversity without good information on species evolutionary history.

  10. Alteration in carboxyhemoglobin concentrations during exposure to 9 ppm carbon monoxide for 8 hours at sea level and 2134 m altitude in a hypobaric chamber

    SciTech Connect

    Horvath, S.M.; Bedi, J.F. )

    1989-10-01

    Seventeen non-smoking young men served as subjects to determine the alteration in carboxyhemoglobin (COHb) concentrations during exposure to 0 or 9 ppm carbon monoxide for 8 hours (CO) at sea level or an altitude of 2134 meters (7000 feet) in a hypobaric chamber. Nine subjects rested during the exposure and 8 exercised for 10 minutes of each exposure hour at a mean ventilation of 25 L (BTPS). All subjects performed a maximal aerobic capacity test at the completion of their respective exposures. Carboxyhemoglobin concentrations fell in all subjects during their exposures to 0 ppm CO at sea level or 2134 m. During the 8-h exposures to 9 ppm CO, COHb rose linearly from approximately 0.2 percent to 0.7 percent. No significant differences in uptake were found whether the subjects were resting or intermittently exercising during their 8-h exposures. COHb levels attained were similar at both sea level and 2134 m. Maximal aerobic capacity was reduced approximately 7-10 percent consequent to altitude exposure during 0 ppm CO exposures. These values were not altered following exposure for 8 h to 9 ppm CO in either the resting or exercising subjects.

  11. Association of Parkinson's disease with altered serum levels of lead and transition metals among South Indian subjects.

    PubMed

    Kumudini, Nadella; Uma, Addepally; Devi, Yalavarthy Prameela; Naushad, Shaik Mohammad; Mridula, Rukmini; Borgohain, Rupam; Kutala, Vijay Kumar

    2014-04-01

    Several epidemiologic studies have suggested an association between the Parkinson's disease (PD) and exposure to heavy metals, such as lead, iron, copper, manganese, etc. A growing body of evidence suggests that heavy metals stimulate free radical formation in the brain and can lead to neurodegeneration. In the present study, we investigated whether such association exists in PD cases from rural and urban areas in our study population. The plasma levels of copper, iron, manganese and lead in PD cases (n = 150) and controls (n = 170) were determined by inductively coupled plasma mass spectrometry (ICP-MS) and correlated with the oxidative stress markers like malondialdehyde (MDA), protein carbonyl and total glutathione. Results indicated significant increase in the levels of copper (17.73 +/- 4.48 vs. 13.0 + 3.22 ng/ml) and iron (554.4 +/- 123.8 vs. 421.7 +/- 126.1 ng/ml) in PD cases compared to controls, whereas no significant differences in the levels of manganese and lead were observed. Further, the data based on urban or rural residence showed that plasma copper, iron, manganese levels were comparatively higher in rural subjects, whereas plasma lead levels were significantly higher in urban subjects. Increased plasma iron showed positive correlation with marker of lipid peroxidation (MDA), suggesting that increased iron levels induced oxidative stress in PD. These results substantiated the earlier observations about the role of environmental exposure and metal-induced oxidative stress in the etiology of PD.

  12. GSM 900 MHz Microwave Radiation-Induced Alterations of Insulin Level and Histopathological Changes of Liver and Pancreas in Rat

    PubMed Central

    Mortazavi, S. M. J.; Owji, S.M.; Shojaei-fard, M.B.; Ghader-Panah, M.; Mortazavi, S.A.R.; Tavakoli-Golpayegani, A.; Haghani, M.; Taeb, S.; Shokrpour, N.; Koohi, O.

    2016-01-01

    Background: The rapidly increasing use of mobile phones has led to public concerns about possible health effects of these popular communication devices. This study is an attempt to investigate the effects of radiofrequency (RF) radiation produced by GSM mobile phones on the insulin release in rats. Methods: Forty two female adult Sprague Dawley rats were randomly divided into 4 groups. Group1 were exposed to RF radiation 6 hours per day for 7 days. Group 2 received sham exposure (6 hours per day for 7 days). Groups 3 and 4 received RF radiation 3 hours per day for 7 days and sham exposure (3 hours per day), respectively. The specific absorption rate (SAR) of RF was 2.0 W/kg. Results: Our results showed that RF radiations emitted from mobile phone could not alter insulin release in rats. However, mild to severe inflammatory changes in the portal spaces of the liver of rats as well as damage in the cells of islet of Langerhans were observed. These changes were linked with the duration of the exposures. Conclusion: RF exposure can induce inflammatory changes in the liver as well causing damage in the cells of islet of Langerhans. PMID:28144593

  13. Nitrogen stress-induced alterations in the leaf proteome of two wheat varieties grown at different nitrogen levels.

    PubMed

    Chandna, Ruby; Ahmad, Altaf

    2015-01-01

    Inorganic nitrogen (N) is a key limiting factor of the agricultural productivity. Nitrogen utilization efficiency has significant impact on crop growth and yield as well as on the reduction in production cost. The excessive nitrogen application is accompanied with severe negative impact on environment. Thus to reduce the environmental contamination, improving NUE is need of an hour. In our study we have deployed comparative proteome analysis using 2-DE to investigate the effect of the nitrogen nutrition on differential expression pattern of leaf proteins in low-N sensitive and low-N tolerant wheat (Triticum aestivum L.) varieties. Results showed a comprehensive picture of the post-transcriptional response to different nitrogen regimes administered which would be expected to serve as a basic platform for further characterization of gene function and regulation. We detected proteins related to photosynthesis, glycolysis, nitrogen metabolism, sulphur metabolism and defence. Our results provide new insights towards the altered protein pattern in response to N stress. Through this study we suggest that genes functioning in many physiological events coordinate the response to availability of nitrogen and also for the improvement of NUE of crops.

  14. Phylogenetic molecular function annotation

    NASA Astrophysics Data System (ADS)

    Engelhardt, Barbara E.; Jordan, Michael I.; Repo, Susanna T.; Brenner, Steven E.

    2009-07-01

    It is now easier to discover thousands of protein sequences in a new microbial genome than it is to biochemically characterize the specific activity of a single protein of unknown function. The molecular functions of protein sequences have typically been predicted using homology-based computational methods, which rely on the principle that homologous proteins share a similar function. However, some protein families include groups of proteins with different molecular functions. A phylogenetic approach for predicting molecular function (sometimes called "phylogenomics") is an effective means to predict protein molecular function. These methods incorporate functional evidence from all members of a family that have functional characterizations using the evolutionary history of the protein family to make robust predictions for the uncharacterized proteins. However, they are often difficult to apply on a genome-wide scale because of the time-consuming step of reconstructing the phylogenies of each protein to be annotated. Our automated approach for function annotation using phylogeny, the SIFTER (Statistical Inference of Function Through Evolutionary Relationships) methodology, uses a statistical graphical model to compute the probabilities of molecular functions for unannotated proteins. Our benchmark tests showed that SIFTER provides accurate functional predictions on various protein families, outperforming other available methods.

  15. Phylogenetic molecular function annotation

    PubMed Central

    Engelhardt, Barbara E; Jordan, Michael I; Repo, Susanna T; Brenner, Steven E

    2010-01-01

    It is now easier to discover thousands of protein sequences in a new microbial genome than it is to biochemically characterize the specific activity of a single protein of unknown function. The molecular functions of protein sequences have typically been predicted using homology-based computational methods, which rely on the principle that homologous proteins share a similar function. However, some protein families include groups of proteins with different molecular functions. A phylogenetic approach for predicting molecular function (sometimes called “phylogenomics”) is an effective means to predict protein molecular function. These methods incorporate functional evidence from all members of a family that have functional characterizations using the evolutionary history of the protein family to make robust predictions for the uncharacterized proteins. However, they are often difficult to apply on a genome-wide scale because of the time-consuming step of reconstructing the phylogenies of each protein to be annotated. Our automated approach for function annotation using phylogeny, the SIFTER (Statistical Inference of Function Through Evolutionary Relationships) methodology, uses a statistical graphical model to compute the probabilities of molecular functions for unannotated proteins. Our benchmark tests showed that SIFTER provides accurate functional predictions on various protein families, outperforming other available methods. PMID:20664722

  16. Music exposure differentially alters the levels of brain-derived neurotrophic factor and nerve growth factor in the mouse hypothalamus.

    PubMed

    Angelucci, Francesco; Ricci, Enzo; Padua, Luca; Sabino, Andrea; Tonali, Pietro Attilio

    2007-12-18

    It has been reported that music may have physiological effects on blood pressure, cardiac heartbeat, respiration, and improve mood state in people affected by anxiety, depression and other psychiatric disorders. However, the physiological bases of these phenomena are not clear. Hypothalamus is a brain region involved in the regulation of body homeostasis and in the pathophysiology of anxiety and depression through the modulation of hypothalamic-pituitary-adrenal (HPA) axis. Hypothalamic functions are also influenced by the presence of the neurotrophins brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), which are proteins involved in the growth, survival and function of neurons in the central nervous system. The aim of this study was to investigate the effect of music exposure in mice on hypothalamic levels of BDNF and NGF. We exposed young adult mice to slow rhythm music (6h per day; mild sound pressure levels, between 50 and 60 dB) for 21 consecutive days. At the end of the treatment mice were sacrificed and BDNF and NGF levels in the hypothalamus were measured by enzyme-linked immunosorbent assay (ELISA). We found that music exposure significantly enhanced BDNF levels in the hypothalamus. Furthermore, we observed that music-exposed mice had decreased NGF hypothalamic levels. Our results demonstrate that exposure to music in mice can influence neurotrophin production in the hypothalamus. Our findings also suggest that physiological effects of music might be in part mediated by modulation of neurotrophins.

  17. Bisphenol A Exposure during Pregnancy Alters the Mortality and Levels of Reproductive Hormones and Genes in Offspring Mice

    PubMed Central

    Shi, Wanyu

    2017-01-01

    The present study investigated the reproductive toxicity of bisphenol A (BPA) exposure to the mother on the offspring mice. BPA was given to pregnant mice at 50 mg/kg, 500 mg/kg, and 2500 mg/kg BW BPA daily by gavage during the whole gestation period. The offspring mice were sacrificed at 8 weeks of age. Results showed that exposure of BPA to the mother increased the mortality (P < 0.05). Maternal exposure of BPA reduced the levels of T (♂) and FSH (♀) (P < 0.01) and elevated E2 (♀) level in the adult offspring (P < 0.01). BPA exposure caused testicular damage as shown by less Leydig cells and ovarian injury as shown by more vacuoles and less corpus granules in the adult offspring mice. Immunohistochemistry revealed that maternal exposure of BPA increased Bax and decreased Bcl-2 at the protein levels in testicular and ovary tissues in the offspring mice. BPA significantly reduced the expression of StAR in male offspring (P < 0.05). Interestingly, the mRNA levels of Cyp11a were significantly decreased in 50 mg/kg groups and were increased in 500 mg/kg group in the males. Reduced Kitlg and elevated Amh at the mRNA levels were detected in the female offspring. PMID:28393075

  18. Exposure to extremely low frequency electromagnetic fields alters the behaviour, physiology and stress protein levels of desert locusts.

    PubMed

    Wyszkowska, Joanna; Shepherd, Sebastian; Sharkh, Suleiman; Jackson, Christopher W; Newland, Philip L

    2016-11-03

    Electromagnetic fields (EMFs) are present throughout the modern world and are derived from many man-made sources including overhead transmission lines. The risks of extremely-low frequency (ELF) electromagnetic fields are particularly poorly understood especially at high field strengths as they are rarely encountered at ground level. Flying insects, however, can approach close to high field strength transmission lines prompting the question as to how these high levels of exposure affect behaviour and physiology. Here we utilise the accessible nervous system of the locust to ask how exposure to high levels of ELF EMF impact at multiple levels. We show that exposure to ELF EMFs above 4 mT leads to reduced walking. Moreover, intracellular recordings from an identified motor neuron, the fast extensor tibiae motor neuron, show increased spike latency and a broadening of its spike in exposed animals. In addition, hind leg kick force, produced by stimulating the extensor tibiae muscle, was reduced following exposure, while stress-protein levels (Hsp70) increased. Together these results suggest that ELF EMF exposure has the capacity to cause dramatic effects from behaviour to physiology and protein expression, and this study lays the foundation to explore the ecological significance of these effects in other flying insects.

  19. Exposure to extremely low frequency electromagnetic fields alters the behaviour, physiology and stress protein levels of desert locusts

    PubMed Central

    Wyszkowska, Joanna; Shepherd, Sebastian; Sharkh, Suleiman; Jackson, Christopher W.; Newland, Philip L.

    2016-01-01

    Electromagnetic fields (EMFs) are present throughout the modern world and are derived from many man-made sources including overhead transmission lines. The risks of extremely-low frequency (ELF) electromagnetic fields are particularly poorly understood especially at high field strengths as they are rarely encountered at ground level. Flying insects, however, can approach close to high field strength transmission lines prompting the question as to how these high levels of exposure affect behaviour and physiology. Here we utilise the accessible nervous system of the locust to ask how exposure to high levels of ELF EMF impact at multiple levels. We show that exposure to ELF EMFs above 4 mT leads to reduced walking. Moreover, intracellular recordings from an identified motor neuron, the fast extensor tibiae motor neuron, show increased spike latency and a broadening of its spike in exposed animals. In addition, hind leg kick force, produced by stimulating the extensor tibiae muscle, was reduced following exposure, while stress-protein levels (Hsp70) increased. Together these results suggest that ELF EMF exposure has the capacity to cause dramatic effects from behaviour to physiology and protein expression, and this study lays the foundation to explore the ecological significance of these effects in other flying insects. PMID:27808167

  20. Altered beta-secretase enzyme kinetics and levels of both BACE1 and BACE2 in the Alzheimer's disease brain.

    PubMed

    Stockley, John H; Ravid, Rivka; O'Neill, Cora

    2006-12-11

    beta-Secretase is the rate limiting enzymatic activity in the production of amyloid-beta peptide, the primary component of senile plaque pathology in Alzheimer's disease (AD). This study performed the first comparative analysis of beta-secretase enzyme kinetics in AD and control brain tissue. Results found V(max) values for beta-secretase to be significantly increased, and K(m) values unchanged in AD temporal cortex compared to matched control temporal cortex. The increased V(max) in AD cases, did not correlate with levels of BACE1, and decreased BACE1 and BACE2 levels correlated with the severity of neurofibrillary pathology (I-VI), and synaptic loss in AD. These results indicate that increased V(max) for beta-secretase is a feature of AD pathogenesis and this increase does not correlate directly with levels of BACE1, the principal beta-secretase in brain.

  1. Altered Levels of Visinin-Like Protein 1 Correspond to Regional Neuronal Loss in Alzheimer Disease and Frontotemporal Lobar Degeneration.

    PubMed

    Kirkwood, Caitlin M; MacDonald, Matthew L; Schempf, Tadhg A; Vatsavayi, Anil V; Ikonomovic, Milos D; Koppel, Jeremy L; Ding, Ying; Sun, Mai; Kofler, Julia K; Lopez, Oscar L; Yates, Nathan A; Sweet, Robert A

    2016-02-01

    Recent studies have implicated the neuronal calcium-sensing protein visinin-like 1 protein (Vilip-1) as a peripheral biomarker in Alzheimer disease (AD), but little is known about expression of Vilip-1 in the brains of patients with AD. We used targeted and quantitative mass spectrometry to measure Vilip-1 peptide levels in the entorhinal cortex (ERC) and the superior frontal gyrus (SF) from cases with early to moderate stage AD, frontotemporal lobar degeneration (FTLD), and cognitively and neuropathologically normal elderly controls. We found that Vilip-1 levels were significantly lower in the ERC, but not in SF, of AD subjects compared to normal controls. In FTLD cases, Vilip-1 levels in the SF were significantly lower than in normal controls. These findings suggest a unique role for cerebrospinal fluid Vilip-1 as a biomarker of ERC neuron loss in AD.

  2. [Alterations in heat shock protein 70 kDa levels in human neutrophils under the heat shock conditions].

    PubMed

    Boĭko, A A; Vetchinin, S S; Sapozhnikov, A M; Kovalenko, E I

    2014-01-01

    Intracellular content of heat shock proteins of 70 kDa family (HSP70) possessing chaperone and cytoprotective functions depends on specialization and functional activity of the cells. The aim of this study was to analyze the dynamics of constitutive and inducible HSP70 levels evoked by heat shock in human neutrophils, the short-lived fraction of white blood cells providing non-specific defense against bacterial pathogens. Biphasic dynamics of the intracellular HSP70 level with an increase and following decrease in 15-30 min after the heat shock was revealed by flow cytometry. This dynamics was similar for constitutive and inducible forms of HSP70. Pre-incubation of neutrophils with cycloheximide, the inhibitor of protein synthesis, did not change the intracellular HSP70 dynamics registered by flow cytometry indicating that the increased HSP70 level detected immediately after the heat shock was not mediated by de novo protein synthesis. It was confirmed by Western blotting analysis of HSP70 intracellular content. It was suggested that the elevated HSP70 level was related to conformational HSP70 molecule changes and to increased availability of HSP70 epitopes for antibody binding. Using a panel of antibodies specific to the N-terminal ATP-binding or C-terminal substrate-binding domains of HSP70 it has been demonstrated by cell immunofluorescence and flow cytometry methods that the heat shock-associated increase of the intracellular HSP70 level was mediated by HSP70 interaction with antibodies recognizing HSP70 substrate-binding domain. It was demonstrated that the decrease of intracellular HSP70 level after heat treatment could be connected with a release of both inducible and constitutive HSP70 into extracellular space. Our data suggest that stress-induced release of HSP70 from neutrophils is regulated by ABC-transporters.

  3. Bisphenol A alters transcript levels of biomarker genes for Major Depressive Disorder in vascular endothelial cells and colon cancer cells.

    PubMed

    Ribeiro-Varandas, Edna; Pereira, H Sofia; Viegas, Wanda; Delgado, Margarida

    2016-06-01

    Bisphenol A (BPA) is capable of mimicking endogenous hormones with potential consequences for human health and BPA exposure has been associated with several human diseases including neuropsychiatric disorders. Here, quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) results show that BPA at low concentrations (10 ng/mL and 1 μg/mL) induces differential transcript levels of four biomarker genes for Major Depressive Disorder (MDD) in HT29 human colon adenocarcinona cell line and Human Umbilical Vein Endothelial Cells (HUVEC). These results substantiate increasing concerns of BPA exposure in levels currently detected in humans.

  4. VimA-Dependent Modulation of Acetyl Coenzyme A Levels and Lipid A Biosynthesis Can Alter Virulence in Porphyromonas gingivalis

    PubMed Central

    Aruni, A. Wilson; Lee, J.; Osbourne, D.; Dou, Y.; Roy, F.; Muthiah, A.; Boskovic, D. S.

    2012-01-01

    The Porphyromonas gingivalis VimA protein has multifunctional properties that can modulate several of its major virulence factors. To further characterize VimA, P. gingivalis FLL406 carrying an additional vimA gene and a vimA-defective mutant in a different P. gingivalis genetic background were evaluated. The vimA-defective mutant (FLL451) in the P. gingivalis ATCC 33277 genetic background showed a phenotype similar to that of the vimA-defective mutant (FLL92) in the P. gingivalis W83 genetic background. In contrast to the wild type, gingipain activity was increased in P. gingivalis FLL406, a vimA chimeric strain. P. gingivalis FLL451 had a five times higher biofilm-forming capacity than the parent strain. HeLa cells incubated with P. gingivalis FLL92 showed a decrease in invasion, in contrast to P. gingivalis FLL451 and FLL406, which showed increases of 30 and 40%, respectively. VimA mediated coenzyme A (CoA) transfer to isoleucine and reduced branched-chain amino acid metabolism. The lipid A content and associated proteins were altered in the vimA-defective mutants. The VimA chimera interacted with several proteins which were found to have an LXXTG motif, similar to the sorting motif of Gram-positive organisms. All the proteins had an N-terminal signal sequence with a putative sorting signal of L(P/T/S)X(T/N/D)G and two unique signatures of EXGXTX and HISXXGXG, in addition to a polar tail. Taken together, these observations further confirm the multifunctional role of VimA in modulating virulence possibly through its involvement in acetyl-CoA transfer and lipid A synthesis and possibly by protein sorting. PMID:22144476

  5. Histopathological alterations of juvenile green (Acipenser medirostris) and white sturgeon (Acipenser transmontanus) exposed to graded levels of dietary methylmercury.

    PubMed

    Lee, Jang-Won; Kim, Jae-Won; De Riu, Nicola; Moniello, Giuseppe; Hung, Silas S O

    2012-03-01

    Triplicate groups of juvenile green and white sturgeon (average weight of 30 ± 2 g) were exposed to one of four concentrations of dietary methylmercury (MeHg; 0, 25, 50, and 100 mg MeHg/kg diet) for 8 weeks to determine and compare the sensitivity of the two sturgeon species from a histopathological perspective. After 4- and 8-week exposure, histological changes were examined in the kidney, liver, gill, skeletal muscle, and heart muscle of both species using light microscopy. Marked abnormalities were observed in the kidney and liver of both sturgeon species after each exposure period; the abnormalities showed progressive histological alterations in severity with increasing doses and duration of exposure. Renal lesions included tubular epithelium degeneration and necrosis, renal corpuscular disintegration, and interstitial tissue degeneration. The changes observed in the livers of both sturgeon species were glycogen depletion and vacuolar degeneration. In the gill and skeletal and heart muscle of green and white sturgeon fed MeHg-added diets, mild histological changes were observed but did not show pronounced difference between the two species. Although the lowest observed effect concentration in both species was the 25 mg MeHg/kg diet, the histological changes in the kidney and liver were more pronounced at all treatments groups of green sturgeon than those of white sturgeon. The current results on structural changes of kidney and liver (i.e., more severe glycogen depletion and tubular epithelium degeneration in green sturgeon) confirmed our previous results, in that green sturgeon exhibited a higher mortality, lower growth rate, and lower protein, lipid, and energy contents in their whole body than white sturgeon under the same MeHg exposures.

  6. Chronic stress induces structural alterations in splenic lymphoid tissue that are associated with changes in corticosterone levels in wistar-kyoto rats.

    PubMed

    Hernandez, María Eugenia; Martinez-Mota, Lucia; Salinas, Citlaltepetl; Marquez-Velasco, Ricardo; Hernandez-Chan, Nancy G; Morales-Montor, Jorge; Pérez-Tapia, Mayra; Streber, María L; Granados-Camacho, Ivonne; Becerril, Enrique; Javier, Baquera-Heredia; Pavón, Lenin

    2013-01-01

    Major depressive disorder patients present chronic stress and decreased immunity. The Wistar-Kyoto rat (WKY) is a strain in which the hypothalamic-pituitary-adrenal axis is overactivated. To determine whether chronic stress induces changes in corticosterone levels and splenic lymphoid tissue, 9-week-old male rats were subject to restraint stress (3 h daily), chemical stress (hydrocortisone treatment, 50 mg/Kg weight), mixed stress (restraint plus hydrocortisone), or control treatment (without stress) for 1, 4, and 7 weeks. The serum corticosterone levels by RIA and spleens morphology were analyzed. Corticosterone levels as did the structure, size of the follicles and morphology of the parenchyma (increase in red pulp) in the spleen, varied depending on time and type of stressor. These changes indicate that chronic stress alters the immune response in the spleen in WKY rats by inducing morphological changes, explaining in part the impaired immunity that develops in organisms that are exposed to chronic stress.

  7. Engineering the expression level of cytosolic nucleoside diphosphate kinase in transgenic Solanum tuberosum roots alters growth, respiration and carbon metabolism.

    PubMed

    Dorion, Sonia; Clendenning, Audrey; Rivoal, Jean

    2017-03-01

    Nucleoside diphosphate kinase (NDPK) is a ubiquitous enzyme that catalyzes the transfer of the γ-phosphate from a donor nucleoside triphosphate to an acceptor nucleoside diphosphate. In this study we used a targeted metabolomic approach and measurement of physiological parameters to report the effects of the genetic manipulation of cytosolic NDPK (NDPK1) expression on physiology and carbon metabolism in potato (Solanum tuberosum) roots. Sense and antisense NDPK1 constructs were introduced in potato using Agrobacterium rhizogenes to generate a population of root clones displaying a 40-fold difference in NDPK activity. Root growth, O2 uptake, flux of carbon between sucrose and CO2 , levels of reactive oxygen species and some tricarboxylic acid cycle intermediates were positively correlated with levels of NDPK1 expression. In addition, NDPK1 levels positively affected UDP-glucose and cellulose contents. The activation state of ADP-glucose pyrophosphorylase, a key enzyme in starch synthesis, was higher in antisense roots than in roots overexpressing NDPK1. Further analyses demonstrated that ADP-glucose pyrophosphorylase was more oxidized, and therefore less active, in sense clones than antisense clones. Consequently, antisense NDPK1 roots accumulated more starch and the starch to cellulose ratio was negatively affected by the level of NDPK1. These data support the idea that modulation of NDPK1 affects the distribution of carbon between starch and cellulose biosynthetic pathways.

  8. Effect of a novel neurotensin analog, NT69L, on nicotine-induced alterations in monoamine levels in rat brain.

    PubMed

    Liang, Yanqi; Boules, Mona; Shaw, Amanda M; Williams, Katrina; Fredrickson, Paul; Richelson, Elliott

    2008-09-22

    NT69L, is a novel neurotensin (8-13) analog that participates in the modulation of the dopaminergic pathways implicated in addiction to psychostimulants. NT69L blocks nicotine-induced hyperactivity as well as the initiation and expression of sensitization in rats. Recent evidence suggests that stimulation of mesocorticolimbic dopamine system, with influences from the other monoamine systems, e.g. norepinephrine and serotonin, is involved in nicotine's reinforcing properties. The aim of the present study was to investigate the effect of pretreatment with NT69L on nicotine-induced changes in monoamine levels in the rat brain using in vivo microdialysis. Acute or chronic (0.4 mg/kg, sc, once daily for 2 weeks) administration of nicotine elicited increases in extracellular levels of dopamine, dopamine metabolites, norepinephrine, or serotonin in medial prefrontal cortex, nucleus accumbens shell, and core of rats. Pretreatment with NT69L (1 mg/kg, intraperitoneally, ip) administered 40 min before nicotine injection significantly attenuated the acute nicotine-evoked increases in norepinephrine levels in medial prefrontal cortex, dopamine and serotonin in nucleus accumbens shell. After chronic nicotine administration, pretreatment of NT69L markedly reversed the increase in dopamine levels in the nucleus accumbens core. NT69L's attenuation of some of the biochemical effects of acute and chronic nicotine is consistent with this peptide's attenuation of nicotine-induced behavioral effects. These data further support a role for NT69L or other neurotensin receptor agonists to treat nicotine addiction.

  9. Sex Hormones in Allergic Conjunctivitis: Altered Levels of Circulating Androgens and Estrogens in Children and Adolescents with Vernal Keratoconjunctivitis

    PubMed Central

    Sacchetti, Marta; Lambiase, Alessandro; Moretti, Costanzo; Bonini, Stefano

    2015-01-01

    Purpose. Vernal keratoconjunctivitis (VKC) is a chronic allergic disease mainly affecting boys in prepubertal age and usually recovering after puberty. To evaluate a possible role of sex hormones in VKC, serum levels of sex hormones in children and adolescents with VKC were assessed. Methods. 12 prepubertal and 7 early pubertal boys with active VKC and 6 male patients with VKC in remission phase at late pubertal age and 48 healthy age and sex-matched subjects were included. Serum concentration of estrone, 17 beta-estradiol, dehydroepiandrosterone-sulfate, total testosterone and free testosterone, dihydrotestosterone (DHT), cortisol, delta-4-androstenedione, follicle-stimulating hormone, luteinizing hormone, and sex-hormones binding globuline (SHBG) were evaluated. Results. Serum levels of Estrone were significantly increased in all groups of patients with VKC when compared to healthy controls (P < 0.001). Prepubertal and early pubertal VKC showed a significant decrease in DHT (P = 0.007 and P = 0.028, resp.) and SHBG (P = 0.01 and P = 0.002, resp.) when compared to controls and serum levels of SHBG were increased in late pubertal VKC in remission phase (P = 0.007). Conclusions and Relevance. VKC patients have different circulating sex hormone levels in different phases of the disease and when compared to nonallergic subjects. These findings suggest a role played by sex hormones in the pathogenesis and/or activity of VKC. PMID:25756057

  10. Obestatin is present in saliva: alterations in obestatin and ghrelin levels of saliva and serum in ischemic heart disease.

