Comprehensive transcriptome analysis reveals novel genes involved in cardiac glycoside biosynthesis and mlncRNAs associated with secondary metabolism and stress response in Digitalis purpurea

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Wu Bin

2012-01-01

Full Text Available Abstract Background Digitalis purpurea is an important ornamental and medicinal plant. There is considerable interest in exploring its transcriptome. Results Through high-throughput 454 sequencing and subsequent assembly, we obtained 23532 genes, of which 15626 encode conserved proteins. We determined 140 unigenes to be candidates involved in cardiac glycoside biosynthesis. It could be grouped into 30 families, of which 29 were identified for the first time in D. purpurea. We identified 2660 mRNA-like npcRNA (mlncRNA candidates, an emerging class of regulators, using a computational mlncRNA identification pipeline and 13 microRNA-producing unigenes based on sequence conservation and hairpin structure-forming capability. Twenty five protein-coding unigenes were predicted to be targets of these microRNAs. Among the mlncRNA candidates, only 320 could be grouped into 140 families with at least two members in a family. The majority of D. purpurea mlncRNAs were species-specific and many of them showed tissue-specific expression and responded to cold and dehydration stresses. We identified 417 protein-coding genes with regions significantly homologous or complementary to 375 mlncRNAs. It includes five genes involved in secondary metabolism. A positive correlation was found in gene expression between protein-coding genes and the homologous mlncRNAs in response to cold and dehydration stresses, while the correlation was negative when protein-coding genes and mlncRNAs were complementary to each other. Conclusions Through comprehensive transcriptome analysis, we not only identified 29 novel gene families potentially involved in the biosynthesis of cardiac glycosides but also characterized a large number of mlncRNAs. Our results suggest the importance of mlncRNAs in secondary metabolism and stress response in D. purpurea.

Precision metabolic engineering: The design of responsive, selective, and controllable metabolic systems.

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McNerney, Monica P; Watstein, Daniel M; Styczynski, Mark P

2015-09-01

Metabolic engineering is generally focused on static optimization of cells to maximize production of a desired product, though recently dynamic metabolic engineering has explored how metabolic programs can be varied over time to improve titer. However, these are not the only types of applications where metabolic engineering could make a significant impact. Here, we discuss a new conceptual framework, termed "precision metabolic engineering," involving the design and engineering of systems that make different products in response to different signals. Rather than focusing on maximizing titer, these types of applications typically have three hallmarks: sensing signals that determine the desired metabolic target, completely directing metabolic flux in response to those signals, and producing sharp responses at specific signal thresholds. In this review, we will first discuss and provide examples of precision metabolic engineering. We will then discuss each of these hallmarks and identify which existing metabolic engineering methods can be applied to accomplish those tasks, as well as some of their shortcomings. Ultimately, precise control of metabolic systems has the potential to enable a host of new metabolic engineering and synthetic biology applications for any problem where flexibility of response to an external signal could be useful. Copyright © 2015 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

Secondary psychosis induced by metabolic disorders

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Olivier eBonnot

2015-05-01

Full Text Available Metabolic disorders are not well recognized by psychiatrists as a possible source of secondary psychoses. Inborn errors of metabolism (IEMs are not frequent. Although, their prompt diagnosis may lead to suitable treatments. IEMs are well known to paediatricians, in particular for their most serious forms, having an early expression most of the time. Recent years discoveries have unveiled later expression forms, and sometimes, very discreet first physical signs. There is a growing body of evidence that supports the hypothesis that IEMs can manifest as atypical psychiatric symptoms, even in the absence of clear neurological symptoms. In the present review, we propose a detailed overview at schizophrenia-like and autism-like symptoms that can lead practitioners to bear in mind an IEM. Other psychiatric manifestations are also found, as behavioral., cognitive, learning and mood disorders. However, they are less frequent. Ensuring an accurate IEM diagnosis, in front of these psychiatric symptoms should be a priority, in order to grant suitable and valuable treatment for these pathologies.

Secondary metabolism and interspecific competition affect accumulation of spontaneous mutants in the gacS/gacA regulatory system in Pseudomonas protegens

NARCIS (Netherlands)

Yan, Qing; Lopes, Lucas D.; Schaffer, Brenda T.; Kidarsa, Teresa; Vining, Oliver; Philmus, Benjamin; Song, C.; Stockwell, Virginia O.; Raaijmakers, J.M.; McPhail, Kerry L.; Andreote, F.D.; Chang, Jeff H.; Loper, Joyce E.

2018-01-01

Secondary metabolites are synthesized by many microorganisms and provide a fitness benefit in the presence of competitors and predators. Secondary metabolism also can be costly, as it shunts energy and intermediates from primary metabolism. In Pseudomonas spp., secondary metabolism is controlled by

Secondary metabolism and interspecific competition affect accumulation of spontaneous mutants in the GacS-GacA regulatory system in Pseudomonas protegens

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Secondary metabolites are synthesized by many microorganisms and provide a fitness benefit in the presence of competitors and predators. Secondary metabolism also can be costly, as it shunts energy and intermediates from primary metabolism. In Pseudomonas spp., secondary metabolism is controlled by ...

Spectral effects of light-emitting diodes on photosynthetic characteristics and secondary metabolism in greenhouse plants

DEFF Research Database (Denmark)

Ouzounis, Theoharis

2014-01-01

, photo-synthetic performance, and secondary metabolism of different plants. As model plants we used rose (Rosa hybrida), chrysanthemum (Chrysanthemum morifolium), campanula (Campanula portenschlagiana), orchid (Phalaenopsis), and lettuce (Lactuca sativa). In our first experiment, by growing roses......; lettuce plants increased both their phenolic and pigment content. The effects were not observed in the same way in all plants, highlighting the fact that plant responses to blue and red LED lighting are species and/or cultivar dependent. LED-based systems are a promising alternative choice for greenhouse...

The rs10401670 variant in resistin gene improved insulin resistance response and metabolic parameters secondaries to weight loss after a hypocaloric diet.

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Antonio de Luis, Daniel; Aller, Rocío; Izaola, Olatz; Primo, David; Bachiller, R

2016-08-01

The SNP 3'UTR C/T (rs10401670), it is a polymorphism that has been associated with diabetes mellitus and it has been scarcely studied before. As far as we know, no studies on interaction among diet intervention, rs10401670 variant of RETN and metabolic response has been realized. Our aim was to analyze the effects of the rs10401670 RETN gene polymorphism on insulin resistance response and metabolic changes secondary to weight loss after 3 months of a hypocaloric diet in adults obese patients without diabetes mellitus. A Caucasian population of 135 obese patients without diabetes mellitus was analyzed. Before and after 3 months on a low fat hypocaloric diet, an anthropometric evaluation, an assessment of nutritional intake and a biochemical analysis were performed. The statistical analysis was performed for the combined CT and TT as a group (minor allele group) and wild type CC as second group (major allele group) (dominant model). Forty nine patients (36.3%) had the genotype CC (major allele group) and 86 (63.7%) patients had the next genotypes; CT (67 patients, 49.6%) or TT (19 patients, 14.1%) (minor allele group). After dietary treatment and in major allele group, weight, BMI, fat mass, systolic blood pressure and waist circumference decreases were similar than minor allele group. In T allele carriers, fasting plasma glucose, insulin, HOMA-IR, total cholesterol and LDL cholesterol levels decreased significantly. In non T allele carriers and after dietary treatment, only LDL cholesterol and total cholesterol decreased. In non T Allele carriers, the decrease in total cholesterol was -15.1 ± 18.3 mg/dl (decrease in T Allele carriers -18.3 ± 15.7 mg/dl: p > 0.05), LDL-cholesterol was -14.3 ± 18.5 mg/dl (decrease in T Allele carriers -17.3 ± 10.1 mg/dl:p > 0.05), fasting glucose plasma -2.2 ± 1.5 mg/dL (decrease in T Allele carriers -4.8 ± 1.2 mg/dL: p = 0.02), insulin -1.1 ± 2.0 mUI/L (decrease in T Allele carriers -6.3�

New opportunities for the regulation of secondary metabolism in plants: focus on microRNAs.

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Bulgakov, Victor P; Avramenko, Tatiana V

2015-09-01

Plant cell cultures are of particular interest in industrial applications as a source of biologically active substances. It is difficult, however, to achieve stable production of secondary metabolites for many plant cell cultures using classical techniques. Novel approaches should be developed for removal of the inhibitor blocks that prevent pathway activation and shift the regulatory balance to the activation of entire biosynthetic pathways. MicroRNAs (miRNAs) are small RNAs that play important regulatory roles in various biological processes. Only recently miRNAs have been demonstrated as active in secondary metabolism regulation. In this work, we summarize recent data on the emerging approaches based on regulation of secondary metabolism by miRNAs.

Biochemical trade-offs: evidence for ecologically linked secondary metabolism of the sponge Oscarella balibaloi.

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Ivanisevic, Julijana; Thomas, Olivier P; Pedel, Laura; Pénez, Nicolas; Ereskovsky, Alexander V; Culioli, Gérald; Pérez, Thierry

2011-01-01

Secondary metabolite production is assumed to be costly and therefore the resource allocation to their production should be optimized with respect to primary biological functions such as growth or reproduction. Sponges are known to produce a great diversity of secondary metabolites with powerful biological activities that may explain their domination in some hard substrate communities both in terms of diversity and biomass. Oscarella balibaloi (Homoscleromorpha) is a recently described, highly dynamic species, which often overgrows other sessile marine invertebrates. Bioactivity measurements (standardized Microtox assay) and metabolic fingerprints were used as indicators of the baseline variations of the O. balibaloi secondary metabolism, and related to the sponge reproductive effort over two years. The bioactivity showed a significant seasonal variation with the lowest values at the end of spring and in early summer followed by the highest bioactivity in the late summer and autumn. An effect of the seawater temperature was detected, with a significantly higher bioactivity in warm conditions. There was also a tendency of a higher bioactivity when O. balibaloi was found overgrowing other sponge species. Metabolic fingerprints revealed the existence of three principal metabolic phenotypes: phenotype 1 exhibited by a majority of low bioactive, female individuals, whereas phenotypes 2 and 3 correspond to a majority of highly bioactive, non-reproductive individuals. The bioactivity was negatively correlated to the reproductive effort, minimal bioactivities coinciding with the period of embryogenesis and larval development. Our results fit the Optimal Defense Theory with an investment in the reproduction mainly shaping the secondary metabolism variability, and a less pronounced influence of other biotic (species interaction) and abiotic (temperature) factors.

Biochemical trade-offs: evidence for ecologically linked secondary metabolism of the sponge Oscarella balibaloi.

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Julijana Ivanisevic

Full Text Available Secondary metabolite production is assumed to be costly and therefore the resource allocation to their production should be optimized with respect to primary biological functions such as growth or reproduction. Sponges are known to produce a great diversity of secondary metabolites with powerful biological activities that may explain their domination in some hard substrate communities both in terms of diversity and biomass. Oscarella balibaloi (Homoscleromorpha is a recently described, highly dynamic species, which often overgrows other sessile marine invertebrates. Bioactivity measurements (standardized Microtox assay and metabolic fingerprints were used as indicators of the baseline variations of the O. balibaloi secondary metabolism, and related to the sponge reproductive effort over two years. The bioactivity showed a significant seasonal variation with the lowest values at the end of spring and in early summer followed by the highest bioactivity in the late summer and autumn. An effect of the seawater temperature was detected, with a significantly higher bioactivity in warm conditions. There was also a tendency of a higher bioactivity when O. balibaloi was found overgrowing other sponge species. Metabolic fingerprints revealed the existence of three principal metabolic phenotypes: phenotype 1 exhibited by a majority of low bioactive, female individuals, whereas phenotypes 2 and 3 correspond to a majority of highly bioactive, non-reproductive individuals. The bioactivity was negatively correlated to the reproductive effort, minimal bioactivities coinciding with the period of embryogenesis and larval development. Our results fit the Optimal Defense Theory with an investment in the reproduction mainly shaping the secondary metabolism variability, and a less pronounced influence of other biotic (species interaction and abiotic (temperature factors.

Substrate metabolism in the metabolic response to injury

NARCIS (Netherlands)

Romijn, J. A.

2000-01-01

In healthy subjects the metabolic response to starvation invokes regulatory mechanisms aimed at conservation of protein mass. This response is characterized by a decrease in energy expenditure and a progressive decrease in urinary N excretion. Many non-endocrine diseases induce anorexia and a

Synergistic effects of drought stress and photoperiods on phenology and secondary metabolism of Silybum marianum.

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Zahir, Adnan; Abbasi, Bilal Haider; Adil, Muhammad; Anjum, Sumaira; Zia, Muhammad; Ihsan-Ul-Haq

2014-09-01

Silybum marianum is an important medicinal plant of the family Asteraceae, well known for its set of bioactive isomeric mixture of secondary metabolites "silymarin", primarily acting as a hepato-protective agent. Abiotic stress augments plant secondary metabolism in different plant tissues to withstand harsh environmental fluctuations. In the current study, our aim was to induce drought stress in vitro on S. marianum under the influence of different photoperiod treatments to study the effects, with respect to variations in secondary metabolic profile and plant growth and development. S. marianum was extremely vulnerable to different levels of mannitol-induced drought stress. Water deficiency inhibited root induction completely and retarded plant growth was observed; however, phytochemical analysis revealed enhanced accumulation of total phenolic content (TPC), total flavonoid content (TFC), and total protein content along with several antioxidative enzymes. Secondary metabolic content was positively regulated with increasing degree of drought stress. A dependent correlation of seed germination frequency at mild drought stress and antioxidative activities was established with 2 weeks dark + 2 weeks 16/8 h photoperiod treatment, respectively, whereas a positive correlation existed for TPC and TFC when 4 weeks 16/8 h photoperiod treatment was applied. The effects of drought stress are discussed in relation to phenology, seed germination frequency, biomass build up, antioxidative potential, and secondary metabolites accumulation.

Metabolic self-destruction in critically ill patients: origins, mechanisms and therapeutic principles.

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Hartl, Wolfgang H; Jauch, Karl-Walter

2014-03-01

The aim of this study was to describe the evolution and nature of self-destructive metabolic responses observed in critically ill patients, and to analyze therapeutic principles on how best to avoid or diminish these responses. We electronically identified articles through a search of PubMed and Google Scholar. Metabolic reactions associated with surgical injury or infections comprise hyperglycemia, insulin resistance, increased hepatic glucose production, and muscle protein breakdown. From an evolutionary perspective, these responses have been necessary and successful to overcome spontaneously survivable insults (minor surgical trauma). If prolonged and exaggerated, however, these reactions may become self-destructive, causing secondary metabolic damage. There is overwhelming evidence that extreme metabolic responses have not been selected by evolution, but are brought about by modern medicine enabling survival of severe, otherwise lethal insults and giving patients the chance to develop such exaggerated self-destructive metabolic reactions. Poorly adapted metabolic responses to severe insults, however, may have persisted because of unavoidable evolutionary constraints. Self-destructive metabolic responses cannot be prevented by adjuvant therapies such as artificial nutrition, which may only help to ameliorate secondary metabolic damage. Minor surgical trauma is associated with a beneficial adaptive metabolic response. After a severe insult, however, emergence of self-destructive responses will be unavoidable if the patient survives the acute phase. Effective treatment is only possible by an aggressive therapy of underlying pathologies (such as shock, trauma or infection) thereby interrupting secondary metabolic trigger mechanisms at an early stage. Copyright © 2014 Elsevier Inc. All rights reserved.

Endophytic actinobacteria: Diversity, secondary metabolism and mechanisms to unsilence biosynthetic gene clusters.

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Dinesh, Raghavan; Srinivasan, Veeraraghavan; T E, Sheeja; Anandaraj, Muthuswamy; Srambikkal, Hamza

2017-09-01

Endophytic actinobacteria, which reside in the inner tissues of host plants, are gaining serious attention due to their capacity to produce a plethora of secondary metabolites (e.g. antibiotics) possessing a wide variety of biological activity with diverse functions. This review encompasses the recent reports on endophytic actinobacterial species diversity, in planta habitats and mechanisms underlying their mode of entry into plants. Besides, their metabolic potential, novel bioactive compounds they produce and mechanisms to unravel their hidden metabolic repertoire by activation of cryptic or silent biosynthetic gene clusters (BGCs) for eliciting novel secondary metabolite production are discussed. The study also reviews the classical conservative techniques (chemical/biological/physical elicitation, co-culturing) as well as modern microbiology tools (e.g. next generation sequencing) that are being gainfully employed to uncover the vast hidden scaffolds for novel secondary metabolites produced by these endophytes, which would subsequently herald a revolution in drug engineering. The potential role of these endophytes in the agro-environment as promising biological candidates for inhibition of phytopathogens and the way forward to thoroughly exploit this unique microbial community by inducing expression of cryptic BGCs for encoding unseen products with novel therapeutic properties are also discussed.

Primary Metabolism during Biosynthesis of Secondary Wall Polymers of Protoxylem Vessel Elements1[OPEN

Science.gov (United States)

Morisaki, Keiko; Sawada, Yuji; Sano, Ryosuke; Yamamoto, Atsushi; Kurata, Tetsuya; Suzuki, Shiro; Matsuda, Mami; Hasunuma, Tomohisa; Hirai, Masami Yokota

2016-01-01

Xylem vessels, the water-conducting cells in vascular plants, undergo characteristic secondary wall deposition and programmed cell death. These processes are regulated by the VASCULAR-RELATED NAC-DOMAIN (VND) transcription factors. Here, to identify changes in metabolism that occur during protoxylem vessel element differentiation, we subjected tobacco (Nicotiana tabacum) BY-2 suspension culture cells carrying an inducible VND7 system to liquid chromatography-mass spectrometry-based wide-target metabolome analysis and transcriptome analysis. Time-course data for 128 metabolites showed dynamic changes in metabolites related to amino acid biosynthesis. The concentration of glyceraldehyde 3-phosphate, an important intermediate of the glycolysis pathway, immediately decreased in the initial stages of cell differentiation. As cell differentiation progressed, specific amino acids accumulated, including the shikimate-related amino acids and the translocatable nitrogen-rich amino acid arginine. Transcriptome data indicated that cell differentiation involved the active up-regulation of genes encoding the enzymes catalyzing fructose 6-phosphate biosynthesis from glyceraldehyde 3-phosphate, phosphoenolpyruvate biosynthesis from oxaloacetate, and phenylalanine biosynthesis, which includes shikimate pathway enzymes. Concomitantly, active changes in the amount of fructose 6-phosphate and phosphoenolpyruvate were detected during cell differentiation. Taken together, our results show that protoxylem vessel element differentiation is associated with changes in primary metabolism, which could facilitate the production of polysaccharides and lignin monomers and, thus, promote the formation of the secondary cell wall. Also, these metabolic shifts correlate with the active transcriptional regulation of specific enzyme genes. Therefore, our observations indicate that primary metabolism is actively regulated during protoxylem vessel element differentiation to alter the cell’s metabolic

Influence of Carbohydrates on Secondary Metabolism in Fusarium avenaceum

OpenAIRE

Jens Laurids Sørensen; Henriette Giese

2013-01-01

Fusarium avenaceum is a widespread pathogen of important crops in the temperate climate zones that can produce many bioactive secondary metabolites, including moniliformin, fusarin C, antibiotic Y, 2-amino-14,16-dimethyloctadecan-3-ol (2-AOD-3-ol), chlamydosporol, aurofusarin and enniatins. Here, we examine the production of these secondary metabolites in response to cultivation on different carbon sources in order to gain insight into the regulation and production of secondary metabolites in...

Legionella shows a diverse secondary metabolism dependent on a broad spectrum Sfp-type phosphopantetheinyl transferase

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Nicholas J. Tobias

2016-11-01

Full Text Available Several members of the genus Legionella cause Legionnaires’ disease, a potentially debilitating form of pneumonia. Studies frequently focus on the abundant number of virulence factors present in this genus. However, what is often overlooked is the role of secondary metabolites from Legionella. Following whole genome sequencing, we assembled and annotated the Legionella parisiensis DSM 19216 genome. Together with 14 other members of the Legionella, we performed comparative genomics and analysed the secondary metabolite potential of each strain. We found that Legionella contains a huge variety of biosynthetic gene clusters (BGCs that are potentially making a significant number of novel natural products with undefined function. Surprisingly, only a single Sfp-like phosphopantetheinyl transferase is found in all Legionella strains analyzed that might be responsible for the activation of all carrier proteins in primary (fatty acid biosynthesis and secondary metabolism (polyketide and non-ribosomal peptide synthesis. Using conserved active site motifs, we predict some novel compounds that are probably involved in cell-cell communication, differing to known communication systems. We identify several gene clusters, which may represent novel signaling mechanisms and demonstrate the natural product potential of Legionella.

Manipulation of the metabolic response in clinical practice

DEFF Research Database (Denmark)

Kehlet, H

2000-01-01

morbidity. Effective afferent neural blockade with continuous epidural local anesthetic techniques inhibits a major part of the endocrine metabolic response, leading to improved protein economy but without important effects on inflammatory or immunologic responses. In contrast, pain treatment with other...... modalities such as nonsteroidal antiinflammatory drugs (NSAIDs) and opioids has only a small inhibitory effect on endocrine metabolic responses. Preoperative high-dose glucocorticoid therapy provides additional pain relief and improves pulmonary function, but it reduces the inflammatory response (acute......-phase proteins, cytokines, hyperthermia) and immune function. Minimally invasive surgery leaves the endocrine metabolic responses largely unaltered but reduces the inflammatory response and immune suppression. Thus several techniques are available to modify the stress responses in elective surgery patients...

Quantitative 1H NMR metabolomics reveals extensive metabolic reprogramming of primary and secondary metabolism in elicitor-treated opium poppy cell cultures

OpenAIRE

Zulak, Katherine G; Weljie, Aalim M; Vogel, Hans J; Facchini, Peter J

2008-01-01

Abstract Background Opium poppy (Papaver somniferum) produces a diverse array of bioactive benzylisoquinoline alkaloids and has emerged as a model system to study plant alkaloid metabolism. The plant is cultivated as the only commercial source of the narcotic analgesics morphine and codeine, but also produces many other alkaloids including the antimicrobial agent sanguinarine. Modulations in plant secondary metabolism as a result of environmental perturbations are often associated with the al...

Two different secondary metabolism gene clusters occupied the same ancestral locus in fungal dermatophytes of the arthrodermataceae.

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Zhang, Han; Rokas, Antonis; Slot, Jason C

2012-01-01

Dermatophyte fungi of the family Arthrodermataceae (Eurotiomycetes) colonize keratinized tissue, such as skin, frequently causing superficial mycoses in humans and other mammals, reptiles, and birds. Competition with native microflora likely underlies the propensity of these dermatophytes to produce a diversity of antibiotics and compounds for scavenging iron, which is extremely scarce, as well as the presence of an unusually large number of putative secondary metabolism gene clusters, most of which contain non-ribosomal peptide synthetases (NRPS), in their genomes. To better understand the historical origins and diversification of NRPS-containing gene clusters we examined the evolution of a variable locus (VL) that exists in one of three alternative conformations among the genomes of seven dermatophyte species. The first conformation of the VL (termed VLA) contains only 539 base pairs of sequence and lacks protein-coding genes, whereas the other two conformations (termed VLB and VLC) span 36 Kb and 27 Kb and contain 12 and 10 genes, respectively. Interestingly, both VLB and VLC appear to contain distinct secondary metabolism gene clusters; VLB contains a NRPS gene as well as four porphyrin metabolism genes never found to be physically linked in the genomes of 128 other fungal species, whereas VLC also contains a NRPS gene as well as several others typically found associated with secondary metabolism gene clusters. Phylogenetic evidence suggests that the VL locus was present in the ancestor of all seven species achieving its present distribution through subsequent differential losses or retentions of specific conformations. We propose that the existence of variable loci, similar to the one we studied, in fungal genomes could potentially explain the dramatic differences in secondary metabolic diversity between closely related species of filamentous fungi, and contribute to host adaptation and the generation of metabolic diversity.

On the developmental and environmental regulation of secondary metabolism in Vaccinium spp. berries

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Katja eKarppinen

2016-05-01

Full Text Available Secondary metabolites have important defense and signaling roles, and they contribute to the overall quality of developing and ripening fruits. Blueberries, bilberries, cranberries and other Vaccinium berries are fleshy berry fruits recognized for the high levels of bioactive compounds, especially anthocyanin pigments. Besides anthocyanins and other products of the phenylpropanoid and flavonoid pathways, these berries also contain other metabolites of interest, such as carotenoid derivatives, vitamins and flavor compounds. Recently, new information has been achieved on the mechanisms related with developmental, environmental and genetic factors involved in the regulation of secondary metabolism in Vaccinium fruits. Especially light conditions and temperature are demonstrated to have a prominent role on the composition of phenolic compounds. The present review focuses on the studies on mechanisms associated with the regulation of key secondary metabolites, mainly phenolic compounds, in Vaccinium berries. The advances in the research concerning biosynthesis of phenolic compounds in Vaccinium species, including specific studies with mutant genotypes in addition to controlled and field experiments on the genotype x environment (GxE interaction, are discussed. The recently published Vaccinium transcriptome and genome databases provide new tools for the studies on the metabolic routes.

FvSet2 regulates fungal growth, pathogenicity, and secondary metabolism in Fusarium verticillioides.

Science.gov (United States)

Gu, Qin; Wang, Zhenzhong; Sun, Xiao; Ji, Tiantian; Huang, Hai; Yang, Yang; Zhang, Hao; Tahir, Hafiz Abdul Samad; Wu, Liming; Wu, Huijun; Gao, Xuewen

2017-10-01

Histone H3 lysine 36 methylation (H3K36me) is generally associated with activation of gene expression in most eukaryotic cells. However, the function of H3K36me in filamentous fungi is largely unknown. Set2 is the sole lysine histone methyltransferase (KHMTase) enzyme responsible for the methylation of H3K36 in Saccharomyces cerevisiae. In the current study, we identified a single ortholog of S. cerevisiae Set2 in Fusarium verticillioides. We report that FvSet2 is responsible for the trimethylation of H3K36 (H3K36me3). The FvSET2 deletion mutant (ΔFvSet2) showed significant defects in vegetative growth, FB 1 biosynthesis, pigmentation, and fungal virulence. Furthermore, trimethylation of H3K36 was found to be important for active transcription of genes involved in FB 1 and bikaverin biosyntheses. These data indicate that FvSet2 plays an important role in the regulation of secondary metabolism, vegetative growth and fungal virulence in F. verticillioides. Copyright © 2017 Elsevier Inc. All rights reserved.

A strong response to selection on mass-independent maximal metabolic rate without a correlated response in basal metabolic rate

DEFF Research Database (Denmark)

Wone, B W M; Madsen, Per; Donovan, E R

2015-01-01

Metabolic rates are correlated with many aspects of ecology, but how selection on different aspects of metabolic rates affects their mutual evolution is poorly understood. Using laboratory mice, we artificially selected for high maximal mass-independent metabolic rate (MMR) without direct selection...... on mass-independent basal metabolic rate (BMR). Then we tested for responses to selection in MMR and correlated responses to selection in BMR. In other lines, we antagonistically selected for mice with a combination of high mass-independent MMR and low mass-independent BMR. All selection protocols...... and data analyses included body mass as a covariate, so effects of selection on the metabolic rates are mass adjusted (that is, independent of effects of body mass). The selection lasted eight generations. Compared with controls, MMR was significantly higher (11.2%) in lines selected for increased MMR...

Quantitative proteome and phosphoproteome analyses of Streptomyces coelicolor reveal proteins and phosphoproteins modulating differentiation and secondary metabolism

DEFF Research Database (Denmark)

Rioseras, Beatriz; Sliaha, Pavel V; Gorshkov, Vladimir

2018-01-01

identified and quantified 3461 proteins corresponding to 44.3% of the S. coelicolor proteome across three developmental stages: vegetative hypha (MI); secondary metabolite producing hyphae (MII); and sporulating hyphae. A total of 1350 proteins exhibited more than 2-fold expression changes during....../Thr/Tyr kinases, making this genus an outstanding model for the study of bacterial protein phosphorylation events. We used mass spectrometry based quantitative proteomics and phosphoproteomics to characterize bacterial differentiation and activation of secondary metabolism of Streptomyces coelicolor. We...... the bacterial differentiation process. These proteins include 136 regulators (transcriptional regulators, transducers, Ser/Thr/Tyr kinases, signalling proteins), as well as 542 putative proteins with no clear homology to known proteins which are likely to play a role in differentiation and secondary metabolism...

Hepatic injury induces contrasting response in liver and kidney to chemicals that are metabolically activated: Role of male sex hormone

International Nuclear Information System (INIS)

Kim, Young C.; Yim, Hye K.; Jung, Young S.; Park, Jae H.; Kim, Sung Y.

2007-01-01

Injury to liver, resulting in loss of its normal physiological/biochemical functions, may adversely affect a secondary organ. We examined the response of the liver and kidney to chemical substances that require metabolic activation for their toxicities in mice with a preceding liver injury. Carbon tetrachloride treatment 24 h prior to a challenging dose of carbon tetrachloride or acetaminophen decreased the resulting hepatotoxicity both in male and female mice as determined by histopathological examination and increases in serum enzyme activities. In contrast, the renal toxicity of the challenging toxicants was elevated markedly in male, but not in female mice. Partial hepatectomy also induced similar changes in the hepatotoxicity and nephrotoxicity of a challenging toxicant, suggesting that the contrasting response of male liver and kidney was associated with the reduction of the hepatic metabolizing capacity. Carbon tetrachloride pretreatment or partial hepatectomy decreased the hepatic xenobiotic-metabolizing enzyme activities in both sexes but elevated the renal p-nitrophenol hydroxylase, p-nitroanisole O-demethylase and aminopyrine N-demethylase activities significantly only in male mice. Increases in Cyp2e1 and Cyp2b expression were also evident in male kidney. Castration of males or testosterone administration to females diminished the sex-related differences in the renal response to an acute liver injury. The results indicate that reduction of the hepatic metabolizing capacity induced by liver injury may render secondary target organs susceptible to chemical substances activated in these organs. This effect may be sex-specific. It is also suggested that an integrated approach should be taken for proper assessment of chemical hazards

Knocking down mitochondrial iron transporter (MIT) reprograms primary and secondary metabolism in rice plants.

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Vigani, Gianpiero; Bashir, Khurram; Ishimaru, Yasuhiro; Lehmann, Martin; Casiraghi, Fabio Marco; Nakanishi, Hiromi; Seki, Motoaki; Geigenberger, Peter; Zocchi, Graziano; Nishizawa, Naoko K

2016-03-01

Iron (Fe) is an essential micronutrient for plant growth and development, and its reduced bioavailability strongly impairs mitochondrial functionality. In this work, the metabolic adjustment in the rice (Oryza sativa) mitochondrial Fe transporter knockdown mutant (mit-2) was analysed. Biochemical characterization of purified mitochondria from rice roots showed alteration in the respiratory chain of mit-2 compared with wild-type (WT) plants. In particular, proteins belonging to the type II alternative NAD(P)H dehydrogenases accumulated strongly in mit-2 plants, indicating that alternative pathways were activated to keep the respiratory chain working. Additionally, large-scale changes in the transcriptome and metabolome were observed in mit-2 rice plants. In particular, a strong alteration (up-/down-regulation) in the expression of genes encoding enzymes of both primary and secondary metabolism was found in mutant plants. This was reflected by changes in the metabolic profiles in both roots and shoots of mit-2 plants. Significant alterations in the levels of amino acids belonging to the aspartic acid-related pathways (aspartic acid, lysine, and threonine in roots, and aspartic acid and ornithine in shoots) were found that are strictly connected to the Krebs cycle. Furthermore, some metabolites (e.g. pyruvic acid, fumaric acid, ornithine, and oligosaccharides of the raffinose family) accumulated only in the shoot of mit-2 plants, indicating possible hypoxic responses. These findings suggest that the induction of local Fe deficiency in the mitochondrial compartment of mit-2 plants differentially affects the transcript as well as the metabolic profiles in root and shoot tissues. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Cytolytic T lymphocyte responses to metabolically inactivated stimulator cells. I. Metabolic inactivation impairs both CD and LD antigen signals

International Nuclear Information System (INIS)

Kelso, A.; Boyle, W.

1982-01-01

The effects of metabolic inactivation of spleen cells on antigen presentation to precursors of alloreactive cytolytic T lymphocytes (T/sub c/) were examined. By serological methods, populations inactivated by ultraviolet irradiation, glutaraldehyde fixation or plasma membrane isolation were found to retain normal levels of H-2K/D and Ia antigens. However, comparison of the antigen doses required to stimulate secondary T/sub c/ responses in mixed leukocyte culture showed that the inactivated preparations were approximately 10-fold less immunogenic than X-irradiated spleen cells. Their total inability to stimulate primary cytolytic responses pointed to at least a 100-fold impairment of immunogenicity for unprimed T/sub c/ precursors in the case of uv-irradiated and glutaraldehyde-treated stimulator cells, and at least a 10-fold impairment for membrane fragments. Experiments showing that the capacity of cell monolayers to absorb precursor T/sub c/ from unprimed spleen populations was reduced following uv-irradiation or glutaraldehyde treatment provided direct evidence that this loss of immunogenicity was due in part to suboptimal antigen presentation to precursor T/sub c/. It is concluded that, in addition to the traditional view that these treatments damage the ''LD'' signal to helper T lymphocytes, metabolic inactivation also impairs recognition of ''CD'' determinants by precursor T/sub c/

Strain-Level Diversity of Secondary Metabolism in Streptomyces albus

Science.gov (United States)

Seipke, Ryan F.

2015-01-01

Streptomyces spp. are robust producers of medicinally-, industrially- and agriculturally-important small molecules. Increased resistance to antibacterial agents and the lack of new antibiotics in the pipeline have led to a renaissance in natural product discovery. This endeavor has benefited from inexpensive high quality DNA sequencing technology, which has generated more than 140 genome sequences for taxonomic type strains and environmental Streptomyces spp. isolates. Many of the sequenced streptomycetes belong to the same species. For instance, Streptomyces albus has been isolated from diverse environmental niches and seven strains have been sequenced, consequently this species has been sequenced more than any other streptomycete, allowing valuable analyses of strain-level diversity in secondary metabolism. Bioinformatics analyses identified a total of 48 unique biosynthetic gene clusters harboured by Streptomyces albus strains. Eighteen of these gene clusters specify the core secondary metabolome of the species. Fourteen of the gene clusters are contained by one or more strain and are considered auxiliary, while 16 of the gene clusters encode the production of putative strain-specific secondary metabolites. Analysis of Streptomyces albus strains suggests that each strain of a Streptomyces species likely harbours at least one strain-specific biosynthetic gene cluster. Importantly, this implies that deep sequencing of a species will not exhaust gene cluster diversity and will continue to yield novelty. PMID:25635820

Cell Wall Metabolism in Response to Abiotic Stress

Science.gov (United States)

Gall, Hyacinthe Le; Philippe, Florian; Domon, Jean-Marc; Gillet, Françoise; Pelloux, Jérôme; Rayon, Catherine

2015-01-01

This review focuses on the responses of the plant cell wall to several abiotic stresses including drought, flooding, heat, cold, salt, heavy metals, light, and air pollutants. The effects of stress on cell wall metabolism are discussed at the physiological (morphogenic), transcriptomic, proteomic and biochemical levels. The analysis of a large set of data shows that the plant response is highly complex. The overall effects of most abiotic stress are often dependent on the plant species, the genotype, the age of the plant, the timing of the stress application, and the intensity of this stress. This shows the difficulty of identifying a common pattern of stress response in cell wall architecture that could enable adaptation and/or resistance to abiotic stress. However, in most cases, two main mechanisms can be highlighted: (i) an increased level in xyloglucan endotransglucosylase/hydrolase (XTH) and expansin proteins, associated with an increase in the degree of rhamnogalacturonan I branching that maintains cell wall plasticity and (ii) an increased cell wall thickening by reinforcement of the secondary wall with hemicellulose and lignin deposition. Taken together, these results show the need to undertake large-scale analyses, using multidisciplinary approaches, to unravel the consequences of stress on the cell wall. This will help identify the key components that could be targeted to improve biomass production under stress conditions. PMID:27135320

Micronutrients evaluation and its influence on secondary metabolism of Bidens pilosa and Salvia officinalis, plants applied in diabetes treatment

International Nuclear Information System (INIS)

Goncalves, Rodolfo Daniel Moreno Reis

2015-01-01

Diabetes mellitus is a disease that affects the carbohydrates, lipids and proteins metabolism characterized by hyperglycemia and glucose excretion by urine. It is estimated that the number of cases of this disease will increase in the coming years, worrying the public health system of the most affected countries. Besides the use of allopathic medicine, complementary treatments such as the use of medicinal plants can contribute to improving the patients quality of life. Among the herbs used, both in Brazil and in other countries, are Bidens pilosa and Salvia officinalis. The mechanisms responsible for antidiabetic activity of the plants, are usually associated with secondary metabolites, however, the influence of micronutrient content should not be discarded. Studies have shown that there is a correlation between the concentration of these elements and the presence and development of the disease. The objective of this work was to study the elements Cr, Fe, Mg, Mn, V and Zn concentration in Bidens pilosa (beggarticks) and Salvia officinalis (sage) cultivated with normal treatment (commercial substrate) and, with the addition of these elements, to verify their influence in the production of secondary metabolites that can act as hypoglycemic agents. The elemental determination and quantification were performed by means of Instrumental Neutron Activation Analysis technique. For the secondary metabolites analysis Liquid Chromatography High Performance technique was used. The results indicated that B. pilosa and S. officinalis may be used as sources of Cr, Fe, Mg, Mn, V and Zn. It was observed that B. pilosa absorbed a larger amount of Fe in the treatment group, and S. officinalis was able to accumulate Zn its in leaves whether treated or not. Considering the secondary metabolism compounds, the results indicated that its production by plants was apparently not altered by the addition of the nutrient solution. (author)

Metabolic and adaptive immune responses induced in mice infected ...

African Journals Online (AJOL)

This study investigated metabolic and immuno-inflammatory responses of mice infected with tissue-dwelling larvae of Trichinella zimbabwensis and explored the relationship between infection, metabolic parameters and Th1/Th17 immune responses. Sixty (60) female BALB/c mice aged between 6 to 8 weeks old were ...

Coupled response spectrum analysis of secondary systems using uncoupled modal properties

International Nuclear Information System (INIS)

Gupta, A.K.; Jaw Jingwen

1986-01-01

A method of performing coupled response spectrum analysis of secondary systems is presented. The response spectrum specified at the base of the primary system is used as the input. The complex coupled mode shapes along with frequencies and damping values are calculated using an efficient and accurate perturbation scheme. The new method is applied to a 2 DOF secondary system coupled with a 6 DOF secondary system. The masses and the stiffness of the secondary system are varied to get nine different cases. The coupled system is subjected to El Centro (S00E, 1940) ground motion. It is shown that the response values from the present method are in good agreement with those from the coupled time history analysis. The conventional floor response spectrum method gives response values which are consistently much higher than the corresponding values from the time history analysis. It is concluded that the present method is sufficiently straightforward and efficient, and that it yields accurate response values. (orig.)

Secondary metabolism and antioxidants are involved in environmental adaptation and stress tolerance in lettuce.

Science.gov (United States)

Oh, Myung-Min; Trick, Harold N; Rajashekar, C B

2009-01-30

Lettuce (Lactuca sativa) plants grown in a protective environment, similar to in vitro conditions, were acclimated in a growth chamber and subjected to water stress to examine the activation of genes involved in secondary metabolism and biosynthesis of antioxidants. The expression of phenylalanine ammonia-lyase (PAL), gamma-tocopherol methyl transferase (gamma-TMT) and l-galactose dehydrogenase (l-GalDH) genes involved in the biosynthesis of phenolic compounds, alpha-tocopherol and ascorbic acid, respectively, were determined during plant adaptation. These genes were activated in tender plants, grown under protective conditions, when exposed to normal growing conditions in a growth chamber. A large increase in transcript level for PAL, a key gene in the phenylpropanoid pathway leading to the biosynthesis of a wide array of phenolics and flavonoids, was observed within 1h of exposure of tender plants to normal growing conditions. Plant growth, especially the roots, was retarded in tender plants when exposed to normal growing conditions. Furthermore, exposure of both protected and unprotected plants to water stress resulted in the activation of PAL. PAL inhibition by 2-aminoindan-2-phosphonic acid (AIP) rendered these plants more sensitive to chilling and heat shock treatments. These results suggest that activation of secondary metabolism as well as the antioxidative metabolism is an integral part of plant adaptation to normal growing conditions in lettuce plants.

Possible stimuli for strength and power adaptation : acute metabolic responses.

Science.gov (United States)

Crewther, Blair; Cronin, John; Keogh, Justin

2006-01-01

The metabolic response to resistance exercise, in particular lactic acid or lactate, has a marked influence upon the muscular environment, which may enhance the training stimulus (e.g. motor unit activation, hormones or muscle damage) and thereby contribute to strength and power adaptation. Hypertrophy schemes have resulted in greater lactate responses (%) than neuronal and dynamic power schemes, suggesting possible metabolic-mediated changes in muscle growth. Factors such as age, sex, training experience and nutrition may also influence the lactate responses to resistance exercise and thereafter, muscular adaptation. Although the importance of the mechanical and hormonal stimulus to strength and power adaptation is well recognised, the contribution of the metabolic stimulus is largely unknown. Relatively few studies for example, have examined metabolic change across neuronal and dynamic power schemes, and not withstanding the fact that those mechanisms underpinning muscular adaptation, in relation to the metabolic stimulus, remain highly speculative. Inconsistent findings and methodological limitations within research (e.g. programme design, sampling period, number of samples) make interpretation further difficult. We contend that strength and power research needs to investigate those metabolic mechanisms likely to contribute to weight-training adaptation. Further research is also needed to examine the metabolic responses to different loading schemes, as well as interactions across age, sex and training status, so our understanding of how to optimise strength and power development is improved.

Metabolic responses of Haliotis diversicolor to Vibrio parahaemolyticus infection.

Science.gov (United States)

Lu, Jie; Shi, Yanyan; Cai, Shuhui; Feng, Jianghua

2017-01-01

Vibrio parahemolyticus is a devastating bacterial pathogen that often causes outbreak of vibriosis in abalone Haliotis diversicolor. Elucidation of metabolic mechanisms of abalones in responding to V. parahemolyticus infection is essential for controlling the epidemic. In this work, 1 H NMR-based metabolomic techniques along with correlation and network analyses are used to investigate characteristic metabolites, as well as corresponding disturbed pathways in hepatopancreas and gill of H. diversicolor after V. parahemolyticus infection for 48 h. Results indicate that obvious gender- and tissue-specific metabolic responses are induced. Metabolic responses in female abalones are more clearly observed than those in males, which are primarily manifested in the accumulation of branched-chain amino acids and the depletion of organic osmolytes (homarine, betaine and taurine) in the infected gills of female abalones, as well as in the depletion of glutamate, branched-chain and aromatic amino acids in the infected hepatopancreases of female abalones. Moreover, based on major metabolic functions of the characteristic metabolites, we have found that V. parahemolyticus infection not only cause the disturbance in energy metabolism, nucleotide metabolism and osmotic balance, but also induce oxidative stress, immune stress and neurotoxic effect in different tissues with various mechanisms. Our study provides details of metabolic responses of abalones to V. parahemolyticus infection and will shed light on biochemical defence mechanisms of male and female hosts against pathogen infection. Copyright © 2016 Elsevier Ltd. All rights reserved.

Elicitor-induced transcription factors for metabolic reprogramming of secondary metabolism in Medicago truncatula

Directory of Open Access Journals (Sweden)

Dixon Richard A

2008-12-01

Full Text Available Abstract Background Exposure of Medicago truncatula cell suspension cultures to pathogen or wound signals leads to accumulation of various classes of flavonoid and/or triterpene defense molecules, orchestrated via a complex signalling network in which transcription factors (TFs are essential components. Results In this study, we analyzed TFs responding to yeast elicitor (YE or methyl jasmonate (MJ. From 502 differentially expressed TFs, WRKY and AP2/EREBP gene families were over-represented among YE-induced genes whereas Basic Helix-Loop-Helix (bHLH family members were more over-represented among the MJ-induced genes. Jasmonate ZIM-domain (JAZ transcriptional regulators were highly induced by MJ treatment. To investigate potential involvement of WRKY TFs in signalling, we expressed four Medicago WRKY genes in tobacco. Levels of soluble and wall bound phenolic compounds and lignin were increased in all cases. WRKY W109669 also induced tobacco endo-1,3-β-glucanase (NtPR2 and enhanced the systemic defense response to tobacco mosaic virus in transgenic tobacco plants. Conclusion These results confirm that Medicago WRKY TFs have broad roles in orchestrating metabolic responses to biotic stress, and that they also represent potentially valuable reagents for engineering metabolic changes that impact pathogen resistance.

Metabolic response to surgery in the cancer patient

International Nuclear Information System (INIS)

Brennan, M.F.

1979-01-01

The metabolic response to uncomplicated surgery in the patient undergoing primary therapy for malignancy is no different than the response to surgery of similar magnitude for benign disease. Hemodynamic, nutritional-endocrine, and convalescent changes are similar. However, with current aggressive approaches to the management of cancer, the patient often comes to surgery with evidence of major debilitating side effects from his progressive malignancy or from aggressive multimodality therapy. The surgeon must be aware of the consequences of the use of combination therapies on the expected metabolic response to surgery. Awareness of such problems such as the nutritional deficit will allow preventive methods to supercede mtabolic salvage procedures

Metabolic features of the cell danger response.

Science.gov (United States)

Naviaux, Robert K

2014-05-01

The cell danger response (CDR) is the evolutionarily conserved metabolic response that protects cells and hosts from harm. It is triggered by encounters with chemical, physical, or biological threats that exceed the cellular capacity for homeostasis. The resulting metabolic mismatch between available resources and functional capacity produces a cascade of changes in cellular electron flow, oxygen consumption, redox, membrane fluidity, lipid dynamics, bioenergetics, carbon and sulfur resource allocation, protein folding and aggregation, vitamin availability, metal homeostasis, indole, pterin, 1-carbon and polyamine metabolism, and polymer formation. The first wave of danger signals consists of the release of metabolic intermediates like ATP and ADP, Krebs cycle intermediates, oxygen, and reactive oxygen species (ROS), and is sustained by purinergic signaling. After the danger has been eliminated or neutralized, a choreographed sequence of anti-inflammatory and regenerative pathways is activated to reverse the CDR and to heal. When the CDR persists abnormally, whole body metabolism and the gut microbiome are disturbed, the collective performance of multiple organ systems is impaired, behavior is changed, and chronic disease results. Metabolic memory of past stress encounters is stored in the form of altered mitochondrial and cellular macromolecule content, resulting in an increase in functional reserve capacity through a process known as mitocellular hormesis. The systemic form of the CDR, and its magnified form, the purinergic life-threat response (PLTR), are under direct control by ancient pathways in the brain that are ultimately coordinated by centers in the brainstem. Chemosensory integration of whole body metabolism occurs in the brainstem and is a prerequisite for normal brain, motor, vestibular, sensory, social, and speech development. An understanding of the CDR permits us to reframe old concepts of pathogenesis for a broad array of chronic, developmental

Role of MicroRNAs in Obesity-Induced Metabolic Disorder and Immune Response.

Science.gov (United States)

Zhong, Hong; Ma, Minjuan; Liang, Tingming; Guo, Li

2018-01-01

In all living organisms, metabolic homeostasis and the immune system are the most fundamental requirements for survival. Recently, obesity has become a global public health issue, which is the cardinal risk factor for metabolic disorder. Many diseases emanating from obesity-induced metabolic dysfunction are responsible for the activated immune system, including innate and adaptive responses. Of note, inflammation is the manifest accountant signal. Deeply studied microRNAs (miRNAs) have participated in many pathways involved in metabolism and immune responses to protect cells from multiple harmful stimulants, and they play an important role in determining the progress through targeting different inflammatory pathways. Thus, immune response and metabolic regulation are highly integrated with miRNAs. Collectively, miRNAs are the new targets for therapy in immune dysfunction.

A strong response to selection on mass-independent maximal metabolic rate without a correlated response in basal metabolic rate.

Science.gov (United States)

Wone, B W M; Madsen, P; Donovan, E R; Labocha, M K; Sears, M W; Downs, C J; Sorensen, D A; Hayes, J P

2015-04-01

Metabolic rates are correlated with many aspects of ecology, but how selection on different aspects of metabolic rates affects their mutual evolution is poorly understood. Using laboratory mice, we artificially selected for high maximal mass-independent metabolic rate (MMR) without direct selection on mass-independent basal metabolic rate (BMR). Then we tested for responses to selection in MMR and correlated responses to selection in BMR. In other lines, we antagonistically selected for mice with a combination of high mass-independent MMR and low mass-independent BMR. All selection protocols and data analyses included body mass as a covariate, so effects of selection on the metabolic rates are mass adjusted (that is, independent of effects of body mass). The selection lasted eight generations. Compared with controls, MMR was significantly higher (11.2%) in lines selected for increased MMR, and BMR was slightly, but not significantly, higher (2.5%). Compared with controls, MMR was significantly higher (5.3%) in antagonistically selected lines, and BMR was slightly, but not significantly, lower (4.2%). Analysis of breeding values revealed no positive genetic trend for elevated BMR in high-MMR lines. A weak positive genetic correlation was detected between MMR and BMR. That weak positive genetic correlation supports the aerobic capacity model for the evolution of endothermy in the sense that it fails to falsify a key model assumption. Overall, the results suggest that at least in these mice there is significant capacity for independent evolution of metabolic traits. Whether that is true in the ancestral animals that evolved endothermy remains an important but unanswered question.

Organ-specific metabolic responses to drought in Pinus pinaster Ait.

Science.gov (United States)

de Miguel, Marina; Guevara, M Ángeles; Sánchez-Gómez, David; de María, Nuria; Díaz, Luis Manuel; Mancha, Jose A; Fernández de Simón, Brígida; Cadahía, Estrella; Desai, Nalini; Aranda, Ismael; Cervera, María-Teresa

2016-05-01

Drought is an important driver of plant survival, growth, and distribution. Water deficit affects different pathways of metabolism, depending on plant organ. While previous studies have mainly focused on the metabolic drought response of a single organ, analysis of metabolic differences between organs is essential to achieve an integrated understanding of the whole plant response. In this work, untargeted metabolic profiling was used to examine the response of roots, stems, adult and juvenile needles from Pinus pinaster Ait. full-sib individuals, subjected to a moderate and long lasting drought period. Cyclitols content showed a significant alteration, in response to drought in all organs examined, but other metabolites increased or decreased differentially depending on the analyzed organ. While a high number of flavonoids were only detected in aerial organs, an induction of the glutathione pathway was mainly detected in roots. This result may reflect different antioxidant mechanisms activated in aerial organs and roots. Metabolic changes were more remarkable in roots than in the other organs, highlighting its prominent role in the response to water stress. Significant changes in flavonoids and ascorbate metabolism were also observed between adult and juvenile needles, consistent with previously proven differential functional responses between the two developmental stages. Genetic polymorphisms in candidate genes coding for a Myb1 transcription factor and a malate dehydrogenase (EC 1.1.1.37) were associated with different concentration of phenylalanine, phenylpropanoids and malate, respectively. The results obtained will support further research on metabolites and genes potentially involved in functional mechanisms related to drought tolerance in trees. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

An Expanding Role For Purine Uptake Permease (PUP -like Transporters In Plant Secondary Metabolism.

Directory of Open Access Journals (Sweden)

John G. Jelesko

2012-05-01

Full Text Available For the past decade, our understanding of the plant purine uptake permease (PUP transporter family of was primarily oriented on purine nucleobase substrates and their tissue-specific expression patterns in Arabidopsis. However, a tobacco PUP-like homolog demonstrating nicotine uptake permease (NUP activity was recently shown to affect both nicotine metabolism and root cell growth. These new findings expand the physiological role for PUP-like transporters to include plant secondary metabolism. Molecular evolution analyses of PUP-like transporters indicate they are distinct group within an ancient super family of drug and metabolite transporters (DMTs. The PUP-like family originated during terrestrial plant evolution sometime between the bryophytes and the lycophytes. A phylogenetic analysis indicates that the PUP-like transporters were likely were derived from a pre-existing nucleotide sugar transporter family within the DMT super family. Within the lycophyte Selaginella, there are three paralogous groups of PUP-like transporters. One of the three PUP-like paralogous groups showed an extensive pattern of gene duplication and diversification within the angiosperm lineage, whereas the other two more ancestral PUP-like paralogous groups did not. Biochemical characterization of four closely-related PUP-like paralogs together with model-based phylogenetic analyses indicate both subfunctionalization and neofunctionalization during the molecular evolution of angiosperm PUP-like transporters. These findings suggest that members of the PUP-like family of DMT transporters are likely involved in diverse primary and secondary plant metabolic pathways.

Role of MicroRNAs in Obesity-Induced Metabolic Disorder and Immune Response

Directory of Open Access Journals (Sweden)

Hong Zhong

2018-01-01

Full Text Available In all living organisms, metabolic homeostasis and the immune system are the most fundamental requirements for survival. Recently, obesity has become a global public health issue, which is the cardinal risk factor for metabolic disorder. Many diseases emanating from obesity-induced metabolic dysfunction are responsible for the activated immune system, including innate and adaptive responses. Of note, inflammation is the manifest accountant signal. Deeply studied microRNAs (miRNAs have participated in many pathways involved in metabolism and immune responses to protect cells from multiple harmful stimulants, and they play an important role in determining the progress through targeting different inflammatory pathways. Thus, immune response and metabolic regulation are highly integrated with miRNAs. Collectively, miRNAs are the new targets for therapy in immune dysfunction.

The alpha hemolysin of Escherichia Coli power the metabolism oxidative of neutrophils human beings in response to the peptide chemotactic FMLP: comparison with the ionophore of calcium A23187

International Nuclear Information System (INIS)

Garcia, J.

2000-01-01

The calcium ionophore ionomycin primes polymorphonuclear leukocytes (PMN) for increased superoxide production upon stimulation with the chemotactic peptide FMLP (Helman Finkel, T. et al J Biol Chem 1987; 262: 12589-12596) In this investigation we assessed the effect of PMN priming with either alpha hemolysin (AH) or the calcium ionophore A23187, both of which increase intracellular calcium, on the oxidative metabolism of PMN (as measured by chemiluminescence) in response to secondary stimulation with FMLP. Both A23187 and AH priming increased, the luminol-enhanced chemiluminescence in response to secondary stimulation with FMLP, indicating overstimulation of PMLP oxidative metabolism. Additional experiments using lucigenin as chemiluminescence enhancer showed that A23187, but not AH priming of PMN, increased superoxide release in a manner similar to that reported for ionomycin. These results are discussed in reference to infectious processes involving hemolytic E. coli (Author) [es

Influence of Carbohydrates on Secondary Metabolism in Fusarium avenaceum

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Jens Laurids Sørensen

2013-09-01

Full Text Available Fusarium avenaceum is a widespread pathogen of important crops in the temperate climate zones that can produce many bioactive secondary metabolites, including moniliformin, fusarin C, antibiotic Y, 2-amino-14,16-dimethyloctadecan-3-ol (2-AOD-3-ol, chlamydosporol, aurofusarin and enniatins. Here, we examine the production of these secondary metabolites in response to cultivation on different carbon sources in order to gain insight into the regulation and production of secondary metabolites in F. avenaceum. Seven monosaccharides (arabinose, xylose, fructose, sorbose, galactose, mannose, glucose, five disaccharides (cellobiose, lactose, maltose, sucrose and trehalose and three polysaccharides (dextrin, inulin and xylan were used as substrates. Three F. avenaceum strains were used in the experiments. These were all able to grow and produce aurofusarin on the tested carbon sources. Moniliformin and enniatins were produced on all carbon types, except on lactose, which suggest a common conserved regulation mechanism. Differences in the strains was observed for production of fusarin C, 2-AOD-3-ol, chlamydosporol and antibiotic Y, which suggests that carbon source plays a role in the regulation of their biosynthesis.

Influence of carbohydrates on secondary metabolism in Fusarium avenaceum.

Science.gov (United States)

Sørensen, Jens Laurids; Giese, Henriette

2013-09-24

Fusarium avenaceum is a widespread pathogen of important crops in the temperate climate zones that can produce many bioactive secondary metabolites, including moniliformin, fusarin C, antibiotic Y, 2-amino-14,16-dimethyloctadecan-3-ol (2-AOD-3-ol), chlamydosporol, aurofusarin and enniatins. Here, we examine the production of these secondary metabolites in response to cultivation on different carbon sources in order to gain insight into the regulation and production of secondary metabolites in F. avenaceum. Seven monosaccharides (arabinose, xylose, fructose, sorbose, galactose, mannose, glucose), five disaccharides (cellobiose, lactose, maltose, sucrose and trehalose) and three polysaccharides (dextrin, inulin and xylan) were used as substrates. Three F. avenaceum strains were used in the experiments. These were all able to grow and produce aurofusarin on the tested carbon sources. Moniliformin and enniatins were produced on all carbon types, except on lactose, which suggest a common conserved regulation mechanism. Differences in the strains was observed for production of fusarin C, 2-AOD-3-ol, chlamydosporol and antibiotic Y, which suggests that carbon source plays a role in the regulation of their biosynthesis.

Analisi dei metaboliti secondari da fonti naturali: isolamento, caratterizzazione strutturale e attività biologiche

OpenAIRE

Nini, Antonella

2015-01-01

L’ attività di ricerca del Dottorato di Ricerca in Scienze e Tecnologie Biologiche, XXVII ciclo, si inserisce nell’ambito della chimica delle sostanze naturali ed è rivolta all’isolamento e alla caratterizzazione strutturale dei metaboliti secondari provenienti da matrici vegetali . Le specie oggetto di studio sono piante, utilizzate nella medicina popolare per le loro caratteristiche fitoterapiche, oppure sono impiegate anche nell’alimentazione. L’indagine chimica si è concentrata sulle ...

Guidelines for secondary analysis in search of response shift

NARCIS (Netherlands)

Schwartz, Carolyn E.; Ahmed, Sara; Sawatzky, Richard; Sajobi, Tolulope; Mayo, Nancy; Finkelstein, Joel; Lix, Lisa; Verdam, Mathilde G. E.; Oort, Frans J.; Sprangers, Mirjam A. G.

2013-01-01

Response shift methods have developed substantially in the past decade, with a notable emphasis on model-based methods for response shift detection that are appropriate for the analysis of existing data sets. These secondary data analyses have yielded useful insights and motivated the continued

Guidelines for secondary analysis in search of response shift

NARCIS (Netherlands)

Schwartz, C.E.; Ahmed, S.; Sawatzky, R.; Sajobi, T.; Mayo, N.; Finkelstein, J.; Verdam, M.G.E.; Oort, F.J.; Sprangers, M.A.G.

2013-01-01

Objective: Response shift methods have developed substantially in the past decade, with a notable emphasis on model-based methods for response shift detection that are appropriate for the analysis of existing data sets. These secondary data analyses have yielded useful insights and motivated the

Responsibility for Racism in the Everyday Talk of Secondary Students

Science.gov (United States)

Halse, Christine

2017-01-01

This article examines the attributions of responsibility for racism in the everyday talk of secondary school students. It draws on focus groups with a cross section of students from different ethnic backgrounds in three, very different, secondary schools. In these focus groups, students deploy six different, sometimes contradictory, racialised…

Induction of secondary metabolism of Aspergillus terreus ATCC 20542 in the batch bioreactor cultures.

Science.gov (United States)

Boruta, Tomasz; Bizukojc, Marcin

2016-04-01

Cultivation of Aspergillus terreus ATCC 20542 in a stirred tank bioreactor was performed to induce the biosynthesis of secondary metabolites and provide the bioprocess-related insights into the metabolic capabilities of the investigated strain. The activation of biosynthetic routes was attempted by the diversification of process conditions and growth media. Several strategies were tested, including the addition of rapeseed oil or inulin, changing the concentration of nitrogen source, reduction of chlorine supply, cultivation under saline conditions, and using various aeration schemes. Fifteen secondary metabolites were identified in the course of the study by using ultra-high performance liquid chromatography coupled with mass spectrometry, namely mevinolinic acid, 4a,5-dihydromevinolinic acid, 3α-hydroxy-3,5-dihydromonacolin L acid, terrein, aspulvinone E, dihydroisoflavipucine, (+)-geodin, (+)-bisdechlorogeodin, (+)-erdin, asterric acid, butyrolactone I, desmethylsulochrin, questin, sulochrin, and demethylasterric acid. The study also presents the collection of mass spectra that can serve as a resource for future experiments. The growth in a salt-rich environment turned out to be strongly inhibitory for secondary metabolism and the formation of dense and compact pellets was observed. Generally, the addition of inulin, reducing the oxygen supply, and increasing the content of nitrogen source did not enhance the production of examined molecules. The most successful strategy involved the addition of rapeseed oil to the chlorine-deficient medium. Under these conditions, the highest levels of butyrolactone I, asterric acid, and mevinolinic acid were achieved and the presence of desmethylsulochrin and (+)-bisdechlorogeodin was detected in the broth. The constant and relatively high aeration rate in the idiophase was shown to be beneficial for terrein and (+)-geodin biosynthesis.

Transcriptome response to nitrogen starvation in rice

Indian Academy of Sciences (India)

N starvation induced or suppressed transcription of 3518 genes, representing 10.88% of the genome. These changes, mostly transient, affected various cellular metabolic pathways, including stress response, primary and secondary metabolism, molecular transport, regulatory process and organismal development. 462 or ...

Deciphering hepatocellular responses to metabolic and oncogenic stress

Directory of Open Access Journals (Sweden)

Kathrina L. Marcelo

2015-08-01

Full Text Available Each cell type responds uniquely to stress and fractionally contributes to global and tissue-specific stress responses. Hepatocytes, liver macrophages (MΦ, and sinusoidal endothelial cells (SEC play functionally important and interdependent roles in adaptive processes such as obesity and tumor growth. Although these cell types demonstrate significant phenotypic and functional heterogeneity, their distinctions enabling disease-specific responses remain understudied. We developed a strategy for the simultaneous isolation and quantification of these liver cell types based on antigenic cell surface marker expression. To demonstrate the utility and applicability of this technique, we quantified liver cell-specific responses to high-fat diet (HFD or diethylnitrosamine (DEN, a liver-specific carcinogen, and found that while there was only a marginal increase in hepatocyte number, MΦ and SEC populations were quantitatively increased. Global gene expression profiling of hepatocytes, MΦ and SEC identified characteristic gene signatures that define each cell type in their distinct physiological or pathological states. Integration of hepatic gene signatures with available human obesity and liver cancer microarray data provides further insight into the cell-specific responses to metabolic or oncogenic stress. Our data reveal unique gene expression patterns that serve as molecular “fingerprints” for the cell-centric responses to pathologic stimuli in the distinct microenvironment of the liver. The technical advance highlighted in this study provides an essential resource for assessing hepatic cell-specific contributions to metabolic and oncogenic stress, information that could unveil previously unappreciated molecular mechanisms for the cellular crosstalk that underlies the continuum from metabolic disruption to obesity and ultimately hepatic cancer.

Metabolic responses in Candida tropicalis to complex inhibitors during xylitol bioconversion.

Science.gov (United States)

Wang, Shizeng; Li, Hao; Fan, Xiaoguang; Zhang, Jingkun; Tang, Pingwah; Yuan, Qipeng

2015-09-01

During xylitol fermentation, Candida tropicalis is often inhibited by inhibitors in hemicellulose hydrolysate. The mechanisms involved in the metabolic responses to inhibitor stress and the resistances to inhibitors are still not clear. To understand the inhibition mechanisms and the metabolic responses to inhibitors, a GC/MS-based metabolomics approach was performed on C. tropicalis treated with and without complex inhibitors (CI, including furfural, phenol and acetic acid). Partial least squares discriminant analysis was used to determine the metabolic variability between CI-treated groups and control groups, and 25 metabolites were identified as possible entities responsible for the discrimination caused by inhibitors. We found that xylose uptake rate and xylitol oxidation rate were promoted by CI treatment. Metabolomics analysis showed that the flux from xylulose to pentose phosphate pathway increased, and tricarboxylic acid cycle was disturbed by CI. Moreover, the changes in levels of 1,3-propanediol, trehalose, saturated fatty acids and amino acids showed different mechanisms involved in metabolic responses to inhibitor stress. The increase of 1,3-propanediol was considered to be correlated with regulating redox balance and osmoregulation. The increase of trehalose might play a role in protein stabilization and cellular membranes protection. Saturated fatty acids could cause the decrease of membrane fluidity and make the plasma membrane rigid to maintain the integrity of plasma membrane. The deeper understanding of the inhibition mechanisms and the metabolic responses to inhibitors will provide us with more information on the metabolism regulation during xylitol bioconversion and the construction of industrial strains with inhibitor tolerance for better utilization of bioresource. Copyright © 2015 Elsevier Inc. All rights reserved.

Metabolic changes in serum metabolome in response to a meal.

Science.gov (United States)

Shrestha, Aahana; Müllner, Elisabeth; Poutanen, Kaisa; Mykkänen, Hannu; Moazzami, Ali A

2017-03-01

The change in serum metabolic response from fasting state to postprandial state provides novel insights into the impact of a single meal on human metabolism. Therefore, this study explored changes in serum metabolite profile after a single meal. Nineteen healthy postmenopausal women with normal glucose tolerance participated in the study. They received a meal consisting of refined wheat bread (50 g carbohydrates, 9 g protein, 4.2 g fat and 2.7 g dietary fibre), 40 g cucumber and 300 mL noncaloric orange drink. Blood samples were collected at fasting and five postprandial time points. Metabolic profile was measured by nuclear magnetic resonance and targeted liquid chromatography-mass spectrometry. Changes over time were assessed with multivariate models and ANOVA, with baseline as control. The metabolomic analyses demonstrated alterations in phospholipids, amino acids and their breakdown products, glycolytic products, acylcarnitines and ketone bodies after a single meal. More specifically, phosphatidylcholines, lysophosphatidylcholines and citrate displayed an overall declining pattern, while leucine, isoleucine, methionine and succinate increased initially but declined thereafter. A sharp decline in acylcarnitines and ketone bodies and increase in glycolytic products postprandially suggest a switch in the body's energy source from β-oxidation to glycolysis. Moreover, individuals with relatively high postprandial insulin responses generated a higher postprandial leucine responses compared to participants with lower insulin responses. The study demonstrated complex changes from catabolic to anabolic metabolism after a meal and indicated that the extent of postprandial responses is different between individuals with high and low insulin response.

Metabolic Communication between Astrocytes and Neurons via Bicarbonate-Responsive Soluble Adenylyl Cyclase

OpenAIRE

Choi, Hyun B.; Gordon, Grant R.J.; Zhou, Ning; Tai, Chao; Rungta, Ravi L.; Martinez, Jennifer; Milner, Teresa A.; Ryu, Jae K.; McLarnon, James G.; Tresguerres, Martin; Levin, Lonny R.; Buck, Jochen; MacVicar, Brian A.

2012-01-01

Astrocytes are proposed to participate in brain energy metabolism by supplying substrates to neurons from their glycogen stores and from glycolysis. However, the molecules involved in metabolic sensing and the molecular pathways responsible for metabolic coupling between different cell types in the brain are not fully understood. Here we show that a recently cloned bicarbonate (HCO3−) sensor, soluble adenylyl cyclase (sAC), is highly expressed in astrocytes and becomes activated in response t...

Global patterns in lake ecosystem responses to warming based on the temperature dependence of metabolism.

Science.gov (United States)

Kraemer, Benjamin M; Chandra, Sudeep; Dell, Anthony I; Dix, Margaret; Kuusisto, Esko; Livingstone, David M; Schladow, S Geoffrey; Silow, Eugene; Sitoki, Lewis M; Tamatamah, Rashid; McIntyre, Peter B

2017-05-01

Climate warming is expected to have large effects on ecosystems in part due to the temperature dependence of metabolism. The responses of metabolic rates to climate warming may be greatest in the tropics and at low elevations because mean temperatures are warmer there and metabolic rates respond exponentially to temperature (with exponents >1). However, if warming rates are sufficiently fast in higher latitude/elevation lakes, metabolic rate responses to warming may still be greater there even though metabolic rates respond exponentially to temperature. Thus, a wide range of global patterns in the magnitude of metabolic rate responses to warming could emerge depending on global patterns of temperature and warming rates. Here we use the Boltzmann-Arrhenius equation, published estimates of activation energy, and time series of temperature from 271 lakes to estimate long-term (1970-2010) changes in 64 metabolic processes in lakes. The estimated responses of metabolic processes to warming were usually greatest in tropical/low-elevation lakes even though surface temperatures in higher latitude/elevation lakes are warming faster. However, when the thermal sensitivity of a metabolic process is especially weak, higher latitude/elevation lakes had larger responses to warming in parallel with warming rates. Our results show that the sensitivity of a given response to temperature (as described by its activation energy) provides a simple heuristic for predicting whether tropical/low-elevation lakes will have larger or smaller metabolic responses to warming than higher latitude/elevation lakes. Overall, we conclude that the direct metabolic consequences of lake warming are likely to be felt most strongly at low latitudes and low elevations where metabolism-linked ecosystem services may be most affected. © 2016 John Wiley & Sons Ltd.

Isolamento, caratterizzazione strutturale e valutazione dell'attività biologica di metaboliti secondari di origine vegetale

OpenAIRE

Incollingo, Filomena

2011-01-01

La tematica di ricerca di questo dottorato si inserisce nell’ambito della chimica delle sostanze naturali. In particolare l’attenzione si è soffermata alle piante officinali e alle piante impiegate nella medicina popolare e alla purificazione e all’isolamento dei metaboliti secondari presenti in maggiore quantità attraverso tecniche cromatografiche quali: cromatografia su colonna, cromatografia su strato sottile, HPLC (high pressure liquid chromatography), DCCC (cromatografia liquida in cont...

Integration of metabolic and gene regulatory networks modulates the C. elegans dietary response.

Science.gov (United States)

Watson, Emma; MacNeil, Lesley T; Arda, H Efsun; Zhu, Lihua Julie; Walhout, Albertha J M

2013-03-28

Expression profiles are tailored according to dietary input. However, the networks that control dietary responses remain largely uncharacterized. Here, we combine forward and reverse genetic screens to delineate a network of 184 genes that affect the C. elegans dietary response to Comamonas DA1877 bacteria. We find that perturbation of a mitochondrial network composed of enzymes involved in amino acid metabolism and the TCA cycle affects the dietary response. In humans, mutations in the corresponding genes cause inborn diseases of amino acid metabolism, most of which are treated by dietary intervention. We identify several transcription factors (TFs) that mediate the changes in gene expression upon metabolic network perturbations. Altogether, our findings unveil a transcriptional response system that is poised to sense dietary cues and metabolic imbalances, illustrating extensive communication between metabolic networks in the mitochondria and gene regulatory networks in the nucleus. Copyright © 2013 Elsevier Inc. All rights reserved.

Irisin in response to exercise in humans with and without metabolic syndrome.

Science.gov (United States)

Huh, Joo Young; Siopi, Aikaterina; Mougios, Vassilis; Park, Kyung Hee; Mantzoros, Christos S

2015-03-01

Irisin is a recently identified exercise-induced myokine. However, the circulating levels of irisin in response to different types of exercise in subjects with metabolic syndrome are unknown. This study aimed to study the levels of irisin in healthy males and subjects with metabolic syndrome at baseline and in response to exercise. Each individual completed high-intensity interval exercise (HIIE), continuous moderate-intensity exercise (CME), and resistance exercise (RE) sessions in a random, crossover design. Percentage change in circulating irisin levels was examined. Two different irisin assays were used to compare the results of the RE study. Circulating irisin increased immediately after HIIE, CME, and RE and declined 1 hour later. The increase was greater in response to resistance compared with either high-intensity intermittent exercise or CME. Change in irisin in response to exercise did not differ between individuals with and without metabolic syndrome. Exercise is able to increase circulating irisin levels in individuals with the metabolic syndrome as well as healthy individuals. Whether this increase may contribute to the beneficial effects of exercise on patients with the metabolic syndrome remains to be studied further.

Sodium signaling and astrocyte energy metabolism

KAUST Repository

Chatton, Jean-Yves; Magistretti, Pierre J.; Barros, L. Felipe

2016-01-01

The Na+ gradient across the plasma membrane is constantly exploited by astrocytes as a secondary energy source to regulate the intracellular and extracellular milieu, and discard waste products. One of the most prominent roles of astrocytes in the brain is the Na+-dependent clearance of glutamate released by neurons during synaptic transmission. The intracellular Na+ load collectively generated by these processes converges at the Na,K-ATPase pump, responsible for Na+ extrusion from the cell, which is achieved at the expense of cellular ATP. These processes represent pivotal mechanisms enabling astrocytes to increase the local availability of metabolic substrates in response to neuronal activity. This review presents basic principles linking the intracellular handling of Na+ following activity-related transmembrane fluxes in astrocytes and the energy metabolic pathways involved. We propose a role of Na+ as an energy currency and as a mediator of metabolic signals in the context of neuron-glia interactions. We further discuss the possible impact of the astrocytic syncytium for the distribution and coordination of the metabolic response, and the compartmentation of these processes in cellular microdomains and subcellular organelles. Finally, we illustrate future avenues of investigation into signaling mechanisms aimed at bridging the gap between Na+ and the metabolic machinery. © 2016 Wiley Periodicals, Inc.

Sodium signaling and astrocyte energy metabolism

KAUST Repository

Chatton, Jean-Yves

2016-03-31

The Na+ gradient across the plasma membrane is constantly exploited by astrocytes as a secondary energy source to regulate the intracellular and extracellular milieu, and discard waste products. One of the most prominent roles of astrocytes in the brain is the Na+-dependent clearance of glutamate released by neurons during synaptic transmission. The intracellular Na+ load collectively generated by these processes converges at the Na,K-ATPase pump, responsible for Na+ extrusion from the cell, which is achieved at the expense of cellular ATP. These processes represent pivotal mechanisms enabling astrocytes to increase the local availability of metabolic substrates in response to neuronal activity. This review presents basic principles linking the intracellular handling of Na+ following activity-related transmembrane fluxes in astrocytes and the energy metabolic pathways involved. We propose a role of Na+ as an energy currency and as a mediator of metabolic signals in the context of neuron-glia interactions. We further discuss the possible impact of the astrocytic syncytium for the distribution and coordination of the metabolic response, and the compartmentation of these processes in cellular microdomains and subcellular organelles. Finally, we illustrate future avenues of investigation into signaling mechanisms aimed at bridging the gap between Na+ and the metabolic machinery. © 2016 Wiley Periodicals, Inc.

Metabolic and Physiological Responses of Shiraz and Cabernet Sauvignon (Vitis vinifera L. to Near Optimal Temperatures of 25 and 35 °C

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Uri Hochberg

2015-10-01

Full Text Available Shiraz and Cabernet Sauvignon (Cs grapevines were grown at near optimal temperatures (25 or 35 °C. Gas exchange, fluorescence, metabolic profiling and correlation based network analysis were used to characterize leaf physiology. When grown at 25 °C, the growth rate and photosynthesis of both cultivars were similar. At 35 °C Shiraz showed increased respiration, non-photochemical quenching and reductions of photosynthesis and growth. In contrast, Cs maintained relatively stable photosynthetic activity and growth regardless of the condition. In both cultivars, growth at 35 °C resulted in accumulations of secondary sugars (raffinose, fucose and ribulose and reduction of primary sugars concentration (glucose, fructose and sucrose, more noticeably in Shiraz than Cs. In spite of similar patterns of metabolic changes in response to growth at 35 °C, significant differences in important leaf antioxidants and antioxidant precursors (DHA/ascorbate, quinates, cathechins characterized the cultivar response. Correlation analysis reinforced Shiraz sensitivity to the 35 °C, showing higher number of newly formed edges at 35 °C and higher modularity in Shiraz as compared to Cs. The results suggest that the optimal growth temperatures of grapevines are cultivar dependent, and allow a first insight into the variability of the metabolic responses of grapevines under varied temperatures.

Metabolic and Physiological Responses of Shiraz and Cabernet Sauvignon (Vitis vinifera L.) to Near Optimal Temperatures of 25 and 35 °C.

Science.gov (United States)

Hochberg, Uri; Batushansky, Albert; Degu, Asfaw; Rachmilevitch, Shimon; Fait, Aaron

2015-10-14

Shiraz and Cabernet Sauvignon (Cs) grapevines were grown at near optimal temperatures (25 or 35 °C). Gas exchange, fluorescence, metabolic profiling and correlation based network analysis were used to characterize leaf physiology. When grown at 25 °C, the growth rate and photosynthesis of both cultivars were similar. At 35 °C Shiraz showed increased respiration, non-photochemical quenching and reductions of photosynthesis and growth. In contrast, Cs maintained relatively stable photosynthetic activity and growth regardless of the condition. In both cultivars, growth at 35 °C resulted in accumulations of secondary sugars (raffinose, fucose and ribulose) and reduction of primary sugars concentration (glucose, fructose and sucrose), more noticeably in Shiraz than Cs. In spite of similar patterns of metabolic changes in response to growth at 35 °C, significant differences in important leaf antioxidants and antioxidant precursors (DHA/ascorbate, quinates, cathechins) characterized the cultivar response. Correlation analysis reinforced Shiraz sensitivity to the 35 °C, showing higher number of newly formed edges at 35 °C and higher modularity in Shiraz as compared to Cs. The results suggest that the optimal growth temperatures of grapevines are cultivar dependent, and allow a first insight into the variability of the metabolic responses of grapevines under varied temperatures.

Diverse and Abundant Secondary Metabolism Biosynthetic Gene Clusters in the Genomes of Marine Sponge Derived Streptomyces spp. Isolates

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Stephen A. Jackson

2018-02-01

Full Text Available The genus Streptomyces produces secondary metabolic compounds that are rich in biological activity. Many of these compounds are genetically encoded by large secondary metabolism biosynthetic gene clusters (smBGCs such as polyketide synthases (PKS and non-ribosomal peptide synthetases (NRPS which are modular and can be highly repetitive. Due to the repeats, these gene clusters can be difficult to resolve using short read next generation datasets and are often quite poorly predicted using standard approaches. We have sequenced the genomes of 13 Streptomyces spp. strains isolated from shallow water and deep-sea sponges that display antimicrobial activities against a number of clinically relevant bacterial and yeast species. Draft genomes have been assembled and smBGCs have been identified using the antiSMASH (antibiotics and Secondary Metabolite Analysis Shell web platform. We have compared the smBGCs amongst strains in the search for novel sequences conferring the potential to produce novel bioactive secondary metabolites. The strains in this study recruit to four distinct clades within the genus Streptomyces. The marine strains host abundant smBGCs which encode polyketides, NRPS, siderophores, bacteriocins and lantipeptides. The deep-sea strains appear to be enriched with gene clusters encoding NRPS. Marine adaptations are evident in the sponge-derived strains which are enriched for genes involved in the biosynthesis and transport of compatible solutes and for heat-shock proteins. Streptomyces spp. from marine environments are a promising source of novel bioactive secondary metabolites as the abundance and diversity of smBGCs show high degrees of novelty. Sponge derived Streptomyces spp. isolates appear to display genomic adaptations to marine living when compared to terrestrial strains.