    PubMed

    Ozbay, Yilmaz; Aydin, Suleyman; Dagli, A Ferda; Akbulut, Mehmet; Dagli, Necati; Kilic, Nermin; Rahman, Ali; Sahin, Ibrahim; Polat, Veli; Ozercan, H Ibrahim; Arslan, Nadi; Sensoy, Dogan

    2008-01-31

    Ghrelin and obestatin are a single gene products and are a multiple functional peptides that regulates energy homeostasis, and food intake. In the present work, we studied the secretion of ghrelin and its co-secreted peptide obestatin in 44 patients with ischemic heart disease with that of 27 healthy matched controls. Here we first conducted using an immunohistochemistry assay to screen whether human salivary glands have any obestatin immunoreactivity. Then, serum and saliva obestatin and acylated ghrelin levels were determined by using Radioimmunoassay. Our immunohistochemical analysis demonstrated that obestatin was localized in the striated and excretory duct of human salivary gland. We also report for the first time that obestatin, like ghrelin, is present in human salivary gland and saliva. No evidence of the role of obestatin or ghrelin saliva levels in the context of ischemic heart disease was found. Salivary ghrelin and obestatin levels are correlated in controls with the blood levels. Determination of salivary values could represent a non-invasive alternative to serum ones that can be useful in clinical practice.

  11. Phylogenetic metrics of community similarity.

    PubMed

    Ives, Anthony R; Helmus, Matthew R

    2010-11-01

    We derive a new metric of community similarity that takes into account the phylogenetic relatedness among species. This metric, phylogenetic community dissimilarity (PCD), can be partitioned into two components, a nonphylogenetic component that reflects shared species between communities (analogous to Sørensen' s similarity metric) and a phylogenetic component that reflects the evolutionary relationships among nonshared species. Therefore, even if a species is not shared between two communities, it will increase the similarity of the two communities if it is phylogenetically related to species in the other community. We illustrate PCD with data on fish and aquatic macrophyte communities from 59 temperate lakes. Dissimilarity between fish communities associated with environmental differences between lakes often has a phylogenetic component, whereas this is not the case for macrophyte communities. With simulations, we then compare PCD with two other metrics of phylogenetic community similarity, II(ST) and UniFrac. Of the three metrics, PCD was best at identifying environmental drivers of community dissimilarity, showing lower variability and greater statistical power. Thus, PCD is a statistically powerful metric that separates the effects of environmental drivers on compositional versus phylogenetic components of community structure.

  12. Alterations in polyamine levels induced by phorbol diesters and other agents that promote differentiation in human promyelocytic leukemia cells

    SciTech Connect

    Huberman, E.; Weeks, C.; Herrmann, A.; Callaham, M.; Slaga, T.

    1981-02-01

    Polyamine levels were evaluated in human HL-60 promyelocytic leukemia cells after treatment with inducers of terminal differentiation. Differentiation in these cells was determined by increases in the percentage of morphologically mature cells and in lysozyme activity. Treatment of the HL-60 cells with phorbol 12-myristate-13-acetate (PMA), phorbol 12,13-didecanoate or other inducers of terminal differentiation such as dimethylsulfoxide and retinoic acid resulted in increased levels of putrescine. However, no increase in putrescine could be detected after PMA treatment of a HL-60 cell variant that exhibited a decreased susceptibility to PMA-induced terminal differentiation. Similarly, no increase in putrescine was observed with two nontumor-promoters (phorbol 12,13-diacetate and 4-O-methyl-PMA) or with anthralin, a non-phorbol tumor promoter. In addition to enhancing putrescine levels, PMA also increased the amount of spermidine and decreased the amount of spermine. The increase in putrescine and spermidine preceded the expression of the various differentiation markers. Unlike the changes observed in the polyamine levels after PMA treatment, the activities of ornithine and S-adenosylmethionine decarboxylases, which are polyamine biosynthetic enzymes, did not significantly change. ..cap alpha..-Methylornithine and ..cap alpha..-difluoromethylornithine and methylglyoxal bis(guanylhydrazone), which are inhibitors of the polyamine biosynthetic enzymes, did not affect differentiation in control or PMA-treated cells. Because of these observations, we suggest that the change in polyamine levels involve biochemical pathways other than the known biosynthetic ones. By-products of these pathways may perhaps be the controlling factors involved in the induction of terminal differentiation in the HL-60 and other cell types as well.

  13. Gelsolin-Cu/ZnSOD interaction alters intracellular reactive oxygen species levels to promote cancer cell invasion

    PubMed Central

    Tochhawng, Lalchhandami; Deng, Shuo; Pugalenthi, Ganesan; Kumar, Alan Prem; Lim, Kiat Hon; Tan, Tuan Zea; Yang, Henry; Hooi, Shing Chuan; Goh, Yaw Chong; Maciver, Sutherland K.; Pervaiz, Shazib; Yap, Celestial T.

    2016-01-01

    The actin-binding protein, gelsolin, is a well known regulator of cancer cell invasion. However, the mechanisms by which gelsolin promotes invasion are not well established. As reactive oxygen species (ROS) have been shown to promote cancer cell invasion, we investigated on the hypothesis that gelsolin-induced changes in ROS levels may mediate the invasive capacity of colon cancer cells. Herein, we show that increased gelsolin enhances the invasive capacity of colon cancer cells, and this is mediated via gelsolin's effects in elevating intracellular superoxide (O2.-) levels. We also provide evidence for a novel physical interaction between gelsolin and Cu/ZnSOD, that inhibits the enzymatic activity of Cu/ZnSOD, thereby resulting in a sustained elevation of intracellular O2.-. Using microarray data of human colorectal cancer tissues from Gene Omnibus, we found that gelsolin gene expression positively correlates with urokinase plasminogen activator (uPA), an important matrix-degrading protease invovled in cancer invasion. Consistent with the in vivo evidence, we show that increased levels of O2.- induced by gelsolin overexpression triggers the secretion of uPA. We further observed reduction in invasion and intracellular O2.- levels in colon cancer cells, as a consequence of gelsolin knockdown using two different siRNAs. In these cells, concurrent repression of Cu/ZnSOD restored intracellular O2.- levels and rescued invasive capacity. Our study therefore identified gelsolin as a novel regulator of intracellular O2.- in cancer cells via interacting with Cu/ZnSOD and inhibiting its enzymatic activity. Taken together, these findings provide insight into a novel function of gelsolin in promoting tumor invasion by directly impacting the cellular redox milieu. PMID:27391159

  14. Deletions of the SACPD-C locus elevate seed stearic acid levels but also result in fatty acid and morphological alterations in nitrogen fixing nodules

    PubMed Central

    2014-01-01

    Background Soybean (Glycine max) seeds are the primary source of edible oil in the United States. Despite its widespread utility, soybean oil is oxidatively unstable. Until recently, the majority of soybean oil underwent chemical hydrogenation, a process which also generates trans fats. An alternative to chemical hydrogenation is genetic modification of seed oil through identification and introgression of mutant alleles. One target for improvement is the elevation of a saturated fat with no negative cardiovascular impacts, stearic acid, which typically constitutes a minute portion of seed oil (~3%). Results We examined radiation induced soybean mutants with moderately increased stearic acid (10-15% of seed oil, ~3-5 X the levels in wild-type soybean seeds) via comparative whole genome hybridization and genetic analysis. The deletion of one SACPD isoform encoding gene (SACPD-C) was perfectly correlated with moderate elevation of seed stearic acid content. However, SACPD-C deletion lines were also found to have altered nodule fatty acid composition and grossly altered morphology. Despite these defects, overall nodule accumulation and nitrogen fixation were unaffected, at least under laboratory conditions. Conclusions Although no yield penalty has been reported for moderate elevated seed stearic acid content in soybean seeds, our results demonstrate that genetic alteration of seed traits can have unforeseen pleiotropic consequences. We have identified a role for fatty acid biosynthesis, and SACPD activity in particular, in the establishment and maintenance of symbiotic nitrogen fixation. PMID:24886084

  15. Altered Concentrations of Copper, Zinc, and Iron are Associated With Increased Levels of Glycated Hemoglobin in Patients With Type 2 Diabetes Mellitus and Their First-Degree Relatives

    PubMed Central

    Atari-Hajipirloo, Somayeh; Valizadeh, Neda; Khadem-Ansari, Mohammad-Hassan; Rasmi, Yousef; Kheradmand, Fatemeh

    2016-01-01

    Background The altered levels of some essential trace elements and antioxidant minerals have been observed in diabetic patients. Objectives The aim of the present study was to compare the concentrations of essential trace elements, copper (Cu), zinc (Zn), and iron (Fe) in the serum of patients who have type 2 diabetes mellitus (T2DM) with those of their non-diabetic first-degree relatives (FDR) and control subjects. The association between glycated hemoglobin (HbA1c) and levels of metals was also evaluated. Patients and Methods We studied 46 subjects with T2DM, 46 FDR, and 50 control subjects matched for age and sex. Serum concentrations of Cu, Zn, and Fe were measured by colorimetric kit. Fasting blood glucose (FBG) and HbA1c were assayed using the standard kit. Results An imbalance in the levels of the studied metals was observed in both patients with T2DM and FDR. We found significantly decreased levels of Zn and higher levels of Cu and Fe in the patients with T2DM and FDR when compared with the control subjects (P < 0.05). HbA1c levels were positively correlated with Cu and Fe and inversely correlated with Zn in the patients with T2DM and FDR (P < 0.05). Conclusions The patients with T2DM and FDR had altered contents of Cu, Zn, and Fe that might be a predisposing factor to the development of diabetes in future or vice versa the result of diabetes development. Impaired metabolism of these elements may contribute to the augmented risk of developing type 2 diabetes mellitus later in the life of their first-degree relatives. PMID:27761143

  16. Patients treated for male pattern hair with finasteride show, after discontinuation of the drug, altered levels of neuroactive steroids in cerebrospinal fluid and plasma.

    PubMed

    Caruso, Donatella; Abbiati, Federico; Giatti, Silvia; Romano, Simone; Fusco, Letizia; Cavaletti, Guido; Melcangi, Roberto Cosimo

    2015-02-01

    Observations performed in a subset of patients treated for male pattern hair loss indicate that persistent sexual side effects as well as anxious/depressive symptomatology have been reported even after discontinuation of finasteride treatment. Due to the capability of finasteride to block the metabolism of progesterone (PROG) and/or testosterone (T) we have evaluated, by liquid chromatography-tandem mass spectrometry, the levels of several neuroactive steroids in paired plasma and cerebrospinal fluid (CSF) samples obtained from post-finasteride patients and in healthy controls. At the examination, post-finasteride patients reported muscular stiffness, cramps, tremors and chronic fatigue in the absence of clinical evidence of any muscular disorder or strength reduction. Although severity of the anxious/depressive symptoms was quite variable in their frequency, overall all the subjects had a fairly complex and constant neuropsychiatric pattern. Assessment of neuroactive steroid levels in CSF showed a decrease of PROG and its metabolites, dihydroprogesterone (DHP) and tetrahydroprogesterone (THP), associated with an increase of its precursor pregnenolone (PREG). Altered levels were also observed for T and its metabolites. Thus, a significant decrease of dihydrotestosterone (DHT) associated with an increase of T as well as of 3α-diol was detected. Changes in neuroactive steroid levels also occurred in plasma. An increase of PREG, T, 3α-diol, 3β-diol and 17β-estradiol was associated with decreased levels of DHP and THP. The present observations show that altered levels of neuroactive steroids, associated with depression symptoms, are present in androgenic alopecia patients even after discontinuation of the finasteride treatment. This article is part of a Special Issue entitled 'Sex steroids and brain disorders'.

  17. Sugar alters the level of serum insulin and plasma glucose and the serum cortisol:DHEAS ratio in female migraine sufferers.

    PubMed

    Kokavec, Anna; Crebbin, Susan J

    2010-12-01

    Early work has highlighted that a large percentage of migraineurs may have an altered glucidic methabolis due to carbohydrate-induced hyperinsulinism. The aim of this study was to assess the effect of sucrose on biomarkers of energy metabolism and utilization in migraineous females. A total of 16 participants (8 = Migraine, 8 = Non-migraine) at the mid-point of their menstrual cycle underwent a 15-h fast prior to ingesting 75 g sucrose dissolved in 175 g water. Blood sampling for the assessment of serum insulin, serum cortisol and serum dehydroepiandrosterone sulfate (DHEAS) and plasma glucose was conducted upon arrival at 09:00 h and then at regular 15-min intervals across a 150-min experimental period. The results showed a significant alteration in serum insulin and plasma glucose following sucrose ingestion in the migraine and non-migraine groups. In addition, significant group differences were observed in the level of serum insulin, serum DHEAS, and the cortisol:DHEAS ratio with migraine participants on average recording a higher sucrose-induced serum insulin level and lower DHEAS level and cortisol:DHEAS ratio when group data was compared. It was concluded that while sucrose consumption may potentiate serum insulin in migraineurs this does not result in the development of sucrose-induced hypoglycemia in migraine or non-migraine participants.

  18. Prozac affects stickleback nest quality without altering androgen, spiggin or aggression levels during a 21-day breeding test.

    PubMed

    Sebire, Marion; Elphinstone Davis, Jessica; Hatfield, Robert; Winberg, Svante; Katsiadaki, Ioanna

    2015-11-01

    Pharmaceuticals are increasingly being used in human and veterinary medicine, and their presence in the aquatic environment may present a threat to non-target aquatic organisms. The selective serotonin reuptake inhibitor fluoxetine (Prozac) has been reported to affect diverse behaviours (feeding, aggression, and reproduction) and also the endocrine system (steroid biosynthesis pathway) in fish. To investigate these claims further, and in particular effects on androgen synthesis, male three-spined sticklebacks (Gasterosteus aculeatus) were exposed to fluoxetine at 0, 3.2, 10 and 32μg/L in a flow-through system for 21 days. Their sex was determined prior to exposure using a non-invasive method to collect DNA for determining the genetic sex, reported here for the first time. This was necessary as the exposure required males of a non-breeding status which had not developed secondary characteristics. Post exposure a number of biochemical (serotonin, steroid and spiggin levels) and apical (aggressive behaviour) endpoints were measured. No effects were detected on morphometric parameters, spiggin or androgen (11-ketotestosterone) levels. However, all fluoxetine-exposed male fish had higher cortisol levels in comparison to the control fish, although this effect only persisted throughout the whole exposure duration at the highest concentration (32μg/L). In addition, the ratio of 5-HIAA/5-HT (serotonin metabolite/serotonin) was significantly lower in the brains of males exposed to fluoxetine at all concentrations tested. Although we found no differences in the number of nests built by the males, the quality of the nests produced by the fluoxetine-exposed males was generally inferior consisting only of a basic, rudimentary structure. Males exposed to 32μg/L of fluoxetine displayed a delayed response to a simulated threat (rival male via own mirror image) and were less aggressive (number of bites and attacks) toward their mirror image, but these differences were not

  19. Postnatal ethanol exposure alters levels of 2-arachidonylglycerol-metabolizing enzymes and pharmacological inhibition of monoacylglycerol does not cause neurodegeneration in neonatal mice

    PubMed Central

    Subbanna, Shivakumar; Psychoyos, Delphine; Xie, Shan; Basavarajappa, Balapal S.

    2015-01-01

    The consumption of ethanol by pregnant women may cause neurological abnormalities, affecting learning and memory processes in children, and are collectively described as fetal alcohol spectrum disorders (FASDs). However, the molecular mechanisms underlying these changes are still poorly understood. In our previous studies, we found that ethanol treatment of postnatal day 7 (P7) mice significantly enhances anandamide (AEA) levels but not 2-arachidonylglycerol (2-AG) levels and induces widespread neurodegeneration, but the reason for the lack of significant effects of ethanol on the 2-AG level is unknown. In this study, we examined developmental changes in diacylglycerol lipase-α, β (DAGL-α and β) and monoacylglycerol lipase (MAGL). We found that the levels of these proteins were significantly higher in adult brains compared to those detected early in brain development. Next, we examined the influence of P7 ethanol treatment on these enzymes, finding that it differentially altered the DAGL-α protein and mRNA levels but consistently enhanced those of the DAGL-β. Interestingly, the ethanol treatment enhanced MAGL protein and mRNA levels. Inhibition of MAGL with KML29 failed to induce neurodegeneration in P7 mice. Collectively, these findings suggest that ethanol significantly activates DAGL-β and MAGL in the neonatal brain, resulting in no net change in 2-AG levels. PMID:25857698

  20. Postnatal ethanol exposure alters levels of 2-arachidonylglycerol-metabolizing enzymes and pharmacological inhibition of monoacylglycerol lipase does not cause neurodegeneration in neonatal mice.

    PubMed

    Subbanna, Shivakumar; Psychoyos, Delphine; Xie, Shan; Basavarajappa, Balapal S

    2015-07-01

    The consumption of ethanol by pregnant women may cause neurological abnormalities, affecting learning and memory processes in children, and are collectively described as fetal alcohol spectrum disorders. However, the molecular mechanisms underlying these changes are still poorly understood. In our previous studies, we found that ethanol treatment of postnatal day 7 (P7) mice significantly enhances the anandamide levels but not the 2-arachidonylglycerol (2-AG) levels and induces widespread neurodegeneration, but the reason for the lack of significant effects of ethanol on the 2-AG level is unknown. In this study, we examined developmental changes in diacylglycerol lipase-α, β (DAGL-α and β) and monoacylglycerol lipase (MAGL). We found that the levels of these proteins were significantly higher in adult brains compared to those detected early in brain development. Next, we examined the influence of P7 ethanol treatment on these enzymes, finding that it differentially altered the DAGL-α protein and mRNA levels but consistently enhanced those of the DAGL-β. Interestingly, the ethanol treatment enhanced MAGL protein and mRNA levels. Inhibition of MAGL with KML29 failed to induce neurodegeneration in P7 mice. Collectively, these findings suggest that ethanol significantly activates DAGL-β and MAGL in the neonatal brain, resulting in no net change in 2-AG levels.

  1. Phylogenetics and the Human Microbiome

    PubMed Central

    Matsen, Frederick A.

    2015-01-01

    The human microbiome is the ensemble of genes in the microbes that live inside and on the surface of humans. Because microbial sequencing information is now much easier to come by than phenotypic information, there has been an explosion of sequencing and genetic analysis of microbiome samples. Much of the analytical work for these sequences involves phylogenetics, at least indirectly, but methodology has developed in a somewhat different direction than for other applications of phylogenetics. In this article, I review the field and its methods from the perspective of a phylogeneticist, as well as describing current challenges for phylogenetics coming from this type of work. PMID:25102857

  2. Phylogenetics and the human microbiome.

    PubMed

    Matsen, Frederick A

    2015-01-01

    The human microbiome is the ensemble of genes in the microbes that live inside and on the surface of humans. Because microbial sequencing information is now much easier to come by than phenotypic information, there has been an explosion of sequencing and genetic analysis of microbiome samples. Much of the analytical work for these sequences involves phylogenetics, at least indirectly, but methodology has developed in a somewhat different direction than for other applications of phylogenetics. In this article, I review the field and its methods from the perspective of a phylogeneticist, as well as describing current challenges for phylogenetics coming from this type of work.

  3. Identifying stimuli that alter immediate and subsequent levels of vocal stereotypy: a further analysis of functionally matched stimulation.

    PubMed

    Lanovaz, Marc J; Fletcher, Sarah E; Rapp, John T

    2009-09-01

    We used a three-component multiple-schedule with a brief reversal design to evaluate the effects of structurally unmatched and matched stimuli on immediate and subsequent vocal stereotypy that was displayed by three children with autism spectrum disorders. For 2 of the 3 participants, access to matched stimuli, unmatched stimuli, and music decreased immediate levels of vocal stereotypy; however, with the exception of matched stimuli for one participant, none of the stimuli produced a clear abolishing operation for subsequent vocal stereotypy. That is, vocal stereotypy typically increased to baseline levels shortly after alternative stimulation was removed. Detection of motivating operations for each participant's vocal stereotypy was aided by the analysis of component distributions. The results are discussed in terms of immediate and subsequent effects of preferred stimuli on automatically reinforced problem behavior.

  4. Histopathological alterations, biochemical responses and acetylcholinesterase levels in Clarias gariepinus as biomarkers of exposure to organophosphates pesticides.

    PubMed

    Doherty, V F; Ladipo, M K; Aneyo, I A; Adeola, A; Odulele, W Y

    2016-05-01

    Organophosphate pesticides, commonly used in large scale farming, have been found to be major contaminants in aquatic environment. Clarias gariepinus was exposed to acute and sublethal concentrations of phostoxin and DD Force to evaluate single and joint action toxicity of the organophosphates. Effects of phostoxin and DD force on antioxidant enzymes, fish organs and acetylcholinesterase levels in fingerlings and juveniles of C. gariepinus were also investigated. The lethal concentrations (96 h LC50) for phostoxin and DD Force were 0.631 and 1.759 mg/l, respectively. The results obtained from the bioassay showed that phostoxin was 2.8× more toxic than DD Force after exposure of C. gariepinus. Joint action toxicity evaluations of phostoxin and DD Force showed that the interaction between the chemicals was synergistic (RTU >1). The biochemical responses in the exposed fish differed significantly (P < 0.05) from the control fish. The result of acetylcholinesterase study revealed significant difference between acetylcholinesterase levels in the exposed fish and control, with reduction in the acetylcholineterase level in fish exposed to sublethal concentrations of phostoxin and DD Force. Haematological studies revealed an increase in WBC, RBC, PCV and platelets in the exposed fish. Histopathology of the gills showed shortened primary lamellae, loss of secondary lamellae and loss of ceratobrachial bones. In the acute toxicity studies, respiratory stress, erratic swimming and instant death of fish were observed in the exposed fish. This study reveals that changes in histopathology and acetylcholinesterase level are good biomarkers and can be successfully used to detect exposure to organophosphates pesticides in fish.

  5. Low β₂-adrenergic receptor level may promote development of castration resistant prostate cancer and altered steroid metabolism.

    PubMed

    Braadland, Peder Rustøen; Grytli, Helene Hartvedt; Ramberg, Håkon; Katz, Betina; Kellman, Ralf; Gauthier-Landry, Louis; Fazli, Ladan; Krobert, Kurt Allen; Wang, Wanzhong; Levy, Finn Olav; Bjartell, Anders; Berge, Viktor; Rennie, Paul S; Mellgren, Gunnar; Mælandsmo, Gunhild Mari; Svindland, Aud; Barbier, Olivier; Taskén, Kristin Austlid

    2016-01-12

    The underlying mechanisms responsible for the development of castration-resistant prostate cancer (CRPC) in patients who have undergone androgen deprivation therapy are not fully understood. This is the first study to address whether β2-adrenergic receptor (ADRB2)- mediated signaling may affect CRPC progression in vivo. By immunohistochemical analyses, we observed that low levels of ADRB2 is associated with a more rapid development of CRPC in a Norwegian patient cohort. To elucidate mechanisms by which ADRB2 may affect CRPC development, we stably transfected LNCaP cells with shRNAs to mimic low and high expression of ADRB2. Two UDP-glucuronosyltransferases, UGT2B15 and UGT2B17, involved in phase II metabolism of androgens, were strongly downregulated in two LNCaP shADRB2 cell lines. The low-ADRB2 LNCaP cell lines displayed lowered glucuronidation activities towards androgens than high-ADRB2 cells. Furthermore, increased levels of testosterone and enhanced androgen responsiveness were observed in LNCaP cells expressing low level of ADRB2. Interestingly, these cells grew faster than high-ADRB2 LNCaP cells, and sustained their low glucuronidation activity in castrated NOD/SCID mice. ADRB2 immunohistochemical staining intensity correlated with UGT2B15 staining intensity in independent TMA studies and with UGT2B17 in one TMA study. Similar to ADRB2, we show that low levels of UGT2B15 are associated with a more rapid CRPC progression. We propose a novel mechanism by which ADRB2 may affect the development of CRPC through downregulation of UGT2B15 and UGT2B17.

  6. Low β2-adrenergic receptor level may promote development of castration resistant prostate cancer and altered steroid metabolism

    PubMed Central

    Katz, Betina; Kellman, Ralf; Gauthier-Landry, Louis; Fazli, Ladan; Krobert, Kurt Allen; Wang, Wanzhong; Levy, Finn Olav; Bjartell, Anders; Berge, Viktor; Rennie, Paul S.; Mellgren, Gunnar; Mælandsmo, Gunhild Mari; Svindland, Aud; Barbier, Olivier; Taskén, Kristin Austlid

    2016-01-01

    The underlying mechanisms responsible for the development of castration-resistant prostate cancer (CRPC) in patients who have undergone androgen deprivation therapy are not fully understood. This is the first study to address whether β2-adrenergic receptor (ADRB2)- mediated signaling may affect CRPC progression in vivo. By immunohistochemical analyses, we observed that low levels of ADRB2 is associated with a more rapid development of CRPC in a Norwegian patient cohort. To elucidate mechanisms by which ADRB2 may affect CRPC development, we stably transfected LNCaP cells with shRNAs to mimic low and high expression of ADRB2. Two UDP-glucuronosyltransferases, UGT2B15 and UGT2B17, involved in phase II metabolism of androgens, were strongly downregulated in two LNCaP shADRB2 cell lines. The low-ADRB2 LNCaP cell lines displayed lowered glucuronidation activities towards androgens than high-ADRB2 cells. Furthermore, increased levels of testosterone and enhanced androgen responsiveness were observed in LNCaP cells expressing low level of ADRB2. Interestingly, these cells grew faster than high-ADRB2 LNCaP cells, and sustained their low glucuronidation activity in castrated NOD/SCID mice. ADRB2 immunohistochemical staining intensity correlated with UGT2B15 staining intensity in independent TMA studies and with UGT2B17 in one TMA study. Similar to ADRB2, we show that low levels of UGT2B15 are associated with a more rapid CRPC progression. We propose a novel mechanism by which ADRB2 may affect the development of CRPC through downregulation of UGT2B15 and UGT2B17. PMID:26646591

  7. An Alteration of Lymphocytes Subpopulations and Immunoglobulins Levels in Patients with Diabetic Foot Ulcers Infected Particularly by Resistant Pathogens

    PubMed Central

    Jirkovská, Alexandra; Dubský, Michal; Game, Frances; Vydláková, Jana; Sekerková, Alena; Franeková, Jana; Kučerová, Monika; Stříž, Ilja; Petkov, Vladimír; Němcová, Andrea; Skibová, Jelena

    2016-01-01

    The aim of our study was to analyse immune abnormalities in patients with chronic infected diabetic foot ulcers (DFUs) especially those infected by resistant microorganisms. Methods. 68 patients treated in our foot clinic for infected chronic DFUs with 34 matched diabetic controls were studied. Patients with infected DFUs were subdivided into two subgroups according to the antibiotic sensitivity of causal pathogen: subgroup S infected by sensitive (n = 50) and subgroup R by resistant pathogens (n = 18). Selected immunological markers were compared between the study groups and subgroups. Results. Patients with infected chronic DFUs had, in comparison with diabetic controls, significantly reduced percentages (p < 0.01) and total numbers of lymphocytes (p < 0.001) involving B lymphocytes (p < 0.01), CD4+ (p < 0.01), and CD8+ T cells (p < 0.01) and their naive and memory effector cells. Higher levels of IgG (p < 0.05) including IgG1 (p < 0.001) and IgG3 (p < 0.05) were found in patients with DFUs compared to diabetic controls. Serum levels of immunoglobulin subclasses IgG2 and IgG3 correlated negatively with metabolic control (p < 0.05). A trend towards an increased frequency of IgG2 deficiency was found in patients with DFUs compared to diabetic controls (22% versus 15%; NS). Subgroup R revealed lower levels of immunoglobulins, especially of IgG4 (p < 0.01) in contrast to patients infected by sensitive bacteria. The innate immunity did not differ significantly between the study groups. Conclusion. Our study showed changes mainly in the adaptive immune system represented by low levels of lymphocyte subpopulations and their memory effector cells, and also changes in humoral immunity in patients with DFUs, even those infected by resistant pathogens, in comparison with diabetic controls. PMID:28050566

  8. Long-term exposure to paraquat alters behavioral parameters and dopamine levels in adult zebrafish (Danio rerio).

    PubMed

    Bortolotto, Josiane W; Cognato, Giana P; Christoff, Raissa R; Roesler, Laura N; Leite, Carlos E; Kist, Luiza W; Bogo, Mauricio R; Vianna, Monica R; Bonan, Carla D

    2014-04-01

    Chronic exposure to paraquat (Pq), a toxic herbicide, can result in Parkinsonian symptoms. This study evaluated the effect of the systemic administration of Pq on locomotion, learning and memory, social interaction, tyrosine hydroxylase (TH) expression, dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) levels, and dopamine transporter (DAT) gene expression in zebrafish. Adult zebrafish received an i.p. injection of either 10 mg/kg (Pq10) or 20 mg/kg (Pq20) of Pq every 3 days for a total of six injections. Locomotion and distance traveled decreased at 24 h after each injection in both treatment doses. In addition, both Pq10- and Pq20-treated animals exhibited differential effects on the absolute turn angle. Nonmotor behaviors were also evaluated, and no changes were observed in anxiety-related behaviors or social interactions in Pq-treated zebrafish. However, Pq-treated animals demonstrated impaired acquisition and consolidation of spatial memory in the Y-maze task. Interestingly, dopamine levels increased while DOPAC levels decreased in the zebrafish brain after both treatments. However, DAT expression decreased in the Pq10-treated group, and there was no change in the Pq20-treated group. The amount of TH protein showed no significant difference in the treated group. Our study establishes a new model to study Parkinson-associated symptoms in zebrafish that have been chronically treated with Pq.

  9. Alteration of serum levels of inflammatory cytokines and polysomnographic indices after uvulopalatal flap surgery in obstructive sleep apnea.