Aluminium stress disrupts metabolic performance of Plantago almogravensis plantlets transiently.

Science.gov (United States)

Grevenstuk, Tomás; Moing, Annick; Maucourt, Mickaël; Deborde, Catherine; Romano, Anabela

2015-12-01

Little is known about how tolerant plants cope with internalized aluminium (Al). Tolerant plants are known to deploy efficient detoxification mechanisms, however it is not known to what extent the primary and secondary metabolism is affected by Al. The aim of this work was to study the metabolic repercussions of Al stress in the tolerant plant Plantago almogravensis. P. almogravensis is well adapted to acid soils where high concentrations of free Al are found and has been classified as a hyperaccumulator. In vitro reared plantlets were used for this purpose in order to control Al exposure rigorously. The metabolome of P. almogravensis plantlets as well as its metabolic response to the supply of sucrose was characterized. The supply of sucrose leads to an accumulation of amino acids and secondary metabolites and consumption of carbohydrates that result from increased metabolic activity. In Al-treated plantlets the synthesis of amino acids and secondary metabolites is transiently impaired, suggesting that P. almogravensis is able to recover from the Al treatment within the duration of the trials. In the presence of Al the consumption of carbohydrate resources is accelerated. The content of some metabolic stress markers also demonstrates that P. almogravensis is highly adapted to Al stress.

Metabolic Profiling of Primary and Secondary Biosynthetic Pathways in Angiosperms: Comparative Metabonomics and Applications of Hyphenated LC-NMR and LC-MS

OpenAIRE

Kaiser, Kayla Anne

2012-01-01

The goal of this dissertation was to advance plant metabolomics through optimization of biological experimental design, sampling and sample preparation, data acquisition and pre-processing, and multivariable data analysis. The analytical platform most employed for comparative metabonomics was nuclear magnetic resonance (NMR). Liquid-chromatography (LC) coupled to NMR and mass spectrometry (MS) extended metabolic profile coverage from primary into secondary metabolic pathways. Comparative p...

Secondary immune response of rainbow trout following repeated immersion vaccination

DEFF Research Database (Denmark)

Jaafar, R. M.; Al-Jubury, A.; Chettri, J. K.

2017-01-01

Teleosts are able to raise a protective immune response, comprising both innate and adaptive elements, against various pathogens. This is the basis for a widespread use of vaccines, administered as injection or immersion, in the aquaculture industry. It has been described that repeated injection...... vaccination of fish raises a secondary immune response, consisting of rapid, accelerated and increased antibody reaction. This study reports how rainbow trout responds to repeated immersion vaccination against yersiniosis (ERM) caused by the bacterial pathogen Yersinia ruckeri. It was found that rainbow trout...... does not raise a classical secondary response following repeated immersion vaccination. Serum antibody titres were merely slightly increased even after three immunizations, using 30-s immersion into a bacterin consisting of formalin-inactivated Y. ruckeri (serotype O1, biotypes 1 and 2), performed over...

Secondary immune response of rainbow trout following repeated immersion vaccination

DEFF Research Database (Denmark)

Jaafar, R. M.; Al-Jubury, Azmi; Chettri, Jiwan Kumar

2018-01-01

Teleosts are able to raise a protective immune response, comprising both innate and adaptive elements, against various pathogens. This is the basis for a widespread use of vaccines, administered as injection or immersion, in the aquaculture industry. It has been described that repeated injection...... vaccination of fish raises a secondary immune response, consisting of rapid, accelerated and increased antibody reaction. This study reports how rainbow trout responds to repeated immersion vaccination against yersiniosis (ERM) caused by the bacterial pathogen Yersinia ruckeri. It was found that rainbow trout...... does not raise a classical secondary response following repeated immersion vaccination. Serum antibody titres were merely slightly increased even after three immunizations, using 30-s immersion into a bacterin consisting of formalin-inactivated Y. ruckeri (serotype O1, biotypes 1 and 2), performed over...

Fagus sylvatica L. provenances maintain different leaf metabolic profiles and functional response

Science.gov (United States)

Aranda, Ismael; Sánchez-Gómez, David; de Miguel, Marina; Mancha, Jose Antonio; Guevara, María Angeles; Cadahía, Estrella; Fernández de Simón, María Brígida

2017-07-01

Most temperate forest tree species will suffer important environmental changes as result of the climate change. Adaptiveness to local conditions could change at different sites in the future. In this context, the study of intra-specific variability is important to clarify the singularity of different local populations. Phenotypic differentiation between three beech provenances covering a wide latitudinal range (Spain/ES, Germany/DE and Sweden/SE), was studied in a greenhouse experiment. Non-target leaf metabolite profiles and ecophysiological response was analyzed in well-watered and water stressed seedlings. There was a provenance-specific pattern in the relative concentrations of some leaf metabolites regardless watering treatment. The DE and SE from the center and north of the distribution area of the species showed a clear differentiation from the ES provenance in the relative concentration of some metabolites. Thus the ES provenance from the south maintained larger relative concentration of some organic and amino acids (e.g. fumaric and succinic acids or valine and isoleucine), and in some secondary metabolites (e.g. kaempferol, caffeic and ferulic acids). The ecophysiological response to mild water stress was similar among the three provenances as a consequence of the moderate water stress applied to seedlings, although leaf N isotope composition (δ15N) and leaf C:N ratio were higher and lower respectively in DE than in the other two provenances. This would suggest potential differences in the capacity to uptake and post-process nitrogen according to provenance. An important focus of the study was to address for the first time inter-provenance leaf metabolic diversity in beech from a non-targeted metabolic profiling approach that allowed differentiation of the three studied provenances.

Erythropoietin Action in Stress Response, Tissue Maintenance and Metabolism

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Yuanyuan Zhang

2014-06-01

Full Text Available Erythropoietin (EPO regulation of red blood cell production and its induction at reduced oxygen tension provides for the important erythropoietic response to ischemic stress. The cloning and production of recombinant human EPO has led to its clinical use in patients with anemia for two and half decades and has facilitated studies of EPO action. Reports of animal and cell models of ischemic stress in vitro and injury suggest potential EPO benefit beyond red blood cell production including vascular endothelial response to increase nitric oxide production, which facilitates oxygen delivery to brain, heart and other non-hematopoietic tissues. This review discusses these and other reports of EPO action beyond red blood cell production, including EPO response affecting metabolism and obesity in animal models. Observations of EPO activity in cell and animal model systems, including mice with tissue specific deletion of EPO receptor (EpoR, suggest the potential for EPO response in metabolism and disease.

Regulation of longevity by FGF21: Interaction between energy metabolism and stress responses.

Science.gov (United States)

Salminen, Antero; Kaarniranta, Kai; Kauppinen, Anu

2017-08-01

Fibroblast growth factor 21 (FGF21) is a hormone-like member of FGF family which controls metabolic multiorgan crosstalk enhancing energy expenditure through glucose and lipid metabolism. In addition, FGF21 acts as a stress hormone induced by endoplasmic reticulum stress and dysfunctions of mitochondria and autophagy in several tissues. FGF21 also controls stress responses and metabolism by modulating the functions of somatotropic axis and hypothalamic-pituitary-adrenal (HPA) pathway. FGF21 is a potent longevity factor coordinating interactions between energy metabolism and stress responses. Recent studies have revealed that FGF21 treatment can alleviate many age-related metabolic disorders, e.g. atherosclerosis, obesity, type 2 diabetes, and some cardiovascular diseases. In addition, transgenic mice overexpressing FGF21 have an extended lifespan. However, chronic metabolic and stress-related disorders involving inflammatory responses can provoke FGF21 resistance and thus disturb healthy aging process. First, we will describe the role of FGF21 in interorgan energy metabolism and explain how its functions as a stress hormone can improve healthspan. Next, we will examine both the induction of FGF21 expression via the integrated stress response and the molecular mechanism through which FGF21 enhances healthy aging. Finally, we postulate that FGF21 resistance, similarly to insulin resistance, jeopardizes human healthspan and accelerates the aging process. Copyright © 2017 Elsevier B.V. All rights reserved.

Chronic myeloid leukemia patients sensitive and resistant to imatinib treatment show different metabolic responses.

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Jiye A

Full Text Available The BCR-ABL tyrosine kinase inhibitor imatinib is highly effective for chronic myeloid leukemia (CML. However, some patients gradually develop resistance to imatinib, resulting in therapeutic failure. Metabonomic and genomic profiling of patients' responses to drug interventions can provide novel information about the in vivo metabolism of low-molecular-weight compounds and extend our insight into the mechanism of drug resistance. Based on a multi-platform of high-throughput metabonomics, SNP array analysis, karyotype and mutation, the metabolic phenotypes and genomic polymorphisms of CML patients and their diverse responses to imatinib were characterized. The untreated CML patients (UCML showed different metabolic patterns from those of healthy controls, and the discriminatory metabolites suggested the perturbed metabolism of the urea cycle, tricarboxylic acid cycle, lipid metabolism, and amino acid turnover in UCML. After imatinib treatment, patients sensitive to imatinib (SCML and patients resistant to imatinib (RCML had similar metabolic phenotypes to those of healthy controls and UCML, respectively. SCML showed a significant metabolic response to imatinib, with marked restoration of the perturbed metabolism. Most of the metabolites characterizing CML were adjusted to normal levels, including the intermediates of the urea cycle and tricarboxylic acid cycle (TCA. In contrast, neither cytogenetic nor metabonomic analysis indicated any positive response to imatinib in RCML. We report for the first time the associated genetic and metabonomic responses of CML patients to imatinib and show that the perturbed in vivo metabolism of UCML is independent of imatinib treatment in resistant patients. Thus, metabonomics can potentially characterize patients' sensitivity or resistance to drug intervention.

Failed Switching off in the MIBI-Parathyroid Scintigraphy in a Dialyzed Patient with Secondary Hyperparathyroidism Responsive to Cinacalcet Therapy

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Piergiorgio Bolasco

2010-01-01

Full Text Available The aims of your case report is to show the predictivity of Tc99m-sestamibi (MIBI scintigraphy and doppler ultrasound imaging on secondary hyperparathyroidism (SHPT in a patient responsive to calcimimetic treatment. Moreover, it has been reported that calcimimetic has great potential in reducing the volume of the parathyroid gland. On the other hand, the MIBI scintigraphy is considered a crucial diagnostic procedure to monitor the response to therapy in terms of turnover and cellular metabolism; whereas, ultrasound to monitor the volume variation in response to treatment. It is described the case of a 73-year-old man on hemodialysis from 1995 for ESRD. Within 2 years the patient gradually developed SHPT with progressively increased iPTH up to 1,000 ρg/ml. The ultrasound, highlighted the presence of two parathyroid hyperplasia, confirmed by scintigraphy, showing focal increase uptake of sestamibi in the same anatomical areas. As a result of the patient's refusal to perform a parathyroidectomy, cinacalcet, was administered (65 mg overage daily dose. After a year of treatment, there was a striking decrease of iPTH (from 1300 to 57 ρg/ml, −95%; but, on the contrary to expectations, this positive metabolic outcome, was not followed by parathyroid changes in ultrasound and scintigraphic findings.

[Response of arbuscular mycorrhizal fungal lipid metabolism to symbiotic signals in mycorrhiza].

Science.gov (United States)

Tian, Lei; Li, Yuanjing; Tian, Chunjie

2016-01-04

Arbuscular mycorrhizal (AM) fungi play an important role in energy flow and nutrient cycling, besides their wide distribution in the cosystem. With a long co-evolution, AM fungi and host plant have formed a symbiotic relationship, and fungal lipid metabolism may be the key point to find the symbiotic mechanism in arbusculart mycorrhiza. Here, we reviewed the most recent progress on the interaction between AM fungal lipid metabolism and symbiotic signaling networks, especially the response of AM fungal lipid metabolism to symbiotic signals. Furthermore, we discussed the response of AM fungal lipid storage and release to symbiotic or non-symbiotic status, and the correlation between fungal lipid metabolism and nutrient transfer in mycorrhiza. In addition, we explored the feedback of the lipolysis process to molecular signals during the establishment of symbiosis, and the corresponding material conversion and energy metabolism besides the crosstalk of fungal lipid metabolism and signaling networks. This review will help understand symbiotic mechanism of arbuscular mycorrhiza fungi and further application in ecosystem.

Tool for generation of seismic floor response spectra for secondary system design

International Nuclear Information System (INIS)

Cardoso, Tarcisio F.; Almeida, Andreia A. Diniz de

2009-01-01

The spectral analysis is still a valuable method to the seismic structure design, especially when one focalizes the topics of secondary systems in large industrial installations, as nuclear power plants. Two aspects of this situation add their arguments to recommend the use of this kind of analysis: the random character of the excitation and the multiplicity and the variability of the secondary systems. The first aspect can be managed if one assumes the site seismicity represented by a power spectrum density function of the ground acceleration, and then, by the systematic resolution of a first passage problem, to develop a uniformly probable response spectrum. The second one suggests also a probabilistic approach to the response spectrum in order to be representative all over the extensive group of systems with different characteristics, which can be enrolled in a plant. The present paper proposes a computational tool to achieve in-structure floor response spectra for secondary system design, which includes a probabilistic approach and considers coupling effects between primary and inelastic secondary systems. The analysis is performed in the frequency domain, with SASSI2000 system. A set of auxiliary programs are developed to consider three-dimensional models and their responses to a generic base excitation, acting in 3 orthogonal directions. The ground excitation is transferred to a secondary system SDOF model conveniently attached to the primary system. Then, a uniformly probable coupled response spectrum is obtained using a first passage analysis. In this work, the ExeSASSI program is created to manage SASSI2000 several modules and a set of auxiliary programs created to perform the probabilistic analyses. (author)

Metabolic Response to Four Weeks of Muscular Endurance Resistance Training

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John W. Farrell III

2017-10-01

Full Text Available Background: Previous investigations have shown that muscular endurance resistance training (MERT is conducive in improving the onset of blood lactate accumulation (OBLA. However, the metabolic response and time course for adaption is still unclear. Objective: The aims of the current study were to evaluate and track the metabolic response to an individual session of MERT as well as to assess performance adaptations of supplementing an aerobic exercise training program with four weeks of MERT. Methods: Seventeen aerobically active men were randomly assigned to either the experimental (EX or control group (CON, 9 EX and 8 CON. Baseline measures included a graded exercise test (GXT and 1-repetition maximum (1RM testing for leg press (LP, leg curl (LC, and leg extension (LE. CON continued their regular aerobic activity while the EX supplemented their regular aerobic exercise with 4 weeks of MERT. Results: No significant group differences were observed for all pre-training variables. Following four weeks of training no significant differences in cardiorespiratory or metabolic variables were observed for either group. However, significant improvements in LC and LE 1-RM were observed in EX compared to CON. Substantial accumulations in blood lactate were observed following each MERT session. Conclusion: Four weeks of MERT did not improve cardiorespiratory or metabolic variables, but did significantly improve LC and LE. MERT was also observed to induce a blood lactate response similar to that of HIIT. These findings suggest greater than four weeks is need to see metabolic adaptations conducive for improved aerobic performance using MERT.

Metabolic communication between astrocytes and neurons via bicarbonate-responsive soluble adenylyl cyclase.

Science.gov (United States)

Choi, Hyun B; Gordon, Grant R J; Zhou, Ning; Tai, Chao; Rungta, Ravi L; Martinez, Jennifer; Milner, Teresa A; Ryu, Jae K; McLarnon, James G; Tresguerres, Martin; Levin, Lonny R; Buck, Jochen; MacVicar, Brian A

2012-09-20

Astrocytes are proposed to participate in brain energy metabolism by supplying substrates to neurons from their glycogen stores and from glycolysis. However, the molecules involved in metabolic sensing and the molecular pathways responsible for metabolic coupling between different cell types in the brain are not fully understood. Here we show that a recently cloned bicarbonate (HCO₃⁻) sensor, soluble adenylyl cyclase (sAC), is highly expressed in astrocytes and becomes activated in response to HCO₃⁻ entry via the electrogenic NaHCO₃ cotransporter (NBC). Activated sAC increases intracellular cAMP levels, causing glycogen breakdown, enhanced glycolysis, and the release of lactate into the extracellular space, which is subsequently taken up by neurons for use as an energy substrate. This process is recruited over a broad physiological range of [K⁺](ext) and also during aglycemic episodes, helping to maintain synaptic function. These data reveal a molecular pathway in astrocytes that is responsible for brain metabolic coupling to neurons. Copyright © 2012 Elsevier Inc. All rights reserved.

Metabolic Response of Maize Roots to Hyperosmotic Shock 1

Science.gov (United States)

Spickett, Corinne M.; Smirnoff, Nicholas; Ratcliffe, R. George

1992-01-01

31P nuclear magnetic resonance spectroscopy was used to study the response of maize (Zea mays L.) root tips to hyperosmotic shock. The aim was to identify changes in metabolism that might be relevant to the perception of low soil water potential and the subsequent adaptation of the tissue to these conditions. Osmotic shock was found to result in two different types of response: changes in metabolite levels and changes in intracellular pH. The most notable metabolic changes, which were produced by all the osmotica tested, were increases in phosphocholine and vacuolar phosphate, with a transient increase in cytoplasmic phosphate. It was observed that treatment with ionic and nonionic osmotica produced different effects on the concentrations of bioenergetically important metabolites. It is postulated that these changes are the result of hydrolysis of phosphatidylcholine and other membrane phospholipids, due to differential activation of specific membrane-associated phospholipases by changes in the surface tension of the plasmalemma. These events may be important in the detection of osmotic shock and subsequent acclimatization. A cytoplasmic alkalinization was also observed during hyperosmotic treatment, and this response, which is consistent with the activation of the plasmalemma H+-ATPase, together with the other metabolic changes, may suggest the existence of a complex and integrated mechanism of osmoregulation. PMID:16669012

The metabolic response of Candida albicans to farnesol under hyphae-inducing conditions.

Science.gov (United States)

Han, Ting-Li; Cannon, Richard D; Villas-Bôas, Silas G

2012-12-01

Farnesol is a quorum-sensing molecule (QSM) produced, and sensed, by the polymorphic fungus, Candida albicans. This cell-to-cell communication molecule is known to suppress the hyphal formation of C. albicans at high cell density. Despite many studies investigating the signalling mechanisms by which QSMs influence the morphogenesis of C. albicans, the downstream metabolic effect of these signalling pathways in response to farnesol-mediated morphogenesis remains obscure. Here, we have used metabolomics to investigate the metabolic response of C. albicans upon exposure to farnesol under hyphae-inducing conditions. We have found a general up-regulation of central carbon metabolic pathways when hyphal formation was suppressed by farnesol evidenced by a considerably larger number of central carbon metabolic intermediates detected under this condition at an overall lower intracellular level. By combining the metabolic profiles from farnesol-exposed cells with previous metabolomics data for C. albicans undergoing morphogenesis, we have identified several metabolic pathways that are likely to be associated with the morphogenetic process of C. albicans, as well as metabolic pathways such as those involved in lipid metabolism that appeared to be specifically affected by farnesol. Therefore, our results provide important new insights into the metabolic role of farnesol in C. albicans metabolism. © 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

Biochemistry of plant secondary metabolism

National Research Council Canada - National Science Library

Wink, Michael

2010-01-01

... (monoterpenes, sesquiterpenes, sterols, cardiac glycosides and steroid saponins). A chapter is also included covering the importance of secondary metabolites in taxonomy, as viewed from the perspective of molecular systematics...

Metabolic response to feeding in Tupinambis merianae: circadian rhythm and a possible respiratory constraint.

Science.gov (United States)

Klein, Wilfried; Perry, Steven F; Abe, Augusto S; Andrade, Denis V

2006-01-01

The diurnal tegu lizard Tupinambis merianae exhibits a marked circadian variation in metabolism that is characterized by the significant increase in metabolism during part of the day. These increases in metabolic rate, found in the fasting animal, are absent during the first 2 d after meal ingestion but reappear subsequently, and the daily increase in metabolic rate is added to the increase in metabolic rate caused by digestion. During the first 2 d after feeding, priority is given to digestion, while on the third and following days, the metabolic demands are clearly added to each other. This response seems to be a regulated response of the animal, which becomes less active after food ingestion, rather than an inability of the respiratory system to support simultaneous demands at the beginning of digestion. The body cavity of Tupinambis is divided into two compartments by a posthepatic septum (PHS). Animals that had their PHS surgically removed showed no significant alteration in the postprandial metabolic response compared to tegus with intact PHS. The maximal metabolic increment during digestion, the relative cost of meal digestion, and the duration of the process were virtually unaffected by the removal of the PHS.

Structural and metabolic responses of Ceratophyllum demersum to ...

African Journals Online (AJOL)

Eutrophication in water bodies affects the growth of aquatic plants. In this study, we conducted static experiments to better understand the structural and metabolic responses of Ceratophyllum demersum under eutrophication conditions. The anatomical structure, nitrogen (N) and phosphorous (P) levels in tissue, ...

Redox signalling and mitochondrial stress responses; lessons from inborn errors of metabolism

DEFF Research Database (Denmark)

Olsen, Rikke K J; Cornelius, Nanna; Gregersen, Niels

2015-01-01

Mitochondria play a key role in overall cell physiology and health by integrating cellular metabolism with cellular defense and repair mechanisms in response to physiological or environmental changes or stresses. In fact, dysregulation of mitochondrial stress responses and its consequences...... in the form of oxidative stress, has been linked to a wide variety of diseases including inborn errors of metabolism. In this review we will summarize how the functional state of mitochondria -- and especially the concentration of reactive oxygen species (ROS), produced in connection with the respiratory...... chain -- regulates cellular stress responses by redox regulation of nuclear gene networks involved in repair systems to maintain cellular homeostasis and health. Based on our own and other's studies we re-introduce the ROS triangle model and discuss how inborn errors of mitochondrial metabolism...

Barriers to Implementing the Response to Intervention Framework in Secondary Schools: Interviews with Secondary Principals

Science.gov (United States)

Bartholomew, Mitch; De Jong, David

2017-01-01

Despite the successful implementation of the Response to Intervention (RtI) framework in many elementary schools, there is little evidence of successful implementation in high school settings. Several themes emerged from the interviews of nine secondary principals, including a lack of knowledge and training for successful implementation, the…

Radiosensitivity of antibody responses and radioresistant secondary tetanus antitoxin responses

International Nuclear Information System (INIS)

Stoner, R.; Terres, G.; Cottier, H.; Hess, M.

1976-01-01

Primary tetanus antitoxin responses were increasingly repressed in mice when gamma radiation doses of 100 to 400 rads were delivered by whole-body exposure prior to immunization with fluid tetanus toxoid (FTT). Nearly normal secondary antitoxin responses were obtained in mice exposed to 600 rads of gamma radiation 4 days after secondary antigenic stimulation with FTT. A rapid transition from radiosensitivity of the antibody-forming system on days 1 to 3 was followed by relative radioresistance on day 4 after the booster injection of toxoid. Studies on lymphoid cellular kinetics in popliteal lymph nodes after injection of 3 H--thymidine ( 3 H--TdR) and incorporation of 3 H--L-histidine into circulating antitoxin were carried out. Analysis of tritium radioactivity in antigen--antibody precipitates of serums 2 hr after injection of the labeled amino acid revealed maximum incorporation into antibody around day 7 after the booster in nonirradiated controls and about day 12, i.e., 8 days after irradiation, in experimental mice. The shift from radiosensitivity to relative radioresistance was attributed to a marked peak of plasma-cell proliferation in the medulla of lymph nodes on day 3. Many medullary plasma cells survived and continued to proliferate after exposure to radiation. Germinal centers were destroyed by radiation within 1 day. Since antibody formation continued after exposure to radiation and after the loss of germinal centers, this supports the view that germinal-center cells were involved more in the generation of memory cells than in antibody synthesis

Citric Acid Metabolism in Resistant Hypertension: Underlying Mechanisms and Metabolic Prediction of Treatment Response.

Science.gov (United States)

Martin-Lorenzo, Marta; Martinez, Paula J; Baldan-Martin, Montserrat; Ruiz-Hurtado, Gema; Prado, Jose Carlos; Segura, Julian; de la Cuesta, Fernando; Barderas, Maria G; Vivanco, Fernando; Ruilope, Luis Miguel; Alvarez-Llamas, Gloria

2017-11-01

Resistant hypertension (RH) affects 9% to 12% of hypertensive adults. Prolonged exposure to suboptimal blood pressure control results in end-organ damage and cardiovascular risk. Spironolactone is the most effective drug for treatment, but not all patients respond and side effects are not negligible. Little is known on the mechanisms responsible for RH. We aimed to identify metabolic alterations in urine. In addition, a potential capacity of metabolites to predict response to spironolactone was investigated. Urine was collected from 29 patients with RH and from a group of 13 subjects with pseudo-RH. For patients, samples were collected before and after spironolactone administration and were classified in responders (n=19) and nonresponders (n=10). Nuclear magnetic resonance was applied to identify altered metabolites and pathways. Metabolites were confirmed by liquid chromatography-mass spectrometry. Citric acid cycle was the pathway most significantly altered ( P citric acid cycle and deregulation of reactive oxygen species homeostasis control continue its activation after hypertension was developed. A metabolic panel showing alteration before spironolactone treatment and predicting future response of patients is shown. These molecular indicators will contribute optimizing the rate of control of RH patients with spironolactone. © 2017 American Heart Association, Inc.

Investigation of the conservatism associated with different combinations between primary and secondary piping responses

International Nuclear Information System (INIS)

Wang, Y.K.; Subudhi, M.; Bezler, P.

1983-01-01

This report includes the findings of an investigation of the conservatism associated with different combinations between the primary and secondary stress components for piping systems under dynamic loading, such as in an earthquake event. The primary stresses are induced by piping response to its mass inertia effects. The secondary stresses are induced by relative displacements of piping supports. The study involves an independnent time history analysis of several typical piping models to predict a best estimate of the actual dynamic and pseudo-static pipe responses to an earthquake. These piping systems are also analyzed using the response spectrum method to obtain the maximum primary stress components. Secondary stresses are next calculated by performing a set of static analyses which provide the worst stress condition. The two components are then combined by both SRSS and absolute sum methods as the results are compared with time history solutions. It is found that the SRSS combination of the primary and secondary stress components yield acceptable results provided the secondary stress component is calculated in the most unfavorable phasing relationship among displacements of piping supports

Systematization of the protein sequence diversity in enzymes related to secondary metabolic pathways in plants, in the context of big data biology inspired by the KNApSAcK motorcycle database.

Science.gov (United States)

Ikeda, Shun; Abe, Takashi; Nakamura, Yukiko; Kibinge, Nelson; Hirai Morita, Aki; Nakatani, Atsushi; Ono, Naoaki; Ikemura, Toshimichi; Nakamura, Kensuke; Altaf-Ul-Amin, Md; Kanaya, Shigehiko

2013-05-01

Biology is increasingly becoming a data-intensive science with the recent progress of the omics fields, e.g. genomics, transcriptomics, proteomics and metabolomics. The species-metabolite relationship database, KNApSAcK Core, has been widely utilized and cited in metabolomics research, and chronological analysis of that research work has helped to reveal recent trends in metabolomics research. To meet the needs of these trends, the KNApSAcK database has been extended by incorporating a secondary metabolic pathway database called Motorcycle DB. We examined the enzyme sequence diversity related to secondary metabolism by means of batch-learning self-organizing maps (BL-SOMs). Initially, we constructed a map by using a big data matrix consisting of the frequencies of all possible dipeptides in the protein sequence segments of plants and bacteria. The enzyme sequence diversity of the secondary metabolic pathways was examined by identifying clusters of segments associated with certain enzyme groups in the resulting map. The extent of diversity of 15 secondary metabolic enzyme groups is discussed. Data-intensive approaches such as BL-SOM applied to big data matrices are needed for systematizing protein sequences. Handling big data has become an inevitable part of biology.

Metabolic response of Candida albicans to phenylethyl alcohol under hyphae-inducing conditions.

Science.gov (United States)

Han, Ting-Li; Tumanov, Sergey; Cannon, Richard D; Villas-Boas, Silas G

2013-01-01

Phenylethyl alcohol was one of the first quorum sensing molecules (QSMs) identified in C. albicans. This extracellular signalling molecule inhibits the hyphal formation of C. albicans at high cell density. Little is known, however, about the underlying mechanisms by which this QSM regulates the morphological switches of C. albicans. Therefore, we have applied metabolomics and isotope labelling experiments to investigate the metabolic changes that occur in C. albicans in response to phenylethyl alcohol under defined hyphae-inducing conditions. Our results showed a global upregulation of central carbon metabolism when hyphal development was suppressed by phenylethyl alcohol. By comparing the metabolic changes in response to phenylethyl alcohol to our previous metabolomic studies, we were able to short-list 7 metabolic pathways from central carbon metabolism that appear to be associated with C. albicans morphogenesis. Furthermore, isotope-labelling data showed that phenylethyl alcohol is indeed taken up and catabolised by yeast cells. Isotope-labelled carbon atoms were found in the majority of amino acids as well as in lactate and glyoxylate. However, isotope-labelled carbon atoms from phenylethyl alcohol accumulated mainly in the pyridine ring of NAD(+)/NADH and NADP(-/)NADPH molecules, showing that these nucleotides were the main products of phenylethyl alcohol catabolism. Interestingly, two metabolic pathways where these nucleotides play an important role, nitrogen metabolism and nicotinate/nicotinamide metabolism, were also short-listed through our previous metabolomics works as metabolic pathways likely to be closely associated with C. albicans morphogenesis.

Histone acetyltransferase TGF-1 regulates Trichoderma atroviride secondary metabolism and mycoparasitism.

Science.gov (United States)

Gómez-Rodríguez, Elida Yazmín; Uresti-Rivera, Edith Elena; Patrón-Soberano, Olga Araceli; Islas-Osuna, María Auxiliadora; Flores-Martínez, Alberto; Riego-Ruiz, Lina; Rosales-Saavedra, María Teresa; Casas-Flores, Sergio

2018-01-01

Some filamentous fungi of the Trichoderma genus are used as biocontrol agents against airborne and soilborne phytopathogens. The proposed mechanism by which Trichoderma spp. antagonizes phytopathogens is through the release of lytic enzymes, antimicrobial compounds, mycoparasitism, and the induction of systemic disease-resistance in plants. Here we analyzed the role of TGF-1 (Trichoderma Gcn Five-1), a histone acetyltransferase of Trichoderma atroviride, in mycoparasitism and antibiosis against the phytopathogen Rhizoctonia solani. Trichostatin A (TSA), a histone deacetylase inhibitor that promotes histone acetylation, slightly affected T. atroviride and R. solani growth, but not the growth of the mycoparasite over R. solani. Application of TSA to the liquid medium induced synthesis of antimicrobial compounds. Expression analysis of the mycoparasitism-related genes ech-42 and prb-1, which encode an endochitinase and a proteinase, as well as the secondary metabolism-related genes pbs-1 and tps-1, which encode a peptaibol synthetase and a terpene synthase, respectively, showed that they were regulated by TSA. A T. atroviride strain harboring a deletion of tgf-1 gene showed slow growth, thinner and less branched hyphae than the wild-type strain, whereas its ability to coil around the R. solani hyphae was not affected. Δtgf-1 presented a diminished capacity to grow over R. solani, but the ability of its mycelium -free culture filtrates (MFCF) to inhibit the phytopathogen growth was enhanced. Intriguingly, addition of TSA to the culture medium reverted the enhanced inhibition growth of Δtgf-1 MFCF on R. solani at levels compared to the wild-type MFCF grown in medium amended with TSA. The presence of R. solani mycelium in the culture medium induced similar proteinase activity in a Δtgf-1 compared to the wild-type, whereas the chitinolytic activity was higher in a Δtgf-1 mutant in the absence of R. solani, compared to the parental strain. Expression of mycoparasitism

Histone acetyltransferase TGF-1 regulates Trichoderma atroviride secondary metabolism and mycoparasitism.

Directory of Open Access Journals (Sweden)

Elida Yazmín Gómez-Rodríguez

Full Text Available Some filamentous fungi of the Trichoderma genus are used as biocontrol agents against airborne and soilborne phytopathogens. The proposed mechanism by which Trichoderma spp. antagonizes phytopathogens is through the release of lytic enzymes, antimicrobial compounds, mycoparasitism, and the induction of systemic disease-resistance in plants. Here we analyzed the role of TGF-1 (Trichoderma Gcn Five-1, a histone acetyltransferase of Trichoderma atroviride, in mycoparasitism and antibiosis against the phytopathogen Rhizoctonia solani. Trichostatin A (TSA, a histone deacetylase inhibitor that promotes histone acetylation, slightly affected T. atroviride and R. solani growth, but not the growth of the mycoparasite over R. solani. Application of TSA to the liquid medium induced synthesis of antimicrobial compounds. Expression analysis of the mycoparasitism-related genes ech-42 and prb-1, which encode an endochitinase and a proteinase, as well as the secondary metabolism-related genes pbs-1 and tps-1, which encode a peptaibol synthetase and a terpene synthase, respectively, showed that they were regulated by TSA. A T. atroviride strain harboring a deletion of tgf-1 gene showed slow growth, thinner and less branched hyphae than the wild-type strain, whereas its ability to coil around the R. solani hyphae was not affected. Δtgf-1 presented a diminished capacity to grow over R. solani, but the ability of its mycelium -free culture filtrates (MFCF to inhibit the phytopathogen growth was enhanced. Intriguingly, addition of TSA to the culture medium reverted the enhanced inhibition growth of Δtgf-1 MFCF on R. solani at levels compared to the wild-type MFCF grown in medium amended with TSA. The presence of R. solani mycelium in the culture medium induced similar proteinase activity in a Δtgf-1 compared to the wild-type, whereas the chitinolytic activity was higher in a Δtgf-1 mutant in the absence of R. solani, compared to the parental strain. Expression

The Host Response in Patients with Sepsis Developing Intensive Care Unit-acquired Secondary Infections.

Science.gov (United States)

van Vught, Lonneke A; Wiewel, Maryse A; Hoogendijk, Arie J; Frencken, Jos F; Scicluna, Brendon P; Klein Klouwenberg, Peter M C; Zwinderman, Aeilko H; Lutter, Rene; Horn, Janneke; Schultz, Marcus J; Bonten, Marc M J; Cremer, Olaf L; van der Poll, Tom

2017-08-15

Sepsis can be complicated by secondary infections. We explored the possibility that patients with sepsis developing a secondary infection while in the intensive care unit (ICU) display sustained inflammatory, vascular, and procoagulant responses. To compare systemic proinflammatory host responses in patients with sepsis who acquire a new infection with those who do not. Consecutive patients with sepsis with a length of ICU stay greater than 48 hours were prospectively analyzed for the development of ICU-acquired infections. Twenty host response biomarkers reflective of key pathways implicated in sepsis pathogenesis were measured during the first 4 days after ICU admission and at the day of an ICU-acquired infection or noninfectious complication. Of 1,237 admissions for sepsis (1,089 patients), 178 (14.4%) admissions were complicated by ICU-acquired infections (at Day 10 [6-13], median with interquartile range). Patients who developed a secondary infection showed higher disease severity scores and higher mortality up to 1 year than those who did not. Analyses of biomarkers in patients who later went on to develop secondary infections revealed a more dysregulated host response during the first 4 days after admission, as reflected by enhanced inflammation, stronger endothelial cell activation, a more disturbed vascular integrity, and evidence for enhanced coagulation activation. Host response reactions were similar at the time of ICU-acquired infectious or noninfectious complications. Patients with sepsis who developed an ICU-acquired infection showed a more dysregulated proinflammatory and vascular host response during the first 4 days of ICU admission than those who did not develop a secondary infection.

Metabolic development of the porcine placenta in response to alterations in maternal or fetal homeostasis

International Nuclear Information System (INIS)

Namsey, T.G.; kasser, T.R.; Hausman, G.J.; Martin, R.J.

1986-01-01

Porcine placenta has been utilized as a model for elucidating contributions of both fetal and maternal tissues to metabolic activity of the placenta in response to a variety of stresses. Alloxan diabetes, food restriction and genetic obesity all produced alterations in placental metablolism with differences in responses of fetal and maternal placentas. Further analysis of nutrient untilization by the placenta produced dramatic differences in the partitioning of substrates by fetal and maternal tissues during placental development. Metabolic activity of maternal tissue contributed to overall placental metabolic activity to a greater degree than fetal tissue. However, experiments with in utero fetal decapitation indicated that some of differences between fetal and maternal placental metabolic activity may be due to the influence of fetal regulatory mechanisms. Maternal endometrium plays a critical role in metabolic response of uteroplacenta and thus availability of nutrients to the fetus and fetal placenta. Differences in metabolic development of fetal and maternal tissues suggested that regulation of placental metabolism may originate from fetal as well as maternal sources

Metabolic mapping of the brain's response to visual stimulation: studies in humans

International Nuclear Information System (INIS)

Phelps, M.E.; Kuhl, D.E.; Mazziotta, J.C.

1981-01-01

These studies demonstrated increasing glucose metabolic rates in the human primary (PVC) and associative (AVC) visual cortex as the complexity of visual scenes increased. The metabolic response of the AVC increased more rapidly with scene complexity than that of the PVC, indicating the greater involvement of the higher order AVC for complex visual interpretations. Increases in local metabolic activity by as much as a factor of 2 above that of control subjects with eyes closed indicate the wide range and metabolic reserve of the visual cortex

Muscular and metabolic responses to different Nordic walking techniques, when style matters.

Science.gov (United States)

Pellegrini, Barbara; Boccia, Gennaro; Zoppirolli, Chiara; Rosa, Raffaela; Stella, Federico; Bortolan, Lorenzo; Rainoldi, Alberto; Schena, Federico

2018-01-01

Due to poling action and upper body engagement, Nordic walking (NW) has additional health benefits with respect to conventional walking. The aim of this study was to evaluate the differences in muscle activation and metabolic responses between NW, performed with the technique suggested by NW instructors, and with some modifications in the way to move upper limb and poles. Ten NW instructors volunteered to walk on a treadmill at 5.5 km•h-1 in five conditions: walking (W), Nordic walking (NW), NW with a weak poling action (NWweak), with straight-upper limbs moving the shoulders (NWshoulder) and with elbow flexion-extension pattern and shoulder freezed (NWelbow). Poling forces, body segments and poles movement, upper and lower body muscle activation, as well as metabolic parameters were measured.All modified NW techniques elicited lower muscular activation and metabolic responses with respect to the suggested NW technique (P walking instructors, sport technicians and practitioners should be aware that any deviation from the technique usually suggested might lead to lower benefits. However it is worth to note that any walking technique with poles elicits higher metabolic responses and muscular activation than walking.

Do diabetes and obesity affect the metabolic response to exercise?

Science.gov (United States)

Plomgaard, Peter; Weigert, Cora

2017-07-01

Exercise is recommended as therapeutic intervention for people at risk to develop type 2 diabetes to prevent or treat the disease. Recent studies on the influence of obesity and type 2 diabetes on the outcome of exercise programs are discussed. Poor glycemic control before an intervention can be a risk factor of reduced therapeutic benefit from exercise. But the acute metabolic response to exercise and the transcriptional profile of the working muscle is similar in healthy controls and type 2 diabetic patients, including but not limited to intact activation of skeletal muscle AMP-activated kinase signaling, glucose uptake and expression of peroxisome proliferator-activated receptor gamma coactivator 1α. The increase in plasma acylcarnitines during exercise is not influenced by type 2 diabetes or obesity. The hepatic response to exercise is dependent on the glucagon/insulin ratio and the exercise-induced increase in hepatokines such as fibroblast growth factor 21 and follistatin is impaired in type 2 diabetes and obesity, but consequences for the benefit from exercise are unknown yet. Severe metabolic dysregulation can reduce the benefit from exercise, but the intact response of key metabolic regulators in exercising skeletal muscle of diabetic patients demonstrates the effectiveness of exercise programs to treat the disease.

The cross-tissue metabolic response of abalone (Haliotis midae) to functional hypoxia.

Science.gov (United States)

Venter, Leonie; Loots, Du Toit; Mienie, Lodewyk J; Jansen van Rensburg, Peet J; Mason, Shayne; Vosloo, Andre; Lindeque, Jeremie Z

2018-03-23

Functional hypoxia is a stress condition caused by the abalone itself as a result of increased muscle activity, which generally necessitates the employment of anaerobic metabolism if the activity is sustained for prolonged periods. With that being said, abalone are highly reliant on anaerobic metabolism to provide partial compensation for energy production during oxygen-deprived episodes. However, current knowledge on the holistic metabolic response for energy metabolism during functional hypoxia, and the contribution of different metabolic pathways and various abalone tissues towards the overall accumulation of anaerobic end-products in abalone are scarce. Metabolomics analysis of adductor muscle, foot muscle, left gill, right gill, haemolymph and epipodial tissue samples indicated that South African abalone ( Haliotis midae) subjected to functional hypoxia utilises predominantly anaerobic metabolism, and depends on all of the main metabolite classes (proteins, carbohydrates and lipids) for energy supply. Functional hypoxia caused increased levels of anaerobic end-products: lactate, alanopine, tauropine, succinate and alanine. Also, elevation in arginine levels was detected, confirming that abalone use phosphoarginine to generate energy during functional hypoxia. Different tissues showed varied metabolic responses to hypoxia, with functional hypoxia showing excessive changes in the adductor muscle and gills. From this metabolomics investigation, it becomes evident that abalone are metabolically able to produce sufficient amounts of energy when functional hypoxia is experienced. Also, tissue interplay enables the adjustment of H. midae energy requirements as their metabolism shifts from aerobic to anaerobic respiration during functional hypoxia.This article has an associated First Person interview with the first author of the paper. © 2018. Published by The Company of Biologists Ltd.

The cross-tissue metabolic response of abalone (Haliotis midae to functional hypoxia

Directory of Open Access Journals (Sweden)

Leonie Venter

2018-03-01

Full Text Available Functional hypoxia is a stress condition caused by the abalone itself as a result of increased muscle activity, which generally necessitates the employment of anaerobic metabolism if the activity is sustained for prolonged periods. With that being said, abalone are highly reliant on anaerobic metabolism to provide partial compensation for energy production during oxygen-deprived episodes. However, current knowledge on the holistic metabolic response for energy metabolism during functional hypoxia, and the contribution of different metabolic pathways and various abalone tissues towards the overall accumulation of anaerobic end-products in abalone are scarce. Metabolomics analysis of adductor muscle, foot muscle, left gill, right gill, haemolymph and epipodial tissue samples indicated that South African abalone (Haliotis midae subjected to functional hypoxia utilises predominantly anaerobic metabolism, and depends on all of the main metabolite classes (proteins, carbohydrates and lipids for energy supply. Functional hypoxia caused increased levels of anaerobic end-products: lactate, alanopine, tauropine, succinate and alanine. Also, elevation in arginine levels was detected, confirming that abalone use phosphoarginine to generate energy during functional hypoxia. Different tissues showed varied metabolic responses to hypoxia, with functional hypoxia showing excessive changes in the adductor muscle and gills. From this metabolomics investigation, it becomes evident that abalone are metabolically able to produce sufficient amounts of energy when functional hypoxia is experienced. Also, tissue interplay enables the adjustment of H. midae energy requirements as their metabolism shifts from aerobic to anaerobic respiration during functional hypoxia. This article has an associated First Person interview with the first author of the paper.

Positron computed tomography studies of cerebral metabolic responses to complex motor tasks

International Nuclear Information System (INIS)

Phelps, M.E.; Mazziotta, J.C.

1984-01-01

Human motor system organization was explored in 8 right-handed male subjects using /sup 18/F-fluorodeoxyglucose and positron computed tomography to measure cerebral glucose metabolism. Five subjects had triple studies (eyes closed) including: control (hold pen in right hand without moving), normal size writing (subject repeatedly writes name) and large (10-15 X normal) name writing. In these studies normal and large size writing had a similar distribution of metabolic responses when compared to control studies. Activations (percent change from control) were in the range of 12-20% and occurred in the striatum bilaterally > contralateral Rolandic cortex > contralateral thalamus. No significant activations were observed in the ipsilateral thalamus, Rolandic cortex or cerebellum (supplementary motor cortex was not examined). The magnitude of the metabolic response in the striatum was greater with the large versus normal sized writing. This differential response may be due to an increased number and topographic distribution of neurons responding with the same average activity between tasks or an increase in the functional activity of the same neuronal population between the two tasks (present spatial resolution inadequate to differentiate). When subjects (N=3) performed novel sequential finger movements, the maximal metabolic response was in the contralateral Rolandic cortex > striatum. Such studies provide a means of exploring human motor system organization, motor learning and provide a basis for examining patients with motor system disorders

Supplementation of Saccharomyces cerevisiae modulates the metabolic response to lipopolysaccharide challenge in feedlot steers

Science.gov (United States)

Live yeast has the potential to serve as an alternative to the use of low-dose supplementation of antibiotics in cattle due to the ability to alter ruminant metabolism; which in turn may influence the immune response. Therefore, the objective of this study was to determine the metabolic response to ...

Metabolome-genome-wide association study dissects genetic architecture for generating natural variation in rice secondary metabolism

Science.gov (United States)

Matsuda, Fumio; Nakabayashi, Ryo; Yang, Zhigang; Okazaki, Yozo; Yonemaru, Jun-ichi; Ebana, Kaworu; Yano, Masahiro; Saito, Kazuki

2015-01-01

Plants produce structurally diverse secondary (specialized) metabolites to increase their fitness for survival under adverse environments. Several bioactive compounds for new drugs have been identified through screening of plant extracts. In this study, genome-wide association studies (GWAS) were conducted to investigate the genetic architecture behind the natural variation of rice secondary metabolites. GWAS using the metabolome data of 175 rice accessions successfully identified 323 associations among 143 single nucleotide polymorphisms (SNPs) and 89 metabolites. The data analysis highlighted that levels of many metabolites are tightly associated with a small number of strong quantitative trait loci (QTLs). The tight association may be a mechanism generating strains with distinct metabolic composition through the crossing of two different strains. The results indicate that one plant species produces more diverse phytochemicals than previously expected, and plants still contain many useful compounds for human applications. PMID:25267402

SU-C-303-02: Correlating Metabolic Response to Radiation Therapy with HIF-1alpha Expression

International Nuclear Information System (INIS)

Campos, D; Peeters, W; Nickel, K; Eliceiri, K; Kimple, R; Van Der Kogel, A; Kissick, M

2015-01-01

Purpose: To understand radiation induced alterations in cellular metabolism which could be used to assess treatment or normal tissue response to aid in patient-specific adaptive radiotherapy. This work aims to compare the metabolic response of two head and neck cell lines, one malignant (UM-SCC-22B) and one benign (Normal Oral Keratinocyte), to ionizing radiation. Responses are compared to alterations in HIF-1alpha expression. These dynamics can potentially serve as biomarkers in assessing treatment response allowing for patient-specific adaptive radiotherapy. Methods: Measurements of metabolism and HIF-1alpha expression were taken before and X minutes after a 10 Gy dose of radiation delivered via an orthovoltage x-ray source. In vitro changes in metabolic activity were measured via fluorescence lifetime imaging (FLIM) to assess the mean lifetime of NADH autofluorescence following a dose of 10 Gy. HIF-1alpha expression was measured via immunohistochemical staining of in vitro treated cells and expression was quantified using the FIJI software package. Results: FLIM demonstrated a decrease in the mean fluorescence lifetime of NADH by 100 ps following 10 Gy indicating a shift towards glycolytic pathways for malignant cells; whereas this benign cell line showed little change in metabolic signature. Immunohistochemical analysis showed significant changes in HIF-1alpha expression in response to 10 Gy of radiation that correlate to metabolic profiles. Conclusion: Radiation induces significant changes in metabolic activity and HIF-1alpha expression. These alterations occur on time scales approximating the duration of common radiation treatments (approximately tens of minutes). Further understanding these dynamics has important implications with regard to improvement of therapy and biomarkers of treatment response

SU-C-303-02: Correlating Metabolic Response to Radiation Therapy with HIF-1alpha Expression

Energy Technology Data Exchange (ETDEWEB)

Campos, D [University of Wisconsin Madison, Madison, WI (United States); Peeters, W [Radboud University Medical Center, Nijmegen, GA (United States); Nickel, K [University of Wisconsin, Madison, WI (United States); Eliceiri, K; Kimple, R; Van Der Kogel, A; Kissick, M [University of Wisconsin, Madison, Wisconsin (United States)

2015-06-15

Purpose: To understand radiation induced alterations in cellular metabolism which could be used to assess treatment or normal tissue response to aid in patient-specific adaptive radiotherapy. This work aims to compare the metabolic response of two head and neck cell lines, one malignant (UM-SCC-22B) and one benign (Normal Oral Keratinocyte), to ionizing radiation. Responses are compared to alterations in HIF-1alpha expression. These dynamics can potentially serve as biomarkers in assessing treatment response allowing for patient-specific adaptive radiotherapy. Methods: Measurements of metabolism and HIF-1alpha expression were taken before and X minutes after a 10 Gy dose of radiation delivered via an orthovoltage x-ray source. In vitro changes in metabolic activity were measured via fluorescence lifetime imaging (FLIM) to assess the mean lifetime of NADH autofluorescence following a dose of 10 Gy. HIF-1alpha expression was measured via immunohistochemical staining of in vitro treated cells and expression was quantified using the FIJI software package. Results: FLIM demonstrated a decrease in the mean fluorescence lifetime of NADH by 100 ps following 10 Gy indicating a shift towards glycolytic pathways for malignant cells; whereas this benign cell line showed little change in metabolic signature. Immunohistochemical analysis showed significant changes in HIF-1alpha expression in response to 10 Gy of radiation that correlate to metabolic profiles. Conclusion: Radiation induces significant changes in metabolic activity and HIF-1alpha expression. These alterations occur on time scales approximating the duration of common radiation treatments (approximately tens of minutes). Further understanding these dynamics has important implications with regard to improvement of therapy and biomarkers of treatment response.

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

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Roze Ludmila V

2010-08-01

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

Metabolic acclimation to excess light intensity in Chlamydomonas reinhardtii.

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Davis, Maria C; Fiehn, Oliver; Durnford, Dion G

2013-07-01

There are several well-described acclimation responses to excess light in green algae but the effect on metabolism has not been thoroughly investigated. This study examines the metabolic changes during photoacclimation to high-light (HL) stress in Chlamydomonas reinhardtii using nuclear magnetic resonance and mass spectrometry. Using principal component analysis, a clear metabolic response to HL intensity was observed on global metabolite pools, with major changes in the levels of amino acids and related nitrogen metabolites. Amino acid pools increased during short-term photoacclimation, but were especially prominent in HL-acclimated cultures. Unexpectedly, we observed an increase in mitochondrial metabolism through downstream photorespiratory pathways. The expression of two genes encoding key enzymes in the photorespiratory pathway, glycolate dehydrogenase and malate synthase, were highly responsive to the HL stress. We propose that this pathway contributes to metabolite pools involved in nitrogen assimilation and may play a direct role in photoacclimation. Our results suggest that primary and secondary metabolism is highly pliable and plays a critical role in coping with the energetic imbalance during HL exposure and a necessary adjustment to support an increased growth rate that is an effective energy sink for the excess reducing power generated during HL stress. © 2013 John Wiley & Sons Ltd.

Metabolic and inflammatory responses to the common sweetener stevioside and a glycemic challenge in horses with equine metabolic syndrome.

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Elzinga, S E; Rohleder, B; Schanbacher, B; McQuerry, K; Barker, V D; Adams, A A

2017-07-01

Extracts derived from the leaves of the stevia plant (stevioside) are commonly used as sweeteners for humans and horses. Stevioside appears to be safe for human consumption, including for individuals with insulin dysregulation. In the horse, the safety or metabolic effects of stevioside on normal animals or on those with metabolic dysfunction are unknown. Furthermore, the inflammatory response to a glycemic challenge or to stevioside in horses is not well defined. Therefore, the objective of this study was to measure the effects of stevioside and a glycemic challenge on insulin, glucose, and inflammatory responses in horses with a common metabolic dysfunction (equine metabolic syndrome or EMS) compared with non-EMS controls. To accomplish this, 15 horses were selected; 8 EMS and 7 age-matched controls. An oral sugar test was performed using Karo corn syrup (karo) or stevioside in a random crossover design. Horses were given 0.15 mL/kg body weight of karo or its equivalent grams of sugar in stevia dissolved in water. Blood samples were collected by jugular venipuncture before administration of either stevia or karo and at 60 and 240 min after administration. Serum was used for glucose and insulin determination and plasma for isolation of peripheral blood mononuclear cells (PBMCs) for inflammatory cytokine analysis via flow cytometry and reverse transcription PCR (RT-PCR). Stevia appeared to stimulate lower glycemic and insulinemic responses when compared to karo, in particular in EMS horses. EMS and control horses had inverse inflammatory responses to administration of either stevia or karo with EMS horses having a proinflammatory response (P ≤ 0.05). These data provide evidence as to why horses with EMS may be predisposed to developing laminitis, potentially as a result of an exaggerated inflammatory response to glycemic and insulinemic responses. Furthermore, the data provide new avenues for exploring mechanisms behind the syndrome, in particular when using a

Long-term salt stress responsive growth, carbohydrate metabolism ...

African Journals Online (AJOL)

We investigated the long-term responses of tobacco tissues to salt stress, with a particular interest for growth parameters, proline (Pro) accumulation, and carbohydrate metabolism. Exposure of 17-day-old tobacco plants to 0.2 M NaCl was followed by a higher decrease in dry matter in roots than shoots with a decrease of ...

Induction of a stringent metabolic response in intracellular stages of Leishmania mexicana leads to increased dependence on mitochondrial metabolism.

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Eleanor C Saunders

2014-01-01

Full Text Available Leishmania parasites alternate between extracellular promastigote stages in the insect vector and an obligate intracellular amastigote stage that proliferates within the phagolysosomal compartment of macrophages in the mammalian host. Most enzymes involved in Leishmania central carbon metabolism are constitutively expressed and stage-specific changes in energy metabolism remain poorly defined. Using (13C-stable isotope resolved metabolomics and (2H2O labelling, we show that amastigote differentiation is associated with reduction in growth rate and induction of a distinct stringent metabolic state. This state is characterized by a global decrease in the uptake and utilization of glucose and amino acids, a reduced secretion of organic acids and increased fatty acid β-oxidation. Isotopomer analysis showed that catabolism of hexose and fatty acids provide C4 dicarboxylic acids (succinate/malate and acetyl-CoA for the synthesis of glutamate via a compartmentalized mitochondrial tricarboxylic acid (TCA cycle. In vitro cultivated and intracellular amastigotes are acutely sensitive to inhibitors of mitochondrial aconitase and glutamine synthetase, indicating that these anabolic pathways are essential for intracellular growth and virulence. Lesion-derived amastigotes exhibit a similar metabolism to in vitro differentiated amastigotes, indicating that this stringent response is coupled to differentiation signals rather than exogenous nutrient levels. Induction of a stringent metabolic response may facilitate amastigote survival in a nutrient-poor intracellular niche and underlie the increased dependence of this stage on hexose and mitochondrial metabolism.

Salt Stress Effects on Secondary Metabolites of Cotton in Relation to Gene Expression Responsible for Aphid Development.

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Qi Wang

Full Text Available Many secondary metabolites have insecticidal efficacy against pests and may be affected by abiotic stress. However, little is known of how plants may respond to such stress as pertains the growth and development of pests. The objective of this study was to determine if and how salt stress on cotton plants affects the population dynamics of aphids. The NaCl treatment (50 mM, 100 mM, 150 mM and 200 mM increased contents of gossypol in cotton by 26.8-51.4%, flavonoids by 22.5-37.6% and tannic by 15.1-24.3% at 7-28 d after salt stress. Compared with non-stressed plants, the population of aphids on 150 and 200 mM NaCl stressed plants was reduced by 46.4 and 65.4% at 7d and by 97.3 and 100% at 14 days after infestation. Reductions in aphid population were possibly attributed to the elevated secondary metabolism under salt stress. A total of 796 clones for aphids transcriptome, 412 clones in the positive- library (TEST and 384 clones in the reverse-library (Ck, were obtained from subtracted cDNA libraries and sequenced. Gene ontology (GO functional classification and KEGG pathway analysis showed more genes related to fatty acid and lipid biosynthesis, and fewer genes related to carbohydrate metabolism, amino acid metabolism, energy metabolism and cell motility pathways in TEST than in Ck library, which might be the reason of aphids population reduction. A comparative analysis with qRT-PCR indicated high expression of transcripts CYP6A14, CYP6A13, CYP303A1, NADH dehydrogenase and fatty acid synthase in the TEST group. However, CYP307A1 and two ecdysone-induced protein genes were down regulated. The results indicate that genes of aphids related to growth and development can express at a higher level in reaction to the enhanced secondary metabolism in cotton under salinity stress. The expression of CYP307A1 was positively correlated with the population dynamics of aphids since it was involved in ecdysone synthesis.

Maternal high-fat diet intensifies the metabolic response to stress in male rat offspring

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Karbaschi, Roxana; Zardooz, Homeira; Khodagholi, Fariba; Dargahi, Leila; Salimi, Mina; Rashidi, FatemehSadat

2017-01-01

Background The mother?s consumption of high-fat food can affect glucose metabolism and the hypothalamic?pituitary?adrenal axis responsiveness in the offspring and potentially affect the metabolic responses to stress as well. This study examines the effect of maternal high-fat diet on the expression of pancreatic glucose transporter 2 and the secretion of insulin in response to stress in offspring. Methods Female rats were randomly divided into normal and high-fat diet groups and were fed in a...

Adipose tissue and metabolic and inflammatory responses to stroke are altered in obese mice

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Michael J. Haley

2017-10-01

Full Text Available Obesity is an independent risk factor for stroke, although several clinical studies have reported that obesity improves stroke outcome. Obesity is hypothesised to aid recovery by protecting against post-stroke catabolism. We therefore assessed whether obese mice had an altered metabolic and inflammatory response to stroke. Obese ob/ob mice underwent a 20-min middle cerebral artery occlusion and 24-h reperfusion. Lipid metabolism and expression of inflammatory cytokines were assessed in the plasma, liver and adipose tissue. The obese-specific metabolic response to stroke was assessed in plasma using non-targeted ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS metabolomics coupled with univariate and multivariate analysis. Obesity had no effect on the extent of weight loss 24 h after stroke but affected the metabolic and inflammatory responses to stroke, predominantly affecting lipid metabolism. Specifically, obese mice had increases in plasma free fatty acids and expression of adipose lipolytic enzymes. Metabolomics identified several classes of metabolites affected by stroke in obese mice, including fatty acids and membrane lipids (glycerophospholipids, lysophospholipids and sphingolipids. Obesity also featured increases in inflammatory cytokines in the plasma and adipose tissue. Overall, these results demonstrate that obesity affected the acute metabolic and inflammatory response to stroke and suggest a potential role for adipose tissue in this effect. These findings could have implications for longer-term recovery and also further highlight the importance of considering comorbidities in preclinical stroke research, especially when identifying biomarkers for stroke. However, further work is required to assess whether these changes translate into long-term effects on recovery.

Globular adiponectin ameliorates metabolic insulin resistance via AMPK-mediated restoration of microvascular insulin responses

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Zhao, Lina; Fu, Zhuo; Wu, Jing; Aylor, Kevin W; Barrett, Eugene J; Cao, Wenhong; Liu, Zhenqi

2015-01-01

Abstract Hypoadiponectinaemia is closely associated with endothelial dysfunction and insulin resistance, and microvasculature plays a critical role in the regulation of insulin action in muscle. Here we tested whether adiponectin replenishment could improve metabolic insulin sensitivity in male rats fed a high-fat diet (HFD) via the modulation of microvascular insulin responses. Male Sprague–Dawley rats were fed either a HFD or low-fat diet (LFD) for 4 weeks. Small resistance artery myograph changes in tension, muscle microvascular recruitment and metabolic response to insulin were determined. Compared with rats fed a LFD, HFD feeding abolished the vasodilatory actions of globular adiponectin (gAd) and insulin on pre-constricted distal saphenous arteries. Pretreatment with gAd improved insulin responses in arterioles isolated from HFD rats, which was blocked by AMP-activated protein kinase (AMPK) inhibition. Similarly, HFD abolished microvascular responses to either gAd or insulin and decreased insulin-stimulated glucose disposal by ∼60%. However, supplementing gAd fully rescued insulin’s microvascular action and significantly improved the metabolic responses to insulin in HFD male rats and these actions were abolished by inhibition of either AMPK or nitric oxide production. We conclude that HFD induces vascular adiponectin and insulin resistance but gAd administration can restore vascular insulin responses and improve insulin’s metabolic action via an AMPK- and nitric oxide-dependent mechanism in male rats. Key points Adiponectin is an adipokine with anti-inflammatory and anti-diabetic properties. Hypoadiponectinaemia is closely associated with endothelial dysfunction and insulin resistance in obesity and diabetes. Insulin resistance is present in muscle microvasculature and this may contribute to decreased insulin delivery to, and action in, muscle. In this study we examined whether adiponectin ameliorates metabolic insulin resistance by affecting muscle

Metabolic Response to NAD Depletion across Cell Lines Is Highly Variable.

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Xiao, Yang; Kwong, Mandy; Daemen, Anneleen; Belvin, Marcia; Liang, Xiaorong; Hatzivassiliou, Georgia; O'Brien, Thomas

2016-01-01

Nicotinamide adenine dinucleotide (NAD) is a cofactor involved in a wide range of cellular metabolic processes and is a key metabolite required for tumor growth. NAMPT, nicotinamide phosphoribosyltransferase, which converts nicotinamide (NAM) to nicotinamide mononucleotide (NMN), the immediate precursor of NAD, is an attractive therapeutic target as inhibition of NAMPT reduces cellular NAD levels and inhibits tumor growth in vivo. However, there is limited understanding of the metabolic response to NAD depletion across cancer cell lines and whether all cell lines respond in a uniform manner. To explore this we selected two non-small cell lung carcinoma cell lines that are sensitive to the NAMPT inhibitor GNE-617 (A549, NCI-H1334), one that shows intermediate sensitivity (NCI-H441), and one that is insensitive (LC-KJ). Even though NAD was reduced in all cell lines there was surprising heterogeneity in their metabolic response. Both sensitive cell lines reduced glycolysis and levels of di- and tri-nucleotides and modestly increased oxidative phosphorylation, but they differed in their ability to combat oxidative stress. H1334 cells activated the stress kinase AMPK, whereas A549 cells were unable to activate AMPK as they contain a mutation in LKB1, which prevents activation of AMPK. However, A549 cells increased utilization of the Pentose Phosphate pathway (PPP) and had lower reactive oxygen species (ROS) levels than H1334 cells, indicating that A549 cells are better able to modulate an increase in oxidative stress. Inherent resistance of LC-KJ cells is associated with higher baseline levels of NADPH and a delayed reduction of NAD upon NAMPT inhibition. Our data reveals that cell lines show heterogeneous response to NAD depletion and that the underlying molecular and genetic framework in cells can influence the metabolic response to NAMPT inhibition.

Metabolic Response to NAD Depletion across Cell Lines Is Highly Variable.

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Yang Xiao

Full Text Available Nicotinamide adenine dinucleotide (NAD is a cofactor involved in a wide range of cellular metabolic processes and is a key metabolite required for tumor growth. NAMPT, nicotinamide phosphoribosyltransferase, which converts nicotinamide (NAM to nicotinamide mononucleotide (NMN, the immediate precursor of NAD, is an attractive therapeutic target as inhibition of NAMPT reduces cellular NAD levels and inhibits tumor growth in vivo. However, there is limited understanding of the metabolic response to NAD depletion across cancer cell lines and whether all cell lines respond in a uniform manner. To explore this we selected two non-small cell lung carcinoma cell lines that are sensitive to the NAMPT inhibitor GNE-617 (A549, NCI-H1334, one that shows intermediate sensitivity (NCI-H441, and one that is insensitive (LC-KJ. Even though NAD was reduced in all cell lines there was surprising heterogeneity in their metabolic response. Both sensitive cell lines reduced glycolysis and levels of di- and tri-nucleotides and modestly increased oxidative phosphorylation, but they differed in their ability to combat oxidative stress. H1334 cells activated the stress kinase AMPK, whereas A549 cells were unable to activate AMPK as they contain a mutation in LKB1, which prevents activation of AMPK. However, A549 cells increased utilization of the Pentose Phosphate pathway (PPP and had lower reactive oxygen species (ROS levels than H1334 cells, indicating that A549 cells are better able to modulate an increase in oxidative stress. Inherent resistance of LC-KJ cells is associated with higher baseline levels of NADPH and a delayed reduction of NAD upon NAMPT inhibition. Our data reveals that cell lines show heterogeneous response to NAD depletion and that the underlying molecular and genetic framework in cells can influence the metabolic response to NAMPT inhibition.

AMPK regulates metabolism and survival in response to ionizing radiation

International Nuclear Information System (INIS)

Zannella, Vanessa E.; Cojocari, Dan; Hilgendorf, Susan; Vellanki, Ravi N.; Chung, Stephen; Wouters, Bradly G.; Koritzinsky, Marianne

2011-01-01

Background and purpose: AMPK is a metabolic sensor and an upstream inhibitor of mTOR activity. AMPK is phosphorylated by ionizing radiation (IR) in an ATM dependent manner, but the cellular consequences of this phosphorylation event have remained unclear. The objective of this study was to assess whether AMPK plays a functional role in regulating cellular responses to IR. Methods: The importance of AMPK expression for radiation responses was investigated using both MEFs (mouse embryo fibroblasts) double knockout for AMPK α1/α2 subunits and human colorectal carcinoma cells (HCT 116) with AMPK α1/α2 shRNA mediated knockdown. Results: We demonstrate here that IR results in phosphorylation of both AMPK and its substrate, ACC. IR moderately stimulated mTOR activity, and this was substantially exacerbated in the absence of AMPK. AMPK was required for IR induced expression of the mTOR inhibitor REDD1, indicating that AMPK restrains mTOR activity through multiple mechanisms. Likewise, cellular metabolism was deregulated following irradiation in the absence of AMPK, as evidenced by a substantial increase in oxygen consumption rates and lactate production. AMPK deficient cells showed impairment of the G1/S cell cycle checkpoint, and were unable to support long-term proliferation during starvation following radiation. Lastly, we show that AMPK proficiency is important for clonogenic survival after radiation during starvation. Conclusions: These data reveal novel functional roles for AMPK in regulating mTOR signaling, cell cycle, survival and metabolic responses to IR.

Ruminant Nutrition Symposium: ruminant production and metabolic responses to heat stress.

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Baumgard, L H; Rhoads, R P

2012-06-01

Heat stress compromises efficient animal production by marginalizing nutrition, management, and genetic selection efforts to maximize performance endpoints. Modifying farm infrastructure has yielded modest success in mitigating heat stress-related losses, yet poor production during the summer remains arguably the costliest issue facing livestock producers. Reduced output (e.g., milk yield and muscle growth) during heat stress was traditionally thought to result from decreased nutrient intake (i.e., a classic biological response shared by all animals during environmental-induced hyperthermia). Our recent observations have begun to challenge this belief and indicate heat-stressed animals employ novel homeorhetic strategies to direct metabolic and fuel selection priorities independently of nutrient intake or energy balance. Alterations in systemic physiology support a shift in carbohydrate metabolism, evident by increased basal and stimulated circulating insulin concentrations. Perhaps most intriguing given the energetic shortfall of the heat-stressed animal is the apparent lack of basal adipose tissue mobilization coupled with a reduced responsiveness to lipolytic stimuli. Thus, the heat stress response markedly alters postabsorptive carbohydrate, lipid, and protein metabolism independently of reduced feed intake through coordinated changes in fuel supply and utilization by multiple tissues. Interestingly, the systemic, cellular, and molecular changes appear conserved amongst different species and physiological states. Ultimately, these changes result in the reprioritization of fuel selection during heat stress, which appears to be primarily responsible for reduced ruminant animal productivity during the warm summer months.

LKB1 promotes metabolic flexibility in response to energy stress.

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Parker, Seth J; Svensson, Robert U; Divakaruni, Ajit S; Lefebvre, Austin E; Murphy, Anne N; Shaw, Reuben J; Metallo, Christian M

2017-09-01

The Liver Kinase B1 (LKB1) tumor suppressor acts as a metabolic energy sensor to regulate AMP-activated protein kinase (AMPK) signaling and is commonly mutated in various cancers, including non-small cell lung cancer (NSCLC). Tumor cells deficient in LKB1 may be uniquely sensitized to metabolic stresses, which may offer a therapeutic window in oncology. To address this question we have explored how functional LKB1 impacts the metabolism of NSCLC cells using 13 C metabolic flux analysis. Isogenic NSCLC cells expressing functional LKB1 exhibited higher flux through oxidative mitochondrial pathways compared to those deficient in LKB1. Re-expression of LKB1 also increased the capacity of cells to oxidize major mitochondrial substrates, including pyruvate, fatty acids, and glutamine. Furthermore, LKB1 expression promoted an adaptive response to energy stress induced by anchorage-independent growth. Finally, this diminished adaptability sensitized LKB1-deficient cells to combinatorial inhibition of mitochondrial complex I and glutaminase. Together, our data implicate LKB1 as a major regulator of adaptive metabolic reprogramming and suggest synergistic pharmacological strategies for mitigating LKB1-deficient NSCLC tumor growth. Copyright © 2016. Published by Elsevier Inc.

System level analysis of cacao seed ripening reveals a sequential interplay of primary and secondary metabolism leading to polyphenol accumulation and preparation of stress resistance.

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Wang, Lei; Nägele, Thomas; Doerfler, Hannes; Fragner, Lena; Chaturvedi, Palak; Nukarinen, Ella; Bellaire, Anke; Huber, Werner; Weiszmann, Jakob; Engelmeier, Doris; Ramsak, Ziva; Gruden, Kristina; Weckwerth, Wolfram

2016-08-01

Theobroma cacao and its popular product, chocolate, are attracting attention due to potential health benefits including antioxidative effects by polyphenols, anti-depressant effects by high serotonin levels, inhibition of platelet aggregation and prevention of obesity-dependent insulin resistance. The development of cacao seeds during fruit ripening is the most crucial process for the accumulation of these compounds. In this study, we analyzed the primary and the secondary metabolome as well as the proteome during Theobroma cacao cv. Forastero seed development by applying an integrative extraction protocol. The combination of multivariate statistics and mathematical modelling revealed a complex consecutive coordination of primary and secondary metabolism and corresponding pathways. Tricarboxylic acid (TCA) cycle and aromatic amino acid metabolism dominated during the early developmental stages (stages 1 and 2; cell division and expansion phase). This was accompanied with a significant shift of proteins from phenylpropanoid metabolism to flavonoid biosynthesis. At stage 3 (reserve accumulation phase), metabolism of sucrose switched from hydrolysis into raffinose synthesis. Lipids as well as proteins involved in lipid metabolism increased whereas amino acids and N-phenylpropenoyl amino acids decreased. Purine alkaloids, polyphenols, and raffinose as well as proteins involved in abiotic and biotic stress accumulated at stage 4 (maturation phase) endowing cacao seeds the characteristic astringent taste and resistance to stress. In summary, metabolic key points of cacao seed development comprise the sequential coordination of primary metabolites, phenylpropanoid, N-phenylpropenoyl amino acid, serotonin, lipid and polyphenol metabolism thereby covering the major compound classes involved in cacao aroma and health benefits. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

Modeling metabolic response to changes of enzyme amount in ...

African Journals Online (AJOL)

Based on the work of Hynne et al. (2001), in an in silico model of glycolysis, Saccharomyces cerevisiae is established by introducing an enzyme amount multiple factor (.) into the kinetic equations. The model is aimed to predict the metabolic response to the change of enzyme amount. With the help of .α, the amounts of ...

Large-scale transcriptome analysis reveals arabidopsis metabolic pathways are frequently influenced by different pathogens.

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Jiang, Zhenhong; He, Fei; Zhang, Ziding

2017-07-01

Through large-scale transcriptional data analyses, we highlighted the importance of plant metabolism in plant immunity and identified 26 metabolic pathways that were frequently influenced by the infection of 14 different pathogens. Reprogramming of plant metabolism is a common phenomenon in plant defense responses. Currently, a large number of transcriptional profiles of infected tissues in Arabidopsis (Arabidopsis thaliana) have been deposited in public databases, which provides a great opportunity to understand the expression patterns of metabolic pathways during plant defense responses at the systems level. Here, we performed a large-scale transcriptome analysis based on 135 previously published expression samples, including 14 different pathogens, to explore the expression pattern of Arabidopsis metabolic pathways. Overall, metabolic genes are significantly changed in expression during plant defense responses. Upregulated metabolic genes are enriched on defense responses, and downregulated genes are enriched on photosynthesis, fatty acid and lipid metabolic processes. Gene set enrichment analysis (GSEA) identifies 26 frequently differentially expressed metabolic pathways (FreDE_Paths) that are differentially expressed in more than 60% of infected samples. These pathways are involved in the generation of energy, fatty acid and lipid metabolism as well as secondary metabolite biosynthesis. Clustering analysis based on the expression levels of these 26 metabolic pathways clearly distinguishes infected and control samples, further suggesting the importance of these metabolic pathways in plant defense responses. By comparing with FreDE_Paths from abiotic stresses, we find that the expression patterns of 26 FreDE_Paths from biotic stresses are more consistent across different infected samples. By investigating the expression correlation between transcriptional factors (TFs) and FreDE_Paths, we identify several notable relationships. Collectively, the current study

Radiographic and metabolic response rates following image-guided stereotactic radiotherapy for lung tumors

International Nuclear Information System (INIS)

Mohammed, Nasiruddin; Grills, Inga S.; Wong, Ching-Yee Oliver; Galerani, Ana Paula; Chao, Kenneth; Welsh, Robert; Chmielewski, Gary; Yan Di; Kestin, Larry L.

2011-01-01

Purpose: To evaluate radiographic and metabolic response after stereotactic body radiotherapy (SBRT) for early lung tumors. Materials and methods: Thirty-nine tumors were treated prospectively with SBRT (dose = 48-60 Gy, 4-5 Fx). Thirty-six cases were primary NSCLC (T1N0 = 67%; T2N0 = 25%); three cases were solitary metastases. Patients were followed using CT and PET at 6, 16, and 52 weeks post-SBRT, with CT follow-up thereafter. RECIST and EORTC criteria were used to evaluate CT and PET responses. Results: At median follow-up of 9 months (0.4-26), RECIST complete response (CR), partial response (PR), and stable disease (SD) rates were 3%, 43%, 54% at 6 weeks; 15%, 38%, 46% at 16 weeks; 27%, 64%, 9% at 52 weeks. Mean baseline tumor volume was reduced by 46%, 70%, 87%, and 96%, respectively at 6, 16, 52, and 72 weeks. Mean baseline maximum standardized uptake value (SUV) was 8.3 (1.1-20.3) and reduced to 3.4, 3.0, and 3.7 at 6, 16, and 52 weeks after SBRT. EORTC metabolic CR/PR, SD, and progressive disease rates were 67%, 22%, 11% at 6 weeks; 86%, 10%, 3% at 16 weeks; 95%, 5%, 0% at 52 weeks. Conclusions: SBRT yields excellent RECIST and EORTC based response. Metabolic response is rapid however radiographic response occurs even after 1-year post treatment.

Estimation method for first excursion probability of secondary system with impact and friction using maximum response

International Nuclear Information System (INIS)

Shigeru Aoki

2005-01-01

The secondary system such as pipings, tanks and other mechanical equipment is installed in the primary system such as building. The important secondary systems should be designed to maintain their function even if they are subjected to destructive earthquake excitations. The secondary system has many nonlinear characteristics. Impact and friction characteristic, which are observed in mechanical supports and joints, are common nonlinear characteristics. As impact damper and friction damper, impact and friction characteristic are used for reduction of seismic response. In this paper, analytical methods of the first excursion probability of the secondary system with impact and friction, subjected to earthquake excitation are proposed. By using the methods, the effects of impact force, gap size and friction force on the first excursion probability are examined. When the tolerance level is normalized by the maximum response of the secondary system without impact or friction characteristics, variation of the first excursion probability is very small for various values of the natural period. In order to examine the effectiveness of the proposed method, the obtained results are compared with those obtained by the simulation method. Some estimation methods for the maximum response of the secondary system with nonlinear characteristics have been developed. (author)

The metabolic cost of mounting an immune response in male brown anoles (Anolis sagrei).

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Cox, Christian L; Peaden, Robert T; Cox, Robert M

2015-09-09

The tradeoff between reproduction and survival is central to life-history theory and is thought to reflect underlying energetic tradeoffs between reproduction and self-maintenance. Immune responses to parasites and pathogens are important components of self-maintenance in many species, but whether these defenses impose significant energetic costs has only been tested in a handful of organisms. We tested for a metabolic cost of mounting an immune response in the male brown anole (Anolis sagrei), a lizard in which we have previously shown that reproduction causes a marked reduction in immune response to the novel antigen phytohaemagglutinin (PHA). We treated captive male anoles with a subcutaneous injection of either PHA, which induces an immune response that manifests as localized swelling, or saline vehicle as a control. Prior to injection and at 24, 48, and 72 hr post-injection, we measured swelling at the site of injection and whole-animal resting metabolic rate (RMR) using stop-flow respirometry. Although we detected a robust swelling response to PHA at 24, 48, and 72 hr post-injection, mean RMR did not differ between treatments at any of these time points. However, within the PHA treatment group, RMR increased with the extent of swelling, suggesting a variable metabolic cost that scales with the magnitude of the induced immune response. Although individual anoles varied considerably in the extent to which they responded to PHA challenge, our results suggest that an immune response can impose a substantial metabolic cost (potentially as much as 63% above baseline RMR) for individuals that do respond maximally. J. Exp. Zool. 9999A:XX-XX, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Effect of radiographic contrast agents on leukocyte metabolic response

International Nuclear Information System (INIS)

Hernanz-Schulman, M.; Vanholder, R.; Waterloos, M.A.; Hakim, R.; Schulman, G.

2000-01-01

Barium, at clinical dilutions, causes a significant increase of baseline ''resting state'' phagocytic activity, which in turn leads to significant blunting of subsequent response to phagocytic challenge and adversely affects the response to all bacteria tested. There is no baseline activation of leukocytes by the water-soluble media, although there was some inhibition (rather than activation) of leukocyte metabolic activity. The effect of the water-soluble media in bacteria was more complex (although inhibition is minor compared to barium). Our data demonstrate that barium is a significant activator of phagocytic cells, which results in deactivation of phagocytic response when challenged; these data serve to explain the enhanced adverse effect of barium in cased of fecal peritonitis. (orig.)

Metabolic responses of primary and transformed cells to intracellular Listeria monocytogenes.