    PubMed

    Mutlu, Murad; Vuralkan, Erkan; Akin, Istemihan; Firat, Hikmet; Ardic, Sadik; Akaydin, Sevgi; Miser, Ece

    2017-02-01

    The aim of the current study was to compare the changes in polysomnographic indices and serum levels of C-reactive protein (CRP), cystatin C, tumor necrosis factor-α (TNF-α), and intercellular adhesion molecule-1 (ICAM-1) in patients with obstructive sleep apnea (OSA) who were treated surgically via a uvulopalatal flap (UPF) technique. Twenty-five patients (14 men, 11 women), average age 46.2 ± 9.3 years, who underwent UPF surgery were included in this study. Serum biochemical analyses and polysomnographic examinations were performed before and 6 months after the surgery. Pre- and postoperative values of apnea hypopnea index (AHI), oxygen desaturation index (ODI), and minimum oxygen concentrations, as well as serum levels of CRP, cystatin C, TNF-α, and ICAM-1 were compared. Comparison of variables before and after UPF surgery demonstrated that AHI (p = 0.001), ODI (p < 0.001) and oxygen saturation (p < 0.001) were significantly improved. In addition, serum levels of CRP (p = 0.036), cystatin C (p = 0.005), TNF-α (p < 0.001), and ICAM-1 (p < 0.001) were significantly reduced 6 months after surgery. Our results suggest that UPF is an effective surgical method that alleviates the severity of OSA. Moreover, it may have the potential to prevent the development of atherosclerosis by attenuating the inflammatory process induced by activation of inflammatory mediators such as CRP, TNF-α, ICAM-1, and cystatin C.

  10. Rubidium and potassium levels are altered in Alzheimer's disease brain and blood but not in cerebrospinal fluid.

    PubMed

    Roberts, Blaine R; Doecke, James D; Rembach, Alan; Yévenes, L Fernanda; Fowler, Christopher J; McLean, Catriona A; Lind, Monica; Volitakis, Irene; Masters, Colin L; Bush, Ashley I; Hare, Dominic J

    2016-11-14

    Loss of intracellular compartmentalization of potassium is a biochemical feature of Alzheimer's disease indicating a loss of membrane integrity and mitochondrial dysfunction. We examined potassium and rubidium (a biological proxy for potassium) in brain tissue, blood fractions and cerebrospinal fluid from Alzheimer's disease and healthy control subjects to investigate the diagnostic potential of these two metal ions. We found that both potassium and rubidium levels were significantly decreased across all intracellular compartments in the Alzheimer's disease brain. Serum from over 1000 participants in the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing (AIBL), showed minor changes according to disease state. Potassium and rubidium levels in erythrocytes and cerebrospinal fluid were not significantly different according to disease state, and rubidium was slightly decreased in Alzheimer's disease patients compared to healthy controls. Our data provides evidence that contrasts the hypothesized disruption of the blood-brain barrier in Alzheimer's disease, with the systemic decrease in cortical potassium and rubidium levels suggesting influx of ions from the blood is minimal and that the observed changes are more likely indicative of an internal energy crisis within the brain. These findings may be the basis for potential diagnostic imaging studies using radioactive potassium and rubidium tracers.

  11. Alterations in nigral NMDA and GABAA receptor control of the striatal dopamine level after repetitive exposures to nitrogen narcosis.

    PubMed

    Lavoute, Cécile; Weiss, Michel; Rostain, Jean-Claude

    2008-07-01

    Nitrogen pressure exposure in rats results in decreased dopamine (DA) release at the striatal terminals of the substantia nigra pars compacta (SNc) dopaminergic neurons, demonstrating the narcotic potency of nitrogen. This effect is attributed to decreased excitatory and increased inhibitory inputs to dopaminergic neurons, involving a change in NMDA and GABA(A) receptor function. We investigated whether repetitive exposures to nitrogen modify the excitatory and inhibitory control of the dopaminergic nigro-striatal pathway. We used voltammetry to measure dopamine levels in freely-moving rats, implanted with dopamine-sensitive electrodes in the striatum. NMDA/GABA(A) receptor agonists (NMDA/muscimol) and antagonists (AP7/gabazine) were administered through a guide-cannula into the SNc, and their effects on striatal dopamine levels were measured under normobaric conditions, before and after five repetitive exposures to 1 MPa nitrogen. NMDA-mediated dopamine release was greater following repetitive exposures, AP7-mediated inhibition of glutamatergic input was blocked, suggesting that NMDA receptor sensitivity was increased and glutamate release reduced. Muscimol did not modify dopamine levels following repetitive exposures, whereas the effect of gabazine was greater after exposures than before. This suggested that interneuronal GABA(A) receptors were desensitized, leading to an increased GABAergic input at dopaminergic cells. Thus, repetitive nitrogen exposure induced persistent changes in glutamatergic and GABAergic control of dopaminergic neurons, resulting in decreased activity of the nigrostriatal pathway.

  12. Canavanine Alters ROS/RNS Level and Leads to Post-translational Modification of Proteins in Roots of Tomato Seedlings

    PubMed Central

    Krasuska, Urszula; Andrzejczak, Olga; Staszek, Paweł; Bogatek, Renata; Gniazdowska, Agnieszka

    2016-01-01

    Canavanine (CAN), a structural analog of arginine (Arg), is used as a selective inhibitor of inducible NOS in mammals. CAN is incorporated into proteins’ structure in the place of Arg, leading to the formation of aberrant compounds. This non-protein amino acid is found in legumes, e.g., Canavalia ensiformis (L.) DC. or Sutherlandia frutescens (L.) R.Br. and acts as a strong toxin against herbivores or plants. Tomato (Solanum lycopersicum L.) seedlings were treated for 24–72 h with CAN (10 or 50 μM) inhibiting root growth by 50 or 100%, without lethal effect. We determined ROS level/production in root extracts, fluorescence of DAF-FM and APF derivatives corresponding to RNS level in roots of tomato seedlings and linked CAN-induced restriction of root growth to the post-translational modifications (PTMs) of proteins: carbonylation and nitration. Both PTMs are stable markers of nitro-oxidative stress, regarded as the plant’s secondary response to phytotoxins. CAN enhanced H2O2 content and superoxide radicals generation in extracts of tomato roots and stimulated formation of protein carbonyl groups. An elevated level of carbonylated proteins was characteristic for the plants after 72 h of the culture, mainly for the roots exposed to 10 μM CAN. The proteolytic activity was stimulated by tested non-protein amino acid. CAN treatment led to decline of fluorescence of DAF-FM derivatives, and transiently stimulated fluorescence of APF derivatives. Short-term exposure of tomato seedlings to CAN lowered the protein nitration level. Activity of peroxidase, polyamine oxidase and NADPH oxidase, enzymes acting as modulators of H2O2 concentration and governing root architecture and growth were determined. Activities of all enzymes were stimulated by CAN, but no strict CAN concentration dependence was observed. We conclude, that although CAN treatment led to a decline in the nitric oxide level, PTMs observed in roots of plants exposed to CAN are linked rather to the

  13. IMPAIRED NATURAL KILLER CELL LYSIS IN BREAST CANCER PATIENTS WITH HIGH LEVELS OF PSYCHOLOGICAL STRESS IS ASSOCIATED WITH ALTERED EXPRESSION OF KILLER IMMUNOGLOBULIN-LIKE RECEPTORS

    PubMed Central

    Varker, Kimberly A.; Terrell, Catherine E.; Welt, Marilyn; Suleiman, Samer; Thornton, Lisa; Andersen, Barbara L.; Carson, William E.

    2007-01-01

    Background We previously reported that cancer-related psychological stress is associated with reduced natural killer (NK) cell lysis. We hypothesized that reduced NK cell cytotoxicity in patients with increased levels of stress would correlate with alterations in the expression of inhibitory NK cell receptors (killer immunoglobulin-like receptors, or KIRs). The specific aim of this study was to examine KIR expression in patients with high or low levels of psychologic stress and correlate alterations in KIR expression with NK cell function. Materials and Methods 227 patients underwent baseline evaluation of cancer-related psychological stress and were randomized to psychosocial intervention versus observation. From this population, two groups were defined based on pre-treatment measurements of NK lytic activity, stress levels, and the availability of cryopreserved peripheral blood mononuclear cells (PBMC). Group I (n = 9) had low stress by the Impact of Events Scale (IES), and high NK cell lysis at the 50:1 effector: target ratio (NK50 = 52–89%). Group II (n = 8) had high stress and low NK50 (27–52%). Lymphokine activated killer (LAK) activity, antibody dependent cellular cytotoxicity (ADCC), and expression of cytokine receptors, adhesion molecules, and killer immunoglobulin-like receptors (KIRs) were assessed in PBMC. Results Incubation of PBMC with NK-stimulatory cytokines (IL-2, IL-12, or IL-15) led to significant increases in cytotoxic activity regardless of IES/NK50 scores. There were no significant group differences in NK cell surface expression of the IL-2 receptor components CD25 and CD122, antibody-dependent lysis of HER2/neu-positive SKBr3 cells treated with an anti-HER2/neu monoclonal antibody, expression of adhesion molecules (CD2, CD11a, CD18) and markers of activation (CD69), or expression of the KIRs CD158a, NKG2a, NKB1, and CD161. However, levels of CD158b were significantly higher in Group I after incubation in media alone or with IL-2, and CD94

  14. Dioxin exposure reduces the steroidogenic capacity of mouse antral follicles mainly at the level of HSD17B1 without altering atresia.

    PubMed

    Karman, Bethany N; Basavarajappa, Mallikarjuna S; Hannon, Patrick; Flaws, Jodi A

    2012-10-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent ovarian toxicant. Previously, we demonstrated that in vitro TCDD (1nM) exposure decreases production/secretion of the sex steroid hormones progesterone (P4), androstenedione (A4), testosterone (T), and 17β-estradiol (E2) in mouse antral follicles. The purpose of this study was to determine the mechanism by which TCDD inhibits steroidogenesis. Specifically, we examined the effects of TCDD on the steroidogenic enzymes, atresia, and the aryl hydrocarbon receptor (AHR) protein. TCDD exposure for 48h increased levels of A4, without changing HSD3B1 protein, HSD17B1 protein, estrone (E1), T or E2 levels. Further, TCDD did not alter atresia ratings compared to vehicle at 48h. TCDD, however, did down regulate the AHR protein at 48h. TCDD exposure for 96h decreased transcript levels for Cyp11a1, Cyp17a1, Hsd17b1, and Cyp19a1, but increased Hsd3b1 transcript. TCDD exposure particularly lowered both Hsd17b1 transcript and HSD17B1 protein. However, TCDD exposure did not affect levels of E1 in the media nor atresia ratings at 96h. TCDD, however, decreased levels of the proapoptotic factor Bax. Collectively, these data suggest that TCDD exposure causes a major block in the steroidogenic enzyme conversion of A4 to T and E1 to E2 and that it regulates apoptotic pathways, favoring survival over death in antral follicles. Finally, the down-regulation of the AHR protein in TCDD exposed follicles persisted at 96h, indicating that the activation and proteasomal degradation of this receptor likely plays a central role in the impaired steroidogenic capacity and altered apoptotic pathway of exposed antral follicles.

  15. Can Resistance Exercise Alter Irisin Levels and Expression Profiles of FNDC5 and UCP1 in Rats?

    PubMed Central

    Reisi, Jalil; Ghaedi, Kamran; Rajabi, Hamid; Marandi, Sayyed Mohammad

    2016-01-01

    Background Irisin is a new myokine secreted from the skeletal muscle and appears to affect the metabolism of adipose tissue. Objectives The mechanisms of cellular and molecular identification by which exercise training exerts its benefits remain unclear and are under investigation. Methods We examined the effect of 8-week resistance exercise on plasma irisin levels and expression profiles of muscle FNDC5 and subcutaneous adipose tissue UCP1 in male rats. Sixteen adult male rats were divided into two groups, control (n = 8) and exercise training (n = 8) groups. The training group received exercise for 3 days/week on a specific ladder (120 cm height) with a carrying load of 50% of body weight, which was attached to their tails. Results The weight of the load was gradually increased during the training sessions, ultimately reaching 200% of the body weight of rats in the final week. There were three sets of five repetitions with a 3-min rest between each set of exercise sessions and 1 minute between repetitions. Plasma irisin levels and relative mRNA expression of the genes UCP1 and FNDC5 were assessed. The results demonstrated a significant increase in the irisin levels after 8 weeks of resistance exercise (P < 0.001, t = 4.48). The relative expression of FNDC5 (P < 0.001, t = 6.18) and UCP1 genes (P < 0.001, t = 13.91) was also significantly increased. Conclusions Therefore, we can conclude from this study that resistance exercise may improve body composition possibly through increased thermogenesis in white adipose tissue through the secretion of irisin. PMID:28144410

  16. Alterations in the neuropeptide galanin system in major depressive disorder involve levels of transcripts, methylation, and peptide

    PubMed Central

    Barde, Swapnali; Rüegg, Joelle; Prud’homme, Josée; Ekström, Tomas J.; Palkovits, Miklos; Turecki, Gustavo; Bagdy, Gyorgy; Ihnatko, Robert; Theodorsson, Elvar; Juhasz, Gabriella; Diaz-Heijtz, Rochellys; Mechawar, Naguib; Hökfelt, Tomas G. M.

    2016-01-01

    Major depressive disorder (MDD) is a substantial burden to patients, families, and society, but many patients cannot be treated adequately. Rodent experiments suggest that the neuropeptide galanin (GAL) and its three G protein-coupled receptors, GAL1–3, are involved in mood regulation. To explore the translational potential of these results, we assessed the transcript levels (by quantitative PCR), DNA methylation status (by bisulfite pyrosequencing), and GAL peptide by RIA of the GAL system in postmortem brains from depressed persons who had committed suicide and controls. Transcripts for all four members were detected and showed marked regional variations, GAL and galanin receptor 1 (GALR1) being most abundant. Striking increases in GAL and GALR3 mRNA levels, especially in the noradrenergic locus coeruleus and the dorsal raphe nucleus, in parallel with decreased DNA methylation, were found in both male and female suicide subjects as compared with controls. In contrast, GAL and GALR3 transcript levels were decreased, GALR1 was increased, and DNA methylation was increased in the dorsolateral prefrontal cortex of male suicide subjects, however, there were no changes in the anterior cingulate cortex. Thus, GAL and its receptor GALR3 are differentially methylated and expressed in brains of MDD subjects in a region- and sex-specific manner. Such an epigenetic modification in GALR3, a hyperpolarizing receptor, might contribute to the dysregulation of noradrenergic and serotonergic neurons implicated in the pathogenesis of MDD. Thus, one may speculate that a GAL3 antagonist could have antidepressant properties by disinhibiting the firing of these neurons, resulting in increased release of noradrenaline and serotonin in forebrain areas involved in mood regulation. PMID:27940914

  17. Metal-supplemented diets alter carbohydrate levels in tissue and hemolymph of gypsy moth larvae (Lymantria dispar, Lymantriidae, Lepidoptera)

    SciTech Connect

    Ortel, J.

    1996-07-01

    Larvae of Lymantria dispar were exposed to two concentrations each of Cd, Pb, Cu, and Zn from hatching to day 3 of the fourth instar. The metals were applied via artificial diet (wheat germ diet); two control groups were reared on either an uncontaminated artificial diet (C) or on a natural diet (oak leaves, EF). High-pressure liquid chromatography (HPLC) was employed to analyze the hemolymph carbohydrates, whereas body glycogen and glucose were determined enzymatically. The results were analyzed with respect to diet-specific differences (oak leaves versus wheat germ diet) and metal exposure compared with the uncontaminated artificial diet. Hemolymph trehalose levels were higher in oak leaf-reared individuals than in those fed on the wheat germ diet (p < 0.01), whereas the opposite applied to the body glycogen and free glucose levels (p < 0.01). The average trehalose value of the control (C) (4.3 mg/ml) was reduced by metal contamination, dependent on both the metal itself and the concentration (Cd, Cu, Zn; 1.4--3.3 mg/ml). Sorbitol was not detected in the hemolymph of EF specimens, whereas it occurred in all artificial diet-fed groups. Metal- and dose-dependent differences in the hemolymph sorbitol levels were observed in the treatment groups, but not in the controls. Glycogen content increased in the low concentration of Cd, Pb, and Cu, whereas a decrease was observed for the low Cd and both Zn concentrations. Tissue free glucose was enhanced only in three of the metal groups. Generally, fresh and dry weights of larvae were reduced in all groups except the high Cu-contaminated one. The results may indicate that mass outbreaks of an important forest pest insect like L. dispar may be facilitated in metal-contaminated areas because parasitization success of antagonistic species may decline due to deterioration of nourishment within the metal-stressed host.

  18. Enhanced polyamine accumulation alters carotenoid metabolism at the transcriptional level in tomato fruit over-expressing spermidine synthase.

    PubMed

    Neily, Mohamed Hichem; Matsukura, Chiaki; Maucourt, Mickaël; Bernillon, Stéphane; Deborde, Catherine; Moing, Annick; Yin, Yong-Gen; Saito, Takeshi; Mori, Kentaro; Asamizu, Erika; Rolin, Dominique; Moriguchi, Takaya; Ezura, Hiroshi

    2011-02-15

    Polyamines are involved in crucial plant physiological events, but their roles in fruit development remain unclear. We generated transgenic tomato plants that show a 1.5- to 2-fold increase in polyamine content by over-expressing the spermidine synthase gene, which encodes a key enzyme for polyamine biosynthesis. Pericarp-columella and placental tissue from transgenic tomato fruits were subjected to (1)H-nuclear magnetic resonance (NMR) for untargeted metabolic profiling and high-performance liquid chromatography-diode array detection for carotenoid profiling to determine the effects of high levels of polyamine accumulation on tomato fruit metabolism. A principal component analysis of the quantitative (1)H NMR data from immature green to red ripe fruit showed a clear discrimination between developmental stages, especially during ripening. Quantification of 37 metabolites in pericarp-columella and 41 metabolites in placenta tissues revealed distinct metabolic profiles between the wild type and transgenic lines, particularly at the late ripening stages. Notably, the transgenic tomato fruits also showed an increase in carotenoid accumulation, especially in lycopene (1.3- to 2.2-fold), and increased ethylene production (1.2- to 1.6-fold) compared to wild-type fruits. Genes responsible for lycopene biosynthesis, including phytoene synthase, phytoene desaturase, and deoxy-d-xylulose 5-phosphate synthase, were significantly up-regulated in ripe transgenic fruits, whereas genes involved in lycopene degradation, including lycopene-epsilon cyclase and lycopene beta cyclase, were down-regulated in the transgenic fruits compared to the wild type. These results suggest that a high level of accumulation of polyamines in the tomato regulates the steady-state level of transcription of genes responsible for the lycopene metabolic pathway, which results in a higher accumulation of lycopene in the fruit.

  19. Expression of heat shock protein 70 is altered by age and diet at the level of transcription.

    PubMed Central

    Heydari, A R; Wu, B; Takahashi, R; Strong, R; Richardson, A

    1993-01-01

    Because heat shock proteins have been shown to play a critical role in protecting cells from hyperthermia and other types of physiological stresses, it was of interest to determine what effect age and caloric restriction have on the ability of cells to regulate the expression of heat shock protein 70 (hsp70), the most prominent and most evolutionarily conserved of the heat shock proteins. Caloric restriction is the only experimental manipulation known to retard aging and increase survival of mammals. The ability of hepatocytes isolated from young/adult (4- to 7-month-old) and old (22- to 28-month-old) male Fischer F344 rats fed ad libitum or a caloric restriction diet (60% of the content of the ad libitum diet) to express hsp70 was determined after a mild heat shock (42.5 degrees C for 30 min). We found that the induction of hsp70 synthesis and mRNA levels by heat shock was 40 to 50% lower in hepatocytes isolated from old rats than in hepatocytes isolated from young rats. Using in situ hybridization, we found that essentially all hepatocytes from the young/adult and old rats expressed hsp70 in response to heat shock; therefore, the age-related decrease in the induction of hsp70 expression was not due to an age-related accumulation of cells that do not respond to heat shock. Measurements of hsp70 mRNA stability and hsp70 transcription demonstrated that the age-related decline in hsp70 expression arose from a decline in hsp70 transcription. Interestingly, the age-related decline in the induction of hsp70 expression was reversed by caloric restriction; e.g., the induction of hsp70 synthesis, mRNA levels, and nuclear transcription were significantly higher in hepatocytes isolated from old rats fed the caloric restricted diet than in hepatocytes isolated from old rats fed ad libitum. The levels of the heat shock transcription factor in nuclear extracts isolated from heat-shocked hepatocytes were measured in a gel shift assay. Binding of the heat shock transcription

  20. Grape juice increases the BDNF levels but not alter the S100B levels in hippocampus and frontal cortex from male Wistar Rats.

    PubMed

    Dani, Caroline; Andreazza, Ana Cristina; Gonçalves, Carlos Alberto; Kapizinski, Flávio; Henriques, João A P; Salvador, Mirian

    2017-03-02

    Several studies have shown that a high consumption of vegetables and fruits is consistently associated with a low risk of oxidative stress-induced diseases, which includes some degenerative diseases such as amyotrophic lateral sclerosis, Alzheimer and Parkinson. Therefore, the objective of this study is to verify the effects of conventional and organic grape juice in the modulation of the neurotrophic factor (BDNF) and astrocytic markers protein (S100B) in hippocampus and frontal cortex of Wistar rats. In this study, 24 male Wistar rats were divided into three groups. To the first one, it was given organic purple grape juice; to the second, conventional grape juice, while the last one received only saline. After 30 days, all rats were sacrificed and hippocampus and frontal cortex were dissected. The animals that received organic and conventional grape juice showed, in frontal cortex, an elevated BNDF levels in relation to saline group. However, S100B levels did not change. These results showed that grape juices are able to modulate important marker in brain tissue, and could be an important factor to prevent brain diseases.

  1. Chrysophanol induces necrosis through the production of ROS and alteration of ATP levels in J5 human liver cancer cells

    PubMed Central

    Lu, Chi-Cheng; Yang, Jai-Sing; Huang, An-Cheng; Hsia, Te-Chun; Chou, Su-Tze; Kuo, Chao-Lin; Lu, Hsu-Feng; Lee, Tsung-Han; Wood, W. G.; Chung, Jing-Gung

    2011-01-01

    Anthraquinone compounds have been shown to induce apoptosis in different cancer cell types. Effects of chrysophanol, an anthraquinone compound, on cancer cell death have not been well-studied. The goal of this study was to examine if chrysophanol had cytotoxic effects and if such effects involved apoptosis or necrosis in J5 human liver cancer cells. Chrysophanol induced necrosis in J5 cells in a dose- and time-dependent manner. Non-apoptotic cell death was induced by chrysophanol in J5 cells and was characterized by caspase independence, delayed externalization of phosphatidylserine and plasma membrane disruption. Blockage of apoptotic induction by a general caspase inhibitor (z-VAD-fmk) failed to protect cells against chrysophanol-induced cell death. The levels of ROS production and loss of mitochondrial membrane potential (ΔΨm) were also determined to assess the effects of chrysophanol. However, reductions in ATP levels and increases in LDH activity indicated that chrysophanol stimulated necrotic cell death. In summary, human liver cancer cells treated with chrysophanol exhibited a cellular pattern associated with necrosis and not apoptosis. PMID:20169580

  2. Inoculation of a phenanthrene-degrading endophytic bacterium reduces the phenanthrene level and alters the bacterial community structure in wheat.

    PubMed

    Liu, Juan; Xiang, Yanbing; Zhang, Zhiming; Ling, Wanting; Gao, Yanzheng

    2017-03-28

    Colonization by polycyclic aromatic hydrocarbon (PAH)-degrading endophytic bacteria (PAHDEB) can reduce the PAH contamination risk in plant. However, little information is available on the impact of PAHDEB colonization on the endophytic bacterial community of inner plant tissues. A phenanthrene-degrading endophytic bacterium (PDEB), Massilia sp. Pn2, was inoculated onto the roots of wheat and subjected to greenhouse container experiments. The endophytic bacterial community structure in wheat was investigated using high-throughput sequencing technology. The majority of endophytic bacteria in wheat were Proteobacteria, and the dominant genus was Pseudomonas. Phenanthrene contamination clearly increased the diversity of endophytic bacteria in wheat. The cultivable endophytic bacteria counts in wheat decreased with increasing the level of phenanthrene contamination; the endophytic bacterial community structure changed correspondingly, and the bacterial richness first increased and then decreased. Inoculation of strain Pn2 reduced the phenanthrene contamination in wheat, enlarged the biomass of wheat roots, changed the bacterial community structure and enhanced the cell counts, diversity and richness of endophytic bacteria in phenanthrene-contaminated wheat in a contamination level-dependent manner. The findings of this investigation provide insight into the responses of endophytic bacterial community in plant to external PAH contamination and PAHDEB colonization.

  3. Sarcopenia, obesity, and natural killer cell immune senescence in aging: altered cytokine levels as a common mechanism.

    PubMed

    Lutz, Charles T; Quinn, LeBris S

    2012-08-01

    Human aging is characterized by both physical and physiological frailty. A key feature of frailty, sarcopenia is the age-associated decline in skeletal muscle mass, strength, and endurance that characterize even the healthy elderly. Increases in adiposity, particularly in visceral adipose tissue, are almost universal in aging individuals and can contribute to sarcopenia and insulin resistance by increasing levels of inflammatory cytokines known collectively as adipokines. Aging also is associated with declines in adaptive and innate immunity, known as immune senescence, which are risk factors for cancer and all-cause mortality. The cytokine interleukin-15 (IL-15) is highly expressed in skeletal muscle tissue and declines in aging rodent models. IL-15 inhibits fat deposition and insulin resistance, is anabolic for skeletal muscle in certain situations, and is required for the development and survival of natural killer (NK) lymphocytes. We review the effect that adipokines and myokines have on NK cells, with special emphasis on IL-15. We posit that increased adipokine and decreased IL-15 levels during aging constitute a common mechanism for sarcopenia, obesity, and immune senescence.

  4. Bacillus sp. QSI-1 Modulate Quorum Sensing Signals Reduce Aeromonas hydrophila Level and Alter Gut Microbial Community Structure in Fish.

    PubMed

    Zhou, Shuxin; Zhang, An; Yin, Hongping; Chu, Weihua

    2016-01-01

    Quorum sensing (QS) is a cell density dependent process that enables bacteria to communicate with each other based on the production, secretion and sensing of the auto-inducer molecules and then subsequently regulate virulence associated gene expression. Interrupting quorum sensing may represent a novel alternative approach to combat bacterial pathogen. Several bacteria can produce quorum quenching (QQ) enzymes. However, the role of QQ bacteria in shaping the microbiota and the level of N-acyl-homoserine lactones (AHLs, a prevalent type of QS molecules) producing bacteria remains largely unknown. The objective of this study was to examine the presence of AHLs in the fish intestine and investigate the modulation of gut microbiota and its effect on Aeromonas hydrophila level by a QQ enzyme producing probiotic Bacillus sp. QSI-1. AHLs were found in fish gut content and were confirmed in Aeromonas species using Chromobacterium violaceum CV026 and Agrobacterium tumefaciens AT 136 (pZLR4) as reporter strains. We demonstrated that the composition of fish gut microbiota was affected by quenching bacteria QSI-1, and the percentage of A. hydrophila was decreased significantly. Taken together, these results provide valuable insights into QQ enzyme producing probiotics can modulate the microbiota structure and decrease the percentage of AHL-producing pathogenic bacteria in the gut. These data strongly suggest that QQ probiotics may serve as non-antibiotic feed additive in aquaculture to control bacterial diseases.

  5. Glucose concentration alters dissolved oxygen levels in liquid cultures of Beauveria bassiana and affects formation and bioefficacy of blastospores.

    PubMed

    Mascarin, Gabriel Moura; Jackson, Mark A; Kobori, Nilce Naomi; Behle, Robert W; Dunlap, Christopher A; Delalibera Júnior, Ítalo

    2015-08-01

    The filamentous fungus Beauveria bassiana is an economically important pathogen of numerous arthropod pests and is able to grow in submerged culture as filaments (mycelia) or as budding yeast-like blastospores. In this study, we evaluated the effect of dissolved oxygen and high glucose concentrations on blastospore production by submerged cultures of two isolates of B. bassiana, ESALQ1432 and GHA. Results showed that maintaining adequate dissolved oxygen levels coupled with high glucose concentrations enhanced blastospore yields by both isolates. High glucose concentrations increased the osmotic pressure of the media and coincided with higher dissolved oxygen levels and increased production of significantly smaller blastospores compared with blastospores produced in media with lower concentrations of glucose. The desiccation tolerance of blastospores dried to less than 2.6 % moisture was not affected by the glucose concentration of the medium but was isolate dependent. Blastospores of isolate ESALQ1432 produced in media containing 140 g glucose L(-1) showed greater virulence toward whitefly nymphs (Bemisia tabaci) as compared with blastospores produced in media containing 40 g glucose L(-1). These results suggest a synergistic effect between glucose concentration and oxygen availability on changing morphology and enhancing the yield and efficacy of blastospores of B. bassiana, thereby facilitating the development of a cost-effective production method for this blastospore-based bioinsecticide.