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Nadine Gillmaier

Full Text Available The metabolic response of host cells, in particular of primary mammalian cells, to bacterial infections is poorly understood. Here, we compare the carbon metabolism of primary mouse macrophages and of established J774A.1 cells upon Listeria monocytogenes infection using (13C-labelled glucose or glutamine as carbon tracers. The (13C-profiles of protein-derived amino acids from labelled host cells and intracellular L. monocytogenes identified active metabolic pathways in the different cell types. In the primary cells, infection with live L. monocytogenes increased glycolytic activity and enhanced flux of pyruvate into the TCA cycle via pyruvate dehydrogenase and pyruvate carboxylase, while in J774A.1 cells the already high glycolytic and glutaminolytic activities hardly changed upon infection. The carbon metabolism of intracellular L. monocytogenes was similar in both host cells. Taken together, the data suggest that efficient listerial replication in the cytosol of the host cells mainly depends on the glycolytic activity of the hosts.

Photoacoustic microscopy of cerebral hemodynamic and oxygen-metabolic responses to anesthetics

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Cao, Rui; Li, Jun; Ning, Bo; Sun, Naidi; Wang, Tianxiong; Zuo, Zhiyi; Hu, Song

2017-02-01

General anesthetics are known to have profound effects on cerebral hemodynamics and neuronal activities. However, it remains a challenge to directly assess anesthetics-induced hemodynamic and oxygen-metabolic changes from the true baseline under wakefulness at the microscopic level, due to the lack of an enabling technology for high-resolution functional imaging of the awake mouse brain. To address this challenge, we have developed head-restrained photoacoustic microscopy (PAM), which enables simultaneous imaging of the cerebrovascular anatomy, total concentration and oxygen saturation of hemoglobin (CHb and sO2), and blood flow in awake mice. From these hemodynamic measurements, two important metabolic parameters, oxygen extraction fraction (OEF) and the cerebral metabolic rate of oxygen (CMRO2), can be derived. Side-by-side comparison of the mouse brain under wakefulness and anesthesia revealed multifaceted cerebral responses to isoflurane, a volatile anesthetic widely used in preclinical research and clinical practice. Key observations include elevated cerebral blood flow (CBF) and reduced oxygen extraction and metabolism.

Effect of paricalcitol on mineral bone metabolism in kidney transplant recipients with secondary hyperparathyroidism.

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Borrego Utiel, Francisco José; Bravo Soto, Juan Antonio; Merino Pérez, María José; González Carmelo, Isabel; López Jiménez, Verónica; García Álvarez, Teresa; Acosta Martínez, Yelenei; Mazuecos Blanca, María Auxiliadora

2015-01-01

Secondary hyperparathyroidism is highly prevalent in kidney transplant recipients, and commonly results in hypercalcaemia; an association to osteopenia and bone fractures has also been observed. Paricalcitol has proved effective to control secondary hyperparathyroidism in chronic kidney disease in both dialysed and non-dialysed patients, with a low hypercalcaemia incidence. Currently available experience on paricalcitol use in kidney transplant recipients is scarce. Our main aim was to show the effect of paricalcitol on mineral bone metabolism in kidney transplant recipients with secondary hyperparathyroidism. A retrospective multicentre study in kidney transplant recipients aged>18 years with a 12-month or longer post-transplantation course, stable renal function, having received paricalcitol for more than 12 months, with available clinical follow-up for a 24-month period. A total of 69 patients with a 120 ± 92-month post-transplantation course were included. Baseline creatinine was 2.2 ± 0.9 mg/dl y GFR-MDRD was 36 ± 20 ml/min/1.73 m(2). Paricalcitol doses were gradually increased during the study: baseline 3.8 ± 1.9 μg/week, 12 months 5.2 ± 2.4 μg/week; 24 months 6.0 ± 2.9 μg/week (P10mg/dl showed gradually decreasing levels. Fifteen (21.7%) patients had received prior calcitriol therapy. When shifted to paricalcitol, such patients required paricalcitol doses significantly larger than those not having received calcitriol. Paricalcitol was used concomitantly to cinacalcet in 11 patients with significant PTH reductions being achieved; clinical course was similar to other patients and paricalcitol doses were also similar. Paricalcitol is an effective therapy for secondary hyperparathyroidism in kidney transplant recipients. Overall, no significant changes were observed in calcium and phosphorus levels or urinary excretion. Patients having previously received calcitriol required higher paricalcitol doses. When used in patients receiving cinacalcet

Regulatory network of secondary metabolism in Brassica rapa: insight into the glucosinolate pathway.

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Dunia Pino Del Carpio

Full Text Available Brassica rapa studies towards metabolic variation have largely been focused on the profiling of the diversity of metabolic compounds in specific crop types or regional varieties, but none aimed to identify genes with regulatory function in metabolite composition. Here we followed a genetical genomics approach to identify regulatory genes for six biosynthetic pathways of health-related phytochemicals, i.e carotenoids, tocopherols, folates, glucosinolates, flavonoids and phenylpropanoids. Leaves from six weeks-old plants of a Brassica rapa doubled haploid population, consisting of 92 genotypes, were profiled for their secondary metabolite composition, using both targeted and LC-MS-based untargeted metabolomics approaches. Furthermore, the same population was profiled for transcript variation using a microarray containing EST sequences mainly derived from three Brassica species: B. napus, B. rapa and B. oleracea. The biochemical pathway analysis was based on the network analyses of both metabolite QTLs (mQTLs and transcript QTLs (eQTLs. Co-localization of mQTLs and eQTLs lead to the identification of candidate regulatory genes involved in the biosynthesis of carotenoids, tocopherols and glucosinolates. We subsequently focused on the well-characterized glucosinolate pathway and revealed two hotspots of co-localization of eQTLs with mQTLs in linkage groups A03 and A09. Our results indicate that such a large-scale genetical genomics approach combining transcriptomics and metabolomics data can provide new insights into the genetic regulation of metabolite composition of Brassica vegetables.

Piriformospora indica root colonization triggers local and systemic root responses and inhibits secondary colonization of distal roots.

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Pedrotti, Lorenzo; Mueller, Martin J; Waller, Frank

2013-01-01

Piriformosporaindica is a basidiomycete fungus colonizing roots of a wide range of higher plants, including crop plants and the model plant Arabidopsis thaliana. Previous studies have shown that P. indica improves growth, and enhances systemic pathogen resistance in leaves of host plants. To investigate systemic effects within the root system, we established a hydroponic split-root cultivation system for Arabidopsis. Using quantitative real-time PCR, we show that initial P. indica colonization triggers a local, transient response of several defense-related transcripts, of which some were also induced in shoots and in distal, non-colonized roots of the same plant. Systemic effects on distal roots included the inhibition of secondary P. indica colonization. Faster and stronger induction of defense-related transcripts during secondary inoculation revealed that a P. indica pretreatment triggers root-wide priming of defense responses, which could cause the observed reduction of secondary colonization levels. Secondary P. indica colonization also induced defense responses in distant, already colonized parts of the root. Endophytic fungi therefore trigger a spatially specific response in directly colonized and in systemic root tissues of host plants.

Secondary Metabolites from Higher Fungi: Discovery, Bioactivity, and Bioproduction

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Zhong, Jian-Jiang; Xiao, Jian-Hui

Medicinal higher fungi such as Cordyceps sinensis and Ganoderma lucidum have been used as an alternative medicine remedy to promote health and longevity for people in China and other regions of the world since ancient times. Nowadays there is an increasing public interest in the secondary metabolites of those higher fungi for discovering new drugs or lead compounds. Current research in drug discovery from medicinal higher fungi involves a multifaceted approach combining mycological, biochemical, pharmacological, metabolic, biosynthetic and molecular techniques. In recent years, many new secondary metabolites from higher fungi have been isolated and are more likely to provide lead compounds for new drug discovery, which may include chemopreventive agents possessing the bioactivity of immunomodulatory, anticancer, etc. However, numerous challenges of secondary metabolites from higher fungi are encountered including bioseparation, identification, biosynthetic metabolism, and screening model issues, etc. Commercial production of secondary metabolites from medicinal mushrooms is still limited mainly due to less information about secondary metabolism and its regulation. Strategies for enhancing secondary metabolite production by medicinal mushroom fermentation include two-stage cultivation combining liquid fermentation and static culture, two-stage dissolved oxygen control, etc. Purification of bioactive secondary metabolites, such as ganoderic acids from G. lucidum, is also very important to pharmacological study and future pharmaceutical application. This review outlines typical examples of the discovery, bioactivity, and bioproduction of secondary metabolites of higher fungi origin.

Program to Promote Personal and Social Responsibility in the Secondary Classroom

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Miguel A. Carbonero

2017-05-01

Full Text Available The performance of school children has been studied by considering partial relationships between several personal variables such as the link between cognition and motivation. However, contextual variables, such as a child’s willingness to accept social responsibility, also influence students’ social and academic performance. Thus, students with greater responsibility have a better attitude toward their studies, resulting in higher academic achievement. This 2-year study aims to reveal to what extent an intervention program affects student performance and is based on the Theory of Positive Action among young people proposed by Don Hellison and the Theory of Reasoned Action by Fishbein and Ajzen. The program focuses on positive influences on social and personal responsibility, taking into consideration parental styles, gender, and academic performance. The program was a part of the educational curricula in participating schools and it targeted four main areas: (a teaching units using academic texts about social responsibility, (b student training in mediation processes, (c teacher training, and (d family training and involvement. A total of 271 students took part from first and second year of Secondary Education (12–14 years old. The experimental group was made up of 132 students while the remaining 139 formed the control group. All participants completed the Assessment Scale of Social Responsibility Attitudes in Secondary Education and the Parent–Adolescent Communication Scale. Results show that students in the experimental group performed significantly better than those in the control group. Additionally, the issue of social responsibility seems to be related to commitment, self-discipline and perseverance. Regarding gender, males appear to score higher in the factor for well-mannered, friendly and tidy. Finally, a positive relationship has been identified between social responsibility attitudes and parenting with an open communicational

Program to Promote Personal and Social Responsibility in the Secondary Classroom.

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Carbonero, Miguel A; Martín-Antón, Luis J; Otero, Lourdes; Monsalvo, Eugenio

2017-01-01

The performance of school children has been studied by considering partial relationships between several personal variables such as the link between cognition and motivation. However, contextual variables, such as a child's willingness to accept social responsibility, also influence students' social and academic performance. Thus, students with greater responsibility have a better attitude toward their studies, resulting in higher academic achievement. This 2-year study aims to reveal to what extent an intervention program affects student performance and is based on the Theory of Positive Action among young people proposed by Don Hellison and the Theory of Reasoned Action by Fishbein and Ajzen. The program focuses on positive influences on social and personal responsibility, taking into consideration parental styles, gender, and academic performance. The program was a part of the educational curricula in participating schools and it targeted four main areas: (a) teaching units using academic texts about social responsibility, (b) student training in mediation processes, (c) teacher training, and (d) family training and involvement. A total of 271 students took part from first and second year of Secondary Education (12-14 years old). The experimental group was made up of 132 students while the remaining 139 formed the control group. All participants completed the Assessment Scale of Social Responsibility Attitudes in Secondary Education and the Parent-Adolescent Communication Scale. Results show that students in the experimental group performed significantly better than those in the control group. Additionally, the issue of social responsibility seems to be related to commitment, self-discipline and perseverance. Regarding gender, males appear to score higher in the factor for well-mannered, friendly and tidy. Finally, a positive relationship has been identified between social responsibility attitudes and parenting with an open communicational style. This paper

Metabolic responses to exogenous ghrelin in obesity and early after Roux-en-Y gastric bypass in humans.

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Tamboli, Robyn A; Antoun, Joseph; Sidani, Reem M; Clements, Austin; Harmata, Emily E; Marks-Shulman, Pam; Gaylinn, Bruce D; Williams, Brandon; Clements, Ronald H; Albaugh, Vance L; Abumrad, Naji N

2017-09-01

Ghrelin is a gastric-derived hormone that stimulates growth hormone (GH) secretion and has a multi-faceted role in the regulation of energy homeostasis, including glucose metabolism. Circulating ghrelin concentrations are modulated in response to nutritional status, but responses to ghrelin in altered metabolic states are poorly understood. We investigated the metabolic effects of ghrelin in obesity and early after Roux-en-Y gastric bypass (RYGB). We assessed central and peripheral metabolic responses to acyl ghrelin infusion (1 pmol kg -1  min -1 ) in healthy, lean subjects (n = 9) and non-diabetic, obese subjects (n = 9) before and 2 weeks after RYGB. Central responses were assessed by GH and pancreatic polypeptide (surrogate for vagal activity) secretion. Peripheral responses were assessed by hepatic and skeletal muscle insulin sensitivity during a hyperinsulinaemic-euglycaemic clamp. Ghrelin-stimulated GH secretion was attenuated in obese subjects, but was restored by RYGB to a response similar to that of lean subjects. The heightened pancreatic polypeptide response to ghrelin infusion in the obese was attenuated after RYGB. Hepatic glucose production and hepatic insulin sensitivity were not altered by ghrelin infusion in RYGB subjects. Skeletal muscle insulin sensitivity was impaired to a similar degree in lean, obese and post-RYGB individuals in response to ghrelin infusion. These data suggest that obesity is characterized by abnormal central, but not peripheral, responsiveness to ghrelin that can be restored early after RYGB before significant weight loss. Further work is necessary to fully elucidate the role of ghrelin in the metabolic changes that occur in obesity and following RYGB. © 2017 John Wiley & Sons Ltd.

L-carnitine: a partner between immune response and lipid metabolism ?

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Giuseppe Famularo

1993-01-01

Full Text Available The authors demonstrated that in vivo administered L-carnitine strongly ameliorated the immune response in both healthy individuals receiving Intralipid and ageing subjects with cardiovascular diseases, as shown by the enhancement of mixed lymphocyte reaction. Notably, in the latter group L-carnitine treatment also resulted in a significant reduction of serum levels of both cholesterol and triglycerides. Therefore, the hypothesis is that L-carnitine supplementation could ameliorate both the dysregulated immune response and the abnormal lipid metabolism in several conditions.

Whole-body CO2 production as an index of the metabolic response to sepsis

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Whole-body carbon dioxide (CO2) production (RaCO2) is an index of substrate oxidation and energy expenditure; therefore, it may provide information about the metabolic response to sepsis. Using stable isotope techniques, we determined RaCO2 and its relationship to protein and glucose metabolism in m...

The Metabolic Response to Stress and Infection in Critically Ill Children: The Opportunity of an Individualized Approach

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Valentina De Cosmi

2017-09-01

Full Text Available The metabolic response to stress and infection is closely related to the corresponding requirements of energy and nutrients. On a general level, the response is driven by a complex endocrine network and related to the nature and severity of the insult. On an individual level, the effects of nutritional interventions are highly variable and a possible source of complications. This narrative review aims to discuss the metabolic changes in critically-ill children and the potential of developing personalized nutritional interventions. Through a literature search strategy, we have investigated the importance of blood glucose levels, the nutritional aspects of the different phases of acute stress response, and the reliability of the available tools to assess the energy expenditure. The dynamics of metabolism during stressful events reveals the difficult balance between risk of hypo- or hyperglycemia and under- or overfeeding. Within this context, individualized and accurate measurement of energy expenditure may help in defining the metabolic needs of patients. Given the variability of the metabolic response in critical conditions, randomized clinical studies in ill children are needed to evaluate the effect of individualized nutritional intervention on health outcomes.

Hypothalamic miR-219 regulates individual metabolic differences in response to diet-induced weight cycling

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Mariana Schroeder

2018-03-01

Full Text Available Consumption of a low calorie diet is the most common approach to lose weight. While generally effective at first, it is frequently followed by a relapse where the pre-diet weight is regained, and often exceeded. This pattern of repeated weight loss/regain is referred to as weight cycling and the resulting metabolic response varies greatly between individuals. Objective: We attempted to address the issue of individual differences in the response to weight cycling in male mice. Methods: We first exposed adult wild type mice to repeated cycles of high/low fat food. Next, using a lentiviral approach, we knocked-down or over-expressed miR-219 in the ventromedial hypothalamus (VMH of an additional mouse cohort and performed a full metabolic assessment. Results: Exposure of wild type males to weight cycling resulted in the division of the cohort into subsets of resistant versus metabolic-syndrome-prone (MS animals, which differed in their metabolic profile and hypothalamic miR-219 levels. Lentiviral knock-down of miR-219 in the VMH led to exacerbation of metabolic syndrome. In contrast, over-expression of miR-219 resulted in moderation of the metabolic syndrome phenotype. Conclusions: Our results suggest a role for miR-219 in the mediation of the metabolic phenotype resulting from repeated weight cycling. Keywords: Weight cycling, Metabolic syndrome, miRNAs, Ventromedial hypothalamus, High fat diet, Diabetes

Effect of radiographic contrast agents on leukocyte metabolic response

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Hernanz-Schulman, M. [Dept. of Pediatric Radiology, Vanderbilt Children' s Hospital, Nashville, TN (United States); Vanholder, R.; Waterloos, M.A. [Dept. of Internal Medicine, Nephrology Section, University Hospital, Gent (Belgium); Hakim, R.; Schulman, G. [Department of Nephrology, Vanderbilt University Medical Center, Nashville, TN (United States)

2000-06-01

Barium, at clinical dilutions, causes a significant increase of baseline ''resting state'' phagocytic activity, which in turn leads to significant blunting of subsequent response to phagocytic challenge and adversely affects the response to all bacteria tested. There is no baseline activation of leukocytes by the water-soluble media, although there was some inhibition (rather than activation) of leukocyte metabolic activity. The effect of the water-soluble media in bacteria was more complex (although inhibition is minor compared to barium). Our data demonstrate that barium is a significat activator of phagocytic cells, which results in deactivation of phagocytic response when challenged; these dsata serve to explain the enhanced adverse effect of barium in cased of fecal peritonitis. (orig.)

Investigating the Cellular and Metabolic Responses of World-Class Canoeists Training: A Sportomics Approach

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Wagner Santos Coelho

2016-11-01

Full Text Available (1 Background: We have been using the Sportomics approach to evaluate biochemical and hematological changes in response to exercise. The aim of this study was to evaluate the metabolic and hematologic responses of world-class canoeists during a training session; (2 Methods: Blood samples were taken at different points and analyzed for their hematological properties, activities of selected enzymes, hormones, and metabolites; (3 Results: Muscle stress biomarkers were elevated in response to exercise which correlated with modifications in the profile of white blood cells, where a leukocyte rise was observed after the canoe session. These results were accompanied by an increase in other exercise intensity parameters such as lactatemia and ammonemia. Adrenocorticotropic hormone and cortisol increased during the exercise sessions. The acute rise in both erythrocytes and white blood profile were probably due to muscle cell damage, rather than hepatocyte integrity impairment; (4 Conclusion: The cellular and metabolic responses found here, together with effective nutrition support, are crucial to understanding the effects of exercise in order to assist in the creation of new training and recovery planning. Also we show that Sportomics is a primal tool for training management and performance improvement, as well as to the understanding of metabolic response to exercise.

Dynamic Responses of Phosphorus Metabolism to Acute and Chronic Dietary Phosphorus-Limitation in Daphnia

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Nicole D. Wagner

2017-06-01

Full Text Available Food quality is highly dynamic within lake ecosystems and varies spatially and temporally over the growing season. Consumers may need to continuously adjust their metabolism in response to this variation in dietary nutrient content. However, the rates of metabolic responses to changes in food nutrient content has received little direct study. Here, we examine responses in two metabolic phosphorus (P pools, ribonucleic acids (RNA and adenosine triphosphate (ATP, along with body mass and body P content in Daphnia magna exposed to chronic and acute dietary P-limitation. First, we examined food quality effects on animals consuming different food carbon (C:P quality over a 14 day period. Then, we raised daphnids on one food quality for 4 days, switched them to contrasting dietary treatments, and measured changes in their metabolic responses at shorter time-scales (over 48 h. Animal P, RNA, and ATP content all changed through ontogeny with adults containing relatively less of these pools with increasing body mass. Irrespective of age, Daphnia consuming high C:P diets had lower body %P, %RNA, %ATP, and mass compared to animals eating low C:P diets. Diet switching experiments revealed diet dependent changes in body %P, %RNA, %ATP, and animal mass within 48 h. We found that Daphnia switched from low to high C:P diets had some metabolic buffering capacity with decreases in body %P occurring after 24 h but mass remaining similar to initial diet conditions for 36 h after the diet switch. Switching Daphnia from low to high C:P diets caused a decrease in the RNA:P ratio after 48 h. Daphnia switched from high to low C:P diets increased their body P, RNA, and ATP content within 8–24 h. This switch from high to low C:P diets also led to increased RNA:P ratios in animal bodies. Overall, our study revealed that consumer P metabolism reflects both current and past diet due to more dynamic and rapid changes in P biochemistry than total body mass. This metabolic

Cardiovascular and metabolic responses to fasting and thermoneutrality are conserved in obese Zucker rats.

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Overton, J M; Williams, T D; Chambers, J B; Rashotte, M E

2001-04-01

The primary purpose of the study was to test the hypothesis that reduced leptin signaling is necessary to elicit the cardiovascular and metabolic responses to fasting. Lean (Fa/?; normal leptin receptor; n = 7) and obese (fa/fa; mutated leptin receptor; n = 8) Zucker rats were instrumented with telemetry transmitters and housed in metabolic chambers at 23 degrees C (12:12-h light-dark cycle) for continuous (24 h) measurement of metabolic and cardiovascular variables. Before fasting, mean arterial pressure (MAP) was higher (MAP: obese = 103 +/- 3; lean = 94 +/- 1 mmHg), whereas oxygen consumption (VO(2): obese = 16.5 +/- 0.3; lean = 18.6 +/- 0.2 ml. min(-1). kg(-0.75)) was lower in obese Zucker rats compared with their lean controls. Two days of fasting had no effect on MAP in either lean or obese Zucker rats, whereas VO(2) (obese = -3.1 +/- 0.3; lean = -2.9 +/- 0.1 ml. min(-1). kg(-0.75)) and heart rate (HR: obese = -56 +/- 4; lean = -42 +/- 4 beats/min) were decreased markedly in both groups. Fasting increased HR variability both in lean (+1.8 +/- 0.4 ms) and obese (+2.6 +/- 0.3 ms) Zucker rats. After a 6-day period of ad libitum refeeding, when all parameters had returned to near baseline levels, the cardiovascular and metabolic responses to 2 days of thermoneutrality (ambient temperature 29 degrees C) were determined. Thermoneutrality reduced VO(2) (obese = -2.4 +/- 0.2; lean = -3.3 +/- 0.2 ml. min(-1). kg(-0.75)), HR (obese = -46 +/- 5; lean = -55 +/- 4 beats/min), and MAP (obese = -13 +/- 6; lean = -10 +/- 1 mmHg) similarly in lean and obese Zucker rats. The results indicate that the cardiovascular and metabolic responses to fasting and thermoneutrality are conserved in Zucker rats and suggest that intact leptin signaling may not be requisite for the metabolic and cardiovascular responses to reduced energy intake.

The structure of wheat bread influences the postprandial metabolic response in healthy men.

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Eelderink, Coby; Noort, Martijn W J; Sozer, Nesli; Koehorst, Martijn; Holst, Jens J; Deacon, Carolyn F; Rehfeld, Jens F; Poutanen, Kaisa; Vonk, Roel J; Oudhuis, Lizette; Priebe, Marion G

2015-10-01

Postprandial high glucose and insulin responses after starchy food consumption, associated with an increased risk of developing several metabolic diseases, could possibly be improved by altering food structure. We investigated the influence of a compact food structure; different wheat products with a similar composition were created using different processing conditions. The postprandial glucose kinetics and metabolic response to bread with a compact structure (flat bread, FB) was compared to bread with a porous structure (control bread, CB) in a randomized, crossover study with ten healthy male volunteers. Pasta (PA), with a very compact structure, was used as the control. The rate of appearance of exogenous glucose (RaE), endogenous glucose production, and glucose clearance rate (GCR) was calculated using stable isotopes. Furthermore, postprandial plasma concentrations of glucose, insulin, several intestinal hormones and bile acids were analyzed. The structure of FB was considerably more compact compared to CB, as confirmed by microscopy, XRT analysis (porosity) and density measurements. Consumption of FB resulted in lower peak glucose, insulin and glucose-dependent insulinotropic polypeptide (ns) responses and a slower initial RaE compared to CB. These variables were similar to the PA response, except for RaE which remained slower over a longer period after PA consumption. Interestingly, the GCR after FB was higher than expected based on the insulin response, indicating increased insulin sensitivity or insulin-independent glucose disposal. These results demonstrate that the structure of wheat bread can influence the postprandial metabolic response, with a more compact structure being more beneficial for health. Bread-making technology should be further explored to create healthier products.

Selected Metabolic Responses to Skateboarding

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Hetzler, Ronald K.; Hunt, Ian; Stickley, Christopher D.; Kimura, Iris F.

2011-01-01

Despite the popularity of skateboarding worldwide, the authors believe that no previous studies have investigated the metabolic demands associated with recreational participation in the sport. Although metabolic equivalents (METs) for skateboarding were published in textbooks, the source of these values is unclear. Therefore, the rise in…

Update on metabolism and nutrition therapy in critically ill burn patients.

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Moreira, E; Burghi, G; Manzanares, W

Major burn injury triggers severe oxidative stress, a systemic inflammatory response, and a persistent hypermetabolic and hypercatabolic state with secondary sarcopenia, multiorgan dysfunction, sepsis and an increased mortality risk. Calorie deficit, negative protein balance and antioxidant micronutrient deficiency after thermal injury have been associated to poor clinical outcomes. In this context, personalized nutrition therapy with early enteral feeding from the start of resuscitation are indicated. Over the last four decades, different nutritional and pharmacological interventions aimed at modulating the immune and metabolic responses have been evaluated. These strategies have been shown to be able to minimize acute malnutrition, as well as modulate the immunoinflammatory response, and improve relevant clinical outcomes in this patient population. The purpose of this updating review is to summarize the most current evidence on metabolic response and nutrition therapy in critically ill burn patients. Copyright © 2017 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

A dual control mechanism synchronizes riboflavin and sulphur metabolism in Bacillus subtilis

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Pedrolli, Danielle Biscaro; Kühm, Christian; Sévin, Daniel C.; Vockenhuber, Michael P.; Sauer, Uwe; Suess, Beatrix; Mack, Matthias

2015-01-01

Flavin mononucleotide (FMN) riboswitches are genetic elements, which in many bacteria control genes responsible for biosynthesis and/or transport of riboflavin (rib genes). Cytoplasmic riboflavin is rapidly and almost completely converted to FMN by flavokinases. When cytoplasmic levels of FMN are sufficient (“high levels”), FMN binding to FMN riboswitches leads to a reduction of rib gene expression. We report here that the protein RibR counteracts the FMN-induced “turn-off” activities of both FMN riboswitches in Bacillus subtilis, allowing rib gene expression even in the presence of high levels of FMN. The reason for this secondary metabolic control by RibR is to couple sulfur metabolism with riboflavin metabolism. PMID:26494285

Metabolomics methods for the synthetic biology of secondary metabolism

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Quoc-Thai Nguyen, [No Value; Merlo, Maria E.; Medema, Marnix H.; Jankevics, Andris; Breitling, Rainer; Takano, Eriko; Just, Wilhelm; Reiss, Thomas

2012-01-01

Many microbial secondary metabolites are of high biotechnological value for medicine, agriculture, and the food industry. Bacterial genome mining has revealed numerous novel secondary metabolite biosynthetic gene clusters, which encode the potential to synthesize a large diversity of compounds that

Metabolic response assessment with 18F-FDG-PET/CT is superior to modified RECIST for the evaluation of response to platinum-based doublet chemotherapy in malignant pleural mesothelioma

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Kanemura, Shingo [Department of Respiratory Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan); Kuribayashi, Kozo, E-mail: kuririn@hyo-med.ac.jp [Department of Respiratory Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan); Funaguchi, Norihiko [Department of Respiratory Medicine, Murakami Memorial Hospital, Asahi University, 3-23 Hashimoto-cho, Gifu 500-8523 (Japan); Shibata, Eisuke; Mikami, Koji [Department of Respiratory Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan); Doi, Hiroshi [Department of Radiology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan); Kitajima, Kazuhiro [Division of Nuclear Medicine and PET center, Department of Radiology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan); Hasegawa, Seiki [Department of Thoracic Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan); Nakano, Takashi [Department of Respiratory Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan)

2017-01-15

Highlights: • 18F-FDG-PET/CT and mRESIST were used for tumour responsiveness evaluation in MPM. • 29% of mRESIST stable disease (SD) patients were metabolic non-responders. • Disease control rate was 93.9% and metabolic response rate was 71.9%. • Progressive metabolic disease patients had lower time to progression. • MRESIST stable disease (SD) patients should be further screened by 18F-FDG-PET/CT. - Abstract: Purpose: Efficient monitoring of tumor responsiveness to chemotherapy is essential to mitigate high mortality risks and cytotoxic effects of chemotherapeutics. However, there is no consensus on the most suitable diagnostic technique/parameters for assessing response to chemotherapy in malignant pleural mesothelioma (MPM). We compared the tumor responsiveness of MPM patients as assessed using modified RECIST (mRECIST) criteria and integrated 18F-FDG-PET/CT. Methods: Histologically confirmed MPM patients (N = 82) who were treated with three cycles of cisplatin and pemetrexed, or carboplatin and pemetrexed, were included. mRECIST and integrated 18F-FDG-PET/CT were used to evaluate MPM tumor response to chemotherapy. Metabolic non-responders were defined as those with a 25% or greater increase in SUVmax compared with the previous value. Time to progression (TTP) and overall survival (OS) were compared between metabolic-responders and non-responders. Results: After three cycles of chemotherapy, 62(75.6%) of the patients were classified as having SD, 15 (18%) with partial remission (PR), and 5 (6%) with progressive disease (PD), based on mRECIST criteria. The cumulative median OS was 728.0 days (95% confidence interval [CI]: 545.9–910.1) and cumulative median TTP was 365.0 days (95% CI: 296.9–433.1). For the 82 patients, the disease control rate was 93.9%, whereas the metabolic response rate was only 71.9% (p < 0.001). All PD and PR patients were found to be metabolic responders on 18F-FDG-PET/CT; however, among the 62mRECIST SD patients, 18 (29

RNA metabolism in Xylella fastidiosa during cold adaptation and survival responses

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Fastidious plant pathogen Xylella fastidiosa has a reduced ability to adapt to cold temperatures, limiting persistence in perennial hosts, such as grapevine, growing in colder regions. RNA metabolism is an essential part of bacterial response to low temperature, including inducible expression of RNA...

Origin of endotoxemia influences the metabolic response to endotoxin in dogs

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Moeniralam, H. S.; Bemelman, W. A.; Romijn, J. A.; Endert, E.; Ackermans, M. T.; van Lanschot, J. J.; Hermsen, R. C.; Sauerwein, H. P.

1997-01-01

Different routes of endotoxin administration have been used to mimic inflammatory and metabolic responses observed during sepsis. Because the origin of endotoxemia may affect the reactions to endotoxin, we compared the induction of tumor necrosis factor (TNF), interleukin-6 (IL-6), hormones, and

Assessment of chitosan-affected metabolic response by peroxisome proliferator-activated receptor bioluminescent imaging-guided transcriptomic analysis.

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Chia-Hung Kao

Full Text Available Chitosan has been widely used in food industry as a weight-loss aid and a cholesterol-lowering agent. Previous studies have shown that chitosan affects metabolic responses and contributes to anti-diabetic, hypocholesteremic, and blood glucose-lowering effects; however, the in vivo targeting sites and mechanisms of chitosan remain to be clarified. In this study, we constructed transgenic mice, which carried the luciferase genes driven by peroxisome proliferator-activated receptor (PPAR, a key regulator of fatty acid and glucose metabolism. Bioluminescent imaging of PPAR transgenic mice was applied to report the organs that chitosan acted on, and gene expression profiles of chitosan-targeted organs were further analyzed to elucidate the mechanisms of chitosan. Bioluminescent imaging showed that constitutive PPAR activities were detected in brain and gastrointestinal tract. Administration of chitosan significantly activated the PPAR activities in brain and stomach. Microarray analysis of brain and stomach showed that several pathways involved in lipid and glucose metabolism were regulated by chitosan. Moreover, the expression levels of metabolism-associated genes like apolipoprotein B (apoB and ghrelin genes were down-regulated by chitosan. In conclusion, these findings suggested the feasibility of PPAR bioluminescent imaging-guided transcriptomic analysis on the evaluation of chitosan-affected metabolic responses in vivo. Moreover, we newly identified that downregulated expression of apoB and ghrelin genes were novel mechanisms for chitosan-affected metabolic responses in vivo.

SirT1 regulates energy metabolism and response to caloric restriction in mice.

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Gino Boily

Full Text Available The yeast sir2 gene and its orthologues in Drosophila and C. elegans have well-established roles in lifespan determination and response to caloric restriction. We have studied mice carrying two null alleles for SirT1, the mammalian orthologue of sir2, and found that these animals inefficiently utilize ingested food. These mice are hypermetabolic, contain inefficient liver mitochondria, and have elevated rates of lipid oxidation. When challenged with a 40% reduction in caloric intake, normal mice maintained their metabolic rate and increased their physical activity while the metabolic rate of SirT1-null mice dropped and their activity did not increase. Moreover, CR did not extend lifespan of SirT1-null mice. Thus, SirT1 is an important regulator of energy metabolism and, like its orthologues from simpler eukaryotes, the SirT1 protein appears to be required for a normal response to caloric restriction.

Cardiovascular, hormonal and metabolic responses to graded exercise in juvenile diabetics with and without autonomic neuropathy

DEFF Research Database (Denmark)

Hilsted, J; Galbo, H; Christensen, N J

1980-01-01

Thirteen juvenile diabetics were studied in order to determine if decreased beat-to-beat variation during deep respiration, indicating abnormal autonomic nerve function, imply that cardiovascular, hormonal and metabolic responses are impaired. Patients with decreased beat-to-beat variation had to...... to be more heavily stressed during exercise to reach a certain heart rate or catecholamine level. The relation between other metabolic and hormonal response is discussed....

Morphologic and Metabolic Comparison of Treatment Responsiveness with 18Fludeoxyglucose-Positron Emission Tomography/Computed Tomography According to Lung Cancer Type

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Mehmet Fatih Börksüz

2016-06-01

Full Text Available Objective: The aim of the present study was to evaluate the response to treatment by histopathologic type in patients with lung cancer and under follow-up with 18F-fluoro-2deoxy-glucose-positron emission tomography/computed tomography (18F-FDG PET/CT imaging by using Response Evaluation Criteria in Solid Tumors (RECIST and European Organisation for Research and Treatment of Cancer (EORTC criteria that evaluate morphologic and metabolic parameters. Methods: On two separate (pre- and post-treatment 18F-FDG PET/CT images, the longest dimension of primary tumor as well as of secondary lesions were measured and sum of these two measurements was recorded as the total dimension in 40 patients. PET parameters such as standardized uptake value (SUVmax, metabolic volume and total lesion glycolysis (TLG were also recorded for these target lesions on two separate 18F-FDG PET/CT images. The percent (% change was calculated for all these parameters. Morphologic evaluation was based on RECIST 1.1 and the metabolic evaluation was based on EORTC. Results: When evaluated before and after treatment, in spite of the statistically significant change (p0.05. In histopathologic typing, when we compare the post-treatment phase change with the treatment responses of RECIST 1.1 and EORTC criteria; for RECIST 1.1 in squamous cell lung cancer group, progression was observed in sixteen patients (57%, stability in seven patients (25%, partial response in five patients (18%; and for EORTC progression was detected in four patients (14%, stability in thirteen patients (47%, partial response in eleven patients (39%, in 12 of these patients an increase in stage (43%, in 4 of them a decrease in stage (14%, and in 12 of them stability in stage (43% were determined. But in adenocancer patients (n=7, for RECIST 1.1, progression was determined in four patients (57%, stability in two patients (29%, partial response in one patient (14%; for EORTC, progression in one patient (14

KdmB, a Jumonji Histone H3 Demethylase, Regulates Genome-Wide H3K4 Trimethylation and Is Required for Normal Induction of Secondary Metabolism in Aspergillus nidulans.

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Agnieszka Gacek-Matthews

2016-08-01

Full Text Available Histone posttranslational modifications (HPTMs are involved in chromatin-based regulation of fungal secondary metabolite biosynthesis (SMB in which the corresponding genes-usually physically linked in co-regulated clusters-are silenced under optimal physiological conditions (nutrient-rich but are activated when nutrients are limiting. The exact molecular mechanisms by which HPTMs influence silencing and activation, however, are still to be better understood. Here we show by a combined approach of quantitative mass spectrometry (LC-MS/MS, genome-wide chromatin immunoprecipitation (ChIP-seq and transcriptional network analysis (RNA-seq that the core regions of silent A. nidulans SM clusters generally carry low levels of all tested chromatin modifications and that heterochromatic marks flank most of these SM clusters. During secondary metabolism, histone marks typically associated with transcriptional activity such as H3 trimethylated at lysine-4 (H3K4me3 are established in some, but not all gene clusters even upon full activation. KdmB, a Jarid1-family histone H3 lysine demethylase predicted to comprise a BRIGHT domain, a zinc-finger and two PHD domains in addition to the catalytic Jumonji domain, targets and demethylates H3K4me3 in vivo and mediates transcriptional downregulation. Deletion of kdmB leads to increased transcription of about ~1750 genes across nutrient-rich (primary metabolism and nutrient-limiting (secondary metabolism conditions. Unexpectedly, an equally high number of genes exhibited reduced expression in the kdmB deletion strain and notably, this group was significantly enriched for genes with known or predicted functions in secondary metabolite biosynthesis. Taken together, this study extends our general knowledge about multi-domain KDM5 histone demethylases and provides new details on the chromatin-level regulation of fungal secondary metabolite production.

Extreme Hypoxic Conditions Induce Selective Molecular Responses and Metabolic Reset in Detached Apple Fruit

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Cukrov, Dubravka; Zermiani, Monica; Brizzolara, Stefano; Cestaro, Alessandro; Licausi, Francesco; Luchinat, Claudio; Santucci, Claudio; Tenori, Leonardo; Van Veen, Hans; Zuccolo, Andrea; Ruperti, Benedetto; Tonutti, Pietro

2016-01-01

The ripening physiology of detached fruit is altered by low oxygen conditions with profound effects on quality parameters. To study hypoxia-related processes and regulatory mechanisms, apple (Malus domestica, cv Granny Smith) fruit, harvested at commercial ripening, were kept at 1°C under normoxic (control) and hypoxic (0.4 and 0.8 kPa oxygen) conditions for up to 60 days. NMR analyses of cortex tissue identified eight metabolites showing significantly different accumulations between samples, with ethanol and alanine displaying the most pronounced difference between hypoxic and normoxic treatments. A rapid up-regulation of alcohol dehydrogenase and pyruvate-related metabolism (lactate dehydrogenase, pyruvate decarboxylase, alanine aminotransferase) gene expression was detected under both hypoxic conditions with a more pronounced effect induced by the lowest (0.4 kPa) oxygen concentration. Both hypoxic conditions negatively affected ACC synthase and ACC oxidase transcript accumulation. Analysis of RNA-seq data of samples collected after 24 days of hypoxic treatment identified more than 1000 genes differentially expressed when comparing 0.4 vs. 0.8 kPa oxygen concentration samples. Genes involved in cell-wall, minor and major CHO, amino acid and secondary metabolisms, fermentation and glycolysis as well as genes involved in transport, defense responses, and oxidation-reduction appeared to be selectively affected by treatments. The lowest oxygen concentration induced a higher expression of transcription factors belonging to AUX/IAA, WRKY, HB, Zinc-finger families, while MADS box family genes were more expressed when apples were kept under 0.8 kPa oxygen. Out of the eight group VII ERF members present in apple genome, two genes showed a rapid up-regulation under hypoxia, and western blot analysis showed that apple MdRAP2.12 proteins were differentially accumulated in normoxic and hypoxic samples, with the highest level reached under 0.4 kPa oxygen. These data suggest

Thermal sensation and thermophysiological responses with metabolic step-changes

DEFF Research Database (Denmark)

Goto, Tomonobu; Toftum, Jørn; deDear, Richard

2006-01-01

at sedentary activity. In a second experimental series, subjects alternated between rest and exercise as well as between exercise at different intensities at two temperature levels. Measurements comprised skin and oesophageal temperatures, heart rate and subjective responses. Thermal sensation started to rise....... The sensitivity of thermal sensation to changes in core temperature was higher for activity down-steps than for up-steps. A model was proposed that estimates transient thermal sensation after metabolic step-changes. Based on predictions by the model, weighting factors were suggested to estimate a representative...... average metabolic rate with varying activity levels, e.g. for the prediction of thermal sensation by steady-state comfort models. The activity during the most recent 5 min should be weighted 65%, during the prior 10-5 min 25% and during the prior 20-10 min 10%....