  6. Comparative study of antibody levels developed by vaccination against polio virus in population after vaccine type alteration.

    PubMed

    Farkas, Ágnes; Magyar, Nóra; Szomor, Katalin N; Takács, Mária

    2015-03-01

    During clinical trials, samples from Hungarian patients of different age groups were tested for antibodies against all 3 serotypes of poliovirus, a member of Picornaviridae family. During the virus neutralization serological test, blood samples were titrated using permanent virus concentration. Based on the cythopathic effect observed under a light microscope, the antibody level of the patient was assessed. The 100 people examined were classified into 5 groups based on age and type of original vaccine: I. Newborns, no vaccination given; II. Immunosuppressed patients; III. Born before 1986, received only OPV vaccine; IV. Born between 1992-2005, received a combination of OPV and IPV vaccines; V. Born after 2006, received only IPV vaccine. Results show that vaccination coverage meets all the criteria. None of the immunized persons was seronegative to all three polioviruses. Both IPV and OPV vaccines are effective against poliovirus. Blood samples from newborn babies with no immunization were also examined. Results show that most newborns have maternal antibodies in their blood. Results of group II show that immunosuppression does not have a negative influence on blood antibody levels against polioviruses. In spite of the low number of samples, our results show that seroconversion after immunization in the Hungarian population is adequate. For more accurate results about vaccination coverage in the population, further trials would be necessary.

  7. Yi-gan san restores behavioral alterations and a decrease of brain glutathione level in a mouse model of schizophrenia.

    PubMed

    Makinodan, Manabu; Yamauchi, Takahira; Tatsumi, Kouko; Okuda, Hiroaki; Noriyama, Yoshinobu; Sadamatsu, Miyuki; Kishimoto, Toshifumi; Wanaka, Akio

    2009-01-01

    The traditional Chinese herbal medicine yi-gan san has been used to cure neuropsychological disorders. Schizophrenia can be one of the target diseases of yi-gan san. We aimed at evaluating the possible use of yi-gan san in improving the schizophrenic symptoms of an animal model. Yi-gan san or distilled water was administered to mice born from pregnant mice injected with polyinosinic-polycytidilic acid or phosphate buffered saline. The former is a model of schizophrenia based on the epidemiological data that maternal infection leads to psychotic disorders including schizophrenia in the offspring. Prepulse inhibition and sensitivity to methamphetamine in open field tests were analyzed and the total glutathione content of whole brains was measured. Yi-gan san reversed the decrease in prepulse inhibition, hypersensitivity to methamphetamine and cognitive deficits found in the model mice to the level of control mice. Total glutathione content in whole brains was reduced in the model mice but was restored to normal levels by yi-gan san treatment. These results suggest that yi-gan san may have ameliorating effects on the pathological symptoms of schizophrenia.

  8. Tumor necrosis factor-α alters integrins and metalloprotease ADAM12 levels and signaling in differentiating myoblasts.

    PubMed

    Grzelkowska-Kowalczyk, K; Tokarska, J; Grabiec, K; Gajewska, M; Milewska, M; Błaszczyk, M

    2016-01-01

    The extracellular matrix (ECM) is important in the regulation of myogenesis. We hypothesized that tumor necrosis factor-α (TNF-α) modifies ECM during differentiation of mouse C2C12 myoblasts. Exogenous TNF-α (1 ng/ml) stimulated myoblast fusion on the 3rd day (by 160% vs control) but not on the 5th day of myogenesis. The level of integrin α5 was significantly augmented by TNF-α during 5 day-differentiation; however, integrin β1 was higher than control only on the 3rd day of cytokine treatment. Both the abundance of integrin α5 bound to actin and the level of integrin β1 complexed with integrin α5 increased in the presence of TNF-α, especially on the 3rd day of differentiation. Similarly, the stimulatory effects of TNF-α on integrin α3, metalloprotease ADAM12 and kinases related to integrins, FAK and ILK, were limited to the 3rd day of differentiation. We concluded that TNF-α-induced changes in ECM components in differentiating myogenic cells, i.e. i) increased expression of integrin α5, β1, α3, and metalloprotease ADAM12, ii) enhanced formation of α5β1 integrin receptors and interaction of integrin α5-cytoskeleton, and iii) increased expression of kinases associated with integrin signaling, FAK and ILK, were temporarily associated with the onset of myocyte fusion.

  9. Bacillus sp. QSI-1 Modulate Quorum Sensing Signals Reduce Aeromonas hydrophila Level and Alter Gut Microbial Community Structure in Fish

    PubMed Central

    Zhou, Shuxin; Zhang, An; Yin, Hongping; Chu, Weihua

    2016-01-01

    Quorum sensing (QS) is a cell density dependent process that enables bacteria to communicate with each other based on the production, secretion and sensing of the auto-inducer molecules and then subsequently regulate virulence associated gene expression. Interrupting quorum sensing may represent a novel alternative approach to combat bacterial pathogen. Several bacteria can produce quorum quenching (QQ) enzymes. However, the role of QQ bacteria in shaping the microbiota and the level of N-acyl-homoserine lactones (AHLs, a prevalent type of QS molecules) producing bacteria remains largely unknown. The objective of this study was to examine the presence of AHLs in the fish intestine and investigate the modulation of gut microbiota and its effect on Aeromonas hydrophila level by a QQ enzyme producing probiotic Bacillus sp. QSI-1. AHLs were found in fish gut content and were confirmed in Aeromonas species using Chromobacterium violaceum CV026 and Agrobacterium tumefaciens AT 136 (pZLR4) as reporter strains. We demonstrated that the composition of fish gut microbiota was affected by quenching bacteria QSI-1, and the percentage of A. hydrophila was decreased significantly. Taken together, these results provide valuable insights into QQ enzyme producing probiotics can modulate the microbiota structure and decrease the percentage of AHL-producing pathogenic bacteria in the gut. These data strongly suggest that QQ probiotics may serve as non-antibiotic feed additive in aquaculture to control bacterial diseases. PMID:28018866

  10. Altered levels of cytokines and inflammatory mediators in plasma and leukocytes of sickle cell anemia patients and effects of hydroxyurea therapy.

    PubMed

    Lanaro, C; Franco-Penteado, C F; Albuqueque, D M; Saad, S T O; Conran, N; Costa, F F

    2009-02-01

    Inflammation, cell adhesion to vascular endothelium, and endothelial injury contribute to sickle cell anemia (SCA) vaso-occlusion. Although alterations in inflammatory cytokines and biomarkers have been related, reports have been conflicting, and a conclusive role for these molecules in the disease remains to be established. Furthermore, the effect of hydroxyurea therapy (HU) on the release of inflammatory mediators is not understood. This study aimed to determine plasma levels and leukocyte gene expressions of inflammatory mediators in healthy controls, steady-state SCA patients, and SCA patients on HU therapy. TNF-alpha, IL-8, and PGE(2) levels were significantly higher in the plasma of SCA individuals when compared with control individuals. HU therapy was associated with a significant reversal of augmented TNF-alpha and, interestingly, increased plasma anti-inflammatory IL-10. IFN-gamma, IL-10, cyclooxygenase 2 (COX-2), and inducible NO synthase (iNOS) gene expressions were unaltered in SCA mononuclear cells (MC); however, gene expressions of TNF-alpha, IL-8, and the protective enzyme heme oxygenase-1 (HO-1) were significantly higher. HU therapy was not associated with significantly altered SCA MC inflammatory gene expression, although COX-2 mRNA expression was decreased. In SCA neutrophils, gene expressions of IL-8, IFN-gamma, iNOS, and HO-1 were significantly higher than those of control subjects. Patients on HU demonstrated lower iNOS and higher IL-10 neutrophil gene expressions. Taken together, data suggest that alterations in the gene expressions and productions of a number of pro- and anti-inflammatory mediators are present in SCA and importantly, in those patients on HU therapy. Knowledge of these pathways may contribute to further the understanding of the pathophysiology of this disease.

  11. CypD(-/-) hearts have altered levels of proteins involved in Krebs cycle, branch chain amino acid degradation and pyruvate metabolism.

    PubMed

    Menazza, Sara; Wong, Renee; Nguyen, Tiffany; Wang, Guanghui; Gucek, Marjan; Murphy, Elizabeth

    2013-03-01

    Cyclophilin D (CypD) is a mitochondrial chaperone that has been shown to regulate the mitochondrial permeability transition pore (MPTP). MPTP opening is a major determinant of mitochondrial dysfunction and cardiomyocyte death during ischemia/reperfusion (I/R) injury. Mice lacking CypD have been widely used to study regulation of the MPTP, and it has been shown recently that genetic depletion of CypD correlates with elevated levels of mitochondrial Ca(2+). The present study aimed to characterize the metabolic changes in CypD(-/-) hearts. Initially, we used a proteomics approach to examine protein changes in CypD(-/-) mice. Using pathway analysis, we found that CypD(-/-) hearts have alterations in branched chain amino acid metabolism, pyruvate metabolism and the Krebs cycle. We tested whether these metabolic changes were due to inhibition of electron transfer from these metabolic pathways into the electron transport chain. As we found decreased levels of succinate dehydrogenase and electron transfer flavoprotein in the proteomics analysis, we examined whether activities of these enzymes might be altered. However, we found no alterations in their activities. The proteomics study also showed a 23% decrease in carnitine-palmitoyltransferase 1 (CPT1), which prompted us to perform a metabolomics analysis. Consistent with the decrease in CPT1, we found a significant decrease in C4/Ci4, C5-OH/C3-DC, C12:1, C14:1, C16:1, and C20:3 acyl carnitines in hearts from CypD(-/-) mice. In summary, CypD(-/-) hearts exhibit changes in many metabolic pathways and caution should be used when interpreting results from these mice as due solely to inhibition of the MPTP.

  12. Protective effect of montelukast against quinolinic acid/malonic acid induced neurotoxicity: possible behavioral, biochemical, mitochondrial and tumor necrosis factor-α level alterations in rats.

    PubMed

    Kalonia, H; Kumar, P; Kumar, A; Nehru, B

    2010-11-24

    The present study has been designed to explore the protective effect of montelukast (leukotriene receptor antagonist) against intrastriatal quinolinic acid (QA; 300 nmol) and malonic acid (MA; 6 μmol) induced Huntington's like symptoms in rats. Quinolinic acid has been reported to induce excitotoxicity by stimulating the N-methyl-D-aspartate receptor, causing calcium overload which in turn leads to the neurodegeneration. On the other hand, MA, being a reversible inhibitor of mitochondrial enzyme complex-II, leads to energy crisis and free radical generation. Recent studies have reported the therapeutic potential of leukotriene receptor antagonists in different neurodegenerative disorders. However, their exact role is yet to be established. The present study accordingly, is an attempt to investigate the effect of montelukast against QA and MA induced behavioral, biochemical and molecular alterations in rat striatum. Oxidative stress, mitochondrial enzyme complex and tumor necrosis factor-alpha (TNF-α) were evaluated on day 21st and 14th post intrastriatal QA and MA treatment, respectively. Findings of the present study demonstrate significant alteration in the locomotor activity and motor coordination as well as oxidative burden (increased lipid peroxidation, nitrite concentration and decreased endogenous antioxidants), mitochondrial enzyme complex (I, II and IV) activities and TNF-α level, in both intrastriatal QA and MA treated animals. Further, montelukast (0.4, 0.8 mg/kg p.o.) treatment for 21 and 14 days respectively, attenuated the behavioral alterations, oxidative stress, mitochondrial dysfunction and TNF-α level in these models of Huntington's disease in a significant manner. In conclusion, the present study emphasizes the neuroprotective potential of montelukast in the therapeutic management of Huntington like symptoms.

  13. Neurobehavioral changes and alteration of gene expression in the brains of metallothionein-I/II null mice exposed to low levels of mercury vapor during postnatal development.

    PubMed

    Yoshida, Minoru; Honda, Masako; Watanabe, Chiho; Satoh, Masahiko; Yasutake, Akira

    2011-10-01

    This study examined the neurobehavioral changes and alteration in gene expression in the brains of metallothionein (MT)-I/II null mice exposed to low-levels of mercury vapor (Hg(0)) during postnatal development. MT-I/II null and wild-type mice were repeatedly exposed to Hg(0) at 0.030 mg/m(3) (range: 0.023-0.043 mg/m(3)), which was similar to the current threshold value (TLV), for 6 hr per day until the 20th day postpartum. The behavioral effects were evaluated with locomotor activity in the open field (OPF), learning ability in the passive avoidance response (PA) and spatial learning ability in the Morris water maze (MM) at 12 weeks of age. Hg(0)-exposed MT-I/II null mice showed a significant decrease in total locomotor activity in females, though learning ability and spatial learning ability were not affected. Immediately after Hg(0) exposure, mercury concentrations in the brain did not exceed 0.5 µg/g in any animals. Hg(0) exposure resulted in significant alterations in gene expression in the brains of both strains using DNA microarray analysis. The number of altered genes in MT-I/II null mice was higher than that in wild-type mice and calcium-calmodulin kinase II (Camk2a) involved in learning and memory in down-regulated genes was detected. These results provide useful information to elucidate the development of behavioral toxicity following low-level exposure to Hg(0).

  14. Alterations in gene expression levels provide early indicators of chemical stress during Xenopus laevis embryo development: A case study with perfluorooctane sulfonate (PFOS).

    PubMed

    San-Segundo, Laura; Guimarães, Laura; Fernández Torija, Carlos; Beltrán, Eulalia M; Guilhermino, Lúcia; Pablos, María Victoria

    2016-05-01

    In the present study, Xenopus laevis embryos were exposed to a range of perfluorooctane sulfonate (PFOS) concentrations (0, 0.5, 6, 12, 24, 48 and 96mg/L) for 96h in laboratorial conditions to establish toxicity along with possible gene expression changes. Mortality and deformities were monitored daily and head-tail length was measured at the end of the assay as an indicator of growth. At 24 and 96h post-exposure (hpe), the mRNA expression levels of the genetic markers involved in general stress responses (hsp70, hsp47, crh-a and ucn1), oxidative stress (cat.2 and sod), lipid metabolism (ppard) and apoptosis (tp53 and bax) were analyzed by RT-qPCR. Malformations were significantly higher in the embryos exposed to the highest PFOS concentration (41.8% to 56.4%) compared to controls (5.5%) at 48, 72 and 96hpe. Growth inhibition was observed in the embryos exposed to PFOS concentrations≥48mg/L. At 24 hpe, a statistically significant up-regulation of genes hsp70, hsp47, ppard, tp53 and bax in relation to controls was found. Similar responses were found for genes hsp70, hsp47, crh-a, ucn1, sod and ppard at 96 hpe. Alterations in the mRNA expression levels indicated both a stress response to PFOS exposure during X. laevis embryo development, and alterations in the regulation of oxidative stress, apoptosis, and differentiation. These molecular alterations were detected at an earlier exposure time or at lower concentrations than those producing developmental toxicity. Therefore, these sensitive warning signals could be used together with other biomarkers to supplement alternative methods (i.e. the frog embryo test) for developmental toxicity safety evaluations, and as tools in amphibian risk assessments for PFOS and its potential substitutes.

  15. Phylogenetics: bats united, microbats divided.

    PubMed

    Springer, Mark S

    2013-11-18

    Phylogenetic analyses on four new bat genomes provide convincing support for the placement of bats relative to other placental mammals, suggest that microbats are an unnatural group, and have important implications for understanding the evolution of echolocation.

  16. Heterologous expression of oxytetracycline biosynthetic gene cluster in Streptomyces venezuelae WVR2006 to improve production level and to alter fermentation process.

    PubMed

    Yin, Shouliang; Li, Zilong; Wang, Xuefeng; Wang, Huizhuan; Jia, Xiaole; Ai, Guomin; Bai, Zishang; Shi, Mingxin; Yuan, Fang; Liu, Tiejun; Wang, Weishan; Yang, Keqian

    2016-12-01

    Heterologous expression is an important strategy to activate biosynthetic gene clusters of secondary metabolites. Here, it is employed to activate and manipulate the oxytetracycline (OTC) gene cluster and to alter OTC fermentation process. To achieve these goals, a fast-growing heterologous host Streptomyces venezuelae WVR2006 was rationally selected among several potential hosts. It shows rapid and dispersed growth and intrinsic high resistance to OTC. By manipulating the expression of two cluster-situated regulators (CSR) OtcR and OtrR and precursor supply, the OTC production level was significantly increased in this heterologous host from 75 to 431 mg/l only in 48 h, a level comparable to the native producer Streptomyces rimosus M4018 in 8 days. This work shows that S. venezuelae WVR2006 is a promising chassis for the production of secondary metabolites, and the engineered heterologous OTC producer has the potential to completely alter the fermentation process of OTC production.

  17. Altered levels of the Taraxacum kok-saghyz (Russian dandelion) small rubber particle protein, TkSRPP3, result in qualitative and quantitative changes in rubber metabolism.

    PubMed

    Collins-Silva, Jillian; Nural, Aise Taban; Skaggs, Amanda; Scott, Deborah; Hathwaik, Upul; Woolsey, Rebekah; Schegg, Kathleen; McMahan, Colleen; Whalen, Maureen; Cornish, Katrina; Shintani, David

    2012-07-01

    Several proteins have been identified and implicated in natural rubber biosynthesis, one of which, the small rubber particle protein (SRPP), was originally identified in Hevea brasiliensis as an abundant protein associated with cytosolic vesicles known as rubber particles. While previous in vitro studies suggest that SRPP plays a role in rubber biosynthesis, in vivo evidence is lacking to support this hypothesis. To address this issue, a transgene approach was taken in Taraxacum kok-saghyz (Russian dandelion or Tk) to determine if altered SRPP levels would influence rubber biosynthesis. Three dandelion SRPPs were found to be highly abundant on dandelion rubber particles. The most abundant particle associated SRPP, TkSRPP3, showed temporal and spatial patterns of expression consistent with patterns of natural rubber accumulation in dandelion. To confirm its role in rubber biosynthesis, TkSRPP3 expression was altered in Russian dandelion using over-expression and RNAi methods. While TkSRPP3 over-expressing lines had slightly higher levels of rubber in their roots, relative to the control, TkSRPP3 RNAi lines showed significant decreases in root rubber content and produced dramatically lower molecular weight rubber than the control line. Not only do results here provide in vivo evidence of TkSRPP proteins affecting the amount of rubber in dandelion root, but they also suggest a function in regulating the molecular weight of the cis-1, 4-polyisoprene polymer.

  18. Nitrophenolates spray can alter boll abscission rate in cotton through enhanced peroxidase activity and increased ascorbate and phenolics levels.

    PubMed

    Djanaguiraman, M; Sheeba, J Annie; Devi, D Durga; Bangarusamy, U; Prasad, P V V

    2010-01-01

    Field studies were conducted from 2002 to 2005 to evaluate foliar spray of Atonik (a plant growth regulator (PGR) containing nitrophenolates) on cotton boll abscission rate by assessing various reactive oxygen species (ROS) contents, antioxidant content and antioxidant enzyme activity from 1 to 9 days after anthesis (DAA). The result indicated that the nitrophenolate spray reduced hydrogen peroxide (H(2)O(2)), superoxide anion (O(2)(-)) accumulation, lipid peroxidation (malondialdehyde--MDA), lipoxygenase (LOX) activity and membrane permeability relative to the control. Antioxidant enzyme activity (superoxide dismutase, SOD; ascorbate peroxidase, APX; peroxidase, POX; glutathione peroxidase, GSH-Px) was significantly increased by the nitrophenolate spray. The POX (217%) and GSH-Px (242%) activities were enhanced compared with APX (7.7%) activity at 9 DAA. Enhanced accumulation of ascorbate (245%), phenol (253%) and proline (150%) was observed in nitrophenolate-sprayed plants compared with control at 9 DAA. Because ascorbate content is increased by higher dehydroascorbate reductase (DHAR) enzyme activity, the ascorbate was able to replenish reducing equivalents to phenoxyl radicals, resulting in an increase of phenolic compounds. The increased phenolic acid content may be involved in scavenging the ROS produced in developing cotton boll. The role of DHAR and glutathione reductase (GR) in keeping higher levels of reduced ascorbate and low levels of endogenous H(2)O(2) in the developing cotton boll may be the prerequisite for boll retention. Based on the present work, we conclude that nitrophenolate-sprayed plants counteracted the deleterious effects of ROS by the peroxide/phenolics/ascorbate system, which causes reduced boll abscission and increased yield.

  19. Alteration of Porcine Serum Albumin Levels in Pork Meat by Marination in Kiwi or Pineapple Juice and Subsequent Pan Broiling.

    PubMed

    Moon, Sung-Sil; Kim, Dongwook; Kim, Il-Suk; Ham, Jun-Sang; Park, Beom-Young; Jang, Aera

    2014-01-01

    This study was conducted to evaluate the changes in porcine serum albumin (PSA), a major allergen, which occur when raw pork ham is marinated with kiwi or pineapple juice, and/or when the ham is pan broiled at 300℃ for 4 min after marination. In this study, raw pork ham was soaked for 4 h or 8 h in marinades containing commercial marinating sauce only, commercial marinating sauce and 7% kiwi juice, or commercial marinating sauce and 7% pineapple juice. When the meat was marinated and then pan-broiled, pork ham meat protein was significantly denatured and hydrolyzed, and the level of PSA in the meat was significantly reduced. The PSA contents of pork broiled without marination, pork that had been marinated in commercial marinating sauce alone, pork that had been marinated in commercial marinating sauce with kiwi juice, and pork that had been marinated in commercial marinating sauce with pineapple juice, were 95.4, 43.3, 14.3, and 5.4 ng/mL, respectively (p<0.05). Marinating with pineapple juice was more effective than marinating with kiwi juice; and marination for 8 h was more effective than marinating for 4 h. These results indicate that the level of PSA in pork ham is effectively reduced, when the meat is first marinated in sauces that contain kiwi or pineapple extracts for 8 h, rather than 4 h, and then cooked. Further study is needed to determine whether marinated pork meat reduces allergenicity in vivo, as well.

  20. Altered Circulating Levels of Matrix Metalloproteinases and Inhibitors Associated with Elevated Type 2 Cytokines in Lymphatic Filarial Disease

    PubMed Central

    Anuradha, Rajamanickam; George, Jovvian P.; Pavankumar, Nathella; Kumaraswami, Vasanthapuram; Nutman, Thomas B.; Babu, Subash

    2012-01-01

    Background Infection with Wuchereria bancrofti can cause severe disease characterized by subcutaneous fibrosis and extracellular matrix remodeling. Matrix metalloproteinases (MMPs) are a family of enzymes governing extracellular remodeling by regulating cellular homeostasis, inflammation, and tissue reorganization, while tissue-inhibitors of metalloproteinases (TIMPs) are endogenous regulators of MMPs. Homeostatic as well as inflammation-induced balance between MMPs and TIMPs is considered critical in mediating tissue pathology. Methods To elucidate the role of MMPs and TIMPs in filarial pathology, we compared the plasma levels of a panel of MMPs, TIMPs, other pro-fibrotic factors, and cytokines in individuals with chronic filarial pathology with (CP Ag+) or without (CP Ag−) active infection to those with clinically asymptomatic infections (INF) and in those without infection (endemic normal [EN]). Markers of pathogenesis were delineated based on comparisons between the two actively infected groups (CP Ag+ compared to INF) and those without active infection (CP Ag− compared to EN). Results and Conclusion Our data reveal that an increase in circulating levels of MMPs and TIMPs is characteristic of the filarial disease process per se and not of active infection; however, filarial disease with active infection is specifically associated with increased ratios of MMP1/TIMP4 and MMP8/TIMP4 as well as with pro-fibrotic cytokines (IL-5, IL-13 and TGF-β). Our data therefore suggest that while filarial lymphatic disease is characterized by a non-specific increase in plasma MMPs and TIMPs, the balance between MMPs and TIMPs is an important factor in regulating tissue pathology during active infection. PMID:22679524

  1. Altered CYP2C9 Activity Following Modulation of CYP3A4 Levels in Human Hepatocytes: an Example of Protein-Protein Interactions

    PubMed Central

    Tweedie, Donald J.; Chan, Tom S.; Tracy, Timothy S.

    2014-01-01

    Cytochrome P450 (P450) protein-protein interactions resulting in modulation of enzyme activities have been well documented using recombinant isoforms. This interaction has been less clearly demonstrated in a more physiologic in vitro system such as human hepatocytes. As an expansion of earlier work (Subramanian et al., 2010), in which recombinant CYP2C9 activity decreased with increasing levels of CYP3A4, the current study modulated CYP3A4 content in human hepatocytes to determine the impact on CYP2C9. Modulation of CYP3A4 levels in situ was enabled by the use of a long-term human hepatocyte culture model (HepatoPac) shown to retain phenotypic hepatocyte function over a number of weeks. The extended period of culture allowed time for knockdown of CYP3A4 protein by small interfering RNA (siRNA) with subsequent recovery, as well as upregulation through induction with a recovery period. CYP3A4 gene silencing resulted in a 60% decrease in CYP3A4 activity and protein levels with a concomitant 74% increase in CYP2C9 activity, with no change in CYP2C9 mRNA levels. Upon removal of siRNA, both CYP2C9 and CYP3A4 activities returned to pre-knockdown levels. Importantly, modulation of CYP3A4 protein levels had no impact on cytochrome P450 reductase activities or levels. However, the possibility for competition for limiting reductase cannot be ruled out. Interestingly, lowering CYP3A4 levels also increased UDP-glucuronosyltransferase 2B7 activity. These studies clearly demonstrate that alterations in CYP3A4 levels can modulate CYP2C9 activity in situ and suggest that further studies are warranted to evaluate the possible clinical consequences of these findings. PMID:25157098

  2. Tris(2-butoxyethyl)phosphate and triethyl phosphate alter embryonic development, hepatic mRNA expression, thyroid hormone levels, and circulating bile acid concentrations in chicken embryos

    SciTech Connect

    Egloff, Caroline; Crump, Doug; Porter, Emily; Williams, Kim L.; Letcher, Robert J.; Gauthier, Lewis T.; Kennedy, Sean W.

    2014-09-15

    The organophosphate flame retardants tris(2-butoxyethyl) phosphate (TBOEP) and triethyl phosphate (TEP) are used in a wide range of applications to suppress or delay the ignition and spread of fire. Both compounds have been detected in the environment and TBOEP was recently measured in free-living avian species. In this study, TBOEP and TEP were injected into the air cell of chicken embryos at concentrations ranging from 0 to 45,400 ng/g and 0 to 241,500 ng/g egg, respectively. Pipping success, development, hepatic mRNA expression of 9 target genes, thyroid hormone levels, and circulating bile acid concentrations were determined. Exposure to the highest doses of TBOEP and TEP resulted in negligible detection of the parent compounds in embryonic contents at pipping indicating their complete metabolic degradation. TBOEP exposure had limited effects on chicken embryos, with the exception of hepatic CYP3A37 mRNA induction. TEP exposure decreased pipping success to 68%, altered growth, increased liver somatic index (LSI) and plasma bile acids, and modulated genes associated with xenobiotic and lipid metabolism and the thyroid hormone pathway. Plasma thyroxine levels were decreased at all TEP doses, including an environmentally-relevant concentration (8 ng/g), and gallbladder hypotrophy was evident at ≥ 43,200 ng/g. Tarsus length and circulating thyroxine concentration emerged as potential phenotypic anchors for the modulation of transthyretin mRNA. The increase in plasma bile acids and LSI, gallbladder hypotrophy, and discoloration of liver tissue represented potential phenotypic outcomes associated with modulation of hepatic genes involved with xenobiotic and lipid metabolism. - Highlights: • TBOEP is not embryolethal to chicken embryos. • TEP affected embryonic viability, morphometric endpoints, and thyroid hormone levels. • TEP altered mRNA levels of xenobiotic and lipid metabolism genes. • TEP increased plasma bile acids and caused gallbladder hypotrophy

  3. Molecular phylogenetics of mastodon and Tyrannosaurus rex.

    PubMed

    Organ, Chris L; Schweitzer, Mary H; Zheng, Wenxia; Freimark, Lisa M; Cantley, Lewis C; Asara, John M

    2008-04-25

    We report a molecular phylogeny for a nonavian dinosaur, extending our knowledge of trait evolution within nonavian dinosaurs into the macromolecular level of biological organization. Fragments of collagen alpha1(I) and alpha2(I) proteins extracted from fossil bones of Tyrannosaurus rex and Mammut americanum (mastodon) were analyzed with a variety of phylogenetic methods. Despite missing sequence data, the mastodon groups with elephant and the T. rex groups with birds, consistent with predictions based on genetic and morphological data for mastodon and on morphological data for T. rex. Our findings suggest that molecular data from long-extinct organisms may have the potential for resolving relationships at critical areas in the vertebrate evolutionary tree that have, so far, been phylogenetically intractable.

  4. A phylogenetic analysis of the phylum Fibrobacteres.

    PubMed

    Jewell, Kelsea A; Scott, Jarrod J; Adams, Sandra M; Suen, Garret

    2013-09-01

    Members of the phylum Fibrobacteres are highly efficient cellulolytic bacteria, best known for their role in rumen function and as potential sources of novel enzymes for bioenergy applications. Despite being key members of ruminants and other digestive microbial communities, our knowledge of this phylum remains incomplete, as much of our understanding is focused on two recognized species, Fibrobacter succinogenes and F. intestinalis. As a result, we lack insights regarding the environmental niche, host range, and phylogenetic organization of this phylum. Here, we analyzed over 1000 16S rRNA Fibrobacteres sequences available from public databases to establish a phylogenetic framework for this phylum. We identify both species- and genus-level clades that are suggestive of previously unknown taxonomic relationships between Fibrobacteres in addition to their putative lifestyles as host-associated or free-living. Our results shed light on this poorly understood phylum and will be useful for elucidating the function, distribution, and diversity of these bacteria in their niches.

  5. Phylogenetic lineages in Pseudocercospora

    PubMed Central

    Crous, P.W.; Braun, U.; Hunter, G.C.; Wingfield, M.J.; Verkley, G.J.M.; Shin, H.-D.; Nakashima, C.; Groenewald, J.Z.

    2013-01-01

    Pseudocercospora is a large cosmopolitan genus of plant pathogenic fungi that are commonly associated with leaf and fruit spots as well as blights on a wide range of plant hosts. They occur in arid as well as wet environments and in a wide range of climates including cool temperate, sub-tropical and tropical regions. Pseudocercospora is now treated as a genus in its own right, although formerly recognised as either an anamorphic state of Mycosphaerella or having mycosphaerella-like teleomorphs. The aim of this study was to sequence the partial 28S nuclear ribosomal RNA gene of a selected set of isolates to resolve phylogenetic generic limits within the Pseudocercospora complex. From these data, 14 clades are recognised, six of which cluster in Mycosphaerellaceae. Pseudocercospora s. str. represents a distinct clade, sister to Passalora eucalypti, and a clade representing the genera Scolecostigmina, Trochophora and Pallidocercospora gen. nov., taxa formerly accommodated in the Mycosphaerella heimii complex and characterised by smooth, pale brown conidia, as well as the formation of red crystals in agar media. Other clades in Mycosphaerellaceae include Sonderhenia, Microcyclosporella, and Paracercospora. Pseudocercosporella resides in a large clade along with Phloeospora, Miuraea, Cercospora and Septoria. Additional clades represent Dissoconiaceae, Teratosphaeriaceae, Cladosporiaceae, and the genera Xenostigmina, Strelitziana, Cyphellophora and Thedgonia. The genus Phaeomycocentrospora is introduced to accommodate Mycocentrospora cantuariensis, primarily distinguished from Pseudocercospora based on its hyaline hyphae, broad conidiogenous loci and hila. Host specificity was considered for 146 species of Pseudocercospora occurring on 115 host genera from 33 countries. Partial nucleotide sequence data for three gene loci, ITS, EF-1α, and ACT suggest that the majority of these species are host specific. Species identified on the basis of host, symptomatology and general

  6. Comparative Study of Alterations in Tri-iodothyronine (T3) and Thyroxine (T4) Hormone Levels in Breast and Ovarian Cancer.

    PubMed

    Rasool, Mahmood; Naseer, Muhammad Imran; Zaigham, Kalsoom; Malik, Arif; Riaz, Naila; Alam, Rabail; Manan, Abdul; Sheikh, Ishfaq Ahmed; Asif, Muhammad

    2014-01-01

    Objective : The present study was designed to investigate variations in the levels of thyroid hormones (T3, T4) in breast and ovarian cancers patients. Methods : A total 120 subjects were recruited (without thyroid history) divided into three groups; A, B and C. Group A as control with healthy individuals. While group B and group C were consisting of breast cancer and ovarian cancer patient respectively. Blood samples (5 ml) were taken and analyzed to estimate the levels of serum T3 (tri-iodothyronine) and T4 (thyroxin) hormones. R esults : Statistically significant difference (P=0.000* and P=0.017*) was obtained among all groups. A significant increase in T3 (P=0.000*) and T4 (0.005*) levels was observed among breast cancer patients as compared to healthy controls. While for ovarian cancer patients conflicting results were found for T3 and T4 levels in the serum i.e. insignificant difference was found in T3 (P=0.209) and T4 (P=0.050) as compared to control. Our results showed that in the breast cancer and ovarian cancer patients the thyroid hormone (T3 and T4) level has been altered from the normal ranges as compared to the normal healthy individuals. Conclusion : We conclude that hyperthyroidism has profound effects on breast cancer and ovarian cancer cells proliferation.

  7. Exaggerated force production in altered Gz-levels during parabolic flight: the role of computational resources allocation.

    PubMed

    Mierau, Andreas; Girgenrath, Michaela

    2010-02-01

    The purpose of the present experiment was to examine whether the previously observed exaggerated isometric force production in changed-Gz during parabolic flight (Mierau et al. 2008) can be explained by a higher computational demand and, thus, inadequate allocation of the brain's computational resources to the task. Subjects (n = 12) were tested during the micro-Gz, high-Gz and normal-Gz episodes of parabolic flight. They produced isometric forces of different magnitudes and directions, according to visually prescribed vectors with their right, dominant hand and performed a choice reaction-time task with their left hand. Tasks were performed either separately (single-task) or simultaneously (dual-task). Dual-task interference was present for both tasks, indicating that each task was resources-demanding. However, this interference remained unaffected by the Gz-level. It was concluded that exaggerated force production in changed-Gz is probably not related to inadequate allocation of the brain's computational resources to the force production task. Statement of Relevance: The present study shows that deficient motor performance in changed-Gz environments (both micro-Gz and high-Gz) is not necessarily related to inadequate computational resources allocation, as was suggested in some previous studies. This finding is of great relevance not only for fundamental research, but also for the training and safety of humans operating in changed-Gz environments, such as astronauts and jet pilots.

  8. Sodium Fluoride Induces Apoptosis in H9c2 Cardiomyocytes by Altering Mitochondrial Membrane Potential and Intracellular ROS Level.

    PubMed

    Yan, Xiaoyan; Yang, Xia; Hao, Xianhui; Ren, Qiurong; Gao, Jiping; Wang, Yu; Chang, Na; Qiu, Yulan; Song, Guohua

    2015-08-01

    Chronic excessive fluoride intake is known to be toxic, and effects of long-term fluorosis on different organ systems have been examined. However, there are few studies about the effects of fluorosis on cardiovascular systems. Here, we studied the fluoride-induced apoptosis in H9c2 cells and determined the underlying molecular mechanisms including the cell viability, intracellular reactive oxygen species (ROS) level, the changes of mitochondrial membrane potential (ΔΨm), and the cell apoptosis. Sodium fluoride (NaF) at concentrations of 0, 2, 4, 8, and 16 mg/L was administered to cultured H9c2 cells for up to 48 h. After the treatment, H9c2 cells were collected and the associated parameters were measured by flow cytometry. Our study found that fluoride not only inhibited H9c2 cell proliferation but also induced cell apoptosis. With the increment of NaF concentration, the apoptotic rates and ROS generation were increased, while the ΔΨm was decreased. In summary, these data suggested that NaF-induced H9c2 cell apoptosis is mediated by direct increased intracellular ROS and downregulated ΔΨm.

  9. Long-term exposure to abnormal glucose levels alters drug metabolism pathways and insulin sensitivity in primary human hepatocytes

    PubMed Central

    Davidson, Matthew D.; Ballinger, Kimberly R.; Khetani, Salman R.

    2016-01-01

    Hyperglycemia in type 2 diabetes mellitus has been linked to non-alcoholic fatty liver disease, which can progress to inflammation, fibrosis/cirrhosis, and hepatocellular carcinoma. Understanding how chronic hyperglycemia affects primary human hepatocytes (PHHs) can facilitate the development of therapeutics for these diseases. Conversely, elucidating the effects of hypoglycemia on PHHs may provide insights into how the liver adapts to fasting, adverse diabetes drug reactions, and cancer. In contrast to declining PHH monocultures, micropatterned co-cultures (MPCCs) of PHHs and 3T3-J2 murine embryonic fibroblasts maintain insulin-sensitive glucose metabolism for several weeks. Here, we exposed MPCCs to hypo-, normo- and hyperglycemic culture media for ~3 weeks. While albumin and urea secretion were not affected by glucose level, hypoglycemic MPCCs upregulated CYP3A4 enzyme activity as compared to other glycemic states. In contrast, hyperglycemic MPCCs displayed significant hepatic lipid accumulation in the presence of insulin, while also showing decreased sensitivity to insulin-mediated inhibition of glucose output relative to a normoglycemic control. In conclusion, we show for the first time that PHHs exposed to hypo- and hyperglycemia can remain highly functional, but display increased CYP3A4 activity and selective insulin resistance, respectively. In the future, MPCCs under glycemic states can aid in novel drug discovery and mechanistic investigations. PMID:27312339

  10. An acute exposure to glyphosate-based herbicide alters aromatase levels in testis and sperm nuclear quality.

    PubMed

    Cassault-Meyer, Estelle; Gress, Steeve; Séralini, Gilles-Éric; Galeraud-Denis, Isabelle

    2014-07-01

    Roundup is the major pesticide used in agriculture worldwide; it is a glyphosate-based herbicide. Its molecular effects are studied following an acute exposure (0.5%) of fifteen 60-day-old male rats during an 8-day period. Endocrine (aromatase, estrogen and androgen receptors, Gper1 in testicular and sperm mRNAs) and testicular functions (organ weights, sperm parameters and expression of the blood-testis barrier markers) were monitored at days 68, 87, and 122 after treatment, spermiogenesis and spermatogenesis. The major disruption is an increase of aromatase mRNA levels at least by 50% in treated rats at all times, as well as the aromatase protein. We have also shown a similar increase of Gper1 expression at day 122 and a light modification of BTB markers. A rise of abnormal sperm morphology and a decrease of the expression of protamine 1 and histone 1 testicular in epididymal sperm are observed despite a normal sperm concentration and motility.

  11. Long-term exposure to abnormal glucose levels alters drug metabolism pathways and insulin sensitivity in primary human hepatocytes

    NASA Astrophysics Data System (ADS)

    Davidson, Matthew D.; Ballinger, Kimberly R.; Khetani, Salman R.

    2016-06-01

    Hyperglycemia in type 2 diabetes mellitus has been linked to non-alcoholic fatty liver disease, which can progress to inflammation, fibrosis/cirrhosis, and hepatocellular carcinoma. Understanding how chronic hyperglycemia affects primary human hepatocytes (PHHs) can facilitate the development of therapeutics for these diseases. Conversely, elucidating the effects of hypoglycemia on PHHs may provide insights into how the liver adapts to fasting, adverse diabetes drug reactions, and cancer. In contrast to declining PHH monocultures, micropatterned co-cultures (MPCCs) of PHHs and 3T3-J2 murine embryonic fibroblasts maintain insulin-sensitive glucose metabolism for several weeks. Here, we exposed MPCCs to hypo-, normo- and hyperglycemic culture media for ~3 weeks. While albumin and urea secretion were not affected by glucose level, hypoglycemic MPCCs upregulated CYP3A4 enzyme activity as compared to other glycemic states. In contrast, hyperglycemic MPCCs displayed significant hepatic lipid accumulation in the presence of insulin, while also showing decreased sensitivity to insulin-mediated inhibition of glucose output relative to a normoglycemic control. In conclusion, we show for the first time that PHHs exposed to hypo- and hyperglycemia can remain highly functional, but display increased CYP3A4 activity and selective insulin resistance, respectively. In the future, MPCCs under glycemic states can aid in novel drug discovery and mechanistic investigations.

  12. Beta-adrenergic receptor agonist decreases VEGF levels through altered eNOS and PKC signaling in diabetic retina

    PubMed Central

    Jiang, Youde; Zhang, Qiuhua; Steinle, Jena J.

    2015-01-01

    Vascular endothelial cell growth factor (VEGF) is increased in diabetic macular edema. Compound 49b, a novel β-adrenergic receptor agonist, is protective in a type 1 diabetic rat model. We questioned whether Compound 49b could decrease VEGF levels, suggesting that Compound 49b may be effective against edema. Two-month diabetic rats received topical Compound 49b for 7 days only and/or insulin-like growth factor binding protein 3 (IGFBP-3) siRNA. We also measured endothelial nitric oxide synthase (eNOS) and protein kinase C (PKC)ζ and PKCδ phosphorylation. Retinal endothelial cells (RECs) cultured in high glucose were treated with Compound 49b and IGFBP-3 siRNA for evaluation of the same signaling pathways. Compound 49b significantly decreased VEGF through increased IGFBP-3 in the diabetic retina. Compound 49b also reduced eNOS, PKCζ and PKCδ phosphorylation in the diabetic retina and REC. Compound 49b regulated a number of proteins involved in REC barrier properties. PMID:26115368

  13. Low level of selenium increases the efficacy of 24-epibrassinolide through altered physiological and biochemical traits of Brassica juncea plants.

    PubMed

    Naz, Fatima Salva; Yusuf, Mohammad; Khan, Tanveer A; Fariduddin, Qazi; Ahmad, Aqil

    2015-10-15

    This study was conducted to provide an insight into the effect of Se (through soil) induced changes in Brassica juncea plants in the presence and absence of 24-epibrassinolide (EBL; foliar). The Se treatments showed dual response, 10 μM of Se significantly increased growth, water relations, photosynthetic attributes along with carbonic anhydrase activity whereas its higher concentrations proved inhibitory in concentration dependent manner. The follow-up application of EBL to the Se stressed plants improved growth, water relations, photosynthesis and simultaneously enhanced the various antioxidant enzymes viz. catalase, peroxidase and superoxide dismutase with the excess accumulation of proline. In addition to this, 10 μM Se increases the efficacy of 10(-8) M of EBL and both in combination showed maximum increase for the growth and photosynthetic traits of plants. On the other hand, the elevated level of antioxidant enzymes as well as proline could have conferred tolerance to the Se-stressed plants resulting in improved growth, water relations and photosynthesis.

  14. Altered NR4A Subfamily Gene Expression Level in Peripheral Blood of Parkinson's and Alzheimer's Disease Patients.

    PubMed

    Montarolo, Francesca; Perga, Simona; Martire, Serena; Navone, Désirée Nicole; Marchet, Alberto; Leotta, Daniela; Bertolotto, Antonio

    2016-10-01

    Parkinson's disease (PD) is a neurodegenerative pathology characterized by the degeneration of midbrain dopamine neurons, whose development and maintenance in brain is related to the transcription factor NR4A2 (also called Nurr1). Notably, NR4A2 is a neuroprotective agent with anti-inflammatory role in microglia and astrocytes. Furthermore, mutations in NR4A2 gene are associated to the familial form of PD, and its gene expression level is down-regulated in blood obtained from PD patients. NR4A2 belongs to the NR4A subfamily consisting of three members: NR4A1, NR4A2, and NR4A3. The NR4A subfamily shares high degree of homology in their molecular structure and cooperates in a spectrum of functions ranging from central nervous system to immune control during physiological and pathological conditions. Considering the close functional link between the member of NR4A subfamily, we performed a gene expression analysis of NR4A1, NR4A2, and NR4A3 in peripheral blood obtained from PD patients and healthy controls (HC). Then, in order to evaluate possible involvement of the NR4A subfamily in other neurodegenerative processes, we carried out the same analysis on blood obtained from Alzheimer's disease (AD) patients. A correlation between clinical features and gene expression was also evaluated. We found a marked down-regulated gene expression of the NR4A subfamily obtained from PD patients, but only a NR4A1 decrease in AD patients compared to HC. This study reports that the entire NR4A subfamily and not only NR4A2 could be systemically involved in PD suggesting that the study of these factors could be a promising approach to develop PD therapy.

  15. Neonatal exposure to a moderate dose of ionizing radiation causes behavioural defects and altered levels of tau protein in mice.

    PubMed

    Buratovic, Sonja; Stenerlöw, Bo; Fredriksson, Anders; Sundell-Bergman, Synnöve; Viberg, Henrik; Eriksson, Per

    2014-12-01

    Medical use of ionizing radiation (IR) has great benefits for treatment and diagnostic imaging, but procedures as computerized tomography (CT) may deliver a significant radiation dose to the patient. Recently, awareness has been raised about possible non-cancer consequences from low dose exposure to IR during critical phases of perinatal and/or neonatal brain development. In the present study neonatal NMRI mice were whole body irradiated with a single dose of gamma radiation (0; 350 and 500 mGy) on postnatal day 10 (PND 10). At 2 and 4 months of age, mice of both sexes were observed for spontaneous behaviour in a novel home environment. The neuroproteins CaMKII, GAP-43, synaptophysin and total tau in male mouse cerebral cortex and hippocampus were analysed 24h post-irradiation and in adults at 6 months of age exposed to 0 or 500 mGy on PND 10. A significantly dose-response related deranged spontaneous behaviour in 2- and 4-month-old mice was observed, where both males and females displayed a modified habituation, indicating reduced cognitive function. The dose of 350 mGy seems to be a tentative threshold. Six-month-old male mice showed a significantly increased level of total tau in cerebral cortex after irradiation to 500 mGy compared to controls. This demonstrates that a single moderate dose of IR, given during a defined critical period of brain development, is sufficient to cause persistently reduced cognitive function. Moreover, an elevation of tau protein was observed in male mice displaying reduced cognitive function.

  16. A novel HSP90 inhibitor delays castrate resistant prostate cancer without altering serum PSA levels and inhibits osteoclastogenesis

    PubMed Central

    Lamoureux, Francois; Thomas, Christian; Yin, Min-Jean; Kuruma, Hidetoshi; Fazli, Ladan; Gleave, Martin E; Zoubeidi, Amina

    2015-01-01

    Purpose Prostate cancer responds initially to anti-androgen therapies, however, progression to castration resistant disease frequently occurs. Therefore there is an urgent need for novel therapeutic agents that can prevent the emergence of castration resistant prostate cancer (CRPC). Hsp90 is a molecular chaperone involved in the stability of many client proteins including Akt and androgen receptor (AR). 17-AAG have been reported to inhibit tumor growth in various cancers, however induces tumor progression in the bone microenvironment. Methods Cell growth, apoptosis, and AR transactivation were examined by crystal violet assay, flow cytometry and luciferase assays respectively. The consequence of HSP90 therapy in vivo was evaluated in LNCaP xenograft model. The consequence of PF-04928473 therapy on bone metastasis was studied using an osteoclastogenesis in vitro assay. Results PF-04928473 inhibits cell growth in a panel of prostate cancer cells, induces cell cycle arrest at sub-G1 and leads to apoptosis and increased caspase-3 activity. These biologic events were accompanied by decreased activation of Akt and Erk as well as decreased expression of Her2, and decreased AR expression and activation in vitro. In contrast to 17-AAG, PF-04928473 abrogates RANKL-induced osteoclast differentiation by affecting NF-kB activation and Src phosphorylation. Finally, PF-04929113 inhibited tumor growth and prolonged survival compared to controls. Surprisingly, PF-04929113 did not reduce serum PSA levels in vivo in parallel these decreases in tumor volume. Conclusion These data identify significant anti-cancer activity of PF-04929113 in CRPC but suggest that serum PSA may not prove useful as pharmaco-dynamic tool for this drug. PMID:21349995

  17. Phylogenetic signal in primate behaviour, ecology and life history.

    PubMed

    Kamilar, Jason M; Cooper, Natalie

    2013-05-19

    Examining biological diversity in an explicitly evolutionary context has been the subject of research for several decades, yet relatively recent advances in analytical techniques and the increasing availability of species-level phylogenies, have enabled scientists to ask new questions. One such approach is to quantify phylogenetic signal to determine how trait variation is correlated with the phylogenetic relatedness of species. When phylogenetic signal is high, closely related species exhibit similar traits, and this biological similarity decreases as the evolutionary distance between species increases. Here, we first review the concept of phylogenetic signal and suggest how to measure and interpret phylogenetic signal in species traits. Second, we quantified phylogenetic signal in primates for 31 variables, including body mass, brain size, life-history, sexual selection, social organization, diet, activity budget, ranging patterns and climatic variables. We found that phylogenetic signal varies extensively across and even within trait categories. The highest values are exhibited by brain size and body mass, moderate values are found in the degree of territoriality and canine size dimorphism, while low values are displayed by most of the remaining variables. Our results have important implications for the evolution of behaviour and ecology in primates and other vertebrates.

  18. A new dynamic null model for phylogenetic community structure.

    PubMed

    Pigot, Alex L; Etienne, Rampal S

    2015-02-01

    Phylogenies are increasingly applied to identify the mechanisms structuring ecological communities but progress has been hindered by a reliance on statistical null models that ignore the historical process of community assembly. Here, we address this, and develop a dynamic null model of assembly by allopatric speciation, colonisation and local extinction. Incorporating these processes fundamentally alters the structure of communities expected due to chance, with speciation leading to phylogenetic overdispersion compared to a classical statistical null model assuming equal probabilities of community membership. Applying this method to bird and primate communities in South America we show that patterns of phylogenetic overdispersion - often attributed to negative biotic interactions - are instead consistent with a species neutral model of allopatric speciation, colonisation and local extinction. Our findings provide a new null expectation for phylogenetic community patterns and highlight the importance of explicitly accounting for the dynamic history of assembly when testing the mechanisms governing community structure.

  19. Acute low dose of MK-801 prevents memory deficits without altering hippocampal DARPP-32 expression and BDNF levels in sepsis survivor rats.

    PubMed

    Cassol-Jr, Omar J; Comim, Clarissa M; Constantino, Larissa S; Rosa, Daniela V F; Mango, Luiz Alexandre V; Stertz, Laura; Kapczinski, Flávio; Romano-Silva, Marco A; Quevedo, João; Dal-Pizzol, Felipe

    2011-01-01

    Sepsis is characterized by an intense inflammatory reaction with potential neurotoxic effects in the central nervous system and damage to memory and learning ability. We assessed the effects of acute low dose of MK-801 on the memory impairment, hippocampal BDNF levels and DARPP-32 expression ten days after sepsis. Under anesthesia, male Wistar rats underwent either cecal ligation and perforation (CLP) or sham. Then, the animals received either a single systemic injection of MK-801 (0.025 mg/kg) or saline solution. Ten days after CLP, the animals were submitted to the step-down inhibitory avoidance and object recognition tests. Also, the hippocampal BDNF protein levels and DARPP-32 expression were evaluated. MK-801 prevented cognitive impairment, but did not affect the hippocampal BDNF levels. DARPP-32 expression was significantly different only in the animals submitted to sepsis that received MK-801 treatment. Thus, we demonstrated that a single low dose of MK-801 prevented memory impairment without altering hippocampal DARPP-32 expression and BDNF levels.

  20. Dioxin exposure reduces the steroidogenic capacity of mouse antral follicles mainly at the level of HSD17B1 without altering atresia

    SciTech Connect

    Karman, Bethany N. Basavarajappa, Mallikarjuna S. Hannon, Patrick Flaws, Jodi A.

    2012-10-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent ovarian toxicant. Previously, we demonstrated that in vitro TCDD (1 nM) exposure decreases production/secretion of the sex steroid hormones progesterone (P4), androstenedione (A4), testosterone (T), and 17β-estradiol (E2) in mouse antral follicles. The purpose of this study was to determine the mechanism by which TCDD inhibits steroidogenesis. Specifically, we examined the effects of TCDD on the steroidogenic enzymes, atresia, and the aryl hydrocarbon receptor (AHR) protein. TCDD exposure for 48 h increased levels of A4, without changing HSD3B1 protein, HSD17B1 protein, estrone (E1), T or E2 levels. Further, TCDD did not alter atresia ratings compared to vehicle at 48 h. TCDD, however, did down regulate the AHR protein at 48 h. TCDD exposure for 96 h decreased transcript levels for Cyp11a1, Cyp17a1, Hsd17b1, and Cyp19a1, but increased Hsd3b1 transcript. TCDD exposure particularly lowered both Hsd17b1 transcript and HSD17B1 protein. However, TCDD exposure did not affect levels of E1 in the media nor atresia ratings at 96 h. TCDD, however, decreased levels of the proapoptotic factor Bax. Collectively, these data suggest that TCDD exposure causes a major block in the steroidogenic enzyme conversion of A4 to T and E1 to E2 and that it regulates apoptotic pathways, favoring survival over death in antral follicles. Finally, the down‐regulation of the AHR protein in TCDD exposed follicles persisted at 96 h, indicating that the activation and proteasomal degradation of this receptor likely plays a central role in the impaired steroidogenic capacity and altered apoptotic pathway of exposed antral follicles. -- Highlights: ► TCDD disrupts steroidogenic enzymes in mouse antral follicles. ► TCDD particularly affects the HSD17B1 enzyme in mouse antral follicles. ► TCDD does not affect atresia ratings in mouse antral follicles. ► TCDD decreases levels of the proapoptitic factor Bax in mouse antral follicles.

  1. Serosorting and Sexual Risk for HIV Infection at the Ego-Alter Dyadic Level: An Egocentric Sexual Network Study Among MSM in Nigeria.

    PubMed

    Rodriguez-Hart, Cristina; Liu, Hongjie; Nowak, Rebecca G; Orazulike, Ifeanyi; Zorowitz, Sam; Crowell, Trevor A; Baral, Stefan D; Blattner, William; Charurat, Man

    2016-11-01

    The objective of this egocentric network study was to investigate engagement in serosorting by HIV status and risk for HIV between seroconcordant and serodiscordant ego-alter dyads. Respondent-driving sampling was used to recruit 433 Nigerian men who have sex with men (MSM) from 2013 to 2014. Participant (ego) characteristics and that of five sex partners (alters) were collected. Seroconcordancy was assessed at the ego level and for each dyad. Among 433 egos, 18 % were seroconcordant with all partners. Among 880 dyads where participants knew their HIV status, 226 (25.7 %) were seroconcordant, with 11.7 % of HIV positive dyads seroconcordant and 37.0 % of HIV negative dyads seroconcordant. Seroconcordant dyads reported fewer casual sex partners, less partner concurrency, and partners who had ever injected drugs, but condom use did not differ significantly. Serosorting may be a viable risk reduction strategy among Nigerian MSM, but awareness of and communication about HIV status should be increased. Future studies should assess serosorting on a partner-by-partner basis.

  2. Phylogenetic community ecology of soil biodiversity using mitochondrial metagenomics.

    PubMed

    Andújar, Carmelo; Arribas, Paula; Ruzicka, Filip; Crampton-Platt, Alex; Timmermans, Martijn J T N; Vogler, Alfried P

    2015-07-01

    High-throughput DNA methods hold great promise for the study of taxonomically intractable mesofauna of the soil. Here, we assess species diversity and community structure in a phylogenetic framework, by sequencing total DNA from bulk specimen samples and assembly of mitochondrial genomes. The combination of mitochondrial metagenomics and DNA barcode sequencing of 1494 specimens in 69 soil samples from three geographic regions in southern Iberia revealed >300 species of soil Coleoptera (beetles) from a broad spectrum of phylogenetic lineages. A set of 214 mitochondrial sequences longer than 3000 bp was generated and used to estimate a well-supported phylogenetic tree of the order Coleoptera. Shorter sequences, including cox1 barcodes, were placed on this mitogenomic tree. Raw Illumina reads were mapped against all available sequences to test for species present in local samples. This approach simultaneously established the species richness, phylogenetic composition and community turnover at species and phylogenetic levels. We find a strong signature of vertical structuring in soil fauna that shows high local community differentiation between deep soil and superficial horizons at phylogenetic levels. Within the two vertical layers, turnover among regions was primarily at the tip (species) level and was stronger in the deep soil than leaf litter communities, pointing to layer-mediated drivers determining species diversification, spatial structure and evolutionary assembly of soil communities. This integrated phylogenetic framework opens the application of phylogenetic community ecology to the mesofauna of the soil, among the most diverse and least well-understood ecosystems, and will propel both theoretical and applied soil science.

  3. A Consistent Phylogenetic Backbone for the Fungi

    PubMed Central

    Ebersberger, Ingo; de Matos Simoes, Ricardo; Kupczok, Anne; Gube, Matthias; Kothe, Erika; Voigt, Kerstin; von Haeseler, Arndt

    2012-01-01

    The kingdom of fungi provides model organisms for biotechnology, cell biology, genetics, and life sciences in general. Only when their phylogenetic relationships are stably resolved, can individual results from fungal research be integrated into a holistic picture of biology. However, and despite recent progress, many deep relationships within the fungi remain unclear. Here, we present the first phylogenomic study of an entire eukaryotic kingdom that uses a consistency criterion to strengthen phylogenetic conclusions. We reason that branches (splits) recovered with independent data and different tree reconstruction methods are likely to reflect true evolutionary relationships. Two complementary phylogenomic data sets based on 99 fungal genomes and 109 fungal expressed sequence tag (EST) sets analyzed with four different tree reconstruction methods shed light from different angles on the fungal tree of life. Eleven additional data sets address specifically the phylogenetic position of Blastocladiomycota, Ustilaginomycotina, and Dothideomycetes, respectively. The combined evidence from the resulting trees supports the deep-level stability of the fungal groups toward a comprehensive natural system of the fungi. In addition, our analysis reveals methodologically interesting aspects. Enrichment for EST encoded data—a common practice in phylogenomic analyses—introduces a strong bias toward slowly evolving and functionally correlated genes. Consequently, the generalization of phylogenomic data sets as collections of randomly selected genes cannot be taken for granted. A thorough characterization of the data to assess possible influences on the tree reconstruction should therefore become a standard in phylogenomic analyses. PMID:22114356

  4. apex: phylogenetics with multiple genes.