Developing Culturally Responsive Mathematics Teachers: Secondary Teachers' Evolving Conceptions of Knowing Students

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Parker, Frieda; Bartell, Tonya Gau; Novak, Jodie D.

2017-01-01

Research advances in teaching, learning, curriculum, and assessment have not changed the continued underperformance of marginalized students in mathematics education. Culturally responsive teaching is a means of addressing the needs of these students. It is sometimes challenging, however, to convince secondary mathematics teachers about the…

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

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

2013-07-17

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

Uncovering transcriptional regulation of metabolism by using metabolic network topology

DEFF Research Database (Denmark)

Patil, Kiran Raosaheb; Nielsen, Jens

2005-01-01

in the metabolic network that follow a common transcriptional response. Thus, the algorithm enables identification of so-called reporter metabolites (metabolites around which the most significant transcriptional changes occur) and a set of connected genes with significant and coordinated response to genetic......Cellular response to genetic and environmental perturbations is often reflected and/or mediated through changes in the metabolism, because the latter plays a key role in providing Gibbs free energy and precursors for biosynthesis. Such metabolic changes are often exerted through transcriptional...... therefore developed an algorithm that is based on hypothesis-driven data analysis to uncover the transcriptional regulatory architecture of metabolic networks. By using information on the metabolic network topology from genome-scale metabolic reconstruction, we show that it is possible to reveal patterns...

Responses to high-fat challenges varying in fat type in subjects with different metabolic risk phenotypes: a randomized trial.

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Susan J van Dijk

Full Text Available The ability of subjects to respond to nutritional challenges can reflect the flexibility of their biological system. Nutritional challenge tests could be used as an indicator of health status but more knowledge on metabolic and immune responses of different subjects to nutritional challenges is needed. The aim of this study was to compare the responses to high-fat challenges varying in fat type in subjects with different metabolic risk phenotypes.In a cross-over design 42 men (age 50-70 y consumed three high-fat shakes containing saturated fat (SFA, monounsaturated fat (MUFA or n-3 polyunsaturated (PUFA. Men were selected on BMI and health status (lean, obese or obese diabetic and phenotyped with MRI for adipose tissue distribution. Before and 2 and 4 h after shake consumption blood was drawn for measurement of expression of metabolic and inflammation-related genes in peripheral blood mononuclear cells (PBMCs, plasma triglycerides (TAG, glucose, insulin, cytokines and ex vivo PBMC immune response capacity. The MUFA and n-3 PUFA challenge, compared to the SFA challenge, induced higher changes in expression of inflammation genes MCP1 and IL1β in PBMCs. Obese and obese diabetic subjects had different PBMC gene expression and metabolic responses to high-fat challenges compared to lean subjects. The MUFA challenge induced the most pronounced TAG response, mainly in obese and obese diabetic subjects.The PBMC gene expression response and metabolic response to high-fat challenges were affected by fat type and metabolic risk phenotype. Based on our results we suggest using a MUFA challenge to reveal differences in response capacity of subjects.ClinicalTrials.gov NCT00977262.

Protein kinase FgSch9 serves as a mediator of the target of rapamycin and high osmolarity glycerol pathways and regulates multiple stress responses and secondary metabolism in Fusarium graminearum.

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Gu, Qin; Zhang, Chengqi; Yu, Fangwei; Yin, Yanni; Shim, Won-Bo; Ma, Zhonghua

2015-08-01

Saccharomyces cerevisiae protein kinase Sch9 is one of the downstream effectors of the target of rapamycin (TOR) complex 1 and plays multiple roles in stress resistance, longevity and nutrient sensing. However, the functions of Sch9 orthologs in filamentous fungi, particularly in pathogenic species, have not been characterized to date. Here, we investigated biological and genetic functions of FgSch9 in Fusarium graminearum. The FgSCH9 deletion mutant (ΔFgSch9) was defective in aerial hyphal growth, hyphal branching and conidial germination. The mutant exhibited increased sensitivity to osmotic and oxidative stresses, cell wall-damaging agents, and to rapamycin, while showing increased thermal tolerance. We identified FgMaf1 as one of the FgSch9-interacting proteins that plays an important role in regulating mycotoxin biosynthesis and virulence of F. graminearum. Co-immunoprecipitation and affinity capture-mass spectrometry assays showed that FgSch9 also interacts with FgTor and FgHog1. More importantly, both ΔFgSch9 and FgHog1 null mutant (ΔFgHog1) exhibited increased sensitivity to osmotic and oxidative stresses. This defect was more severe in the FgSch9/FgHog1 double mutant. Taken together, we propose that FgSch9 serves as a mediator of the TOR and high osmolarity glycerol pathways, and regulates vegetative differentiation, multiple stress responses and secondary metabolism in F. graminearum. © 2014 Society for Applied Microbiology and John Wiley & Sons Ltd.

Larval starvation improves metabolic response to adult starvation in honey bees (Apis mellifera L.).

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Wang, Ying; Campbell, Jacob B; Kaftanoglu, Osman; Page, Robert E; Amdam, Gro V; Harrison, Jon F

2016-04-01

Environmental changes during development have long-term effects on adult phenotypes in diverse organisms. Some of the effects play important roles in helping organisms adapt to different environments, such as insect polymorphism. Others, especially those resulting from an adverse developmental environment, have a negative effect on adult health and fitness. However, recent studies have shown that those phenotypes influenced by early environmental adversity have adaptive value under certain (anticipatory) conditions that are similar to the developmental environment, though evidence is mostly from morphological and behavioral observations and it is still rare at physiological and molecular levels. In the companion study, we applied a short-term starvation treatment to fifth instar honey bee larvae and measured changes in adult morphology, starvation resistance, hormonal and metabolic physiology and gene expression. Our results suggest that honey bees can adaptively respond to the predicted nutritional stress. In the present study, we further hypothesized that developmental starvation specifically improves the metabolic response of adult bees to starvation instead of globally affecting metabolism under well-fed conditions. Here, we produced adult honey bees that had experienced a short-term larval starvation, then we starved them for 12 h and monitored metabolic rate, blood sugar concentrations and metabolic reserves. We found that the bees that experienced larval starvation were able to shift to other fuels faster and better maintain stable blood sugar levels during starvation. However, developmental nutritional stress did not change metabolic rates or blood sugar levels in adult bees under normal conditions. Overall, our study provides further evidence that early larval starvation specifically improves the metabolic responses to adult starvation in honey bees. © 2016. Published by The Company of Biologists Ltd.

Diurnal changes in CN metabolism and response of rice seedlings to UV-B radiation.

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Yun, Hyejin; Lim, Sunhyung; Kim, Yangmin X; Lee, Yejin; Lee, Seulbi; Lee, Deogbae; Park, Keewoong; Sung, Jwakyung

2018-03-13

Plants regulate a number of primary metabolites, including carbohydrates, organic acids, and amino acids, in response to UV-B radiation. Therefore, it is essential to understand the time-dependent response of rice plants to UV-B stress. This study focused on the response of plants to UV-B at different leaf developmental phases (emerging, growing, and maturing) in an attempt to fully comprehend the metabolic shift. We analyzed the expression levels of genes related to starch/sucrose metabolism in the leaf blades of rice seedlings (Oryza sativa L. "Saechuchenog") exposed to UV-B irradiation for short (1 day) and long terms (5 days) using quantitative real-time polymerase chain reaction. We also examined the diurnal variations in the contents of primary metabolites using an established GCTOF-MS (gas chromatography time of flight-mass spectrometry) method. The results showed that the levels of primary metabolites were largely dependent upon the diurnal rhythm and leaf developmental phase. The young leaves (sink) produced and accumulated starch rather than sucrose. The short-term (4 h, 1 day) UV-B exposure inhibited sucrose synthesis, which could be the first target of UV-B radiation. Following short- and long-term (5 days) exposure to UV-B radiation, the dynamic response of primary metabolites was evaluated. It was found that the content of carbohydrates decreased throughout the period of exposure to UV-B stress, especially in terms of sucrose concentration. However, the content of the majority of amino acids increased after an early decrease. Our data revealed that the metabolic response, as well as the gene expression, differed with the period (intensity) of exposure to UV-B radiation and with the phase of leaf development. These findings provide new insights for a better understanding of the metabolic response of a variety of plant species exposed to a wide range of UV-B radiation. Copyright © 2018. Published by Elsevier GmbH.

System-Level and Granger Network Analysis of Integrated Proteomic and Metabolomic Dynamics Identifies Key Points of Grape Berry Development at the Interface of Primary and Secondary Metabolism

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Lei Wang

2017-06-01

Full Text Available Grapevine is a fruit crop with worldwide economic importance. The grape berry undergoes complex biochemical changes from fruit set until ripening. This ripening process and production processes define the wine quality. Thus, a thorough understanding of berry ripening is crucial for the prediction of wine quality. For a systemic analysis of grape berry development we applied mass spectrometry based platforms to analyse the metabolome and proteome of Early Campbell at 12 stages covering major developmental phases. Primary metabolites involved in central carbon metabolism, such as sugars, organic acids and amino acids together with various bioactive secondary metabolites like flavonols, flavan-3-ols and anthocyanins were annotated and quantified. At the same time, the proteomic analysis revealed the protein dynamics of the developing grape berries. Multivariate statistical analysis of the integrated metabolomic and proteomic dataset revealed the growth trajectory and corresponding metabolites and proteins contributing most to the specific developmental process. K-means clustering analysis revealed 12 highly specific clusters of co-regulated metabolites and proteins. Granger causality network analysis allowed for the identification of time-shift correlations between metabolite-metabolite, protein- protein and protein-metabolite pairs which is especially interesting for the understanding of developmental processes. The integration of metabolite and protein dynamics with their corresponding biochemical pathways revealed an energy-linked metabolism before veraison with high abundances of amino acids and accumulation of organic acids, followed by protein and secondary metabolite synthesis. Anthocyanins were strongly accumulated after veraison whereas other flavonoids were in higher abundance at early developmental stages and decreased during the grape berry developmental processes. A comparison of the anthocyanin profile of Early Campbell to other

System-Level and Granger Network Analysis of Integrated Proteomic and Metabolomic Dynamics Identifies Key Points of Grape Berry Development at the Interface of Primary and Secondary Metabolism.

Science.gov (United States)

Wang, Lei; Sun, Xiaoliang; Weiszmann, Jakob; Weckwerth, Wolfram

2017-01-01

Grapevine is a fruit crop with worldwide economic importance. The grape berry undergoes complex biochemical changes from fruit set until ripening. This ripening process and production processes define the wine quality. Thus, a thorough understanding of berry ripening is crucial for the prediction of wine quality. For a systemic analysis of grape berry development we applied mass spectrometry based platforms to analyse the metabolome and proteome of Early Campbell at 12 stages covering major developmental phases. Primary metabolites involved in central carbon metabolism, such as sugars, organic acids and amino acids together with various bioactive secondary metabolites like flavonols, flavan-3-ols and anthocyanins were annotated and quantified. At the same time, the proteomic analysis revealed the protein dynamics of the developing grape berries. Multivariate statistical analysis of the integrated metabolomic and proteomic dataset revealed the growth trajectory and corresponding metabolites and proteins contributing most to the specific developmental process. K-means clustering analysis revealed 12 highly specific clusters of co-regulated metabolites and proteins. Granger causality network analysis allowed for the identification of time-shift correlations between metabolite-metabolite, protein- protein and protein-metabolite pairs which is especially interesting for the understanding of developmental processes. The integration of metabolite and protein dynamics with their corresponding biochemical pathways revealed an energy-linked metabolism before veraison with high abundances of amino acids and accumulation of organic acids, followed by protein and secondary metabolite synthesis. Anthocyanins were strongly accumulated after veraison whereas other flavonoids were in higher abundance at early developmental stages and decreased during the grape berry developmental processes. A comparison of the anthocyanin profile of Early Campbell to other cultivars revealed

Partitioning between primary and secondary metabolism of carbon allocated to roots in four maize genotypes under water deficit and its effects on productivity

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Alyne Oliveira Lavinsky

2015-10-01

Full Text Available Plants may respond to drought by altering biomass allocation to shoots and roots or by changing the metabolic activities in these organs. To determine how drought changes the partitioning of carbon allocated to growth and secondary metabolism in maize roots and how it affects photosynthesis (A and productivity in maize, we evaluated leaf gas exchange, yield componentes, root morphology, and primary and secondary metabolites including total soluble sugars (TSS, starch (S, phenolics (PHE, and lignin (LIG. Data were collected from pot-grown plants of four maize genotypes: BRS 1010 and 2B710 (sensitive genotypes and DKB390 and BRS1055 (tolerant genotypes under two soil water tensions: field capacity (FC, − 18 kPa and water deficit (WD, − 138 kPa. WD was applied at the pre-flowering stage for 12 days and then the water supply was restored and maintained at optimum levels until the end of the cycle. For genotype BRS 1055 under FC, the greatest A did not result in greater grain biomass (DGB because the accumulated photoassimilates had already filled the cells, and thus the excessive TSS synthesized in leaves was allocated to roots in large amounts. However, the sharp decrease in A caused by WD imposition in this genotype did not affect the influx pressure of leaf TSS, which was due largely to conversion of primary metabolites to PHE compounds to increase the length of fine roots. In leaves of DKB390 under WD, both S and TSS were reduced, whereas PHE were increased to prevent excessive water loss and xylem cavitation. Under WD, both BRS1010 and 2B710 genotypes displayed reduced allocation of biomass to shoots and roots and LIG content in leaves, as well as lower A and DGB values. In BRS1010 this response was coupled to S decrease in leaves and TSS increase in roots, whereas in 2B710 there was a concomitant S increase in roots.

Metabolic response to optic centers to visual stimuli in the albino rat: anatomical and physiological considerations

International Nuclear Information System (INIS)

Toga, A.W.; Collins, R.C.

1981-01-01

The functional organization of the visual system was studied in the albino rat. Metabolic differences were measured using the 14 C-2-deoxyglucose (DG) autoradiographic technique during visual stimulation of one entire retina in unrestrained animals. All optic centers responded to changes in light intensity but to different degrees. The greatest change occurred in the superior colliculus, less in the lateral geniculate, and considerably less in second-order sites such as layer IV of visual cortex. These optic centers responded in particular to on/off stimuli, but showed no incremental change during pattern reversal or movement of orientation stimuli. Both the superior colliculus and lateral geniculate increased their metabolic rate as the frequency of stimulation increased, but the magnitude was twice as great in the colliculus. The histological pattern of metabolic change in the visual system was not homogenous. In the superior colliculus glucose utilization increased only in stratum griseum superficiale and was greatest in visuotopic regions representing the peripheral portions of the visual field. Similarly, in the lateral geniculate, only the dorsal nucleus showed an increased response to greater stimulus frequencies. Second-order regions of the visual system showed changes in metabolism in response to visual stimulation, but no incremental response specific for type or frequency of stimuli. To label proteins of axoplasmic transport to study the terminal fields of retinal projections 14 C-amino acids were used. This was done to study how the differences in the magnitude of the metabolic response among optic centers were related to the relative quantity of retinofugal projections to these centers

An extensive case study of hairy-root cultures for enhanced secondary-metabolite production through metabolic-pathway engineering.

Science.gov (United States)

Mehrotra, Shakti; Rahman, Laiq Ur; Kukreja, Arun Kumar

2010-08-23

An intrinsic improvement is taking place in the methodologies for the development of culture systems with first-rate production of plant-based molecules. The blending of HR (hairy root) cultures with ME (metabolic engineering) approaches offers new insights into, and possibilities for, improving the system productivity for known and/or novel high-value plant-derived active compounds. The introduction and expression of foreign genes in plants results in improvement of cellular activities by manipulating enzymatic, regulatory and transport function of the cell. The rational amendments in the rate-limiting steps of a biosynthetic pathway as well as inactivating the inefficient pathway(s) for by-product formation can be accomplished either through single-step engineering or through the multi-step engineering. The hierarchical control of any metabolic process can lead the engineer to apply the ME ideas and principles to any of the strata, including transcriptional, moving on to translational and enzymatic activity. The HR culture systems offer a remarkable potential for commercial production of a number of low-volume, but high-value, secondary metabolites. Taking HR as a model system, in the present review, we discuss engineering principles and perceptions to exploit secondary-metabolite pathways for the production of important bioactive compounds. We also talk about requisites and possible challenges that occur during ME, with emphasis on examples of various HR systems. Furthermore, it also highlights the utilization of global information obtained from '-omic' platforms in order to explore pathway architecture, structural and functional aspects of important enzymes and genes that can support the design of sets of engineering, resulting in the generation of wide-ranging views of DNA sequence-to-metabolite passageway networking and their control to obtain desired results.

Giant cell tumor with secondary aneurysmal bone cyst shows heterogeneous metabolic pattern on {sup 18}F-FDG PET.CT: A case reort

Energy Technology Data Exchange (ETDEWEB)

Park, Hee Jeong; Kwon, Seong Young; Yoon, Yeon Hong [Chonnam National University Hwasun Hospital, Huasun (Korea, Republic of); Cho, Sang Geon; Kim, Jahae; Song, Ho Chun; Kim, Sung Sun; Park, Jin Gyoon [Chonnam National University Hospital, Gwangju (Korea, Republic of)

2016-12-15

Giant cell tumor (GCT) is a generally benign bone tumor accounting for approximately 5 % of all primary bone neoplasms. Cystic components in GCTs that indicate secondary aneurysmal bone cysts (ABCs) are reported in 14 % of GCTs. Although both of them have been described separately in previous reports that may show considerable fluorodeoxyglucose (FDG) uptake despite their benign nature, the findings of GCT with secondary ABC on 18F-FDG positron emission tomography/computed tomography (PET/CT) have not been well-known. We report a case of GCT with secondary ABC in a 26-year-old woman. 18F-FDG PET/CT revealed a heterogeneous hypermetabolic lesion in the left proximal femur with the maximum standardized uptake value of 4.7. The solid components of the tumor showed higher FDG uptake than the cystic components. These observations suggest that the ABC components in GCTs show heterogeneous metabolic patterns on {sup 18}F-FDG PET/CT.

Giant cell tumor with secondary aneurysmal bone cyst shows heterogeneous metabolic pattern on "1"8F-FDG PET.CT: A case reort

International Nuclear Information System (INIS)

Park, Hee Jeong; Kwon, Seong Young; Yoon, Yeon Hong; Cho, Sang Geon; Kim, Jahae; Song, Ho Chun; Kim, Sung Sun; Park, Jin Gyoon

2016-01-01

Giant cell tumor (GCT) is a generally benign bone tumor accounting for approximately 5 % of all primary bone neoplasms. Cystic components in GCTs that indicate secondary aneurysmal bone cysts (ABCs) are reported in 14 % of GCTs. Although both of them have been described separately in previous reports that may show considerable fluorodeoxyglucose (FDG) uptake despite their benign nature, the findings of GCT with secondary ABC on 18F-FDG positron emission tomography/computed tomography (PET/CT) have not been well-known. We report a case of GCT with secondary ABC in a 26-year-old woman. 18F-FDG PET/CT revealed a heterogeneous hypermetabolic lesion in the left proximal femur with the maximum standardized uptake value of 4.7. The solid components of the tumor showed higher FDG uptake than the cystic components. These observations suggest that the ABC components in GCTs show heterogeneous metabolic patterns on "1"8F-FDG PET/CT

Developmental and Metabolic Plasticity of White-Skinned Grape Berries in Response to Botrytis cinerea during Noble Rot1[OPEN

Science.gov (United States)

Collins, Thomas S.; Vicente, Ariel R.; Doyle, Carolyn L.; Ye, Zirou; Allen, Greg; Heymann, Hildegarde

2015-01-01

Noble rot results from exceptional infections of ripe grape (Vitis vinifera) berries by Botrytis cinerea. Unlike bunch rot, noble rot promotes favorable changes in grape berries and the accumulation of secondary metabolites that enhance wine grape composition. Noble rot-infected berries of cv Sémillon, a white-skinned variety, were collected over 3 years from a commercial vineyard at the same time that fruit were harvested for botrytized wine production. Using an integrated transcriptomics and metabolomics approach, we demonstrate that noble rot alters the metabolism of cv Sémillon berries by inducing biotic and abiotic stress responses as well as ripening processes. During noble rot, B. cinerea induced the expression of key regulators of ripening-associated pathways, some of which are distinctive to the normal ripening of red-skinned cultivars. Enhancement of phenylpropanoid metabolism, characterized by a restricted flux in white-skinned berries, was a common outcome of noble rot and red-skinned berry ripening. Transcript and metabolite analyses together with enzymatic assays determined that the biosynthesis of anthocyanins is a consistent hallmark of noble rot in cv Sémillon berries. The biosynthesis of terpenes and fatty acid aroma precursors also increased during noble rot. We finally characterized the impact of noble rot in botrytized wines. Altogether, the results of this work demonstrated that noble rot causes a major reprogramming of berry development and metabolism. This desirable interaction between a fruit and a fungus stimulates pathways otherwise inactive in white-skinned berries, leading to a greater accumulation of compounds involved in the unique flavor and aroma of botrytized wines. PMID:26450706

Changes in energy metabolism in response to 48 h of overfeeding and fasting in Caucasians and Pima Indians

DEFF Research Database (Denmark)

Weyer, C; Vozarova, B; Ravussin, E

2001-01-01

Differences in the metabolic response to overfeeding and starvation may confer susceptibility or resistance to obesity in humans. To further examine this hypothesis, we assessed the changes in 24 h energy metabolism in response to short-term overfeeding and fasting in Caucasians (C) and Pima...... Indians (I), a population with a very high propensity for obesity....

Estimation of induced secondary metabolites in chickpea tissues in response to elicitor preparation of seaweeds

International Nuclear Information System (INIS)

Bi, F.; Iqbal, S.

2000-01-01

Disease response of plants in terms of induced browning and phytoalexin (induced secondary metabolites) production were recorded in the tissues of Cicer arietinum (Chick pea) treated with the High Molecular Crude Elicitor Preparations, HMWCEP 'Polysaccharides' of Hypnea musciformis (red algae), Padina tetrastromatica (brown algae) and Ulva lactulus (green algae). A UV-visible spectrophotometric method has been developed for the quantification of induced secondary metabolites with time. (author)

Protein-DNA binding dynamics predict transcriptional response to nutrients in archaea.

Science.gov (United States)

Todor, Horia; Sharma, Kriti; Pittman, Adrianne M C; Schmid, Amy K

2013-10-01

Organisms across all three domains of life use gene regulatory networks (GRNs) to integrate varied stimuli into coherent transcriptional responses to environmental pressures. However, inferring GRN topology and regulatory causality remains a central challenge in systems biology. Previous work characterized TrmB as a global metabolic transcription factor in archaeal extremophiles. However, it remains unclear how TrmB dynamically regulates its ∼100 metabolic enzyme-coding gene targets. Using a dynamic perturbation approach, we elucidate the topology of the TrmB metabolic GRN in the model archaeon Halobacterium salinarum. Clustering of dynamic gene expression patterns reveals that TrmB functions alone to regulate central metabolic enzyme-coding genes but cooperates with various regulators to control peripheral metabolic pathways. Using a dynamical model, we predict gene expression patterns for some TrmB-dependent promoters and infer secondary regulators for others. Our data suggest feed-forward gene regulatory topology for cobalamin biosynthesis. In contrast, purine biosynthesis appears to require TrmB-independent regulators. We conclude that TrmB is an important component for mediating metabolic modularity, integrating nutrient status and regulating gene expression dynamics alone and in concert with secondary regulators.

Metabolic Response to Food Restriction in Military-Eligible Women, with a Gender Comparison

National Research Council Canada - National Science Library

Young, Vernon

1998-01-01

Two major series of investigations are being undertaken to explore the metabolic responses of women who meet military standards for body-weight and percent body-fat to the nutritional stressors of food restriction...

Metabolic Response to Food Restriction in Military-Eligible Women, With a Gender Comparison

National Research Council Canada - National Science Library

Young, Vernon

1996-01-01

Two major series of investigations will be undertaken to explore the metabolic responses of women, who meet military standards of body-weight and percent body-fat to the nutritional stressors of food restriction...

Metabolic Response to Food Restriction in Military-Eligible Women, with a Gender Comparison

National Research Council Canada - National Science Library

Young, Vernon

1997-01-01

Two major series of investigations are being undertaken to explore the metabolic responses of women who meet military standards for body-weight and percent body-fat to the nutritional stressors of food restriction...

Liposoluble vitamins in Crustacean feed: Metabolic and Histological responses.

Science.gov (United States)

Fernández-Gimenez, Analía Verónica

2016-05-01

Vitamins are vital for normal growth and survival of living organisms and they are distributed in feedstuffs in small quantities. This review is focused on the liposoluble vitamins (A, D, E and K) in the diets and metabolic responses of the Argentine penaeoid shrimps Pleoticus muelleri and Artemesia longinaris, distributed along the South American coast line. Growth, survival and histological analyses serve as indicators of the nutritional value derived from vitamin deficiency. Liposoluble vitamins are also related to stress, antioxidant defense and immune response of shrimps. Effective diet for shrimp culture that provide not only macronutrients including protein and lipid but also micronutrients such as vitamins for optimal growth is an ever improving subject. This review may help formulating suitable feeds for shrimps.

Magnetic resonance metabolic profiling of breast cancer tissue obtained with core needle biopsy for predicting pathologic response to neoadjuvant chemotherapy.

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Ji Soo Choi

Full Text Available The purpose of this study was to determine whether metabolic profiling of core needle biopsy (CNB samples using high-resolution magic angle spinning (HR-MAS magnetic resonance spectroscopy (MRS could be used for predicting pathologic response to neoadjuvant chemotherapy (NAC in patients with locally advanced breast cancer. After institutional review board approval and informed consent were obtained, CNB tissue samples were collected from 37 malignant lesions in 37 patients before NAC treatment. The metabolic profiling of CNB samples were performed by HR-MAS MRS. Metabolic profiles were compared according to pathologic response to NAC using the Mann-Whitney test. Multivariate analysis was performed with orthogonal projections to latent structure-discriminant analysis (OPLS-DA. Various metabolites including choline-containing compounds were identified and quantified by HR-MAS MRS in all 37 breast cancer tissue samples obtained by CNB. In univariate analysis, the metabolite concentrations and metabolic ratios of CNB samples obtained with HR-MAS MRS were not significantly different between different pathologic response groups. However, there was a trend of lower levels of phosphocholine/creatine ratio and choline-containing metabolite concentrations in the pathologic complete response group compared to the non-pathologic complete response group. In multivariate analysis, the OPLS-DA models built with HR-MAS MR metabolic profiles showed visible discrimination between the pathologic response groups. This study showed OPLS-DA multivariate analysis using metabolic profiles of pretreatment CNB samples assessed by HR- MAS MRS may be used to predict pathologic response before NAC, although we did not identify the metabolite showing statistical significance in univariate analysis. Therefore, our preliminary results raise the necessity of further study on HR-MAS MR metabolic profiling of CNB samples for a large number of cancers.

Role of the Mixed-Lineage Protein Kinase Pathway in the Metabolic Stress Response to Obesity

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Shashi Kant

2013-08-01

Full Text Available Saturated free fatty acid (FFA is implicated in the metabolic response to obesity. In vitro studies indicate that FFA signaling may be mediated by the mixed-lineage protein kinase (MLK pathway that activates cJun NH2-terminal kinase (JNK. Here, we examined the role of the MLK pathway in vivo using a mouse model of diet-induced obesity. The ubiquitously expressed MLK2 and MLK3 protein kinases have partially redundant functions. We therefore compared wild-type and compound mutant mice that lack expression of MLK2 and MLK3. MLK deficiency protected mice against high-fat-diet-induced insulin resistance and obesity. Reduced JNK activation and increased energy expenditure contribute to the metabolic effects of MLK deficiency. These data confirm that the MLK pathway plays a critical role in the metabolic response to obesity.

Response to The Lost Thing: Notes from a Secondary Classroom

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Sandie Mourão

2013-05-01

Full Text Available This paper discusses students’ responses to the picturebook The Lost Thing (Tan, 2000 and its film (2010. It describes a small-scale project in a secondary school in Portugal, which involved 16-18 year-old students, learning English as a foreign language. Following a socio-constructivist approach to language learning and the basic tenets of reader response theory, discussion and an interpretative stance to meaning making were encouraged. The aim was to foster students’ appreciation of the visual during their interpretative discussions as well as developing their English language skills. This paper demonstrates how the picturebook in particular afforded the students with opportunities for language development through talk. It closes with notes on the implications of using picturebooks and their films in the classroom.

Motif-Independent De Novo Detection of Secondary Metabolite Gene Clusters – Towards Identification of Novel Secondary Metabolisms from Filamentous Fungi -

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Myco eUmemura

2015-05-01

Full Text Available Secondary metabolites are produced mostly by clustered genes that are essential to their biosynthesis. The transcriptional expression of these genes is often cooperatively regulated by a transcription factor located inside or close to a cluster. Most of the secondary metabolism biosynthesis (SMB gene clusters identified to date contain so-called core genes with distinctive sequence features, such as polyketide synthase (PKS and non-ribosomal peptide synthetase (NRPS. Recent efforts in sequencing fungal genomes have revealed far more SMB gene clusters than expected based on the number of core genes in the genomes. Several bioinformatics tools have been developed to survey SMB gene clusters using the sequence motif information of the core genes, including SMURF and antiSMASH.More recently, accompanied by the development of sequencing techniques allowing to obtain large-scale genomic and transcriptomic data, motif-independent prediction methods of SMB gene clusters, including MIDDAS-M, have been developed. Most these methods detect the clusters in which the genes are cooperatively regulated at transcriptional levels, thus allowing the identification of novel SMB gene clusters regardless of the presence of the core genes. Another type of the method, MIPS-CG, uses the characteristics of SMB genes, which are highly enriched in non-syntenic blocks (NSBs, enabling the prediction even without transcriptome data although the results have not been evaluated in detail. Considering that large portion of SMB gene clusters might be sufficiently expressed only in limited uncommon conditions, it seems that prediction of SMB gene clusters by bioinformatics and successive experimental validation is an only way to efficiently uncover hidden SMB gene clusters. Here, we describe and discuss possible novel approaches for the determination of SMB gene clusters that have not been identified using conventional methods.

Production of L-carnitine by secondary metabolism of bacteria

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Iborra José L

2007-10-01

Full Text Available Abstract The increasing commercial demand for L-carnitine has led to a multiplication of efforts to improve its production with bacteria. The use of different cell environments, such as growing, resting, permeabilized, dried, osmotically stressed, freely suspended and immobilized cells, to maintain enzymes sufficiently active for L-carnitine production is discussed in the text. The different cell states of enterobacteria, such as Escherichia coli and Proteus sp., which can be used to produce L-carnitine from crotonobetaine or D-carnitine as substrate, are analyzed. Moreover, the combined application of both bioprocess and metabolic engineering has allowed a deeper understanding of the main factors controlling the production process, such as energy depletion and the alteration of the acetyl-CoA/CoA ratio which are coupled to the end of the biotransformation. Furthermore, the profiles of key central metabolic activities such as the TCA cycle, the glyoxylate shunt and the acetate metabolism are seen to be closely interrelated and affect the biotransformation efficiency. Although genetically modified strains have been obtained, new strain improvement strategies are still needed, especially in Escherichia coli as a model organism for molecular biology studies. This review aims to summarize and update the state of the art in L-carnitine production using E. coli and Proteus sp, emphasizing the importance of proper reactor design and operation strategies, together with metabolic engineering aspects and the need for feed-back between wet and in silico work to optimize this biotransformation.

Effects of Secondary Plant Metabolites on Microbial Populations: Changes in Community Structure and Metabolic Activity in Contaminated Environments

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Lucie Musilova

2016-07-01

Full Text Available Secondary plant metabolites (SPMEs play an important role in plant survival in the environment and serve to establish ecological relationships between plants and other organisms. Communication between plants and microorganisms via SPMEs contained in root exudates or derived from litter decomposition is an example of this phenomenon. In this review, the general aspects of rhizodeposition together with the significance of terpenes and phenolic compounds are discussed in detail. We focus specifically on the effect of SPMEs on microbial community structure and metabolic activity in environments contaminated by polychlorinated biphenyls (PCBs and polyaromatic hydrocarbons (PAHs. Furthermore, a section is devoted to a complex effect of plants and/or their metabolites contained in litter on bioremediation of contaminated sites. New insights are introduced from a study evaluating the effects of SPMEs derived during decomposition of grapefruit peel, lemon peel, and pears on bacterial communities and their ability to degrade PCBs in a long-term contaminated soil. The presented review supports the “secondary compound hypothesis” and demonstrates the potential of SPMEs for increasing the effectiveness of bioremediation processes.

Insulin response of the glucose and fatty acid metabolism in dry dairy cows across a range of body condition scores.

Science.gov (United States)

De Koster, J; Hostens, M; Van Eetvelde, M; Hermans, K; Moerman, S; Bogaert, H; Depreester, E; Van den Broeck, W; Opsomer, G

2015-07-01

The objective of the present research was to determine the insulin response of the glucose and fatty acid metabolism in dry dairy cows with a variable body condition score (BCS). Ten pregnant Holstein Friesian dairy cows (upcoming parity 2 to 5) were selected based on BCS at the beginning of the study (2mo before expected parturition date). During the study, animals were monitored weekly for BCS and backfat thickness and in the last 2wk, blood samples were taken for determination of serum nonesterified fatty acid (NEFA) concentration. Animals underwent a hyperinsulinemic euglycemic clamp test in the third week before the expected parturition date. The hyperinsulinemic euglycemic clamp test consisted of 4 consecutive insulin infusions with increasing insulin doses: 0.1, 0.5, 2, and 5mIU/kg per minute. For each insulin infusion period, a steady state was defined as a period of 30min where no or minor changes of the glucose infusion were necessary to keep the blood glucose concentration constant and near basal levels. During the steady state, the glucose infusion rate [steady state glucose infusion rate (SSGIR) in µmol/kg per minute] and NEFA concentration [steady state NEFA concentration (SSNEFA) in mmol/L] were determined and reflect the insulin response of the glucose and fatty acid metabolism. Dose response curves were created based on the insulin concentrations during the steady state and the SSGIR or SSNEFA. The shape of the dose response curves is determined by the concentration of insulin needed to elicit the half maximal effect (EC50) and the maximal SSGIR or the minimal SSNEFA for the glucose or fatty acid metabolism, respectively. The maximal SSGIR was negatively associated with variables reflecting adiposity of the cows (BCS, backfat thickness, NEFA concentration during the dry period, and absolute weight of the different adipose depots determined after euthanasia and dissection of the different depots), whereas the EC50 of the glucose metabolism was

Shear and dielectric responses of propylene carbonate, tripropylene glycol, and a mixture of two secondary amides

DEFF Research Database (Denmark)

Gainaru, Catalin; Hecksher, Tina; Olsen, Niels Boye

2012-01-01

Propylene carbonate and a mixture of two secondary amides, N-ethylformamide and Nethylacetamide, are investigated by means of broadband dielectric and mechanical shear spectroscopy. The similarities between the rheological and the dielectric responses of these liquids and of the previously invest...... in the secondary amides. In addition, the predictions of the shoving model are confirmed for the investigated liquids...

Type 2 responses at the interface between immunity and fat metabolism.

Science.gov (United States)

Odegaard, Justin I; Chawla, Ajay

2015-10-01

Adipose tissue resident leukocytes are often cast solely as the effectors of obesity and its attendant pathologies; however, recent observations have demonstrated that these cells support and effect 'healthy' physiologic function as well as pathologic dysfunction. Importantly, these two disparate outcomes are underpinned by similarly disparate immune programs; type 2 responses instruct and promote metabolic normalcy, while type 1 responses drive tissue dysfunction. In this Review, we summarize the literature regarding type 2 immunity's role in adipose tissue physiology and allude to its potential therapeutic implications. Copyright © 2015 Elsevier Ltd. All rights reserved.

Sleep fragmentation alters brain energy metabolism without modifying hippocampal electrophysiological response to novelty exposure.

Science.gov (United States)

Baud, Maxime O; Parafita, Julia; Nguyen, Audrey; Magistretti, Pierre J; Petit, Jean-Marie

2016-10-01

Sleep is viewed as a fundamental restorative function of the brain, but its specific role in neural energy budget remains poorly understood. Sleep deprivation dampens brain energy metabolism and impairs cognitive functions. Intriguingly, sleep fragmentation, despite normal total sleep duration, has a similar cognitive impact, and in this paper we ask the question of whether it may also impair brain energy metabolism. To this end, we used a recently developed mouse model of 2 weeks of sleep fragmentation and measured 2-deoxy-glucose uptake and glycogen, glucose and lactate concentration in different brain regions. In order to homogenize mice behaviour during metabolic measurements, we exposed them to a novel environment for 1 h. Using an intra-hippocampal electrode, we first showed that hippocampal electroencephalograph (EEG) response to exploration was unaltered by 1 or 14 days of sleep fragmentation. However, after 14 days, sleep fragmented mice exhibited a lower uptake of 2-deoxy-glucose in cortex and hippocampus and lower cortical lactate levels than control mice. Our results suggest that long-term sleep fragmentation impaired brain metabolism to a similar extent as total sleep deprivation without affecting the neuronal responsiveness of hippocampus to a novel environment. © 2016 European Sleep Research Society.

Sleep fragmentation alters brain energy metabolism without modifying hippocampal electrophysiological response to novelty exposure

KAUST Repository

Baud, Maxime O.

2016-05-03

© 2016 European Sleep Research Society. Sleep is viewed as a fundamental restorative function of the brain, but its specific role in neural energy budget remains poorly understood. Sleep deprivation dampens brain energy metabolism and impairs cognitive functions. Intriguingly, sleep fragmentation, despite normal total sleep duration, has a similar cognitive impact, and in this paper we ask the question of whether it may also impair brain energy metabolism. To this end, we used a recently developed mouse model of 2 weeks of sleep fragmentation and measured 2-deoxy-glucose uptake and glycogen, glucose and lactate concentration in different brain regions. In order to homogenize mice behaviour during metabolic measurements, we exposed them to a novel environment for 1 h. Using an intra-hippocampal electrode, we first showed that hippocampal electroencephalograph (EEG) response to exploration was unaltered by 1 or 14 days of sleep fragmentation. However, after 14 days, sleep fragmented mice exhibited a lower uptake of 2-deoxy-glucose in cortex and hippocampus and lower cortical lactate levels than control mice. Our results suggest that long-term sleep fragmentation impaired brain metabolism to a similar extent as total sleep deprivation without affecting the neuronal responsiveness of hippocampus to a novel environment.

The effect of metabolic alkalosis on the ventilatory response in healthy subjects.