    PubMed

    Jombart, Thibaut; Archer, Frederick; Schliep, Klaus; Kamvar, Zhian; Harris, Rebecca; Paradis, Emmanuel; Goudet, Jérome; Lapp, Hilmar

    2017-01-01

    Genetic sequences of multiple genes are becoming increasingly common for a wide range of organisms including viruses, bacteria and eukaryotes. While such data may sometimes be treated as a single locus, in practice, a number of biological and statistical phenomena can lead to phylogenetic incongruence. In such cases, different loci should, at least as a preliminary step, be examined and analysed separately. The r software has become a popular platform for phylogenetics, with several packages implementing distance-based, parsimony and likelihood-based phylogenetic reconstruction, and an even greater number of packages implementing phylogenetic comparative methods. Unfortunately, basic data structures and tools for analysing multiple genes have so far been lacking, thereby limiting potential for investigating phylogenetic incongruence. In this study, we introduce the new r package apex to fill this gap. apex implements new object classes, which extend existing standards for storing DNA and amino acid sequences, and provides a number of convenient tools for handling, visualizing and analysing these data. In this study, we introduce the main features of the package and illustrate its functionalities through the analysis of a simple data set.

  5. The impact of synapsin III gene on the neurometabolite level alterations after single-dose methylphenidate in attention-deficit hyperactivity disorder patients

    PubMed Central

    Başay, Ömer; Kabukcu Basay, Burge; Alacam, Huseyin; Ozturk, Onder; Buber, Ahmet; Gorucu Yilmaz, Senay; Kıroğlu, Yılmaz; Erdal, Mehmet Emin; Herken, Hasan

    2016-01-01

    Objective To investigate the neurometabolite level changes according to synapsin III gene rs133945G>A and rs133946C>G polymorphisms by using magnetic resonance spectroscopy (MRS) in patients with attention-deficit hyperactivity disorder (ADHD). Methods Fifty-seven adults diagnosed with ADHD were recruited for the study. The participants were examined by single-voxel 1H MRS when medication naïve and 30 minutes after oral administration of 10 mg methylphenidate (Mph). Those who had been on a stimulant discontinued the medication 48 hours before MRS imaging. Spectra were taken from the anterior cingulate cortex, dorsolateral prefrontal cortex, striatum, and cerebellum, and N-acetylaspartate (NAA), choline, and creatine levels were examined. For genotyping of the synapsin III gene polymorphisms, DNA was isolated from peripheral blood leukocytes. The effects of age, sex, and ADHD subtypes were controlled in the analyses. Results After a single dose of Mph, choline levels increased significantly in the striatum of rs133945G>A polymorphism-GG genotypes (P=0.020) and NAA levels rose in the anterior cingulate cortex of rs133946C>G polymorphism-CG genotypes (P=0.014). Both rs133945G>A and rs133946C>G polymorphisms were found to statistically significantly affect the alteration of NAA levels in response to Mph in dorsolateral prefrontal cortex with two-way repeated measure of analysis of variance. Post hoc comparisons revealed a significant difference between CG and GG genotypes of rs133946C>G polymorphisms after Bonferroni adjustment (P=0.016). Conclusion Synapsin III gene polymorphisms may be affecting the changes in neurometabolite levels in response to Mph in adult ADHD patients. Future studies are needed to confirm our findings. PMID:27274248

  6. Bayesian phylogenetic estimation of fossil ages

    PubMed Central

    Drummond, Alexei J.; Stadler, Tanja

    2016-01-01

    Recent advances have allowed for both morphological fossil evidence and molecular sequences to be integrated into a single combined inference of divergence dates under the rule of Bayesian probability. In particular, the fossilized birth–death tree prior and the Lewis-Mk model of discrete morphological evolution allow for the estimation of both divergence times and phylogenetic relationships between fossil and extant taxa. We exploit this statistical framework to investigate the internal consistency of these models by producing phylogenetic estimates of the age of each fossil in turn, within two rich and well-characterized datasets of fossil and extant species (penguins and canids). We find that the estimation accuracy of fossil ages is generally high with credible intervals seldom excluding the true age and median relative error in the two datasets of 5.7% and 13.2%, respectively. The median relative standard error (RSD) was 9.2% and 7.2%, respectively, suggesting good precision, although with some outliers. In fact, in the two datasets we analyse, the phylogenetic estimate of fossil age is on average less than 2 Myr from the mid-point age of the geological strata from which it was excavated. The high level of internal consistency found in our analyses suggests that the Bayesian statistical model employed is an adequate fit for both the geological and morphological data, and provides evidence from real data that the framework used can accurately model the evolution of discrete morphological traits coded from fossil and extant taxa. We anticipate that this approach will have diverse applications beyond divergence time dating, including dating fossils that are temporally unconstrained, testing of the ‘morphological clock', and for uncovering potential model misspecification and/or data errors when controversial phylogenetic hypotheses are obtained based on combined divergence dating analyses. This article is part of the themed issue ‘Dating species divergences

  7. Correlation of serum cytokine and acute phase reactant levels with alterations in weight and serum albumin in patients receiving immunotherapy with recombinant IL-2.

    PubMed Central

    Deehan, D J; Heys, S D; Simpson, W; Herriot, R; Broom, J; Eremin, O

    1994-01-01

    Recombinant IL-2 (rIL-2) has been used alone or in combination with other chemotherapeutic agents to enhance host defences against cancer. Prolonged administration of high doses, required for clinical efficacy, may precipitate serious dose-limiting toxicity. rIL-2-induced 'vascular leak syndrome' leads to hypotension, renal insufficiency, respiratory disturbances and other organ dysfunctions. Serial measurements of serum cytokines and the acute phase protein C-reactive protein (CRP) were performed on nine patients who received high-dose i.v. continuous therapy with rIL-2. The influence of these immunological parameters upon alterations in patients' weight and serum albumin, as indicators of toxicity, was assessed. All patients experienced weight increases during the cycle (3-11% of total body weight). The serum levels of tumour necrosis factor (TNF-alpha) and CRP were highly predictive of alterations in patients' weight (both P < 0.001), while no correlation was found with IL-6 and weight change. Serum albumin fell linearly throughout the infusion cycle, but this showed no correlation with variations in serum levels of IL-6, TNF-alpha, or CRP. The complement components C3 and C4 were significantly reduced at the end of the infusion, suggesting a possible role for this cascade system in mediating these clinical changes. The strong association between serum TNF-alpha and weight change, not previously documented, further supports the hypothesis that TNF-alpha is a key mediator in the pathogenesis of the 'vascular leak syndrome'. PMID:7511074

  8. Integration of mRNA expression profile, copy number alterations, and microRNA expression levels in breast cancer to improve grade definition.

    PubMed

    Cava, Claudia; Bertoli, Gloria; Ripamonti, Marilena; Mauri, Giancarlo; Zoppis, Italo; Della Rosa, Pasquale Anthony; Gilardi, Maria Carla; Castiglioni, Isabella

    2014-01-01

    Defining the aggressiveness and growth rate of a malignant cell population is a key step in the clinical approach to treating tumor disease. The correct grading of breast cancer (BC) is a fundamental part in determining the appropriate treatment. Biological variables can make it difficult to elucidate the mechanisms underlying BC development. To identify potential markers that can be used for BC classification, we analyzed mRNAs expression profiles, gene copy numbers, microRNAs expression and their association with tumor grade in BC microarray-derived datasets. From mRNA expression results, we found that grade 2 BC is most likely a mixture of grade 1 and grade 3 that have been misclassified, being described by the gene signature of either grade 1 or grade 3. We assessed the potential of the new approach of integrating mRNA expression profile, copy number alterations, and microRNA expression levels to select a limited number of genomic BC biomarkers. The combination of mRNA profile analysis and copy number data with microRNA expression levels led to the identification of two gene signatures of 42 and 4 altered genes (FOXM1, KPNA4, H2AFV and DDX19A) respectively, the latter obtained through a meta-analytical procedure. The 42-based gene signature identifies 4 classes of up- or down-regulated microRNAs (17 microRNAs) and of their 17 target mRNA, and the 4-based genes signature identified 4 microRNAs (Hsa-miR-320d, Hsa-miR-139-5p, Hsa-miR-567 and Hsa-let-7c). These results are discussed from a biological point of view with respect to pathological features of BC. Our identified mRNAs and microRNAs were validated as prognostic factors of BC disease progression, and could potentially facilitate the implementation of assays for laboratory validation, due to their reduced number.

  9. Phylogenetic and functional diversity in large carnivore assemblages.

    PubMed

    Dalerum, F

    2013-06-07

    Large terrestrial carnivores are important ecological components and prominent flagship species, but are often extinction prone owing to a combination of biological traits and high levels of human persecution. This study combines phylogenetic and functional diversity evaluations of global and continental large carnivore assemblages to provide a framework for conservation prioritization both between and within assemblages. Species-rich assemblages of large carnivores simultaneously had high phylogenetic and functional diversity, but species contributions to phylogenetic and functional diversity components were not positively correlated. The results further provide ecological justification for the largest carnivore species as a focus for conservation action, and suggests that range contraction is a likely cause of diminishing carnivore ecosystem function. This study highlights that preserving species-rich carnivore assemblages will capture both high phylogenetic and functional diversity, but that prioritizing species within assemblages will involve trade-offs between optimizing contemporary ecosystem function versus the evolutionary potential for future ecosystem performance.

  10. Phylogenetic Approaches Toward Crocodylian History

    NASA Astrophysics Data System (ADS)

    Brochu, Christopher A.

    A review of crocodylian phylogeny reveals a more complex history than might have been anticipated from a direct reading of the fossil record without consideration of phylogenetic relationships. The three main extant crocodylian lineagesGavialoidea, Alligatoroidea, Crocodyloideaare known from fossils in the Late Cretaceous, and the group is found nearly worldwide during the Cenozoic. Some groups have distributions that are best explained by the crossing of marine barriers during the Tertiary. Early Tertiary crocodylian faunas are phylogenetically composite, and clades tend to be morphologically uniform and geographically widespread. Later in the Tertiary, Old World crocodylian faunas are more endemic. Crocodylian phylogeneticists face numerous challenges, the most important being the phylogenetic relationships and time of divergence of the two living gharials (Gavialis gangeticus and Tomistoma schlegelii), the relationships among living true crocodiles (Crocodylus), and the relationships among caimans.

  11. Chronic Stress Induces Structural Alterations in Splenic Lymphoid Tissue That Are Associated with Changes in Corticosterone Levels in Wistar-Kyoto Rats

    PubMed Central

    Hernandez, María Eugenia; Martinez-Mota, Lucia; Salinas, Citlaltepetl; Marquez-Velasco, Ricardo; Hernandez-Chan, Nancy G.; Morales-Montor, Jorge; Pérez-Tapia, Mayra; Streber, María L.; Granados-Camacho, Ivonne; Becerril, Enrique; Javier, Baquera-Heredia; Pavón, Lenin

    2013-01-01

    Major depressive disorder patients present chronic stress and decreased immunity. The Wistar-Kyoto rat (WKY) is a strain in which the hypothalamic-pituitary-adrenal axis is overactivated. To determine whether chronic stress induces changes in corticosterone levels and splenic lymphoid tissue, 9-week-old male rats were subject to restraint stress (3 h daily), chemical stress (hydrocortisone treatment, 50 mg/Kg weight), mixed stress (restraint plus hydrocortisone), or control treatment (without stress) for 1, 4, and 7 weeks. The serum corticosterone levels by RIA and spleens morphology were analyzed. Corticosterone levels as did the structure, size of the follicles and morphology of the parenchyma (increase in red pulp) in the spleen, varied depending on time and type of stressor. These changes indicate that chronic stress alters the immune response in the spleen in WKY rats by inducing morphological changes, explaining in part the impaired immunity that develops in organisms that are exposed to chronic stress. PMID:23533999

  12. Levels of plasma sodium and potassium as well as alterations in adrenal cortex of Rattus norvegicus in response to sublethal heroin administration.

    PubMed

    Barai, S R; Suryawanshi, S A; Pandey, A K

    2009-03-01

    In order to record the effects of sublethal heroin administration on plasma mineral metabolism, the drug was administered intramuscularly (16.4 mg kg(-1) body weight day(-1); 0.75 LD50 dose) in Rattus norvegicus for 30 days. Plasma sodium and potassium levels of the control rats fluctuated between 153.14 +/- 2.88 - 157.23 +/- 2.16 meq l(-1) and 5.04 +/- 0.32 - 5.63 +/- 0.41 meq l(-1), respectively. Plasma sodium level of the treated rats registered a progressive decline (p<0.01) at 24 hr with the minimum value (126.53 +/- 2.68 meq l(-1)) on day 30 whereas plasma potassium level registered a progressive increase during entire period of the treatment with peak (8.78 +/- 0.23 meq l(-1)) on day 30. Though sublethal herion administration for 30 days elcited cytoplasmic vacuolation in all the three zones of adrenal cortex, much of cytological alterations were observed in zona glomerulosa and zona fasciculata cells. In zona glomerulosa cells, degenerative changes in the organelles were more pronounced as evident by the loss of typical cristae in the mitochondria and hormone granules were rarely seen in these cells. Though rough endoplasmic reticula were scanty, many lipid granules encountered in zona glomerulosa cells of the treated rats.

  13. In Vivo Bystander Effect: Cranial X-Irradiation Leads to Elevated DNA Damage, Altered Cellular Proliferation and Apoptosis, and Increased p53 Levels in Shielded Spleen

    SciTech Connect

    Koturbash, Igor; Loree, Jonathan; Kutanzi, Kristy; Koganow, Clayton; Pogribny, Igor; Kovalchuk, Olga

    2008-02-01

    Purpose: It is well accepted that irradiated cells may 'forward' genome instability to nonirradiated neighboring cells, giving rise to the 'bystander effect' phenomenon. Although bystander effects were well studied by using cell cultures, data for somatic bystander effects in vivo are relatively scarce. Methods and Materials: We set out to analyze the existence and molecular nature of bystander effects in a radiation target-organ spleen by using a mouse model. The animal's head was exposed to X-rays while the remainder of the body was completely protected by a medical-grade shield. Using immunohistochemistry, we addressed levels of DNA damage, cellular proliferation, apoptosis, and p53 protein in the spleen of control animals and completely exposed and head-exposed/body bystander animals. Results: We found that localized head radiation exposure led to the induction of bystander effects in the lead-shielded distant spleen tissue. Namely, cranial irradiation led to increased levels of DNA damage and p53 expression and also altered levels of cellular proliferation and apoptosis in bystander spleen tissue. The observed bystander changes were not caused by radiation scattering and were observed in two different mouse strains; C57BL/6 and BALB/c. Conclusion: Our study proves that bystander effects occur in the distant somatic organs on localized exposures. Additional studies are required to characterize the nature of an enigmatic bystander signal and analyze the long-term persistence of these effects and possible contribution of radiation-induced bystander effects to secondary radiation carcinogenesis.

  14. Fire modifies the phylogenetic structure of soil bacterial co-occurrence networks.

    PubMed

    Pérez-Valera, Eduardo; Goberna, Marta; Faust, Karoline; Raes, Jeroen; García, Carlos; Verdú, Miguel

    2017-01-01

    Fire alters ecosystems by changing the composition and community structure of soil microbes. The phylogenetic structure of a community provides clues about its main assembling mechanisms. While environmental filtering tends to reduce the community phylogenetic diversity by selecting for functionally (and hence phylogenetically) similar species, processes like competitive exclusion by limiting similarity tend to increase it by preventing the coexistence of functionally (and phylogenetically) similar species. We used co-occurrence networks to detect co-presence (bacteria that co-occur) or exclusion (bacteria that do not co-occur) links indicative of the ecological interactions structuring the community. We propose that inspecting the phylogenetic structure of co-presence or exclusion links allows to detect the main processes simultaneously assembling the community. We monitored a soil bacterial community after an experimental fire and found that fire altered its composition, richness and phylogenetic diversity. Both co-presence and exclusion links were more phylogenetically related than expected by chance. We interpret such a phylogenetic clustering in co-presence links as a result of environmental filtering, while that in exclusion links reflects competitive exclusion by limiting similarity. This suggests that environmental filtering and limiting similarity operate simultaneously to assemble soil bacterial communities, widening the traditional view that only environmental filtering structures bacterial communities.

  15. A correlation between altered O-GlcNAcylation, migration and with changes in E-cadherin levels in ovarian cancer cells

    SciTech Connect

    Jin, Feng-zhen; Yu, Chao; Zhao, De-zhang; Wu, Ming-jun; Yang, Zhu

    2013-06-10

    O-GlcNAcylation is a dynamic and reversible posttranslational modification of nuclear and cytoplasmic proteins. In recent years, the roles of O-GlcNAcylation in several human malignant tumors have been investigated, and O-GlcNAcylation was found to be linked to cellular features relevant to metastasis. In this study, we modeled four diverse ovarian cancer cells and investigated the effects of O-GlcNAcylation on ovarian cancer cell migration. We found that total O-GlcNAcylation level was elevated in HO-8910PM cells compared to OVCAR3 cells. Additionally, through altering the total O-GlcNAcylation level by OGT silencing or OGA inhibition, we found that the migration of OVCAR3 cells was dramatically enhanced by PUGNAc and Thiamet G treatment, and the migration ability of HO-8910PM cells was significantly inhibited by OGT silencing. Furthermore, we also found that the expression of E-cadherin, an O-GlcNAcylated protein in ovarian cancer cells, was reduced by OGA inhibition in OVCAR3 cells and elevated by OGT silencing in HO-8910PM cells. These results indicate that O-GlcNAcylation could enhance ovarian cancer cell migration and decrease the expression of E-cadherin. Our studies also suggest that O-GlcNAcylation might become another potential target for the therapy of ovarian cancer. -- Highlights: • We examine the migration potential of diverse ovarian cancer cells. • We examine the total O-GlcNAcylation level of diverse ovarian cancer cells. • Increasing O-GlcNAcylation level will enhance the migration of ovarian cancer cells. • Reducing O-GlcNAcylation level will inhibit the migration of ovarian cancer cells. • The mechanism explains O-GlcNAcylation enhance ovarian cancer cell migration.

  16. Nutrition modulates Fto and Irx3 gene transcript levels, but does not alter their DNA methylation profiles in rat white adipose tissues.

    PubMed

    Nowacka-Woszuk, Joanna; Pruszynska-Oszmalek, Ewa; Szydlowski, Maciej; Szczerbal, Izabela

    2017-04-30

    The fat mass and obesity associated (Fto) and iroquois homeobox 3 (Irx3) genes have been recognised as important obesity-related genes. Studies on the expression of these genes in the fat tissue of human and mouse have produced inconsistent results, while similar data on rat are limited. Environmental factors such as diet, should be considered as potential modulators of gene transcript levels through epigenetic mechanisms including DNA methylation. The aim of this study was to evaluate transcription levels and DNA methylation profiles of rat Fto and Irx3 genes in two white adipose tissue depots in response to high-fat and high-protein diets. The relative transcript levels of Fto and Irx3 were shown to be tissue-specific with higher levels detected in subcutaneous fat tissue than in abdominal fat tissue. Moreover, negative correlations between the transcripts of both genes were observed for subcutaneous fat tissue. The identified interactions (e.g. diet×duration of diet regimen) indicated that the diet had an impact on the transcript level; however, this effect was dependent on the duration of the diet regimen. The high-fat diet led to upregulation of Fto and Irx3 linearly with time across the two tissues. DNA methylation of the regulatory regions of the studied genes was very low and not related with the tissue, diet, or duration of diet regimen. Our study revealed that diet was an important factor modulating transcription of Fto and Irx3, but its effect is time-dependent. In contrast, the DNA methylation profiles of Fto and Irx3 were not altered by nutrition, which may indicate that the feeding type, when applied postnatally, did not affect DNA methylation of these genes.

  17. Nociceptors: a phylogenetic view.

    PubMed

    Smith, Ewan St John; Lewin, Gary R

    2009-12-01

    The ability to react to environmental change is crucial for the survival of an organism and an essential prerequisite is the capacity to detect and respond to aversive stimuli. The importance of having an inbuilt "detect and protect" system is illustrated by the fact that most animals have dedicated sensory afferents which respond to noxious stimuli called nociceptors. Should injury occur there is often sensitization, whereby increased nociceptor sensitivity and/or plasticity of nociceptor-related neural circuits acts as a protection mechanism for the afflicted body part. Studying nociception and nociceptors in different model organisms has demonstrated that there are similarities from invertebrates right through to humans. The development of technology to genetically manipulate organisms, especially mice, has led to an understanding of some of the key molecular players in nociceptor function. This review will focus on what is known about nociceptors throughout the Animalia kingdom and what similarities exist across phyla; especially at the molecular level of ion channels.

  18. Evolutionary Phylogenetic Networks: Models and Issues

    NASA Astrophysics Data System (ADS)

    Nakhleh, Luay

    Phylogenetic networks are special graphs that generalize phylogenetic trees to allow for modeling of non-treelike evolutionary histories. The ability to sequence multiple genetic markers from a set of organisms and the conflicting evolutionary signals that these markers provide in many cases, have propelled research and interest in phylogenetic networks to the forefront in computational phylogenetics. Nonetheless, the term 'phylogenetic network' has been generically used to refer to a class of models whose core shared property is tree generalization. Several excellent surveys of the different flavors of phylogenetic networks and methods for their reconstruction have been written recently. However, unlike these surveys, this chapte focuses specifically on one type of phylogenetic networks, namely evolutionary phylogenetic networks, which explicitly model reticulate evolutionary events. Further, this chapter focuses less on surveying existing tools, and addresses in more detail issues that are central to the accurate reconstruction of phylogenetic networks.

  19. Phylogenetic signals and ecotoxicological responses: potential implications for aquatic biomonitoring.

    PubMed

    Carew, Melissa E; Miller, Adam D; Hoffmann, Ary A

    2011-05-01

    Macroinvertebrates can be successfully used as biomonitors of pollutants and environmental health because some groups are sensitive whereas, others are relatively tolerant to pollutants. An issue of ongoing debate is what constitutes an appropriate group for biomonitoring; should the group represent species, genera or higher taxonomic levels? A phylogenetic framework can provide new insights into this issue. By developing phylogenies for chironomids and mayflies, this investigation shows that there is strong phylogenetic signal for pollution responses, and that phylogenetic nodes are common to tolerant and sensitive groups of species. A phylogenetic analysis of biotic indices developed for mayflies based on their response to organic pollution shows that mayfly families varied in pollution tolerance. In contrast, based on sediment zinc concentrations as an indicator of pollution tolerance, Australian chironomids tend to vary in tolerance at lower taxonomic levels. Published data on North American chironomids shows much of the signal for pollution responses is contained within genera rather than sub-families. Tools are now available to distinguish whether this signal reflects historical evolutionary constraints or environmental effects leading to common evolved responses. This suggests that ideally higher taxonomic levels should be used for biomonitoring when there are strong phylogenetic constraints at higher levels. Evolutionary considerations can therefore help to guide the development of macroinvertebrate biomonitors and provide insights into processes that produce sensitive and tolerant taxa.

  20. Over-expression of JcDGAT1 from Jatropha curcas increases seed oil levels and alters oil quality in transgenic Arabidopsis thaliana.

    PubMed

    Misra, Aparna; Khan, Kasim; Niranjan, Abhishek; Nath, Pravendra; Sane, Vidhu A

    2013-12-01

    The increasing consumption of fossil fuels and petroleum products is leading to their rapid depletion and is a matter of concern around the globe. Substitutes of fossil fuels are required to sustain the pace of economic development. In this context, oil from the non food crops (biofuel) has shown potential to substitute fossil fuels. Jatropha curcas is an excellent shrub spread and naturalized across the globe. Its oil contains a high percentage of unsaturated fatty acids (about 78-84% of total fatty acid content) making the oil suitable for biodiesel production. Despite its high oil content, it has been poorly studied in terms of important enzymes/genes responsible for oil biosynthesis. Here, we describe the isolation of the full length cDNA clone of JcDGAT1, a key enzyme involved in oil biosynthesis, from J. curcas seeds and manipulation of oil content and composition in transgenic Arabidopsis plants by its expression. Transcript analysis of JcDGAT1 reveals a gradual increase from early seed development to its maturation. Homozygous transgenic Arabidopsis lines expressing JcDGAT1 both under CaMV35S promoter and a seed specific promoter show an enhanced level of total oil content (up by 30-41%) in seeds but do not show any phenotypic differences. In addition, our studies also show alterations in the oil composition through JcDGAT1 expression. While the levels of saturated FAs such as palmitate and stearate in the oil do not change, there is significant reproducible decrease in the levels of oleic acid and a concomitant increase in levels of linolenic acid both under the CaMV35S promoter as well as the seed specific promoter. Our studies thus confirm that DGAT is involved in flux control in oil biosynthesis and show that JcDGAT1 could be used specifically to manipulate and improve oil content and composition in plants.

  1. Alterations in Low-Level Perceptual Networks Related to Clinical Severity in PTSD after an Earthquake: A Resting-State fMRI Study

    PubMed Central

    Shang, Jing; Meng, Yajing; Zhu, Hongru; Qiu, Changjian; Gong, Qiyong; Liao, Wei

    2014-01-01

    Background Several task-based functional MRI (fMRI) studies have highlighted abnormal activation in specific regions involving the low-level perceptual (auditory, visual, and somato-motor) network in posttraumatic stress disorder (PTSD) patients. However, little is known about whether the functional connectivity of the low-level perceptual and higher-order cognitive (attention, central-execution, and default-mode) networks change in medication-naïve PTSD patients during the resting state. Methods We investigated the resting state networks (RSNs) using independent component analysis (ICA) in 18 chronic Wenchuan earthquake-related PTSD patients versus 20 healthy survivors (HSs). Results Compared to the HSs, PTSD patients displayed both increased and decreased functional connectivity within the salience network (SN), central executive network (CEN), default mode network (DMN), somato-motor network (SMN), auditory network (AN), and visual network (VN). Furthermore, strengthened connectivity involving the inferior temporal gyrus (ITG) and supplementary motor area (SMA) was negatively correlated with clinical severity in PTSD patients. Limitations Given the absence of a healthy control group that never experienced the earthquake, our results cannot be used to compare alterations between the PTSD patients, physically healthy trauma survivors, and healthy controls. In addition, the breathing and heart rates were not monitored in our small sample size of subjects. In future studies, specific task paradigms should be used to reveal perceptual impairments. Conclusions These findings suggest that PTSD patients have widespread deficits in both the low-level perceptual and higher-order cognitive networks. Decreased connectivity within the low-level perceptual networks was related to clinical symptoms, which may be associated with traumatic reminders causing attentional bias to negative emotion in response to threatening stimuli and resulting in emotional dysregulation. PMID

  2. Phylogenetic relationships among Maloideae species

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Maloideae is a highly diverse sub-family of the Rosaceae containing several agronomically important species (Malus sp. and Pyrus sp.) and their wild relatives. Previous phylogenetic work within the group has revealed extensive intergeneric hybridization and polyploidization. In order to develop...

  3. Molecular phylogenetics: testing evolutionary hypotheses.

    PubMed

    Walsh, David A; Sharma, Adrian K

    2009-01-01

    A common approach for investigating evolutionary relationships between genes and organisms is to compare extant DNA or protein sequences and infer an evolutionary tree. This methodology is known as molecular phylogenetics and may be the most informative means for exploring phage evolution, since there are few morphological features that can be used to differentiate between these tiny biological entities. In addition, phage genomes can be mosaic, meaning different genes or genomic regions can exhibit conflicting evolutionary histories due to lateral gene transfer or homologous recombination between different phage genomes. Molecular phylogenetics can be used to identify and study such genome mosaicism. This chapter provides a general introduction to the theory and methodology used to reconstruct phylogenetic relationships from molecular data. Also included is a discussion on how the evolutionary history of different genes within the same set of genomes can be compared, using a collection of T4-type phage genomes as an example. A compilation of programs and packages that are available for conducting phylogenetic analyses is supplied as an accompanying appendix.

  4. Regeneration of eye tissues is modulated by altered levels of gravity at 1g, 2g, and in microgravity during spaceflight

    NASA Astrophysics Data System (ADS)

    Grigoryan, Eleonora; Almeida, Eduardo; Mitashov, Victor

    The pursuit of human space exploration requires detailed knowledge of microgravity-related changes in fundamental biological processes, and their effects on health. Normal regeneration of organs and tissues is one such fundamental process that allows maintenance of vitality and function of living organisms. Animal models of tissue regeneration include the newt (Pleurodeles waltl, Urodela) eye, which has been extensively used by our team in Russian Bion and Foton microgravity experiments since 1985, and in recent NASA 2.5 meter diameter centrifuge hypergravity experiments. In total, these experiments allow us to draw several broad conclusions: Newt lens regeneration is significantly altered in microgravity and hypergravity relative to 1g controls. Lenses formed in microgravity are larger and more developed than those regenerated in 1g controls; Microgravity alterations of lens regeneration can persist after spaceflight, and continue to affect repeated removal and regeneration of the lens after return to 1g; Microgravity increases the numbers of early stage regenerative proliferating BrdU-labeled cells in dorsal iris progenitors and in the lens regenerate. Regeneration under hypergravity conditions at 2g inhibits lens regeneration, and often causes retinal detachment. Molecular mechanisms regulating lens regeneration rate include FGF2 signaling, (a key pathway for eye tissue development and regeneration), and an expression of stress-related proteins - HSPs. In conclusion, regeneration of lens and other eye tissues in the newt is sensitive to, and regulated by the level of gravity mechanotransduction and developmental signaling pathways, with microgravity favoring stem cell progenitor proliferation, and gravity at 1g promoting terminal differentiation, while hypergravity at 2g often causes damage of delicate regenerating tissues.

  5. Ethanol elevates physiological all-trans-retinoic acid levels in select loci through altering retinoid metabolism in multiple loci: a potential mechanism of ethanol toxicity.

    PubMed

    Kane, Maureen A; Folias, Alexandra E; Wang, Chao; Napoli, Joseph L

    2010-03-01

    All-trans-retinoic acid (atRA) supports embryonic development, central nervous system function, and the immune response. atRA initiates neurogenesis and dendritic growth in the hippocampus and is required for spatial memory; superphysiological atRA inhibits neurogenesis, causes teratology and/or embryo toxicity, and alters cognitive function and behavior. Because abnormal atRA shares pathological conditions with alcoholism, inhibition of retinol (vitamin A) activation into atRA has been credited widely as a mechanism of ethanol toxicity. Here, we analyze the effects of ethanol on retinoid concentrations in vivo during normal vitamin A nutriture, using sensitive and analytically robust assays. Ethanol either increased or had no effect on atRA, regardless of changes in retinol and retinyl esters. Acute ethanol (3.5 g/kg) increased atRA in adult hippocampus (1.6-fold), liver (2.4-fold), and testis (1.5-fold). Feeding dams a liquid diet with 6.5% ethanol from embryonic day 13 (e13) to e19 increased atRA in fetal hippocampus (up to 20-fold) and cortex (up to 50-fold), depending on blood alcohol content. One-month feeding of the 6.5% ethanol diet increased atRA in adult hippocampus (20-fold), cortex (2-fold), testis (2-fold), and serum (10-fold). Tissue-specific increases in retinoid dehydrogenase mRNAs and activities, extrahepatic retinol concentrations, and atRA catabolism combined to produce site-specific effects. Because a sustained increase in atRA has deleterious effects on the central nervous system and embryo development, these data suggest that superphysiological atRA contributes to ethanol pathological conditions, including cognitive dysfunction and fetal alcohol syndrome.-Kane, M. A., Folias, A. E., Wang, C., Napoli, J. L. Ethanol elevates physiological all-trans-retinoic acid levels in select loci through altering retinoid metabolism in multiple loci: a potential mechanism of ethanol toxicity.

  6. The conductive hearing loss due to an experimentally induced middle ear effusion alters the interaural level and time difference cues to sound location.

    PubMed

    Thornton, Jennifer L; Chevallier, Keely M; Koka, Kanthaiah; Lupo, J Eric; Tollin, Daniel J

    2012-10-01

    Otitis media with effusion (OME) is a pathologic condition of the middle ear that leads to a mild to moderate conductive hearing loss as a result of fluid in the middle ear. Recurring OME in children during the first few years of life has been shown to be associated with poor detection and recognition of sounds in noisy environments, hypothesized to result due to altered sound localization cues. To explore this hypothesis, we simulated a middle ear effusion by filling the middle ear space of chinchillas with different viscosities and volumes of silicone oil to simulate varying degrees of OME. While the effects of middle ear effusions on the interaural level difference (ILD) cue to location are known, little is known about whether and how middle ear effusions affect interaural time differences (ITDs). Cochlear microphonic amplitudes and phases were measured in response to sounds delivered from several locations in azimuth before and after filling the middle ear with fluid. Significant attenuations (20-40 dB) of sound were observed when the middle ear was filled with at least 1.0 ml of fluid with a viscosity of 3.5 Poise (P) or greater. As expected, ILDs were altered by ~30 dB. Additionally, ITDs were shifted by ~600 μs for low frequency stimuli (<4 kHz) due to a delay in the transmission of sound to the inner ear. The data show that in an experimental model of OME, ILDs and ITDs are shifted in the spatial direction of the ear without the experimental effusion.

  7. Ethanol elevates physiological all-trans-retinoic acid levels in select loci through altering retinoid metabolism in multiple loci: a potential mechanism of ethanol toxicity

    PubMed Central

    Kane, Maureen A.; Folias, Alexandra E.; Wang, Chao; Napoli, Joseph L.

    2010-01-01

    All-trans-retinoic acid (atRA) supports embryonic development, central nervous system function, and the immune response. atRA initiates neurogenesis and dendritic growth in the hippocampus and is required for spatial memory; superphysiological atRA inhibits neurogenesis, causes teratology and/or embryo toxicity, and alters cognitive function and behavior. Because abnormal atRA shares pathological conditions with alcoholism, inhibition of retinol (vitamin A) activation into atRA has been credited widely as a mechanism of ethanol toxicity. Here, we analyze the effects of ethanol on retinoid concentrations in vivo during normal vitamin A nutriture, using sensitive and analytically robust assays. Ethanol either increased or had no effect on atRA, regardless of changes in retinol and retinyl esters. Acute ethanol (3.5 g/kg) increased atRA in adult hippocampus (1.6-fold), liver (2.4-fold), and testis (1.5-fold). Feeding dams a liquid diet with 6.5% ethanol from embryonic day 13 (e13) to e19 increased atRA in fetal hippocampus (up to 20-fold) and cortex (up to 50-fold), depending on blood alcohol content. One-month feeding of the 6.5% ethanol diet increased atRA in adult hippocampus (20-fold), cortex (2-fold), testis (2-fold), and serum (10-fold). Tissue-specific increases in retinoid dehydrogenase mRNAs and activities, extrahepatic retinol concentrations, and atRA catabolism combined to produce site-specific effects. Because a sustained increase in atRA has deleterious effects on the central nervous system and embryo development, these data suggest that superphysiological atRA contributes to ethanol pathological conditions, including cognitive dysfunction and fetal alcohol syndrome.—Kane, M. A., Folias, A. E., Wang, C., Napoli, J. L. Ethanol elevates physiological all-trans-retinoic acid levels in select loci through altering retinoid metabolism in multiple loci: a potential mechanism of ethanol toxicity. PMID:19890016

  8. Induction of Embryogenesis in Brassica Napus Microspores Produces a Callosic Subintinal Layer and Abnormal Cell Walls with Altered Levels of Callose and Cellulose

    PubMed Central

    Parra-Vega, Verónica; Corral-Martínez, Patricia; Rivas-Sendra, Alba; Seguí-Simarro, Jose M.

    2015-01-01

    The induction of microspore embryogenesis produces dramatic changes in different aspects of the cell physiology and structure. Changes at the cell wall level are among the most intriguing and poorly understood. In this work, we used high pressure freezing and freeze substitution, immunolocalization, confocal, and electron microscopy to analyze the structure and composition of the first cell walls formed during conventional Brassica napus microspore embryogenesis, and in cultures treated to alter the intracellular Ca2+ levels. Our results revealed that one of the first signs of embryogenic commitment is the formation of a callose-rich, cellulose-deficient layer beneath the intine (the subintinal layer), and of irregular, incomplete cell walls. In these events, Ca2+ may have a role. We propose that abnormal cell walls are due to a massive callose synthesis and deposition of excreted cytoplasmic material, and the parallel inhibition of cellulose synthesis. These features were absent in pollen-like structures and in microspore-derived embryos, few days after the end of the heat shock, where abnormal cell walls were no longer produced. Together, our results provide an explanation to a series of relevant aspects of microspore embryogenesis including the role of Ca2+ and the occurrence of abnormal cell walls. In addition, our discovery may be the explanation to why nuclear fusions take place during microspore embryogenesis. PMID:26635844

  9. Il-6 Serum Levels and Production Is Related to an Altered Immune Response in Polycystic Ovary Syndrome Girls with Insulin Resistance

    PubMed Central

    Fulghesu, Anna M.; Sanna, Francesca; Uda, Sabrina; Magnini, Roberta; Portoghese, Elaine; Batetta, Barbara

    2011-01-01

    Polycystic ovarian syndrome (PCOS) is frequently characterized by obesity and metabolic diseases including hypertension, insulin resistance, and diabetes in adulthood, all leading to an increased risk of atherosclerosis. The present study aimed to evaluate serum and production of inflammatory markers in adolescent Sardinian PCOS. On the basis of HOMA findings, patients were divided into noninsulin resistant (NIR) and insulin resistant (IR), and were weight- and age-matched with healthy girls. Inflammatory cytokines (TNF-α, IL-6, Il-10, TGF-β) and lipokines (leptin, adiponectin), the reactant hs-CRP, and in vitro inflammatory lympho-monocyte response to microbial stimulus were evaluated. In healthy and PCOS subjects, leptin and hs-CRP were correlated with BMI, whereas adiponectin was significantly reduced in all PCOS groups. Although cytokines were similar in all groups, Interleukin-6 (IL-6) was significantly higher in IR PCOS. Moreover, in the latter group lipopolysaccharide-activated monocytes secreted significantly higher levels of IL-6 compared to NIR and control subjects. To conclude, IR PCOS displayed increased IL-6 serum levels and higher secretion in LPS-activated monocytes, whilst revealing no differences for other inflammatory cytokines. These results suggest that in PCOS patients an altered immune response to inflammatory stimuli is present in IR, likely contributing towards determining onset of a low grade inflammation. PMID:21547256

  10. Circulating levels of endocannabinoids respond acutely to voluntary exercise, are altered in mice selectively bred for high voluntary wheel running, and differ between the sexes.

    PubMed

    Thompson, Zoe; Argueta, Donovan; Garland, Theodore; DiPatrizio, Nicholas

    2017-03-01

    concentrations than males. For mice housed with wheels, the amount of running during the 30min before sampling was a significant positive predictor of plasma AEA within groups, and HR mice had significantly lower levels of AEA than C mice. Our results suggest that voluntary exercise alters circulating levels of endocannabinoids, and further demonstrate that selective breeding for voluntary exercise is associated with evolutionary changes in the endocannabinoid system.

  11. Deep-time phylogenetic clustering of extinctions in an evolutionarily dynamic clade (Early Jurassic ammonites).

    PubMed

    Hardy, Clotilde; Fara, Emmanuel; Laffont, Rémi; Dommergues, Jean-Louis; Meister, Christian; Neige, Pascal

    2012-01-01

    Conservation biologists and palaeontologists are increasingly investigating the phylogenetic distribution of extinctions and its evolutionary consequences. However, the dearth of palaeontological studies on that subject and the lack of methodological consensus hamper our understanding of that major evolutionary phenomenon. Here we address this issue by (i) reviewing the approaches used to quantify the phylogenetic selectivity of extinctions and extinction risks; (ii) investigating with a high-resolution dataset whether extinctions and survivals were phylogenetically clustered among early Pliensbachian (Early Jurassic) ammonites; (iii) exploring the phylogenetic and temporal maintenance of this signal. We found that ammonite extinctions were significantly clumped phylogenetically, a pattern that prevailed throughout the 6.6 Myr-long early Pliensbachian interval. Such a phylogenetic conservatism did not alter--or may even have promoted--the evolutionary success of this major cephalopod clade. However, the comparison of phylogenetic autocorrelation among studies remains problematic because the notion of phylogenetic conservatism is scale-dependent and the intensity of the signal is sensitive to temporal resolution. We recommend a combined use of Moran's I, Pearson's ϕ and Fritz and Purvis' D statistics because they highlight different facets of the phylogenetic pattern of extinctions and/or survivals.

  12. A Deliberate Practice Approach to Teaching Phylogenetic Analysis

    ERIC Educational Resources Information Center

    Hobbs, F. Collin; Johnson, Daniel J.; Kearns, Katherine D.

    2013-01-01

    One goal of postsecondary education is to assist students in developing expert-level understanding. Previous attempts to encourage expert-level understanding of phylogenetic analysis in college science classrooms have largely focused on isolated, or "one-shot," in-class activities. Using a deliberate practice instructional approach, we…

  13. Description of new mitochondrial genomes (Spodoptera litura, Noctuoidea and Cnaphalocrocis medinalis, Pyraloidea) and phylogenetic reconstruction of Lepidoptera with the comment on optimization schemes.

    PubMed

    Wan, Xinlong; Kim, Min Jee; Kim, Iksoo

    2013-11-01

    We newly sequenced mitochondrial genomes of Spodoptera litura and Cnaphalocrocis medinalis belonging to Lepidoptera to obtain further insight into mitochondrial genome evolution in this group and investigated the influence of optimal strategies on phylogenetic reconstruction of Lepidoptera. Estimation of p-distances of each mitochondrial gene for available taxonomic levels has shown the highest value in ND6, whereas the lowest values in COI and COII at the nucleotide level, suggesting different utility of each gene for different hierarchical group when individual genes are utilized for phylogenetic analysis. Phylogenetic analyses mainly yielded the relationships (((((Bombycoidea + Geometroidea) + Noctuoidea) + Pyraloidea) + Papilionoidea) + Tortricoidea), evidencing the polyphyly of Macrolepidoptera. The Noctuoidea concordantly recovered the familial relationships (((Arctiidae + Lymantriidae) + Noctuidae) + Notodontidae). The tests of optimality strategies, such as exclusion of third codon positions, inclusion of rRNA and tRNA genes, data partitioning, RY recoding approach, and recoding nucleotides into amino acids suggested that the majority of the strategies did not substantially alter phylogenetic topologies or nodal supports, except for the sister relationship between Lycaenidae and Pieridae only in the amino acid dataset, which was in contrast to the sister relationship between Lycaenidae and Nymphalidae in Papilionoidea in the remaining datasets.

  14. High serotonin levels during brain development alter the structural input-output connectivity of neural networks in the rat somatosensory layer IV

    PubMed Central

    Miceli, Stéphanie; Negwer, Moritz; van Eijs, Fenneke; Kalkhoven, Carla; van Lierop, Ilja; Homberg, Judith; Schubert, Dirk

    2013-01-01

    Homeostatic regulation of serotonin (5-HT) concentration is critical for “normal” topographical organization and development of thalamocortical (TC) afferent circuits. Down-regulation of the serotonin transporter (SERT) and the consequent impaired reuptake of 5-HT at the synapse, results in a reduced terminal branching of developing TC afferents within the primary somatosensory cortex (S1). Despite the presence of multiple genetic models, the effect of high extracellular 5-HT levels on the structure and function of developing intracortical neural networks is far from being understood. Here, using juvenile SERT knockout (SERT−/−) rats we investigated, in vitro, the effect of increased 5-HT levels on the structural organization of (i) the TC projections of the ventroposteromedial thalamic nucleus toward S1, (ii) the general barrel-field pattern, and (iii) the electrophysiological and morphological properties of the excitatory cell population in layer IV of S1 [spiny stellate (SpSt) and pyramidal cells]. Our results confirmed previous findings that high levels of 5-HT during development lead to a reduction of the topographical precision of TCA projections toward the barrel cortex. Also, the barrel pattern was altered but not abolished in SERT−/− rats. In layer IV, both excitatory SpSt and pyramidal cells showed a significantly reduced intracolumnar organization of their axonal projections. In addition, the layer IV SpSt cells gave rise to a prominent projection toward the infragranular layer Vb. Our findings point to a structural and functional reorganization of TCAs, as well as early stage intracortical microcircuitry, following the disruption of 5-HT reuptake during critical developmental periods. The increased projection pattern of the layer IV neurons suggests that the intracortical network changes are not limited to the main entry layer IV but may also affect the subsequent stages of the canonical circuits of the barrel cortex. PMID:23761736

  15. First evidence of altered vitellogenin-like protein levels in clam Tapes philippinarum and in cockle Cerastoderma glaucum from the Lagoon of Venice.

    PubMed

    Matozzo, Valerio; Marin, Maria Gabriella

    2007-01-01

    Possible xenoestrogenic effects were investigated, for the first time, in two bivalve species from the Lagoon of Venice (Italy): the clam Tapes philippinarum and the cockle Cerastoderma glaucum. Bivalves were collected far from their reproductive phase at the very early stage of gametogenesis (January), and in the pre-spawning period (June) in six sites. Vitellogenin (Vg)-like proteins (a biomarker of exposure to estrogenic compounds) were measured by the alkali-labile phosphate method (ALP), in both haemolymph and digestive gland from males and females (when it was possible to distinguish sex by microscopic observation of gonadal tissue). Haemolymph calcium concentrations (a parameter considered closely related to the presence of Vg-like proteins) and the bivalve condition index (CI) were also measured. In both seasons, bivalves collected at Campalto (near a sewage treatment plant) and Marghera (a highly contaminated area) had higher Vg-like protein levels, particularly in haemolymph, than animals from the other sampling sites. Interestingly, CI had high values in these polluted sites. In June only, Vg-like proteins and Ca(2+) levels in haemolymph exhibited similar trends in both bivalve species at most sampling sites. The responsiveness of bivalves to environmental xenoestrogens was higher in June, allowing better discrimination among sites. The present study demonstrates that animals from highly polluted areas have increased Vg-like protein levels. As endocrine disruption due to exposure to estrogenic compounds may cause fertility reduction, alterations in the sex ratio, and a decrease in reproductive rate, a condition of potential risk for bivalve populations in estuarine areas is highlighted.

  16. Expression of gibberellin 20-oxidase1 (AtGA20ox1) in Arabidopsis seedlings with altered auxin status is regulated at multiple levels.

    PubMed

    Desgagné-Penix, Isabel; Sponsel, Valerie M

    2008-01-01

    Bioactive gibberellins (GAs) affect many biological processes including germination, stem growth, transition to flowering, and fruit development. The location, timing, and level of bioactive GA are finely tuned to ensure that optimal growth and development occur. The balance between GA biosynthesis and deactivation is controlled by external factors such as light and by internal factors that include auxin. The role of auxin transport inhibitors (ATIs) and auxins on GA homeostasis in intact light-grown Arabidopsis thaliana (L.) Heynh. seedlings was investigated. Two ATIs, 1-N-naphthylthalamic acid (NPA) and 1-naphthoxyacetic acid (NOA) caused elevated expression of the GA biosynthetic enzyme AtGA20-oxidase1 (AtGA20ox1) in shoot but not in root tissues, and only at certain developmental stages. It was investigated whether enhanced AtGA20ox1 gene expression was a consequence of altered flow through the GA biosynthetic pathway, or was due to impaired GA signalling that can lead to enhanced AtGA20ox1 expression and accumulation of a DELLA protein, Repressor of ga1-3 (RGA). Both ATIs promoted accumulation of GFP-fused RGA in shoots and roots, and this increase was counteracted by the application of GA(4). These results suggest that in ATI-treated seedlings the impediment to DELLA protein degradation may be a deficiency of bioactive GA at sites of GA response. It is proposed that the four different levels of AtGA20ox1 regulation observed here are imposed in a strict hierarchy: spatial (organ-, tissue-, cell-specific) > developmental > metabolic > auxin regulation. Thus results show that, in intact auxin- and auxin transport inhibitor-treated light-grown Arabidopsis seedlings, three other levels of regulation supersede the effects of auxin on AtGA20ox1.

  17. Expression of gibberellin 20-oxidase1 (AtGA20ox1) in Arabidopsis seedlings with altered auxin status is regulated at multiple levels

    PubMed Central

    Desgagné-Penix, Isabel; Sponsel, Valerie M.

    2008-01-01

    Bioactive gibberellins (GAs) affect many biological processes including germination, stem growth, transition to flowering, and fruit development. The location, timing, and level of bioactive GA are finely tuned to ensure that optimal growth and development occur. The balance between GA biosynthesis and deactivation is controlled by external factors such as light and by internal factors that include auxin. The role of auxin transport inhibitors (ATIs) and auxins on GA homeostasis in intact light-grown Arabidopsis thaliana (L.) Heynh. seedlings was investigated. Two ATIs, 1-N-naphthylthalamic acid (NPA) and 1-naphthoxyacetic acid (NOA) caused elevated expression of the GA biosynthetic enzyme AtGA20-oxidase1 (AtGA20ox1) in shoot but not in root tissues, and only at certain developmental stages. It was investigated whether enhanced AtGA20ox1 gene expression was a consequence of altered flow through the GA biosynthetic pathway, or was due to impaired GA signalling that can lead to enhanced AtGA20ox1 expression and accumulation of a DELLA protein, Repressor of ga1-3 (RGA). Both ATIs promoted accumulation of GFP-fused RGA in shoots and roots, and this increase was counteracted by the application of GA4. These results suggest that in ATI-treated seedlings the impediment to DELLA protein degradation may be a deficiency of bioactive GA at sites of GA response. It is proposed that the four different levels of AtGA20ox1 regulation observed here are imposed in a strict hierarchy: spatial (organ-, tissue-, cell-specific) > developmental > metabolic > auxin regulation. Thus results show that, in intact auxin- and auxin transport inhibitor-treated light-grown Arabidopsis seedlings, three other levels of regulation supersede the effects of auxin on AtGA20ox1. PMID:18440929

  18. Anacetrapib and dalcetrapib differentially alters HDL metabolism and macrophage-to-feces reverse cholesterol transport at similar levels of CETP inhibition in hamsters.

    PubMed

    Briand, François; Thieblemont, Quentin; Muzotte, Elodie; Burr, Noémie; Urbain, Isabelle; Sulpice, Thierry; Johns, Douglas G

    2014-10-05

    Cholesteryl ester transfer protein (CETP) inhibitors dalcetrapib and anacetrapib differentially alter LDL- and HDL-cholesterol levels, which might be related to the potency of each drug to inhibit CETP activity. We evaluated the effects of both drugs at similar levels of CETP inhibition on macrophage-to-feces reverse cholesterol transport (RCT) in hamsters. In normolipidemic hamsters, both anacetrapib 30 mg/kg QD and dalcetrapib 200 mg/kg BID inhibited CETP activity by ~60%. After injection of 3H-cholesteryl oleate labeled HDL, anacetrapib and dalcetrapib reduced HDL-cholesteryl esters fractional catabolic rate (FCR) by 30% and 26% (both P<0.001 vs. vehicle) respectively, but only dalcetrapib increased HDL-derived 3H-tracer fecal excretion by 30% (P<0.05 vs. vehicle). After 3H-cholesterol labeled macrophage intraperitoneal injection, anacetrapib stimulated 3H-tracer appearance in HDL, but both drugs did not promote macrophage-derived 3H-tracer fecal excretion. In dyslipidemic hamsters, both anacetrapib 1 mg/kg QD and dalcetrapib 200 mg/kg BID inhibited CETP activity by ~65% and reduced HDL-cholesteryl ester FCR by 36% (both P<0.001 vs. vehicle), but only anacetrapib increased HDL-derived 3H-tracer fecal excretion significantly by 39%. After 3H-cholesterol labeled macrophage injection, only anacetrapib 1 mg/kg QD stimulated macrophage-derived 3H-tracer appearance in HDL. These effects remained weaker than those observed with anacetrapib 60 mg/kg QD, which induced a maximal inhibition of CETP and stimulation of macrophage-derived 3H-tracer fecal excretion. In contrast, dalcetrapib 200 mg/kg BID reduced macrophage-derived 3H-tracer fecal excretion by 23% (P<0.05 vs. vehicle). In conclusion, anacetrapib and dalcetrapib differentially alter HDL metabolism and RCT in hamsters. A stronger inhibition of CETP may be required to promote macrophage-to-feces reverse cholesterol transport in dyslipidemic hamsters.

  19. L-carnitine Mediated Reduction in Oxidative Stress and Alteration in Transcript Level of Antioxidant Enzymes in Sheep Embryos Produced In Vitro.

    PubMed

    Mishra, A; Reddy, I J; Gupta, P S P; Mondal, S

    2016-04-01

    The objective of this study was to find out the effect of L-carnitine on oocyte maturation and subsequent embryo development, with L-carnitine-mediated alteration if any in transcript level of antioxidant enzymes (GPx, Cu/Zn-SOD (SOD1) and Mn-SOD (SOD2) in oocytes and developing sheep embryos produced in vitro. Different concentrations of L-carnitine (0 mm, 2.5 mm, 5 mm, 7.5 mm and 10 mm) were used in maturation medium. Oocytes matured with 10 mm L-carnitine showed significantly (p < 0.05) higher cleavage (66.80% vs 39.66, 41.76, 44.64, 64.31%), morula (48.50% vs 20.88, 26.01, 26.99, 44.72%) and blastocyst (33.22% vs 7.66, 9.19, 10.71, 28.57%) percentage as compared to lower concentrations (0 mm, 2.5 mm, 5 mm and 7.5 mm). Cleavage percentage between 10 mm and 7.5 mm L-carnitine were not significantly different. Maturation rate was not influenced by supplementation of any experimental concentration of L-carnitine. There was a significant (p < 0.05) decrease in intracellular ROS and increase in intracellular GSH in 10 mm L-carnitine-treated oocytes and embryos than control group. Antioxidant effect of L-carnitine was proved by culturing oocytes and embryos with H2O2 in the presence of L-carnitine which could be able to protect oocytes and embryos from H2O2-induced oxidative damage. L-carnitine supplementation significantly (p < 0.05) upregulated the expression of GPx and downregulated the expression of SOD2 genes, whereas the expression pattern of SOD1 and GAPDH (housekeeping gene) genes was unaffected in oocytes and embryos. It was concluded from the study that L-carnitine supplementation during in vitro maturation reduces oxidative stress-induced embryo toxicity by decreasing intracellular ROS and increasing intracellular GSH that in turn improved developmental potential of oocytes and embryos and alters transcript level of antioxidant enzymes.

  20. High-resolution phylogenetic microbial community profiling

    PubMed Central

    Singer, Esther; Bushnell, Brian; Coleman-Derr, Devin; Bowman, Brett; Bowers, Robert M; Levy, Asaf; Gies, Esther A; Cheng, Jan-Fang; Copeland, Alex; Klenk, Hans-Peter; Hallam, Steven J; Hugenholtz, Philip; Tringe, Susannah G; Woyke, Tanja

    2016-01-01

    Over the past decade, high-throughput short-read 16S rRNA gene amplicon sequencing has eclipsed clone-dependent long-read Sanger sequencing for microbial community profiling. The transition to new technologies has provided more quantitative information at the expense of taxonomic resolution with implications for inferring metabolic traits in various ecosystems. We applied single-molecule real-time sequencing for microbial community profiling, generating full-length 16S rRNA gene sequences at high throughput, which we propose to name PhyloTags. We benchmarked and validated this approach using a defined microbial community. When further applied to samples from the water column of meromictic Sakinaw Lake, we show that while community structures at the phylum level are comparable between PhyloTags and Illumina V4 16S rRNA gene sequences (iTags), variance increases with community complexity at greater water depths. PhyloTags moreover allowed less ambiguous classification. Last, a platform-independent comparison of PhyloTags and in silico generated partial 16S rRNA gene sequences demonstrated significant differences in community structure and phylogenetic resolution across multiple taxonomic levels, including a severe underestimation in the abundance of specific microbial genera involved in nitrogen and methane cycling across the Lake's water column. Thus, PhyloTags provide a reliable adjunct or alternative to cost-effective iTags, enabling more accurate phylogenetic resolution of microbial communities and predictions on their metabolic potential. PMID:26859772

  1. Altered sex hormone concentrations and gonadal mRNA expression levels of activin signaling factors in hatchling alligators from a contaminated Florida lake.

    PubMed

    Moore, Brandon C; Kohno, Satomi; Cook, Robert W; Alvers, Ashley L; Hamlin, Heather J; Woodruff, Teresa K; Guillette, Louis J

    2010-04-01

    Activins and estrogens participate in regulating the breakdown of ovarian germ cell nests and follicle assembly in mammals. In 1994, our group reported elevated frequencies of abnormal, multioocytic ovarian follicles in 6 month old, environmental contaminant-exposed female alligators after gonadotropin challenge. Here, we investigated if maternal contribution of endocrine disrupting contaminants to the egg subsequently alters estrogen/inhibin/activin signaling in hatchling female offspring, putatively predisposing an increased frequency of multioocytic follicle formation. We quantified basal and exogenous gonadotropin-stimulated concentrations of circulating plasma steroid hormones and ovarian activin signaling factor mRNA abundance in hatchling alligators from the same contaminated (Lake Apopka) and reference (Lake Woodruff) Florida lakes, as examined in 1994. Basal circulating plasma estradiol and testosterone concentrations were greater in alligators from the contaminated environment, whereas activin/inhibin betaA subunit and follistatin mRNA abundances were lower than values measured in ovaries from reference lake animals. Challenged, contaminant-exposed animals showed a more robust increase in plasma estradiol concentration following an acute follicle stimulating hormone (FSH) challenge compared with reference site alligators. Aromatase and follistatin mRNA levels increased in response to an extended FSH challenge in the reference site animals, but not in the contaminant-exposed animals. In hatchling alligators, ovarian follicles have not yet formed; therefore, these endocrine differences are likely to affect subsequent ovarian development, including ovarian follicle assembly.