Science.gov (United States)

Oppersma, E; Doorduin, J; van der Hoeven, J G; Veltink, P H; van Hees, H W H; Heunks, L M A

2018-02-01

Patients with acute respiratory failure may develop respiratory acidosis. Metabolic compensation by bicarbonate production or retention results in posthypercapnic alkalosis with an increased arterial bicarbonate concentration. The hypothesis of this study was that elevated plasma bicarbonate levels decrease respiratory drive and minute ventilation. In an intervention study in 10 healthy subjects the ventilatory response using a hypercapnic ventilatory response (HCVR) test was assessed, before and after administration of high dose sodium bicarbonate. Total dose of sodiumbicarbonate was 1000 ml 8.4% in 3 days. Plasma bicarbonate increased from 25.2 ± 2.2 to 29.2 ± 1.9 mmol/L. With increasing inspiratory CO 2 pressure during the HCVR test, RR, V t , Pdi, EAdi and V E increased. The clinical ratio ΔV E /ΔP et CO 2 remained unchanged, but Pdi, EAdi and V E were significantly lower after bicarbonate administration for similar levels of inspired CO 2 . This study demonstrates that in healthy subjects metabolic alkalosis decreases the neural respiratory drive and minute ventilation, as a response to inspiratory CO 2 . Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

CYP2A6 metabolism in the development of smoking behaviors in young adults.

Science.gov (United States)

Olfson, Emily; Bloom, Joseph; Bertelsen, Sarah; Budde, John P; Breslau, Naomi; Brooks, Andrew; Culverhouse, Robert; Chan, Grace; Chen, Li-Shiun; Chorlian, David; Dick, Danielle M; Edenberg, Howard J; Hartz, Sarah; Hatsukami, Dorothy; Hesselbrock, Victor M; Johnson, Eric O; Kramer, John R; Kuperman, Samuel; Meyers, Jacquelyn L; Nurnberger, John; Porjesz, Bernice; Saccone, Nancy L; Schuckit, Marc A; Stitzel, Jerry; Tischfield, Jay A; Rice, John P; Goate, Alison; Bierut, Laura J

2018-01-01

Cytochrome P450 2A6 (CYP2A6) encodes the enzyme responsible for the majority of nicotine metabolism. Previous studies support that slow metabolizers smoke fewer cigarettes once nicotine dependent but provide conflicting results on the role of CYP2A6 in the development of dependence. By focusing on the critical period of young adulthood, this study examines the relationship of CYP2A6 variation and smoking milestones. A total of 1209 European American young adults enrolled in the Collaborative Study on the Genetics of Alcoholism were genotyped for CYP2A6 variants to calculate a previously well-validated metric that estimates nicotine metabolism. This metric was not associated with the transition from never smoking to smoking initiation nor with the transition from initiation to daily smoking (P > 0.4). But among young adults who had become daily smokers (n = 506), decreased metabolism was associated with increased risk of nicotine dependence (P = 0.03) (defined as Fagerström Test for Nicotine Dependence score ≥4). This finding was replicated in the Collaborative Genetic Study of Nicotine Dependence with 335 young adult daily smokers (P = 0.02). Secondary meta-analysis indicated that slow metabolizers had a 53 percent increased odds (OR = 1.53, 95 percent CI 1.11-2.11, P = 0.009) of developing nicotine dependence compared with normal metabolizers. Furthermore, secondary analyses examining four-level response of time to first cigarette after waking (>60, 31-60, 6-30, ≤5 minutes) demonstrated a robust effect of the metabolism metric in Collaborative Study on the Genetics of Alcoholism (P = 0.03) and Collaborative Genetic Study of Nicotine Dependence (P = 0.004), illustrating the important role of this measure of dependence. These findings highlight the complex role of CYP2A6 variation across different developmental stages of smoking behaviors. © 2016 Society for the Study of Addiction.

Metabolic regulation of inflammation.

Science.gov (United States)

Gaber, Timo; Strehl, Cindy; Buttgereit, Frank

2017-05-01

Immune cells constantly patrol the body via the bloodstream and migrate into multiple tissues where they face variable and sometimes demanding environmental conditions. Nutrient and oxygen availability can vary during homeostasis, and especially during the course of an immune response, creating a demand for immune cells that are highly metabolically dynamic. As an evolutionary response, immune cells have developed different metabolic programmes to supply them with cellular energy and biomolecules, enabling them to cope with changing and challenging metabolic conditions. In the past 5 years, it has become clear that cellular metabolism affects immune cell function and differentiation, and that disease-specific metabolic configurations might provide an explanation for the dysfunctional immune responses seen in rheumatic diseases. This Review outlines the metabolic challenges faced by immune cells in states of homeostasis and inflammation, as well as the variety of metabolic configurations utilized by immune cells during differentiation and activation. Changes in cellular metabolism that contribute towards the dysfunctional immune responses seen in rheumatic diseases are also briefly discussed.

The Future of Metabolic Engineering and Synthetic Biology: Towards a Systematic Practice

Science.gov (United States)

Yadav, Vikramaditya G.; De Mey, Marjan; Lim, Chin Giaw; Ajikumar, Parayil Kumaran; Stephanopoulos, Gregory

2012-01-01

Industrial biotechnology promises to revolutionize conventional chemical manufacturing in the years ahead, largely owing to the excellent progress in our ability to re-engineer cellular metabolism. However, most successes of metabolic engineering have been confined to over-producing natively synthesized metabolites in E. coli and S. cerevisiae. A major reason for this development has been the descent of metabolic engineering, particularly secondary metabolic engineering, to a collection of demonstrations rather than a systematic practice with generalizable tools. Synthetic biology, a more recent development, faces similar criticisms. Herein, we attempt to lay down a framework around which bioreaction engineering can systematize itself just like chemical reaction engineering. Central to this undertaking is a new approach to engineering secondary metabolism known as ‘multivariate modular metabolic engineering’ (MMME), whose novelty lies in its assessment and elimination of regulatory and pathway bottlenecks by re-defining the metabolic network as a collection of distinct modules. After introducing the core principles of MMME, we shall then present a number of recent developments in secondary metabolic engineering that could potentially serve as its facilitators. It is hoped that the ever-declining costs of de novo gene synthesis; the improved use of bioinformatic tools to mine, sort and analyze biological data; and the increasing sensitivity and sophistication of investigational tools will make the maturation of microbial metabolic engineering an autocatalytic process. Encouraged by these advances, research groups across the world would take up the challenge of secondary metabolite production in simple hosts with renewed vigor, thereby adding to the range of products synthesized using metabolic engineering. PMID:22629571

Biosynthesis of secondary metabolites in sugarcane

Directory of Open Access Journals (Sweden)

S.C. França

2001-12-01

Full Text Available A set of genes related to secondary metabolism was extracted from the sugarcane expressed sequence tag (SUCEST database and was used to investigate both the gene expression pattern of key enzymes regulating the main biosynthetic secondary metabolism pathways and the major classes of metabolites involved in the response of sugarcane to environmental and developmental cues. The SUCEST database was constructed with tissues in different physiological conditions which had been collected under varied situation of environmental stress. This database allows researchers to identify and characterize the expressed genes of a wide range of putative enzymes able to catalyze steps in the phenylpropanoid, isoprenoid and other pathways of the special metabolic mechanisms involved in the response of sugarcane to environmental changes. Our results show that sugarcane cDNAs encoded putative ultra-violet induced sesquiterpene cyclases (SC; chalcone synthase (CHS, the first enzyme in the pathway branch for flavonoid biosynthesis; isoflavone synthase (IFS, involved in plant defense and root nodulation; isoflavone reductase (IFR, a key enzyme in phenylpropanoid phytoalexin biosynthesis; and caffeic acid-O-methyltransferase, a key enzyme in the biosynthesis of lignin cell wall precursors. High levels of CHS transcripts from plantlets infected with Herbaspirillum rubri or Gluconacetobacter diazotroficans suggests that agents of biotic stress can elicit flavonoid biosynthesis in sugarcane. From this data we have predicted the profile of isoprenoid and phenylpropanoid metabolism in sugarcane and pointed the branches of secondary metabolism activated during tissue-specific stages of development and the adaptive response of sugarcane to agents of biotic and abiotic stress, although our assignment of enzyme function should be confirmed by careful biochemical and genetic supporting evidence.Este trabalho foi realizado com os objetivos de gerar uma coleção de genes

Metabolic response of Geobacter sulfurreducens towards electron donor/acceptor variation

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Lovley Derek R

2010-11-01

Full Text Available Abstract Background Geobacter sulfurreducens is capable of coupling the complete oxidation of organic compounds to iron reduction. The metabolic response of G. sulfurreducens towards variations in electron donors (acetate, hydrogen and acceptors (Fe(III, fumarate was investigated via 13C-based metabolic flux analysis. We examined the 13C-labeling patterns of proteinogenic amino acids obtained from G. sulfurreducens cultured with 13C-acetate. Results Using 13C-based metabolic flux analysis, we observed that donor and acceptor variations gave rise to differences in gluconeogenetic initiation, tricarboxylic acid cycle activity, and amino acid biosynthesis pathways. Culturing G. sulfurreducens cells with Fe(III as the electron acceptor and acetate as the electron donor resulted in pyruvate as the primary carbon source for gluconeogenesis. When fumarate was provided as the electron acceptor and acetate as the electron donor, the flux analysis suggested that fumarate served as both an electron acceptor and, in conjunction with acetate, a carbon source. Growth on fumarate and acetate resulted in the initiation of gluconeogenesis by phosphoenolpyruvate carboxykinase and a slightly elevated flux through the oxidative tricarboxylic acid cycle as compared to growth with Fe(III as the electron acceptor. In addition, the direction of net flux between acetyl-CoA and pyruvate was reversed during growth on fumarate relative to Fe(III, while growth in the presence of Fe(III and acetate which provided hydrogen as an electron donor, resulted in decreased flux through the tricarboxylic acid cycle. Conclusions We gained detailed insight into the metabolism of G. sulfurreducens cells under various electron donor/acceptor conditions using 13C-based metabolic flux analysis. Our results can be used for the development of G. sulfurreducens as a chassis for a variety of applications including bioremediation and renewable biofuel production.

Exercise electrocardiographic responses and serum cystatin C levels among metabolic syndrome patients without overt diabetes mellitus

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Tanindi A

2011-02-01

Full Text Available Asli Tanindi1 Hilal Olgun1 Ayse Tuncel2 Bulent Celik3 Hatice Pasaoglu2 Bulent Boyaci11Department of Cardiology, 2Department of Medical Biochemistry, Faculty of Medicine, 3Department of Statistics, Faculty of Health Sciences, Gazi University, Ankara, TurkeyObjectives: An impaired heart rate response during exercise (chronotropic incompetence and an impaired heart rate recovery (HRR after exercise are predictors of cardiovascular risk and mortality. Cystatin C is a novel marker for cardiovascular disease. We aimed to investigate exercise electrocardiographic responses in patients with metabolic syndrome who were without overt diabetes mellitus, in addition to the association of serum cystatin C levels with the exercise electrocardiographic test results.Method: Forty-three consecutive patients admitted to a cardiology outpatient clinic without angina pectoris were recruited if they met criteria for metabolic syndrome but did not have overt diabetes mellitus. Serum cystatin C levels were measured, and all participants underwent exercise electrocardiographic testing. Patients who were found to have ischemia had a coronary angiography procedure.Results: The mean cystatin C level of patients was higher in metabolic syndrome group than healthy controls (610.1 ± 334.02 vs 337.3 ± 111.01 µg/L; P < 0.001. The percentage of patients with ischemia confirmed by coronary angiography was 13.9% in the metabolic syndrome group. Cystatin C levels in the ischemic patients of the metabolic syndrome group were higher than that in nonischemic patients (957.00 ± 375.6 vs 553.8 ± 295.3 µg /L; P = 0.005. Chronotropic incompetence was observed in 30.2% of the patients with metabolic syndrome compared with 16.7% in the control group (P = 0.186. Chronotropic response indices were 0.8 ± 0.18 versus 0.9 ± 0.10 for the two groups, respectively (P = 0.259. HRR was significantly lower in the metabolic syndrome patients compared with the controls (20.1 ± 8.01 vs 25.2 �

The metabolic responses to aerial diffusion of essential oils.

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Yani Wu

Full Text Available Anxiety disorders are the most prevalent psychiatric disorders and affect a great number of people worldwide. Essential oils, take effects through inhalation or topical application, are believed to enhance physical, emotional, and spiritual well-being. Although clinical studies suggest that the use of essential oils may have therapeutic potential, evidence for the efficacy of essential oils in treating medical conditions remains poor, with a particular lack of studies employing rigorous analytical methods that capture its identifiable impact on human biology. Here, we report a comprehensive gas chromatography time-of-flight mass spectrometry (GC-TOFMS based metabonomics study that reveals the aromas-induced metabolic changes and the anxiolytic effect of aromas in elevated plus maze (EPM induced anxiety model rats. The significant alteration of metabolites in the EPM group was attenuated by aromas treatment, concurrent with the behavioral improvement with significantly increased open arms time and open arms entries. Brain tissue and urinary metabonomic analysis identified a number of altered metabolites in response to aromas intervention. These metabolic changes included the increased carbohydrates and lowered levels of neurotransmitters (tryptophan, serine, glycine, aspartate, tyrosine, cysteine, phenylalanine, hypotaurine, histidine, and asparagine, amino acids, and fatty acids in the brain. Elevated aspartate, carbohydrates (sucrose, maltose, fructose, and glucose, nucleosides and organic acids such as lactate and pyruvate were also observed in the urine. The EPM induced metabolic differences observed in urine or brain tissue was significantly reduced after 10 days of aroma inhalation, as noted with the loss of statistical significance on many of the metabolites in the aroma-EPM group. This study demonstrates, for the first time, that the metabonomics approach can capture the subtle metabolic changes resulting from exposure to essential oils

Combined effect of water loss and wounding stress on gene activation of metabolic pathways associated with phenolic biosynthesis in carrot

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Alejandro eBecerra-Moreno

2015-10-01

Full Text Available Abstract: The application of postharvest abiotic stresses is an effective strategy to activate the primary and secondary metabolism of plants inducing the accumulation of antioxidant phenolic compounds. In the present study, the effect of water stress applied alone and in combination with wounding stress on the activation of primary (shikimic acid and secondary (phenylpropanoid metabolic pathways related with the accumulation of phenolic compound in plants was evaluated. Carrot (Daucus carota was used as model system for this study, and the effect of abiotic stresses was evaluated at the gene expression level and on the accumulation of metabolites. As control of the study, whole carrots were stored under the same conditions. Results demonstrated that water stress activated the primary and secondary metabolism of carrots, favoring the lignification process. Likewise, wounding stress induced higher activation of the primary and secondary metabolism of carrots as compared to water stress alone, leading to higher accumulation of shikimic acid, phenolic compounds and lignin. Additional water stress applied on wounded carrots exerted a synergistic effect on the wound-response at the gene expression level. For instance, when wounded carrots were treated with water stress, the tissue showed 20- and 14-fold increases in the relative expression of 3-deoxy-D-arabino-heptulosanate synthase and phenylalanine ammonia-lyase genes, respectively. However, since lignification was increased, lower accumulation of phenolic compounds was detected. Indicatively, at 48 h of storage, wounded carrots treated with water stress showed ~31% lower levels of phenolic compounds and ~23% higher lignin content as compared with wounded controls. In the present study, it was demonstrated that water stress is one of the pivotal mechanism of the wound-response in carrot. Results allowed the elucidation of strategies to induce the accumulation of specific primary or secondary

Metabolic cost of neuronal information in an empirical stimulus-response model

Czech Academy of Sciences Publication Activity Database

Košťál, Lubomír; Lánský, Petr; McDonnell, M.D.

2013-01-01

Roč. 107, č. 3 (2013), s. 355-365 ISSN 0340-1200 R&D Projects: GA ČR(CZ) GBP304/12/G069; GA ČR(CZ) GAP103/11/0282; GA ČR(CZ) GPP103/12/P558 Institutional support: RVO:67985823 Keywords : information capacity * metabolic cost * stimulus-response curve Subject RIV: FH - Neurology Impact factor: 1.933, year: 2013

Metabolic responses to high protein diet in Korean elite bodybuilders with high-intensity resistance exercise

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Choue Ryowon

2011-07-01

Full Text Available Abstract Background High protein diet has been known to cause metabolic acidosis, which is manifested by increased urinary excretion of nitrogen and calcium. Bodybuilders habitually consumed excessive dietary protein over the amounts recommended for them to promote muscle mass accretion. This study investigated the metabolic response to high protein consumption in the elite bodybuilders. Methods Eight elite Korean bodybuilders within the age from 18 to 25, mean age 21.5 ± 2.6. For data collection, anthropometry, blood and urinary analysis, and dietary assessment were conducted. Results They consumed large amounts of protein (4.3 ± 1.2 g/kg BW/day and calories (5,621.7 ± 1,354.7 kcal/day, as well as more than the recommended amounts of vitamins and minerals, including potassium and calcium. Serum creatinine (1.3 ± 0.1 mg/dl and potassium (5.9 ± 0.8 mmol/L, and urinary urea nitrogen (24.7 ± 9.5 mg/dl and creatinine (2.3 ± 0.7 mg/dl were observed to be higher than the normal reference ranges. Urinary calcium (0.3 ± 0.1 mg/dl, and phosphorus (1.3 ± 0.4 mg/dl were on the border of upper limit of the reference range and the urine pH was in normal range. Conclusions Increased urinary excretion of urea nitrogen and creatinine might be due to the high rates of protein metabolism that follow high protein intake and muscle turnover. The obvious evidence of metabolic acidosis in response to high protein diet in the subjects with high potassium intake and intensive resistance exercise were not shown in this study results. However, this study implied that resistance exercise with adequate mineral supplementation, such as potassium and calcium, could reduce or offset the negative effects of protein-generated metabolic changes. This study provides preliminary information of metabolic response to high protein intake in bodybuilders who engaged in high-intensity resistance exercise. Further studies will be needed to determine the effects of the intensity

Introduction to metabolic genetic engineering for the production of valuable secondary metabolites in in vivo and in vitro plant systems.

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Benedito, Vagner A; Modolo, Luzia V

2014-01-01

Plants are capable of producing a myriad of chemical compounds. While these compounds serve specific functions in the plant, many have surprising effects on the human body, often with positive action against diseases. These compounds are often difficult to synthesize ex vivo and require the coordinated and compartmentalized action of enzymes in living organisms. However, the amounts produced in whole plants are often small and restricted to single tissues of the plant or even cellular organelles, making their extraction an expensive process. Since most natural products used in therapeutics are specialized, secondary plant metabolites, we provide here an overview of the classification of the main classes of these compounds, with its biochemical pathways and how this information can be used to create efficient in and ex planta production pipelines to generate highly valuable compounds. Metabolic genetic engineering is introduced in light of physiological and genetic methods to enhance production of high-value plant secondary metabolites.

The structure of wheat bread influences the postprandial metabolic response in healthy men

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Eelderink, Coby; Noort, Martijn W. J.; Sozer, Nesli; Koehorst, Martijn; Holst, Jens J.; Deacon, Carolyn F.; Rehfeld, Jens F.; Poutanen, Kaisa; Vonk, Roel J.; Oudhuis, Lizette; Priebe, Marion G.

2015-01-01

Postprandial high glucose and insulin responses after starchy food consumption, associated with an increased risk of developing several metabolic diseases, could possibly be improved by altering food structure. We investigated the influence of a compact food structure; different wheat products with

Integrating the protein and metabolic engineering toolkits for next-generation chemical biosynthesis.

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Pirie, Christopher M; De Mey, Marjan; Jones Prather, Kristala L; Ajikumar, Parayil Kumaran

2013-04-19

Through microbial engineering, biosynthesis has the potential to produce thousands of chemicals used in everyday life. Metabolic engineering and synthetic biology are fields driven by the manipulation of genes, genetic regulatory systems, and enzymatic pathways for developing highly productive microbial strains. Fundamentally, it is the biochemical characteristics of the enzymes themselves that dictate flux through a biosynthetic pathway toward the product of interest. As metabolic engineers target sophisticated secondary metabolites, there has been little recognition of the reduced catalytic activity and increased substrate/product promiscuity of the corresponding enzymes compared to those of central metabolism. Thus, fine-tuning these enzymatic characteristics through protein engineering is paramount for developing high-productivity microbial strains for secondary metabolites. Here, we describe the importance of protein engineering for advancing metabolic engineering of secondary metabolism pathways. This pathway integrated enzyme optimization can enhance the collective toolkit of microbial engineering to shape the future of chemical manufacturing.

Sex differences in metabolic and adipose tissue responses to juvenile-onset obesity in sheep.

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Bloor, Ian D; Sébert, Sylvain P; Saroha, Vivek; Gardner, David S; Keisler, Duane H; Budge, Helen; Symonds, Michael E; Mahajan, Ravi P

2013-10-01

Sex is a major factor determining adipose tissue distribution and the subsequent adverse effects of obesity-related disease including type 2 diabetes. The role of gender on juvenile obesity and the accompanying metabolic and inflammatory responses is not well established. Using an ovine model of juvenile onset obesity induced by reduced physical activity, we examined the effect of gender on metabolic, circulatory, and related inflammatory and energy-sensing profiles of the major adipose tissue depots. Despite a similar increase in fat mass with obesity between genders, males demonstrated a higher storage capacity of lipids within perirenal-abdominal adipocytes and exhibited raised insulin. In contrast, obese females became hypercortisolemic, a response that was positively correlated with central fat mass. Analysis of gene expression in perirenal-abdominal adipose tissue demonstrated the stimulation of inflammatory markers in males, but not females, with obesity. Obese females displayed increased expression of genes involved in the glucocorticoid axis and energy sensing in perirenal-abdominal, but not omental, adipose tissue, indicating a depot-specific mechanism that may be protective from the adverse effects of metabolic dysfunction and inflammation. In conclusion, young males are at a greater risk than females to the onset of comorbidities associated with juvenile-onset obesity. These sex-specific differences in cortisol and adipose tissue could explain the earlier onset of the metabolic-related diseases in males compared with females after obesity.

Methyl Jasmonate-Elicited Transcriptional Responses and Pentacyclic Triterpene Biosynthesis in Sweet Basil1[C][W

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Misra, Rajesh Chandra; Maiti, Protiti; Chanotiya, Chandan Singh; Shanker, Karuna; Ghosh, Sumit

2014-01-01

Sweet basil (Ocimum basilicum) is well known for its diverse pharmacological properties and has been widely used in traditional medicine for the treatment of various ailments. Although a variety of secondary metabolites with potent biological activities are identified, our understanding of the biosynthetic pathways that produce them has remained largely incomplete. We studied transcriptional changes in sweet basil after methyl jasmonate (MeJA) treatment, which is considered an elicitor of secondary metabolites, and identified 388 candidate MeJA-responsive unique transcripts. Transcript analysis suggests that in addition to controlling its own biosynthesis and stress responses, MeJA up-regulates transcripts of the various secondary metabolic pathways, including terpenoids and phenylpropanoids/flavonoids. Furthermore, combined transcript and metabolite analysis revealed MeJA-induced biosynthesis of the medicinally important ursane-type and oleanane-type pentacyclic triterpenes. Two MeJA-responsive oxidosqualene cyclases (ObAS1 and ObAS2) that encode for 761- and 765-amino acid proteins, respectively, were identified and characterized. Functional expressions of ObAS1 and ObAS2 in Saccharomyces cerevisiae led to the production of β-amyrin and α-amyrin, the direct precursors of oleanane-type and ursane-type pentacyclic triterpenes, respectively. ObAS1 was identified as a β-amyrin synthase, whereas ObAS2 was a mixed amyrin synthase that produced both α-amyrin and β-amyrin but had a product preference for α-amyrin. Moreover, transcript and metabolite analysis shed light on the spatiotemporal regulation of pentacyclic triterpene biosynthesis in sweet basil. Taken together, these results will be helpful in elucidating the secondary metabolic pathways of sweet basil and developing metabolic engineering strategies for enhanced production of pentacyclic triterpenes. PMID:24367017

Metabolic responses to pyruvate kinase deletion in lysine producing Corynebacterium glutamicum

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Wittmann Christoph

2008-03-01

Full Text Available Abstract Background Pyruvate kinase is an important element in flux control of the intermediate metabolism. It catalyzes the irreversible conversion of phosphoenolpyruvate into pyruvate and is under allosteric control. In Corynebacterium glutamicum, this enzyme was regarded as promising target for improved production of lysine, one of the major amino acids in animal nutrition. In pyruvate kinase deficient strains the required equimolar ratio of the two lysine precursors oxaloacetate and pyruvate can be achieved through concerted action of the phosphotransferase system (PTS and phosphoenolpyruvate carboxylase (PEPC, whereby a reduced amount of carbon may be lost as CO2 due to reduced flux into the tricarboxylic acid (TCA cycle. In previous studies, deletion of pyruvate kinase in lysine-producing C. glutamicum, however, did not yield a clear picture and the exact metabolic consequences are not fully understood. Results In this work, deletion of the pyk gene, encoding pyruvate kinase, was carried out in the lysine-producing strain C. glutamicum lysCfbr, expressing a feedback resistant aspartokinase, to investigate the cellular response to deletion of this central glycolytic enzyme. Pyk deletion was achieved by allelic replacement, verified by PCR analysis and the lack of in vitro enzyme activity. The deletion mutant showed an overall growth behavior (specific growth rate, glucose uptake rate, biomass yield which was very similar to that of the parent strain, but differed in slightly reduced lysine formation, increased formation of the overflow metabolites dihydroxyacetone and glycerol and in metabolic fluxes around the pyruvate node. The latter involved a flux shift from pyruvate carboxylase (PC to PEPC, by which the cell maintained anaplerotic supply of the TCA cycle. This created a metabolic by-pass from PEP to pyruvate via malic enzyme demonstrating its contribution to metabolic flexibility of C. glutamicum on glucose. Conclusion The metabolic

The future of metabolic engineering and synthetic biology: towards a systematic practice.

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Yadav, Vikramaditya G; De Mey, Marjan; Lim, Chin Giaw; Ajikumar, Parayil Kumaran; Stephanopoulos, Gregory

2012-05-01

Industrial biotechnology promises to revolutionize conventional chemical manufacturing in the years ahead, largely owing to the excellent progress in our ability to re-engineer cellular metabolism. However, most successes of metabolic engineering have been confined to over-producing natively synthesized metabolites in E. coli and S. cerevisiae. A major reason for this development has been the descent of metabolic engineering, particularly secondary metabolic engineering, to a collection of demonstrations rather than a systematic practice with generalizable tools. Synthetic biology, a more recent development, faces similar criticisms. Herein, we attempt to lay down a framework around which bioreaction engineering can systematize itself just like chemical reaction engineering. Central to this undertaking is a new approach to engineering secondary metabolism known as 'multivariate modular metabolic engineering' (MMME), whose novelty lies in its assessment and elimination of regulatory and pathway bottlenecks by re-defining the metabolic network as a collection of distinct modules. After introducing the core principles of MMME, we shall then present a number of recent developments in secondary metabolic engineering that could potentially serve as its facilitators. It is hoped that the ever-declining costs of de novo gene synthesis; the improved use of bioinformatic tools to mine, sort and analyze biological data; and the increasing sensitivity and sophistication of investigational tools will make the maturation of microbial metabolic engineering an autocatalytic process. Encouraged by these advances, research groups across the world would take up the challenge of secondary metabolite production in simple hosts with renewed vigor, thereby adding to the range of products synthesized using metabolic engineering. Copyright © 2011 Elsevier Inc. All rights reserved.

IMG-ABC: new features for bacterial secondary metabolism analysis and targeted biosynthetic gene cluster discovery in thousands of microbial genomes.

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Hadjithomas, Michalis; Chen, I-Min A; Chu, Ken; Huang, Jinghua; Ratner, Anna; Palaniappan, Krishna; Andersen, Evan; Markowitz, Victor; Kyrpides, Nikos C; Ivanova, Natalia N

2017-01-04

Secondary metabolites produced by microbes have diverse biological functions, which makes them a great potential source of biotechnologically relevant compounds with antimicrobial, anti-cancer and other activities. The proteins needed to synthesize these natural products are often encoded by clusters of co-located genes called biosynthetic gene clusters (BCs). In order to advance the exploration of microbial secondary metabolism, we developed the largest publically available database of experimentally verified and predicted BCs, the Integrated Microbial Genomes Atlas of Biosynthetic gene Clusters (IMG-ABC) (https://img.jgi.doe.gov/abc/). Here, we describe an update of IMG-ABC, which includes ClusterScout, a tool for targeted identification of custom biosynthetic gene clusters across 40 000 isolate microbial genomes, and a new search capability to query more than 700 000 BCs from isolate genomes for clusters with similar Pfam composition. Additional features enable fast exploration and analysis of BCs through two new interactive visualization features, a BC function heatmap and a BC similarity network graph. These new tools and features add to the value of IMG-ABC's vast body of BC data, facilitating their in-depth analysis and accelerating secondary metabolite discovery. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Deciphering the Cryptic Genome: Genome-wide Analyses of the Rice Pathogen Fusarium fujikuroi Reveal Complex Regulation of Secondary Metabolism and Novel Metabolites

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Studt, Lena; Niehaus, Eva-Maria; Espino, Jose J.; Huß, Kathleen; Michielse, Caroline B.; Albermann, Sabine; Wagner, Dominik; Bergner, Sonja V.; Connolly, Lanelle R.; Fischer, Andreas; Reuter, Gunter; Kleigrewe, Karin; Bald, Till; Wingfield, Brenda D.; Ophir, Ron; Freeman, Stanley; Hippler, Michael; Smith, Kristina M.; Brown, Daren W.; Proctor, Robert H.; Münsterkötter, Martin; Freitag, Michael; Humpf, Hans-Ulrich; Güldener, Ulrich; Tudzynski, Bettina

2013-01-01

The fungus Fusarium fujikuroi causes “bakanae” disease of rice due to its ability to produce gibberellins (GAs), but it is also known for producing harmful mycotoxins. However, the genetic capacity for the whole arsenal of natural compounds and their role in the fungus' interaction with rice remained unknown. Here, we present a high-quality genome sequence of F. fujikuroi that was assembled into 12 scaffolds corresponding to the 12 chromosomes described for the fungus. We used the genome sequence along with ChIP-seq, transcriptome, proteome, and HPLC-FTMS-based metabolome analyses to identify the potential secondary metabolite biosynthetic gene clusters and to examine their regulation in response to nitrogen availability and plant signals. The results indicate that expression of most but not all gene clusters correlate with proteome and ChIP-seq data. Comparison of the F. fujikuroi genome to those of six other fusaria revealed that only a small number of gene clusters are conserved among these species, thus providing new insights into the divergence of secondary metabolism in the genus Fusarium. Noteworthy, GA biosynthetic genes are present in some related species, but GA biosynthesis is limited to F. fujikuroi, suggesting that this provides a selective advantage during infection of the preferred host plant rice. Among the genome sequences analyzed, one cluster that includes a polyketide synthase gene (PKS19) and another that includes a non-ribosomal peptide synthetase gene (NRPS31) are unique to F. fujikuroi. The metabolites derived from these clusters were identified by HPLC-FTMS-based analyses of engineered F. fujikuroi strains overexpressing cluster genes. In planta expression studies suggest a specific role for the PKS19-derived product during rice infection. Thus, our results indicate that combined comparative genomics and genome-wide experimental analyses identified novel genes and secondary metabolites that contribute to the evolutionary success of F

Metabolic response to glatiramer acetate therapy in multiple sclerosis patients

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Lidia De Riccardis

2016-12-01

Full Text Available Glatiramer acetate (GA; Copaxone is a random copolymer of glutamic acid, lysine, alanine, and tyrosine used for the treatment of patients with multiple sclerosis (MS. Its mechanism of action has not been already fully elucidated, but it seems that GA has an immune-modulatory effect and neuro-protective properties. Lymphocyte mitochondrial dysfunction underlines the onset of several autoimmune disorders. In MS first diagnosis patients, CD4+, the main T cell subset involved in the pathogenesis of MS, undergo a metabolic reprogramming that consist in the up-regulation of glycolysis and in the down-regulation of oxidative phosphorylation. Currently, no works exist about CD4+ T cell metabolism in response to GA treatment. In order to provide novel insight into the potential use of GA in MS treatment, blood samples were collected from 20 healthy controls (HCs and from 20 RR MS patients prior and every 6 months during the 12 months of GA administration. GA treated patients' CD4+ T cells were compared with those from HCs analysing their mitochondrial activity through polarographic and enzymatic methods in association with their antioxidant status, through the analysis of SOD, GPx and CAT activities. Altogether, our findings suggest that GA is able to reduce CD4+ T lymphocytes' dysfunctions by increasing mitochondrial activity and their response to oxidative stress.

Metabolic response to glatiramer acetate therapy in multiple sclerosis patients.

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De Riccardis, Lidia; Ferramosca, Alessandra; Danieli, Antonio; Trianni, Giorgio; Zara, Vincenzo; De Robertis, Francesca; Maffia, Michele

2016-12-01

Glatiramer acetate (GA; Copaxone) is a random copolymer of glutamic acid, lysine, alanine, and tyrosine used for the treatment of patients with multiple sclerosis (MS). Its mechanism of action has not been already fully elucidated, but it seems that GA has an immune-modulatory effect and neuro-protective properties. Lymphocyte mitochondrial dysfunction underlines the onset of several autoimmune disorders. In MS first diagnosis patients, CD4 + , the main T cell subset involved in the pathogenesis of MS, undergo a metabolic reprogramming that consist in the up-regulation of glycolysis and in the down-regulation of oxidative phosphorylation. Currently, no works exist about CD4 + T cell metabolism in response to GA treatment. In order to provide novel insight into the potential use of GA in MS treatment, blood samples were collected from 20 healthy controls (HCs) and from 20 RR MS patients prior and every 6 months during the 12 months of GA administration. GA treated patients' CD4 + T cells were compared with those from HCs analysing their mitochondrial activity through polarographic and enzymatic methods in association with their antioxidant status, through the analysis of SOD, GPx and CAT activities. Altogether, our findings suggest that GA is able to reduce CD4 + T lymphocytes' dysfunctions by increasing mitochondrial activity and their response to oxidative stress.

Tryptophan Metabolism in Patients With Chronic Kidney Disease Secondary to Type 2 Diabetes: Relationship to Inflammatory Markers

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Subrata Debnath

2017-03-01

Full Text Available Objective: Type 2 diabetes (T2D is the primary case of chronic kidney disease (CKD. Inflammation is associated with metabolic dysregulation in patients with T2D and CKD. Tryptophan (TRP metabolism may have relevance to the CKD outcomes and associated symptoms. We investigated the relationships of TRP metabolism with inflammatory markers in patients with T2D and CKD. Methods: Data were collected from a well-characterized cohort of type 2 diabetic individuals with all stages of CKD, including patients on hemodialysis. Key TRP metabolites (kynurenine [KYN], kynurenic acid [KYNA], and quinolinic acid [QA], proinflammatory cytokines (tumor necrosis factor-α [TNF-α] and interleukin-6 [IL-6], and C-reactive protein were measured in plasma. The KYN/TRP ratio was utilized as a surrogate marker for indoleamine 2,3-dioxygenase 1 (IDO1 enzyme activity. Results: There was a significant inverse association between circulating TRP level and stages of CKD ( P  < 0.0001. Downstream bioactive TRP metabolites KYN, KYNA, and QA were positively and robustly correlated with the severity of kidney disease ( P  < 0.0001. In multiple linear regression, neither TNF-α nor IL-6 was independently related to KYN/TRP ratio after adjusting for estimated glomerular filtration rate (eGFR. Only TNF-α was independently related to KYN after taking into account the effect of eGFR. Conclusions: Chronic kidney disease secondary to T2D may be associated with accumulation of toxic TRP metabolites due to both inflammation and impaired kidney function. Future longitudinal studies to determine whether the accumulation of KYN directly contributes to CKD progression and associated symptoms in patients with T2D are warranted.

Thyroid disorders and bone mineral metabolism

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Dinesh Kumar Dhanwal

2011-01-01

Full Text Available Thyroid diseases have widespread systemic manifestations including their effect on bone metabolism. On one hand, the effects of thyrotoxicosis including subclinical disease have received wide attention from researchers over the last century as it an important cause of secondary osteoporosis. On the other hand, hypothyroidism has received lesser attention as its effect on bone mineral metabolism is minimal. Therefore, this review will primarily focus on thyrotoxicosis and its impact on bone mineral metabolism.

A Case Study on Primary, Secondary and University Students' Environmentally Responsible Behaviors in Turkey

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Kahyaoglu, Mustafa

2013-01-01

The purpose of the study is to prove the environmentally responsible behaviors of primary, secondary and university students in Turkey. The students', who attended the study as participants, environmentally political behaviors, consumer/economical behaviors, direct behaviors toward protecting the environment and individual and public persuasion…

Chromium supplementation enhances the metabolic response of steers to lipopolysaccharide (LPS) challenge

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The effect of chromium (Cr; KemTRACE®brandChromiumProprionate 0.04%, Kemin Industries) supplementation on the metabolic response to LPS challenge was examined. Steers (n=20; 235±4 kg body weight (BW)) received a premix that added 0 (Con) or 0.2 mg/kg Cr to the total diet (DM (dry matter) basis) for ...

Plant physiology meets phytopathology: plant primary metabolism and plant-pathogen interactions.

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Berger, Susanne; Sinha, Alok K; Roitsch, Thomas

2007-01-01

Phytopathogen infection leads to changes in secondary metabolism based on the induction of defence programmes as well as to changes in primary metabolism which affect growth and development of the plant. Therefore, pathogen attack causes crop yield losses even in interactions which do not end up with disease or death of the plant. While the regulation of defence responses has been intensively studied for decades, less is known about the effects of pathogen infection on primary metabolism. Recently, interest in this research area has been growing, and aspects of photosynthesis, assimilate partitioning, and source-sink regulation in different types of plant-pathogen interactions have been investigated. Similarly, phytopathological studies take into consideration the physiological status of the infected tissues to elucidate the fine-tuned infection mechanisms. The aim of this review is to give a summary of recent advances in the mutual interrelation between primary metabolism and pathogen infection, as well as to indicate current developments in non-invasive techniques and important strategies of combining modern molecular and physiological techniques with phytopathology for future investigations.

Investigation of the metabolism of ergot alkaloids in cell culture by fourier transformation mass spectrometry.

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Mulac, Dennis; Grote, Anna-Karina; Kleigrewe, Karin; Humpf, Hans-Ulrich

2011-07-27

Ergot alkaloids are known toxic secondary metabolites of the fungus Claviceps purpurea occurring in various grains, especially rye products. The liver is responsible for converting the ergot alkaloids into metabolites; however, the toxic impact of these end products of metabolism is still unknown. The aim of this study was to analyze the metabolism of ergot alkaloids in colon and liver cell lines (HT-29, HepG2), as well as in human primary renal cells (RPTEC). It was shown that cells in vitro are able to metabolize ergot alkaloids, forming a variety of metabolic compounds. Significant differences between the used cell types could be identified, and a suitable model system was established using HT-29 cells, performing an intensive metabolism to hydroxylated metabolites. The formed substances were analyzed by coupling of high-performance liquid chromatography with fluorescence detection and Fourier transformation mass spectrometry (HPLC-FLD-FTMS) as a powerful tool to identify known and unknown metabolites.

Developmental changes in the metabolic network of snapdragon flowers.