  2. Mice deficient in Endothelin-Converting Enzyme-2 exhibit abnormal responses to morphine and altered peptide levels in the spinal cord

    PubMed Central

    Miller, L.K.; Hou, X.; Rodriguiz, R.M.; Gagnidze, K.; Sweedler, J. V.; Wetsel, W.C.; Devi, L.A.

    2011-01-01

    An increasing body of evidence suggests that Endothelin-converting enzyme-2 (ECE-2) is a non-classical neuropeptide processing enzyme. Similar to other neuropeptide processing enzymes, ECE-2 exhibits restricted neuroendocrine distribution, intracellular localization, and an acidic pH optimum. However, unlike classical neuropeptide processing enzymes, ECE-2 exhibits a non-classical cleavage site preference for aliphatic and aromatic residues. We previously reported that ECE-2 cleaves a number of neuropeptides at non-classical sites in vitro; however its role in peptide processing in vivo is poorly understood. Given the recognized roles of neuropeptides in pain and opiate responses, we hypothesized that ECE-2 knockout (KO) mice might show altered pain and morphine responses compared to wild-type (WT) mice. We find that ECE-2 KO mice show decreased response to a single injection of morphine in hot-plate and tail-flick tests. ECE-2 KO mice also show more rapid development of tolerance with prolonged morphine treatment and fewer signs of naloxone-precipitated withdrawal. Peptidomic analyses revealed changes in the levels of a number of spinal cord peptides in ECE-2 KO as compared to WT mice. Taken together, our findings suggest a role for ECE-2 in the non-classical processing of spinal cord peptides and morphine responses; however, the precise mechanisms through which ECE-2 influences morphine tolerance and withdrawal remain unclear. PMID:21972895

  3. Alteration layer formation of Ca- and Zn-oxide bearing alkali borosilicate glasses for immobilisation of UK high level waste: A vapour hydration study

    NASA Astrophysics Data System (ADS)

    Cassingham, N. J.; Corkhill, C. L.; Stennett, M. C.; Hand, R. J.; Hyatt, N. C.

    2016-10-01

    The UK high level nuclear waste glass modified with CaO/ZnO was investigated using the vapour phase hydration test, performed at 200 °C, with the aim of understanding the impact of the modification on the chemical composition and microstructure of the alteration layer. Experiments were undertaken on non-modified and CaO/ZnO-modified base glass, with or without 25 wt% of simulant Magnox waste calcine. The modification resulted in a dramatic reduction in gel layer thickness and also a reduction in the reaction rate, from 3.4 ± 0.3 g m-2 d-1 without CaO/ZnO modification to 0.9 ± 0.1 g m-2 d-1 with CaO/ZnO. The precipitated phase assemblage for the CaO/ZnO-modified compositions was identified as hydrated Ca- and Zn-bearing silicate phases, which were absent from the non-modified counterpart. These results are in agreement with other recent studies showing the beneficial effects of ZnO additions on glass durability.

  4. Modulation of TGFbeta 2 levels by lamin A in U2-OS osteoblast-like cells: understanding the osteolytic process triggered by altered lamins

    PubMed Central

    Evangelisti, Camilla; Bernasconi, Pia; Cavalcante, Paola; Cappelletti, Cristina; D'Apice, Maria Rosaria; Sbraccia, Paolo; Novelli, Giuseppe; Prencipe, Sabino; Lemma, Silvia; Baldini, Nicola; Avnet, Sofia; Squarzoni, Stefano; Martelli, Alberto M.; Lattanzi, Giovanna

    2015-01-01

    Transforming growth factor beta (TGFbeta) plays an essential role in bone homeostasis and deregulation of TGFbeta occurs in bone pathologies. Patients affected by Mandibuloacral Dysplasia (MADA), a progeroid disease linked to LMNA mutations, suffer from an osteolytic process. Our previous work showed that MADA osteoblasts secrete excess amount of TGFbeta 2, which in turn elicits differentiation of human blood precursors into osteoclasts. Here, we sought to determine how altered lamin A affects TGFbeta signaling. Our results show that wild-type lamin A negatively modulates TGFbeta 2 levels in osteoblast-like U2-OS cells, while the R527H mutated prelamin A as well as farnesylated prelamin A do not, ultimately leading to increased secretion of TGFbeta 2. TGFbeta 2 in turn, triggers the Akt/mTOR pathway and upregulates osteoprotegerin and cathepsin K. TGFbeta 2 neutralization rescues Akt/mTOR activation and the downstream transcriptional effects, an effect also obtained by statins or RAD001 treatment. Our results unravel an unexpected role of lamin A in TGFbeta 2 regulation and indicate rapamycin analogs and neutralizing antibodies to TGFbeta 2 as new potential therapeutic tools for MADA. PMID:25823658

  5. An acute stressor alters steroid hormone levels and activity but not sexual behavior in male and female Ocoee salamanders (Desmognathus ocoee).

    PubMed

    Woodley, Sarah K; Lacy, Eva L

    2010-08-01

    Stressors that are chronic have clear suppressive effects on reproductive behaviors in both males and females. Stressors that are acute have effects on reproductive behavior that are less clear. We measured the effects of an acute bout of handling in laboratory-housed male and female Ocoee salamanders (Desmognathus ocoee), a species with a prolonged mating season. Handling resulted in decreased locomotory activity and elevated plasma corticosterone, a hallmark of the vertebrate stress response. Handling also decreased plasma testosterone in males and elevated plasma estradiol in females. Despite the handling-induced changes in hormone levels, handling had minimal impact on courtship and mating. Other species in which reproduction is insensitive to acute stressors may live in extreme environments with limited reproductive opportunities, whereas Ocoee salamanders live in a relatively temperate environment with multiple reproductive opportunities. Together, these data indicate that an allostatic response to a stressor can alter locomotory activity and elevate corticosterone without suppressing nonessential behaviors like courtship and mating in a species in which reproductive opportunities can occur over a period of multiple months. The lack of reproductive suppression in Ocoee salamanders might be due to the low energetic cost of courtship and mating in this species combined with potentially elevated energetic stores, highlighting the importance of considering energy budgets when making predictions about behavioral effects of acute stressors.

  6. Leveling

    USGS Publications Warehouse

    1966-01-01

    Geodetic leveling by the U.S. Geological Survey provides a framework of accurate elevations for topographic mapping. Elevations are referred to the Sea Level Datum of 1929. Lines of leveling may be run either with automatic or with precise spirit levels, by either the center-wire or the three-wire method. For future use, the surveys are monumented with bench marks, using standard metal tablets or other marking devices. The elevations are adjusted by least squares or other suitable method and are published in lists of control.

  7. Phylogenetic diversity of nonmarine picocyanobacteria.

    PubMed

    Callieri, Cristiana; Coci, Manuela; Corno, Gianluca; Macek, Miroslav; Modenutti, Beatriz; Balseiro, Esteban; Bertoni, Roberto

    2013-08-01

    We studied the phylogenetic diversity of nonmarine picocyanobacteria broadening the sequence data set with 43 new sequences of the 16S rRNA gene. The sequences were derived from monoclonal strains isolated from four volcanic high-altitude athalassohaline lakes in Mexico, five glacial ultraoligotrophic North Patagonian lakes and six Italian lakes of glacial, volcanic and morenic origin. The new sequences fall into a number of both novel and previously described clades within the phylogenetic tree of 16S rRNA gene. The new cluster of Lake Nahuel Huapi (North Patagonia) forms a sister clade to the subalpine cluster II and the marine Synechococcus subcluster 5.2. Our finding of the novel clade of 'halotolerants' close to the marine subcluster 5.3 (Synechococcus RCC307) constitutes an important demonstration that euryhaline and marine strains affiliate closely. The intriguing results obtained shed new light on the importance of the nonmarine halotolerants in the phylogenesis of picocyanobacteria.

  8. Cold stress-induced protein Rbm3 binds 60S ribosomal subunits, alters microRNA levels, and enhances global protein synthesis.

    PubMed

    Dresios, John; Aschrafi, Armaz; Owens, Geoffrey C; Vanderklish, Peter W; Edelman, Gerald M; Mauro, Vincent P

    2005-02-08

    The expression of Rbm3, a glycine-rich RNA-binding protein, is enhanced under conditions of mild hypothermia, and Rbm3 has been postulated to facilitate protein synthesis at colder temperatures. To investigate this possibility, Rbm3 was overexpressed as a c-Myc fusion protein in mouse neuroblastoma N2a cells. Cells expressing this fusion protein showed a 3-fold increase in protein synthesis at both 37 degrees C and 32 degrees C compared with control cells. Although polysome profiles of cells expressing the fusion protein and control cells were similar, several differences were noted, suggesting that Rbm3 might enhance the association of 40S and 60S ribosomal subunits at 32 degrees C. Studies to assess a direct interaction of Rbm3 with ribosomes showed that a fraction of Rbm3 was associated with 60S ribosomal subunits in an RNA-independent manner. It appeared unlikely that this association could explain the global enhancement of protein synthesis, however, because cells expressing the Rbm3 fusion protein showed no substantial increase in the size of their monosome and polysome peaks, suggesting that similar numbers of mRNAs were being translated at approximately the same rates. In contrast, a complex that sedimented between the top of the gradient and 40S subunits was less abundant in cells expressing recombinant Rbm3. Further analysis showed that the RNA component of this fraction was microRNA. We discuss the possibility that Rbm3 expression alters global protein synthesis by affecting microRNA levels and suggest that both Rbm3 and microRNAs are part of a homeostatic mechanism that regulates global levels of protein synthesis under normal and cold-stress conditions.

  9. Increased Symmetric Dimethylarginine Level Is Associated with Worse Hospital Outcomes through Altered Left Ventricular Ejection Fraction in Patients with Acute Myocardial Infarction

    PubMed Central

    Lorin, Julie; Guilland, Jean-Claude; Stamboul, Karim; Guenancia, Charles; Cottin, Yves; Rochette, Luc; Vergely, Catherine; Zeller, Marianne

    2017-01-01

    Objectives We aimed to investigate whether SDMA- symmetric dimethylarginine -the symmetrical stereoisomer of ADMA- might be a marker of left ventricular function in AMI. Background Asymmetric dimethylarginine (ADMA) has been implicated in the prognosis after acute myocardial infarction (AMI) and heart failure (HF). Methods Cross sectional prospective study from 487 consecutive patients hospitalized <24 hours after AMI. Patients with HF on admission were excluded. Serum levels of ADMA, SDMA and L-arginine were determined using HPLC. Glomerular filtration rate (eGFR) was estimated based on creatinine levels. Outcomes were in-hospital severe HF, as defined by Killip class >2, and death. Results Patients were analysed based on SDMA tertiles. Sex, diabetes, dyslipidemia, and prior MI were similar for all tertiles. In contrast, age and hypertension increased across the tertiles (p<0.001). From the first to the last tertile, GRACE risk score was elevated while LVEF and eGFR was reduced. The rate of severe HF and death were gradually increased across the SDMA tertiles (from 0.6% to 7.4%, p = 0.006 and from 0.6% to 5.0%, p = 0.034, respectively). Backward logistic multivariate analysis showed that SDMA was an independent estimate of developing severe HF, even when adjusted for confounding (OR(95%CI): 8.2(3.0–22.5), p<0.001). Further, SDMA was associated with mortality, even after adjustment for GRACE risk score (OR(95%CI): 4.56(1.34–15.52), p = 0.015). Conclusions Our study showed for the first time that SDMA is associated with hospital outcomes, through altered LVEF and may have biological activity beyond renal function. PMID:28125604

  10. Prenatal alcohol exposure potentiates chronic neuropathic pain, spinal glial and immune cell activation and alters sciatic nerve and DRG cytokine levels.

    PubMed

    Noor, Shahani; Sanchez, Joshua J; Vanderwall, Arden G; Sun, Melody S; Maxwell, Jessie R; Davies, Suzy; Jantzie, Lauren L; Petersen, Timothy R; Savage, Daniel D; Milligan, Erin D

    2017-03-01

    A growing body of evidence indicates that prenatal alcohol exposure (PAE) may predispose individuals to secondary medical disabilities later in life. Animal models of PAE reveal neuroimmune sequelae such as elevated brain astrocyte and microglial activation with corresponding region-specific changes in immune signaling molecules such as cytokines and chemokines. The aim of this study was to evaluate the effects of moderate PAE on the development and maintenance of allodynia induced by chronic constriction injury (CCI) of the sciatic nerve in adult male rat offspring. Because CCI allodynia requires the actions of glial cytokines, we analyzed lumbar spinal cord glial and immune cell surface markers indicative of their activation levels, as well as sciatic nerve and dorsal root ganglia (DRG) cytokines in PAE offspring in adulthood. While PAE did not alter basal sensory thresholds before or after sham manipulations, PAE significantly potentiated adult onset and maintenance of allodynia. Microscopic analysis revealed exaggerated astrocyte and microglial activation, while flow cytometry data demonstrated increased proportions of immune cells with cell surface major histocompatibility complex II (MHCII) and β-integrin adhesion molecules, which are indicative of PAE-induced immune cell activation. Sciatic nerves from CCI rats revealed that PAE potentiated the proinflammatory cytokines interleukin (IL)-1β, IL-6 and tumor necrosis factor-alpha (TNFα) protein levels with a simultaneous robust suppression of the anti-inflammatory cytokine, IL-10. A profound reduction in IL-10 expression in the DRG of PAE neuropathic rats was also observed. Taken together, our results provide novel insights into the vulnerability that PAE produces for adult-onset central nervous system (CNS) pathological conditions from peripheral nerve injury.

  11. Feeding bovine milks with low or high IgA levels is associated with altered re-establishment of murine intestinal microbiota after antibiotic treatment

    PubMed Central

    Young, Wayne; Cakebread, Julie A.; Haigh, Brendan J.

    2016-01-01

    Antibiotics are a vital and commonly used therapeutic tool, but their use also results in profound changes in the intestinal microbiota that can, in turn, have significant health consequences. Understanding how the microbiota recovers after antibiotic treatment will help to devise strategies for mitigating the adverse effects of antibiotics. Using a mouse model, we have characterized the changes occurring in the intestinal microbiota immediately after five days exposure to ampicillin, and then at three and fourteen days thereafter. During the fourteen day period of antibiotic recovery, groups of mice were fed either water, cows’ milk containing high levels of IgA, or cows’ milk containing low levels of IgA as their sole source of liquid. Effects on microbiota of feeding milks for 14 days were also assessed in groups of mice that had no ampicillin exposure. Changes in microbiota were measured by high throughput sequencing of the V4 to V6 variable regions of the 16S ribosomal RNA gene. As expected, exposure to ampicillin led to profound changes to the types and abundance of bacteria present, along with a loss of diversity. At 14 days following antibiotic exposure, mice fed water had recovered microbiota compositions similar to that prior to antibiotics. However, feeding High-IgA milk to mice that has been exposed to antibiotics was associated with altered microbiota compositions, including increased relative abundance of Lactobacillus and Barnesiella compared to the start of the study. Mice exposed to antibiotics then fed Low-IgA milk also showed increased Barnesiella at day 14. Mice without antibiotic perturbation, showed no change in their microbiota after 14 days of milk feeding. Overall, these findings add to a knowledge platform for optimizing intestinal function after treatment with antibiotics in the human population. PMID:27703861

  12. Point estimates in phylogenetic reconstructions

    PubMed Central

    Benner, Philipp; Bačák, Miroslav; Bourguignon, Pierre-Yves

    2014-01-01

    Motivation: The construction of statistics for summarizing posterior samples returned by a Bayesian phylogenetic study has so far been hindered by the poor geometric insights available into the space of phylogenetic trees, and ad hoc methods such as the derivation of a consensus tree makeup for the ill-definition of the usual concepts of posterior mean, while bootstrap methods mitigate the absence of a sound concept of variance. Yielding satisfactory results with sufficiently concentrated posterior distributions, such methods fall short of providing a faithful summary of posterior distributions if the data do not offer compelling evidence for a single topology. Results: Building upon previous work of Billera et al., summary statistics such as sample mean, median and variance are defined as the geometric median, Fréchet mean and variance, respectively. Their computation is enabled by recently published works, and embeds an algorithm for computing shortest paths in the space of trees. Studying the phylogeny of a set of plants, where several tree topologies occur in the posterior sample, the posterior mean balances correctly the contributions from the different topologies, where a consensus tree would be biased. Comparisons of the posterior mean, median and consensus trees with the ground truth using simulated data also reveals the benefits of a sound averaging method when reconstructing phylogenetic trees. Availability and implementation: We provide two independent implementations of the algorithm for computing Fréchet means, geometric medians and variances in the space of phylogenetic trees. TFBayes: https://github.com/pbenner/tfbayes, TrAP: https://github.com/bacak/TrAP. Contact: philipp.benner@mis.mpg.de PMID:25161244

  13. Vestige: Maximum likelihood phylogenetic footprinting

    PubMed Central

    Wakefield, Matthew J; Maxwell, Peter; Huttley, Gavin A

    2005-01-01

    Background Phylogenetic footprinting is the identification of functional regions of DNA by their evolutionary conservation. This is achieved by comparing orthologous regions from multiple species and identifying the DNA regions that have diverged less than neutral DNA. Vestige is a phylogenetic footprinting package built on the PyEvolve toolkit that uses probabilistic molecular evolutionary modelling to represent aspects of sequence evolution, including the conventional divergence measure employed by other footprinting approaches. In addition to measuring the divergence, Vestige allows the expansion of the definition of a phylogenetic footprint to include variation in the distribution of any molecular evolutionary processes. This is achieved by displaying the distribution of model parameters that represent partitions of molecular evolutionary substitutions. Examination of the spatial incidence of these effects across regions of the genome can identify DNA segments that differ in the nature of the evolutionary process. Results Vestige was applied to a reference dataset of the SCL locus from four species and provided clear identification of the known conserved regions in this dataset. To demonstrate the flexibility to use diverse models of molecular evolution and dissect the nature of the evolutionary process Vestige was used to footprint the Ka/Ks ratio in primate BRCA1 with a codon model of evolution. Two regions of putative adaptive evolution were identified illustrating the ability of Vestige to represent the spatial distribution of distinct molecular evolutionary processes. Conclusion Vestige provides a flexible, open platform for phylogenetic footprinting. Underpinned by the PyEvolve toolkit, Vestige provides a framework for visualising the signatures of evolutionary processes across the genome of numerous organisms simultaneously. By exploiting the maximum-likelihood statistical framework, the complex interplay between mutational processes, DNA repair and

  14. Alteration at translational but not transcriptional level of transferrin receptor expression following manganese exposure at the blood-CSF barrier in vitro

    SciTech Connect

    Li, G. Jane; Zhao Qiuqu; Zheng Wei . E-mail: wzheng@purdue.edu

    2005-06-01

    Manganese exposure alters iron homeostasis in blood and cerebrospinal fluid (CSF), possibly by acting on iron transport mechanisms localized at the blood-brain barrier and/or blood-CSF barrier. This study was designed to test the hypothesis that manganese exposure may change the binding affinity of iron regulatory proteins (IRPs) to mRNAs encoding transferrin receptor (TfR), thereby influencing iron transport at the blood-CSF barrier. A primary culture of choroidal epithelial cells was adapted to grow on a permeable membrane sandwiched between two culture chambers to mimic blood-CSF barrier. Trace {sup 59}Fe was used to determine the transepithelial transport of iron. Following manganese treatment (100 {mu}M for 24 h), the initial flux rate constant (K {sub i}) of iron was increased by 34%, whereas the storage of iron in cells was reduced by 58%, as compared to controls. A gel shift assay demonstrated that manganese exposure increased the binding of IRP1 and IRP2 to the stem loop-containing mRNAs. Consequently, the cellular concentrations of TfR proteins were increased by 84% in comparison to controls. Assays utilizing RT-PCR, quantitative real-time reverse transcriptase-PCR, and nuclear run off techniques showed that manganese treatment did not affect the level of heterogeneous nuclear RNA (hnRNA) encoding TfR, nor did it affect the level of nascent TfR mRNA. However, manganese exposure resulted in a significantly increased level of TfR mRNA and reduced levels of ferritin mRNA. Taken together, these results suggest that manganese exposure increases iron transport at the blood-CSF barrier; the effect is likely due to manganese action on translational events relevant to the production of TfR, but not due to its action on transcriptional, gene expression of TfR. The disrupted protein-TfR mRNA interaction in the choroidal epithelial cells may explain the toxicity of manganese at the blood-CSF barrier.

  15. Genomic biodiversity, phylogenetics, and coevolution in proteins

    PubMed Central

    Pollock, David D

    2010-01-01

    Comprehensive sampling of genomic biodiversity is fast becoming a reality for some genomic regions and complete organelle genomes. Genomic biodiversity is defined as large genomic sequences from many species, and here some recent work is reviewed that demonstrates the potential benefits of genomic biodiversity for molecular evolutionary analysis and phylogenetic reconstruction. This work shows that using likelihood-based approaches, taxon addition can dramatically improve phylogenetic reconstruction. Features or dynamics of the evolutionary process are much more easily inferred with large numbers of taxa, and large numbers are essential for discriminating differences in evolutionary patterns between sites. Accurate prediction of site-specific patterns can improve phylogenetic reconstruction by an amount equivalent to quadrupling sequence length. Genomic biodiversity is particularly central to research relating patterns of evolution, adaptation and coevolution to structural and functional features of proteins. Research on detecting coevolution between amino acid residues in proteins demonstrates a clear need for much greater numbers of closely related taxa to better discriminate site-specific patterns of interaction, and to allow more detailed analysis of coevolutionary interactions between subunits in protein complexes. It is argued that parsing out coevolutionary and other context-dependent substitution probabilities is essential for discriminating between coevolution and adaptation, and for more realistically modelling the evolution of proteins. Also reviewed is research that argues for increasing the efficiency of acquiring genomic biodiversity, and suggests that this might be done by simultaneously shotgun cloning and sequencing genomic mixtures from many species. Increased efficiency is a prerequisite if genomic biodiversity levels are to rapidly increase by orders of magnitude, and thus lead to dramatically improved understanding of interactions between

  16. High-resolution phylogenetic microbial community profiling

    SciTech Connect

    Singer, Esther; Coleman-Derr, Devin; Bowman, Brett; Schwientek, Patrick; Clum, Alicia; Copeland, Alex; Ciobanu, Doina; Cheng, Jan-Fang; Gies, Esther; Hallam, Steve; Tringe, Susannah; Woyke, Tanja

    2014-03-17

    The representation of bacterial and archaeal genome sequences is strongly biased towards cultivated organisms, which belong to merely four phylogenetic groups. Functional information and inter-phylum level relationships are still largely underexplored for candidate phyla, which are often referred to as microbial dark matter. Furthermore, a large portion of the 16S rRNA gene records in the GenBank database are labeled as environmental samples and unclassified, which is in part due to low read accuracy, potential chimeric sequences produced during PCR amplifications and the low resolution of short amplicons. In order to improve the phylogenetic classification of novel species and advance our knowledge of the ecosystem function of uncultivated microorganisms, high-throughput full length 16S rRNA gene sequencing methodologies with reduced biases are needed. We evaluated the performance of PacBio single-molecule real-time (SMRT) sequencing in high-resolution phylogenetic microbial community profiling. For this purpose, we compared PacBio and Illumina metagenomic shotgun and 16S rRNA gene sequencing of a mock community as well as of an environmental sample from Sakinaw Lake, British Columbia. Sakinaw Lake is known to contain a large age of microbial species from candidate phyla. Sequencing results show that community structure based on PacBio shotgun and 16S rRNA gene sequences is highly similar in both the mock and the environmental communities. Resolution power and community representation accuracy from SMRT sequencing data appeared to be independent of GC content of microbial genomes and was higher when compared to Illumina-based metagenome shotgun and 16S rRNA gene (iTag) sequences, e.g. full-length sequencing resolved all 23 OTUs in the mock community, while iTags did not resolve closely related species. SMRT sequencing hence offers various potential benefits when characterizing uncharted microbial communities.

  17. Prohormone convertase 2 (PC2) null mice have increased mu opioid receptor levels accompanied by altered morphine-induced antinociception, tolerance and dependence.

    PubMed

    Lutfy, K; Parikh, D; Lee, D L; Liu, Y; Ferrini, M G; Hamid, A; Friedman, T C

    2016-08-04

    Chronic morphine treatment increases the levels of prohormone convertase 2 (PC2) in brain regions involved in nociception, tolerance and dependence. Thus, we tested if PC2 null mice exhibit altered morphine-induced antinociception, tolerance and dependence. PC2 null mice and their wild-type controls were tested for baseline hot plate latency, injected with morphine (1.25-10mg/kg) and tested for antinociception 30min later. For tolerance studies, mice were tested in the hot plate test before and 30min following morphine (5mg/kg) on day 1. Mice then received an additional dose so that the final dose of morphine was 10mg/kg on this day. On days 2-4, mice received additional doses of morphine (20, 40 and 80mg/kg on days 1, 2, 3, and 4, respectively). On day 5, mice were tested in the hot plate test before and 30min following morphine (5mg/kg). For withdrawal studies, mice were treated with the escalating doses of morphine (10, 20, 40 and 80mg/kg) for 4days, implanted with a morphine pellet on day 5 and 3 days later injected with naloxone (1mg/kg) and signs of withdrawal were recorded. Morphine dose-dependently induced antinociception and the magnitude of this response was greater in PC2 null mice. Tolerance to morphine was observed in wild-type mice and this phenomenon was blunted in PC2 null mice. Withdrawal signs were also reduced in PC2 null mice. Immunohistochemical studies showed up-regulation of the mu opioid receptor (MOP) protein expression in the periaqueductal gray area, ventral tegmental area, lateral hypothalamus, medial hypothalamus, nucleus accumbens, and somatosensory cortex in PC2 null mice. Likewise, naloxone specific binding was increased in the brains of these mice compared to their wild-type controls. The results suggest that the PC2-derived peptides may play a functional role in morphine-induced antinociception, tolerance and dependence. Alternatively, lack of opioid peptides led to up-regulation of the MOP and altered morphine

  18. Complete mitogenome of asiatic lion resolves phylogenetic status within Panthera

    PubMed Central

    2013-01-01

    Background The origin, evolution and speciation of the lion, has been subject of interest, debate and study. The present surviving lions of the genus Panthera comprise of eight sub-species inclusive of Asiatic lion Panthera leo persica of India's Gir forest. Except for the Asiatic lion, the other seven subspecies are found in different parts of Africa. There have been different opinions regarding the phylogenetic status of Panthera leo, as well as classifying lions of different geographic regions into subspecies and races. In the present study, mitogenome sequence of P. leo persica deduced, using Ion Torrent PGM to assess phylogeny and evolution which may play an increasingly important role in conservation biology. Results The mtDNA sequence of P. leo persica is 17,057 bp in length with 40.8% GC content. Annotation of mitogenome revealed total 37 genes, including 13 protein coding, 2 rRNA and 22 tRNA. Phylogenetic analysis based on whole mitogenome, suggests Panthera pardus as a neighbouring species to P. leo with species divergence at ~2.96 mya. Conclusion This work presents first report on complete mitogenome of Panthera leo persica. It sheds light on the phylogenetic and evolutionary status within and across Felidae members. The result compared and evaluated with earlier reports of Felidae shows alteration of phylogenetic status and species evolution. This study may provide information on genetic diversity and population stability. PMID:23968279

  19. Phylogenetic versus functional signals in the evolution of form-function relationships in terrestrial vision.

    PubMed

    Motani, Ryosuke; Schmitz, Lars

    2011-08-01

    Phylogeny is deeply pertinent to evolutionary studies. Traits that perform a body function are expected to be strongly influenced by physical "requirements" of the function. We investigated if such traits exhibit phylogenetic signals, and, if so, how phylogenetic noises bias quantification of form-function relationships. A form-function system that is strongly influenced by physics, namely the relationship between eye morphology and visual optics in amniotes, was used. We quantified the correlation between form (i.e., eye morphology) and function (i.e., ocular optics) while varying the level of phylogenetic bias removal through adjusting Pagel's λ. Ocular soft-tissue dimensions exhibited the highest correlation with ocular optics when 1% of phylogenetic bias expected from Brownian motion was removed (i.e., λ= 0.01); the value for hard-tissue data were 8%. A small degree of phylogenetic bias therefore exists in morphology despite of the stringent functional constraints. We also devised a phylogenetically informed discriminant analysis and recorded the effects of phylogenetic bias on this method using the same data. Use of proper λ values during phylogenetic bias removal improved misidentification rates in resulting classifications when prior probabilities were assumed to be equal. Even a small degree of phylogenetic bias affected the classification resulting from phylogenetically informed discriminant analysis.

  20. Comparison of tree-child phylogenetic networks.

    PubMed

    Cardona, Gabriel; Rosselló, Francesc; Valiente, Gabriel

    2009-01-01

    Phylogenetic networks are a generalization of phylogenetic trees that allow for the representation of nontreelike evolutionary events, like recombination, hybridization, or lateral gene transfer. While much progress has been made to find practical algorithms for reconstructing a