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Joëlle K Muhlemann

Full Text Available Evolutionary and reproductive success of angiosperms, the most diverse group of land plants, relies on visual and olfactory cues for pollinator attraction. Previous work has focused on elucidating the developmental regulation of pathways leading to the formation of pollinator-attracting secondary metabolites such as scent compounds and flower pigments. However, to date little is known about how flowers control their entire metabolic network to achieve the highly regulated production of metabolites attracting pollinators. Integrative analysis of transcripts and metabolites in snapdragon sepals and petals over flower development performed in this study revealed a profound developmental remodeling of gene expression and metabolite profiles in petals, but not in sepals. Genes up-regulated during petal development were enriched in functions related to secondary metabolism, fatty acid catabolism, and amino acid transport, whereas down-regulated genes were enriched in processes involved in cell growth, cell wall formation, and fatty acid biosynthesis. The levels of transcripts and metabolites in pathways leading to scent formation were coordinately up-regulated during petal development, implying transcriptional induction of metabolic pathways preceding scent formation. Developmental gene expression patterns in the pathways involved in scent production were different from those of glycolysis and the pentose phosphate pathway, highlighting distinct developmental regulation of secondary metabolism and primary metabolic pathways feeding into it.

Effect of dietary restriction on immune response of laboratory mice divergently selected for basal metabolic rate.

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Książek, Aneta; Konarzewski, Marek

2012-01-01

To study whether dietary restriction (DR; 70% of ad lib. feeding)-elicited immunosuppression results from the trade-off between the costs of mounting an immune response and the metabolic costs of maintenance, we subjected mice from two divergent lines selected for high basal metabolic rate (H-BMR) and low BMR (L-BMR) to 4 wk of DR and then challenged them with keyhole limpet hemocyanin (KLH) antigen. Those line types differ genetically with respect to BMR and to the mass of metabolically expensive internal organs, which are larger in H-BMR mice. In mice of both line types, DR resulted in a significant reduction of body mass, an immune response, and the downsizing of spleen, lymph nodes, thymus, heart, and kidneys but not small intestines. DR resulted in a greater reduction of the spleen and lymph nodes in mice of the H-BMR line type, whereas the thymus was more affected in L-BMR line type. In contrast, immunization resulted in an increase of liver mass in DR mice of both line types. A comparison of the results of current and earlier studies on the same mouse line types suggests that metabolic trade-offs involving the costs of an immune response are more apparent when animals are forced to increase energy demands (e.g., by cold exposure) compared to when energy demands are decreased through DR. Our findings also suggest that divelrgent selection on BMR resulted in between-line-type differences in T-cell- and B-cell-mediated types of an immune response. More generally, our results indicate that production of a wide repertoire of antibodies is not correlated with high BMR.

School Responsiveness to Quality Rankings. An Empirical Analysis of Secondary Education in the Netherlands

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Koning, P.W.C.; van der Wiel, K.

2012-01-01

This paper assesses the response of Dutch secondary schools to the publication of relative quality ratings in a national newspaper (Trouw). Our research design exploits the discontinuities in the ranking formula that was used to generate five consecutive levels for the overall quality of schools. We

Transcriptional and metabolic effects of glucose on Streptococcus pneumoniae sugar metabolism

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Laura ePaixão

2015-10-01

Full Text Available Streptococcus pneumoniae is a strictly fermentative human pathogen that relies on carbohydrate metabolism to generate energy for growth. The nasopharynx colonised by the bacterium is poor in free sugars, but mucosa lining glycans can provide a source of sugar. In blood and inflamed tissues glucose is the prevailing sugar. As a result during progression from colonisation to disease S. pneumoniae has to cope with a pronounced shift in carbohydrate nature and availability. Thus, we set out to assess the pneumococcal response to sugars found in glycans and the influence of glucose (Glc on this response at the transcriptional, physiological and metabolic levels. Galactose (Gal, N-acetylglucosamine (GlcNAc and mannose (Man affected the expression of 8 to 14% of the genes covering cellular functions including central carbon metabolism and virulence. The pattern of end-products as monitored by in vivo 13C-NMR is in good agreement with the fermentation profiles during growth, while the pools of phosphorylated metabolites are consistent with the type of fermentation observed (homolactic vs. mixed and regulation at the metabolic level. Furthermore, the accumulation of α-Gal6P and Man6P indicate metabolic bottlenecks in the metabolism of Gal and Man, respectively. Glc added to cells actively metabolizing other sugar(s was readily consumed and elicited a metabolic shift towards a homolactic profile. The transcriptional response to Glc was large (over 5% of the genome. In central carbon metabolism (most represented category, Glc exerted mostly negative regulation. The smallest response to Glc was observed on a sugar mix, suggesting that exposure to varied sugars improves the fitness of S. pneumoniae. The expression of virulence factors was negatively controlled by Glc in a sugar-dependent manner. Overall, our results shed new light on the link between carbohydrate metabolism, adaptation to host niches and virulence.

Transcriptional and metabolic effects of glucose on Streptococcus pneumoniae sugar metabolism.

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Paixão, Laura; Caldas, José; Kloosterman, Tomas G; Kuipers, Oscar P; Vinga, Susana; Neves, Ana R

2015-01-01

Streptococcus pneumoniae is a strictly fermentative human pathogen that relies on carbohydrate metabolism to generate energy for growth. The nasopharynx colonized by the bacterium is poor in free sugars, but mucosa lining glycans can provide a source of sugar. In blood and inflamed tissues glucose is the prevailing sugar. As a result during progression from colonization to disease S. pneumoniae has to cope with a pronounced shift in carbohydrate nature and availability. Thus, we set out to assess the pneumococcal response to sugars found in glycans and the influence of glucose (Glc) on this response at the transcriptional, physiological, and metabolic levels. Galactose (Gal), N-acetylglucosamine (GlcNAc), and mannose (Man) affected the expression of 8 to 14% of the genes covering cellular functions including central carbon metabolism and virulence. The pattern of end-products as monitored by in vivo (13)C-NMR is in good agreement with the fermentation profiles during growth, while the pools of phosphorylated metabolites are consistent with the type of fermentation observed (homolactic vs. mixed) and regulation at the metabolic level. Furthermore, the accumulation of α-Gal6P and Man6P indicate metabolic bottlenecks in the metabolism of Gal and Man, respectively. Glc added to cells actively metabolizing other sugar(s) was readily consumed and elicited a metabolic shift toward a homolactic profile. The transcriptional response to Glc was large (over 5% of the genome). In central carbon metabolism (most represented category), Glc exerted mostly negative regulation. The smallest response to Glc was observed on a sugar mix, suggesting that exposure to varied sugars improves the fitness of S. pneumoniae. The expression of virulence factors was negatively controlled by Glc in a sugar-dependent manner. Overall, our results shed new light on the link between carbohydrate metabolism, adaptation to host niches and virulence.

Adrenal Mass Causing Secondary Hypertension.

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Robinson, Darlene Y

2015-11-01

Most hypertensive patients have essential (primary) hypertension; only 5% to 10% have a secondary cause. Two clinical characteristics suggestive of secondary hypertension are early onset (hypertension (>180/110 mm Hg). When faced with these findings, clinicians should consider a secondary cause of hypertension. A 22-year-old woman being evaluated for asthma exacerbation in the emergency department was noted to have severe persistent hypertension. Additional evaluation revealed severe hypokalemia, metabolic alkalosis, and hypernatremia. The patient was admitted to the hospital for blood pressure management, electrolyte replacement, and further evaluation of presumed hyperaldosteronism. Diagnostic imaging revealed a large adrenal mass. Surgical resection was performed, leading to a diagnosis of hyperaldosteronism caused by adrenal carcinoma. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Secondary hypertension is far less common than essential hypertension; however, considering the large volume of patients seen in emergency departments, it is likely that some will have secondary hypertension. Emergency physicians should be aware of the clinical characteristics that suggest secondary hypertension so that the appropriate diagnostic and treatment pathways can be pursued. Copyright © 2015 Elsevier Inc. All rights reserved.

Metabolic responses to high protein diet in Korean elite bodybuilders with high-intensity resistance exercise

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Kim, Hyerang; Lee, Saningun; Choue, Ryowon

2011-01-01

Abstract Background High protein diet has been known to cause metabolic acidosis, which is manifested by increased urinary excretion of nitrogen and calcium. Bodybuilders habitually consumed excessive dietary protein over the amounts recommended for them to promote muscle mass accretion. This study investigated the metabolic response to high protein consumption in the elite bodybuilders. Methods Eight elite Korean bodybuilders within the age from 18 to 25, mean age 21.5 ± 2.6. For data collec...

Alterations in cellular metabolism modulate CD1d-mediated NKT-cell responses.

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Webb, Tonya J; Carey, Gregory B; East, James E; Sun, Wenji; Bollino, Dominique R; Kimball, Amy S; Brutkiewicz, Randy R

2016-08-01

Natural killer T (NKT) cells play a critical role in the host's innate immune response. CD1d-mediated presentation of glycolipid antigens to NKT cells has been established; however, the mechanisms by which NKT cells recognize infected or cancerous cells remain unclear. 5(')-AMP activated protein kinase (AMPK) is a master regulator of lipogenic pathways. We hypothesized that activation of AMPK during infection and malignancy could alter the repertoire of antigens presented by CD1d and serve as a danger signal to NKT cells. In this study, we examined the effect of alterations in metabolism on CD1d-mediated antigen presentation to NKT cells and found that an infection with lymphocytic choriomeningitis virus rapidly increased CD1d-mediated antigen presentation. Hypoxia inducible factors (HIF) enhance T-cell effector functions during infection, therefore antigen presenting cells pretreated with pharmacological agents that inhibit glycolysis, induce HIF and activate AMPK were assessed for their ability to induce NKT-cell responses. Pretreatment with 2-deoxyglucose, cobalt chloride, AICAR and metformin significantly enhanced CD1d-mediated NKT-cell activation. In addition, NKT cells preferentially respond to malignant B cells and B-cell lymphomas express HIF-1α. These data suggest that targeting cellular metabolism may serve as a novel means of inducing innate immune responses. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Metabolomics Analysis of Hormone-Responsive and Triple-Negative Breast Cancer Cell Responses to Paclitaxel Identify Key Metabolic Differences.

Science.gov (United States)

Stewart, Delisha A; Winnike, Jason H; McRitchie, Susan L; Clark, Robert F; Pathmasiri, Wimal W; Sumner, Susan J

2016-09-02

To date, no targeted therapies are available to treat triple negative breast cancer (TNBC), while other breast cancer subtypes are responsive to current therapeutic treatment. Metabolomics was conducted to reveal differences in two hormone receptor-negative TNBC cell lines and two hormone receptor-positive Luminal A cell lines. Studies were conducted in the presence and absence of paclitaxel (Taxol). TNBC cell lines had higher levels of amino acids, branched-chain amino acids, nucleotides, and nucleotide sugars and lower levels of proliferation-related metabolites like choline compared with Luminal A cell lines. In the presence of paclitaxel, each cell line showed unique metabolic responses, with some similarities by type. For example, in the Luminal A cell lines, levels of lactate and creatine decreased while certain choline metabolites and myo-inositol increased with paclitaxel. In the TNBC cell lines levels of glutamine, glutamate, and glutathione increased, whereas lysine, proline, and valine decreased in the presence of drug. Profiling secreted inflammatory cytokines in the conditioned media demonstrated a greater response to paclitaxel in the hormone-positive Luminal cells compared with a secretion profile that suggested greater drug resistance in the TNBC cells. The most significant differences distinguishing the cell types based on pathway enrichment analyses were related to amino acid, lipid and carbohydrate metabolism pathways, whereas several biological pathways were differentiated between the cell lines following treatment.

Antioxidant gene expression and metabolic responses of earthworms (Eisenia fetida) after exposure to various concentrations of hexabromocyclododecane.

Science.gov (United States)

Shi, Yajuan; Xu, Xiangbo; Chen, Juan; Liang, Ruoyu; Zheng, Xiaoqi; Shi, Yajing; Wang, Yurong

2018-01-01

Hexabromocyclododecane (HBCD), a ubiquitous suspected contaminant, is one of the world's most prominent brominated flame retardants (BFRs). In the present study, earthworms (Eisenia fetida) were exposed to HBCD. The expression of selected antioxidant enzyme genes was measured, and the metabolic responses were assessed using nuclear magnetic resonance (NMR) to identify the molecular mechanism of the antioxidant stress reaction and the metabolic reactions of earthworms to HBCD. A significant up-regulation (p  0.05). Principal component analysis (PCA) of the metabolic responses showed that all groups could be clearly differentiated, and the highest concentration dose group was the most distant from the control group. Except for fumarate, the measured metabolites, which included adenosine triphosphate (ATP), valine, lysine, glycine, betaine and lactate, revealed significant (p earthworm exposure studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

An insight into the metabolic responses of ultra-small superparamagnetic particles of iron oxide using metabonomic analysis of biofluids

International Nuclear Information System (INIS)

Feng Jianghua; Liu Huili; Zhang Limin; Bhakoo, Kishore; Lu Lehui

2010-01-01

Ultra-small superparamagnetic particles of iron oxides (USPIO) have been developed as intravenous organ/tissue-targeted contrast agents to improve magnetic resonance imaging (MRI) in vivo. However, their potential toxicity and effects on metabolism have attracted particular attention. In the present study, uncoated and dextran-coated USPIO were investigated by analyzing both rat urine and plasma metabonomes using high-resolution NMR-based metabonomic analysis in combination with multivariate statistical analysis. The wealth of information gathered on the metabolic profiles from rat urine and plasma has revealed subtle metabolic changes in response to USPIO administration. The metabolic changes include the elevation of urinary α-hydroxy-n-valerate, o- and p-HPA, PAG, nicotinate and hippurate accompanied by decreases in the levels of urinary α-ketoglutarate, succinate, citrate, N-methylnicotinamide, NAG, DMA, allantoin and acetate following USPIO administration. The changes associated with USPIO administration included a gradual increase in plasma glucose, N-acetyl glycoprotein, saturated fatty acid, citrate, succinate, acetate, GPC, ketone bodies (β-hydroxybutyrate, acetone and acetoacetate) and individual amino acids, such as phenylalanine, lysine, isoleucine, glycine, glutamine and glutamate and a gradual decrease of myo-inositol, unsaturated fatty acid and triacylglycerol. Hence USPIO administration effects are reflected in changes in a number of metabolic pathways including energy, lipid, glucose and amino acid metabolism. The size- and surface chemistry-dependent metabolic responses and possible toxicity were observed using NMR analysis of biofluids. These changes may be attributed to the disturbances of hepatic, renal and cardiac functions following USPIO administrations. The potential biotoxicity can be derived from metabonomic analysis and serum biochemistry analysis. Metabonomic strategy offers a promising approach for the detection of subtle

An insight into the metabolic responses of ultra-small superparamagnetic particles of iron oxide using metabonomic analysis of biofluids

Science.gov (United States)

Feng, Jianghua; Liu, Huili; Zhang, Limin; Bhakoo, Kishore; Lu, Lehui

2010-10-01

Ultra-small superparamagnetic particles of iron oxides (USPIO) have been developed as intravenous organ/tissue-targeted contrast agents to improve magnetic resonance imaging (MRI) in vivo. However, their potential toxicity and effects on metabolism have attracted particular attention. In the present study, uncoated and dextran-coated USPIO were investigated by analyzing both rat urine and plasma metabonomes using high-resolution NMR-based metabonomic analysis in combination with multivariate statistical analysis. The wealth of information gathered on the metabolic profiles from rat urine and plasma has revealed subtle metabolic changes in response to USPIO administration. The metabolic changes include the elevation of urinary α-hydroxy-n-valerate, o- and p-HPA, PAG, nicotinate and hippurate accompanied by decreases in the levels of urinary α-ketoglutarate, succinate, citrate, N-methylnicotinamide, NAG, DMA, allantoin and acetate following USPIO administration. The changes associated with USPIO administration included a gradual increase in plasma glucose, N-acetyl glycoprotein, saturated fatty acid, citrate, succinate, acetate, GPC, ketone bodies (β-hydroxybutyrate, acetone and acetoacetate) and individual amino acids, such as phenylalanine, lysine, isoleucine, glycine, glutamine and glutamate and a gradual decrease of myo-inositol, unsaturated fatty acid and triacylglycerol. Hence USPIO administration effects are reflected in changes in a number of metabolic pathways including energy, lipid, glucose and amino acid metabolism. The size- and surface chemistry-dependent metabolic responses and possible toxicity were observed using NMR analysis of biofluids. These changes may be attributed to the disturbances of hepatic, renal and cardiac functions following USPIO administrations. The potential biotoxicity can be derived from metabonomic analysis and serum biochemistry analysis. Metabonomic strategy offers a promising approach for the detection of subtle

An insight into the metabolic responses of ultra-small superparamagnetic particles of iron oxide using metabonomic analysis of biofluids

Energy Technology Data Exchange (ETDEWEB)

Feng Jianghua [Department of Physics, Fujian Key Laboratory of Plasma and Magnetic Resonance, State Key Laboratory of Physical Chemistry of Solid Surfaces, Xiamen University, Xiamen, 361005 (China); Liu Huili; Zhang Limin [State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan 430071 (China); Bhakoo, Kishore [Singapore Bioimaging Consortium, Agency for Science, Technology and Research (A-STAR) 138667 (Singapore); Lu Lehui, E-mail: jianghua.feng@hotmail.com, E-mail: jianghua.feng@wipm.ac.cn [State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022 (China)

2010-10-01

Ultra-small superparamagnetic particles of iron oxides (USPIO) have been developed as intravenous organ/tissue-targeted contrast agents to improve magnetic resonance imaging (MRI) in vivo. However, their potential toxicity and effects on metabolism have attracted particular attention. In the present study, uncoated and dextran-coated USPIO were investigated by analyzing both rat urine and plasma metabonomes using high-resolution NMR-based metabonomic analysis in combination with multivariate statistical analysis. The wealth of information gathered on the metabolic profiles from rat urine and plasma has revealed subtle metabolic changes in response to USPIO administration. The metabolic changes include the elevation of urinary {alpha}-hydroxy-n-valerate, o- and p-HPA, PAG, nicotinate and hippurate accompanied by decreases in the levels of urinary {alpha}-ketoglutarate, succinate, citrate, N-methylnicotinamide, NAG, DMA, allantoin and acetate following USPIO administration. The changes associated with USPIO administration included a gradual increase in plasma glucose, N-acetyl glycoprotein, saturated fatty acid, citrate, succinate, acetate, GPC, ketone bodies ({beta}-hydroxybutyrate, acetone and acetoacetate) and individual amino acids, such as phenylalanine, lysine, isoleucine, glycine, glutamine and glutamate and a gradual decrease of myo-inositol, unsaturated fatty acid and triacylglycerol. Hence USPIO administration effects are reflected in changes in a number of metabolic pathways including energy, lipid, glucose and amino acid metabolism. The size- and surface chemistry-dependent metabolic responses and possible toxicity were observed using NMR analysis of biofluids. These changes may be attributed to the disturbances of hepatic, renal and cardiac functions following USPIO administrations. The potential biotoxicity can be derived from metabonomic analysis and serum biochemistry analysis. Metabonomic strategy offers a promising approach for the detection of

Metabolic and cardiovascular responses to epinephrine in diabetic autonomic neuropathy

DEFF Research Database (Denmark)

Hilsted, J; Richter, E; Madsbad, S

1987-01-01

with autonomic neuropathy (P less than 0.01) but was unchanged in the other groups. Since cardiac output increased to a similar extent in the three groups, the decrease in blood pressure was due to a significantly larger decrease (P less than 0.01) in total peripheral vascular resistance in the patients......Norepinephrine-induced vasoconstriction, which is mediated by alpha-adrenergic receptors, is accentuated in patients with autonomic neuropathy. In contrast, responses mediated by beta-adrenergic receptors, including vasodilatation and metabolic changes, have not been evaluated in these patients....... To study these responses, we administered epinephrine in a graded intravenous infusion (0.5 to 5 micrograms per minute) to seven diabetic patients without neuropathy, seven diabetic patients with autonomic neuropathy, and seven normal subjects. Mean arterial pressure decreased significantly in the patients...

Discerning Primary and Secondary Factors Responsible for Clinical Fatigue in Multisystem Diseases

Directory of Open Access Journals (Sweden)

David Maughan

2014-09-01

Full Text Available Fatigue is a common symptom of numerous acute and chronic diseases, including myalgic encephalomyelitis/chronic fatigue syndrome, multiple sclerosis, heart failure, cancer, and many others. In these multi-system diseases the physiological determinants of enhanced fatigue encompass a combination of metabolic, neurological, and myofibrillar adaptations. Previous research studies have focused on adaptations specific to skeletal muscle and their role in fatigue. However, most have neglected the contribution of physical inactivity in assessing disease syndromes, which, through deconditioning, likely contributes to symptomatic fatigue. In this commentary, we briefly review disease-related muscle phenotypes in the context of whether they relate to the primary disease or whether they develop secondary to reduced physical activity. Knowledge of the etiology of the skeletal muscle adaptations in these conditions and their contribution to fatigue symptoms is important for understanding the utility of exercise rehabilitation as an intervention to alleviate the physiological precipitants of fatigue.

Secondary IgG responses to type III pneumococcal polysaccharide. II. Different cellular requirements for induction and elicitation.

Science.gov (United States)

Braley-Mullen, H

1976-04-01

Mice primed with a thymus- (T) dependent form of Type III pneumococcal polysaccharide (S3), i.e., S3 coupled to erythrocytes (S3-RBC) produce S3-specific IgG antibody after secondary challenge with either S3 or S3-RBC. The production of IgG antibody by mice challenged with S3 was shown to be T independent since secondary responses were enhanced when mice were treated with anti-lymphocyte serum (ALS) at the time of secondary challenge with S3 and T-depleted spleen cells responded as well as unfractionated spleen cells to S3 in an adoptive transfer system. Secondary S3-specific IgG responses in mice challenged with S3-RBC were shown to be T dependent by the same criteria. The results obtained by using S3 as the antigen indicate that IgG-producing B cells (B lambda cells) can recognize and respond to antigen in the absence of helper T cells. On the other hand, T cells were required for the induction of S3-specific memory B lambda cells since mice depleted of T cells by treatment with ALS at the time of priming with S3-RBC failed to produce S3-specific IgG antibody after secondary challenge with either S3-specific IgG antibody after secondary chall-nge with either S3 or S3rbc. Since RBC-specific memory cells were induced in T-deprived mice the results suggest that T cell regulation of IgG antibody production may vary for different antigens.

Humoral and cell-mediated immune responses to influenza vaccination in equine metabolic syndrome (EMS) horses.

Science.gov (United States)

Elzinga, Sarah; Reedy, Stephanie; Barker, Virginia D; Chambers, Thomas M; Adams, Amanda A

2018-05-01

Obesity is an increasing problem in the equine population with recent reports indicating that the percentage of overweight horses may range anywhere from 20.6-51%. Obesity in horses has been linked to more serious health concerns such as equine metabolic syndrome (EMS). EMS is a serious problem in the equine industry given its defining characteristics of insulin dysregualtion and obesity, as well as the involvement of laminitis. Little research however has been conducted to determine the effects of EMS on routine healthcare of these horses, in particular how they respond to vaccination. It has been shown that obese humans and mice have decreased immune responses to vaccination. EMS may have similar effects on vaccine responses in horses. If this is the case, these animals may be more susceptible to disease, acting as unknown disease reservoirs. Therefore, we investigated the effects of EMS on immune responses to routine influenza vaccination. Twenty-five adult horses of mixed-sex and mixed-breed (8-21 years old) horses; 13 EMS and 12 non-EMS were selected. Within each group, 4 horses served as non-vaccinate saline controls and the remaining horses were vaccinated with a commercially available equine influenza vaccine. Vaccination (influenza or saline) was administered on weeks 0 and 3, and peripheral blood samples taken on week 0 prior to vaccination and on weeks 1, 2, 3, 4, and 5 post vaccination. Blood samples were used to measure hemagglutination inhibition (HI) titers and equine influenza specific IgGa, IgGb, and IgGT levels. Blood samples were also used to isolate peripheral blood mononuclear cells (PBMCs) for analysis of cell mediated immune (CMI) responses via real-time polymerase chain reaction (RT-PCR). All horses receiving influenza vaccination responded with significant increases (P equine influenza specific antibodies following vaccination compared to saline controls. EMS did not significantly affect (P > 0.05) humoral immune responses as measured

Cytokine profiles in tears accompanying the secondary conjunctival responses induced by nasal allergy.

Science.gov (United States)

Pelikan, Zdenek

2014-02-01

Allergic conjunctivitis (AC) occurs either in a primary form, due to the allergic reaction localized in the conjunctivae or in a secondary form, induced by an allergic reaction initiated primarily in the nasal mucosa. The purpose of this study was to investigate the cytokine profiles in tears associated with the secondary conjunctival response (SCR) types. In 47 AC patients developing 16 immediate (SICR; p tears. The SCRs were associated with significant concentration changes of particular cytokines in tears (p tears during the phosphate-buffered saline controls or negative SCRs. Different cytokine profiles in the tears accompanying the immediate, late and delayed types of SCR, induced by nasal allergy, would indicate involvement of different hypersensitivity mechanisms in the particular SCR types. The low cytokine concentrations in tears recorded during the SCRs may suggest their origin from the nasal mucosa. These results emphasize the diagnostic value of NPTs with allergens combined with monitoring of various ocular features in patients suffering from the secondary form of AC. These results may also have an impact on the therapeutical approach to this clinical entity.

Distinct mechanisms underlie adaptation of proximal tubule Na+/H+ exchanger isoform 3 in response to chronic metabolic and respiratory acidosis.

Science.gov (United States)

Silva, Pedro Henrique Imenez; Girardi, Adriana Castello Costa; Neri, Elida Adalgisa; Rebouças, Nancy Amaral

2012-04-01

The Na(+/)H(+) exchanger isoform 3 (NHE3) is essential for HCO(3)(-) reabsorption in renal proximal tubules. The expression and function of NHE3 must adapt to acid-base conditions. The goal of this study was to elucidate the mechanisms responsible for higher proton secretion in proximal tubules during acidosis and to evaluate whether there are differences between metabolic and respiratory acidosis with regard to NHE3 modulation and, if so, to identify the relevant parameters that may trigger these distinct adaptive responses. We achieved metabolic acidosis by lowering HCO(3)(-) concentration in the cell culture medium and respiratory acidosis by increasing CO(2) tension in the incubator chamber. We found that cell-surface NHE3 expression was increased in response to both forms of acidosis. Mild (pH 7.21 ± 0.02) and severe (6.95 ± 0.07) metabolic acidosis increased mRNA levels, at least in part due to up-regulation of transcription, whilst mild (7.11 ± 0.03) and severe (6.86 ± 0.01) respiratory acidosis did not up-regulate NHE3 expression. Analyses of the Nhe3 promoter region suggested that the regulatory elements sensitive to metabolic acidosis are located between -466 and -153 bp, where two consensus binding sites for SP1, a transcription factor up-regulated in metabolic acidosis, were localised. We conclude that metabolic acidosis induces Nhe3 promoter activation, which results in higher mRNA and total protein level. At the plasma membrane surface, NHE3 expression was increased in metabolic and respiratory acidosis alike, suggesting that low pH is responsible for NHE3 displacement to the cell surface.

Deciphering the mechanisms involved in Portulaca oleracea (C4) response to drought: metabolic changes including crassulacean acid-like metabolism induction and reversal upon re-watering.

Science.gov (United States)

D'Andrea, Rodrigo Matías; Andreo, Carlos Santiago; Lara, María Valeria

2014-11-01

Portulaca oleracea is a C(4) plant; however, under drought it can change its carbon fixation metabolism into a crassulacean acid metabolism (CAM)-like one. While the C(3) -CAM shift is well known, the C(4) -CAM transition has only been described in Portulaca. Here, a CAM-like metabolism was induced in P. oleracea by drought and then reversed by re-watering. Physiological and biochemical approaches were undertaken to evaluate the drought and recovery responses. In CAM-like plants, chlorophyll fluorescence parameters were transitory affected and non-radiative energy dissipation mechanisms were induced. Induction of flavonoids, betalains and antioxidant machinery may be involved in photosynthetic machinery protection. Metabolic analysis highlights a clear metabolic shift, when a CAM-like metabolism is induced and then reversed. Increases in nitrogenous compounds like free amino acids and urea, and of pinitol could contribute to withstand drought. Reciprocal variations in arginase and urease in drought-stressed and in re-watered plants suggest urea synthesis is strictly regulated. Recovery of C(4) metabolism was accounted by CO(2) assimilation pattern and malate levels. Increases in glycerol and in polyamines would be of importance of re-watered plants. Collectively, in P. oleracea multiple strategies, from induction of several metabolites to the transitory development of a CAM-like metabolism, participate to enhance its adaptation to drought. © 2014 Scandinavian Plant Physiology Society.

Metabolic Responses and Pacing Strategies during Successive Sprint Skiing Time Trials

DEFF Research Database (Denmark)

Andersson, Erik; Holmberg, Hans-Christer; Ørtenblad, Niels

2016-01-01

PURPOSE: To examine the metabolic responses and pacing strategies during the performance of successive sprint time trials (STTs) in cross-country skiing. METHODS: Ten well-trained male cross-country skiers performed four self-paced 1300-m STTs on a treadmill, each separated by 45 min of recovery...... to estimate the anaerobic energy supply. RESULTS: The individual trial-to-trial variability in STT performance time was 1.3%, where variations in O2 deficit and V˙O2 explained 69% (P 0.05) of the variation in performance. The first and last STTs were equally fast (228 ± 10 s), and ~ 1...... on the first than second course half. In addition, metabolic rates were substantially higher (~_30%) for uphill than for flat skiing, indicating that pacing was regulated to the terrain. CONCLUSIONS: The fastest STTs were characterized primarily by a greater anaerobic energy production, which also explained 69...

Proteomic Analysis of Metabolic Responses to Biofuels and Chemicals in Photosynthetic Cyanobacteria.

Science.gov (United States)

Sun, T; Chen, L; Zhang, W

2017-01-01

Recent progresses in various "omics" technologies have enabled quantitative measurements of biological molecules in a high-throughput manner. Among them, high-throughput proteomics is a rapidly advancing field that offers a new means to quantify metabolic changes at protein level, which has significantly facilitated our understanding of cellular process, such as protein synthesis, posttranslational modifications, and degradation in responding to environmental perturbations. Cyanobacteria are autotrophic prokaryotes that can perform oxygenic photosynthesis and have recently attracted significant attentions as one promising alternative to traditionally biomass-based "microbial cell factories" to produce green fuels and chemicals. However, early studies have shown that the low tolerance to toxic biofuels and chemicals represented one major hurdle for further improving productivity of the cyanobacterial production systems. To address the issue, metabolic responses and their regulation of cyanobacterial cells to toxic end-products need to be defined. In this chapter, we discuss recent progresses in interpreting cyanobacterial responses to biofuels and chemicals using high-throughput proteomics approach, aiming to provide insights and guidelines on how to enhance tolerance and productivity of biofuels or chemicals in the renewable cyanobacteria systems in the future. © 2017 Elsevier Inc. All rights reserved.

Correlations of Eisenia fetida metabolic responses to extractable phenanthrene concentrations through time

Energy Technology Data Exchange (ETDEWEB)

McKelvie, Jennifer R.; Wolfe, David M.; Celejewski, Magda; Simpson, Andre J. [Department of Physical and Environmental Sciences, University of Toronto, 1265 Military Trail, Toronto, Ontario, M1C 1A4 (Canada); Simpson, Myrna J., E-mail: myrna.simpson@utoronto.c [Department of Physical and Environmental Sciences, University of Toronto, 1265 Military Trail, Toronto, Ontario, M1C 1A4 (Canada)

2010-06-15

Eisenia fetida earthworms were exposed to phenanthrene for thirty days to compare hydroxypropyl-beta-cyclodextrin (HPCD) extraction of soil and {sup 1}H NMR earthworm metabolomics as indicators of bioavailability. The phenanthrene 28-d LC{sub 50} value was 750 mg/kg (632-891, 95% confidence intervals) for the peat soil tested. The initial phenanthrene concentration was 319 mg/kg, which biodegraded to 16 mg/kg within 15 days, at which time HPCD extraction suggested that phenanthrene was no longer bioavailable. Multivariate statistical analysis of {sup 1}H NMR spectra for E. fetida tissue extracts indicated that phenanthrene exposed and control earthworms differed throughout the 30 day experiment despite the low phenanthrene concentrations present after 15 days. This metabolic response was better correlated to total phenanthrene concentrations (Q{sup 2} = 0.59) than HPCD-extractable phenanthrene concentrations (Q{sup 2} = 0.46) suggesting that {sup 1}H NMR metabolomics offers considerable promise as a novel, molecular-level method to directly monitor the bioavailability of contaminants to earthworms in the environment. - Metabolic responses of Eisenia fetida earthworms to phenanthrene exposure are better correlated to total phenanthrene concentrations than to cyclodextrin-extractable concentrations through time.

Correlations of Eisenia fetida metabolic responses to extractable phenanthrene concentrations through time

International Nuclear Information System (INIS)

McKelvie, Jennifer R.; Wolfe, David M.; Celejewski, Magda; Simpson, Andre J.; Simpson, Myrna J.

2010-01-01

Eisenia fetida earthworms were exposed to phenanthrene for thirty days to compare hydroxypropyl-β-cyclodextrin (HPCD) extraction of soil and 1 H NMR earthworm metabolomics as indicators of bioavailability. The phenanthrene 28-d LC 50 value was 750 mg/kg (632-891, 95% confidence intervals) for the peat soil tested. The initial phenanthrene concentration was 319 mg/kg, which biodegraded to 16 mg/kg within 15 days, at which time HPCD extraction suggested that phenanthrene was no longer bioavailable. Multivariate statistical analysis of 1 H NMR spectra for E. fetida tissue extracts indicated that phenanthrene exposed and control earthworms differed throughout the 30 day experiment despite the low phenanthrene concentrations present after 15 days. This metabolic response was better correlated to total phenanthrene concentrations (Q 2 = 0.59) than HPCD-extractable phenanthrene concentrations (Q 2 = 0.46) suggesting that 1 H NMR metabolomics offers considerable promise as a novel, molecular-level method to directly monitor the bioavailability of contaminants to earthworms in the environment. - Metabolic responses of Eisenia fetida earthworms to phenanthrene exposure are better correlated to total phenanthrene concentrations than to cyclodextrin-extractable concentrations through time.

Metabonomics-based analysis of Brachyspira pilosicoli's response to tiamulin reveals metabolic activity despite significant growth inhibition.

Science.gov (United States)

Le Roy, Caroline Ivanne; Passey, Jade Louise; Woodward, Martin John; La Ragione, Roberto Marcello; Claus, Sandrine Paule

2017-06-01

Pathogenic anaerobes Brachyspira spp. are responsible for an increasing number of Intestinal Spirochaetosis (IS) cases in livestock against which few approved treatments are available. Tiamulin is used to treat swine dysentery caused by Brachyspira spp. and recently has been used to handle avian intestinal spirochaetosis (AIS). The therapeutic dose used in chickens requires further evaluation since cases of bacterial resistance to tiamulin have been reported. In this study, we evaluated the impact of tiamulin at varying concentrations on the metabolism of B. pilosicoli using a 1 H-NMR-based metabonomics approach allowing the capture of the overall bacterial metabolic response to antibiotic treatment. Based on growth curve studies, tiamulin impacted bacterial growth even at very low concentration (0.008 μg/mL) although its metabolic activity was barely affected 72 h post exposure to antibiotic treatment. Only the highest dose of tiamulin tested (0.250 μg/mL) caused a major metabolic shift. Results showed that below this concentration, bacteria could maintain a normal metabolic trajectory despite significant growth inhibition by the antibiotic, which may contribute to disease reemergence post antibiotic treatment. Indeed, we confirmed that B. pilosicoli remained viable even after exposition to the highest antibiotic dose. This paper stresses the need to ensure new evaluation of bacterial viability post bacteriostatic exposure such as tiamulin to guarantee treatment efficacy and decrease antibiotic resistance development. Copyright © 2017 Elsevier Ltd. All rights reserved.

Modification of nucleotide metabolism in relationship with differentiation and in response to irradiation in human tumour cells

International Nuclear Information System (INIS)

Wei, Shuang

1998-01-01

This research thesis reports the study of the metabolism of nucleotides in human tumour cells. The first part addresses the modifications of nucleotide (more specifically purine) metabolism in relationship with human melanoma cell proliferation and differentiation. The second part addresses the modifications of this metabolism in response to an irradiation in human colon tumour cells. For each part, the author proposes a bibliographic synthesis, and a presentation of studied cells and of methods used to grow cells, and respectively to proliferate and differentiate them or to irradiate them, and then discusses the obtained results [fr

In silico analysis of phytohormone metabolism and communication pathways in citrus transcriptome

Directory of Open Access Journals (Sweden)

Vera Quecini

2007-01-01

Full Text Available Plant hormones play a crucial role in integrating endogenous and exogenous signals and in determining developmental responses to form the plant body throughout its life cycle. In citrus species, several economically important processes are controlled by phytohormones, including seed germination, secondary growth, fruit abscission and ripening. Integrative genomics is a powerful tool for linking newly researched organisms, such as tropical woody species, to functional studies already carried out on established model organisms. Based on gene orthology analyses and expression patterns, we searched the Citrus Genome Sequencing Consortium (CitEST database for Expressed Sequence Tags (EST consensus sequences sharing similarity to known components of hormone metabolism and signaling pathways in model species. More than 600 homologs of functionally characterized hormone metabolism and signal transduction members from model species were identified in citrus, allowing us to propose a framework for phytohormone signaling mechanisms in citrus. A number of components from hormone-related metabolic pathways were absent in citrus, suggesting the presence of distinct metabolic pathways. Our results demonstrated the power of comparative genomics between model systems and economically important crop species to elucidate several aspects of plant physiology and metabolism.

Renal responses of trout to chronic respiratory and metabolic acidoses and metabolic alkalosis.

Science.gov (United States)

Wood, C M; Milligan, C L; Walsh, P J

1999-08-01

Exposure to hyperoxia (500-600 torr) or low pH (4.5) for 72 h or NaHCO(3) infusion for 48 h were used to create chronic respiratory (RA) or metabolic acidosis (MA) or metabolic alkalosis in freshwater rainbow trout. During alkalosis, urine pH increased, and [titratable acidity (TA) - HCO(-)(3)] and net H(+) excretion became negative (net base excretion) with unchanged NH(+)(4) efflux. During RA, urine pH did not change, but net H(+) excretion increased as a result of a modest rise in NH(+)(4) and substantial elevation in [TA - HCO(-)(3)] efflux accompanied by a large increase in inorganic phosphate excretion. However, during MA, urine pH fell, and net H(+) excretion was 3.3-fold greater than during RA, reflecting a similar increase in [TA - HCO(-)(3)] and a smaller elevation in phosphate but a sevenfold greater increase in NH(+)(4) efflux. In urine samples of the same pH, [TA - HCO(-)(3)] was greater during RA (reflecting phosphate secretion), and [NH(+)(4)] was greater during MA (reflecting renal ammoniagenesis). Renal activities of potential ammoniagenic enzymes (phosphate-dependent glutaminase, glutamate dehydrogenase, alpha-ketoglutarate dehydrogenase, alanine aminotransferase, phosphoenolpyruvate carboxykinase) and plasma levels of cortisol, phosphate, ammonia, and most amino acids (including glutamine and alanine) increased during MA but not during RA, when only alanine aminotransferase increased. The differential responses to RA vs. MA parallel those in mammals; in fish they may be keyed to activation of phosphate secretion by RA and cortisol mobilization by MA.

Plant-endophytes interaction influences the secondary metabolism in Echinacea purpurea (L.) Moench: an in vitro model.

Science.gov (United States)

Maggini, Valentina; De Leo, Marinella; Mengoni, Alessio; Gallo, Eugenia Rosaria; Miceli, Elisangela; Reidel, Rose Vanessa Bandeira; Biffi, Sauro; Pistelli, Luisa; Fani, Renato; Firenzuoli, Fabio; Bogani, Patrizia

2017-12-05

The influence of the interaction(s) between the medicinal plant Echinacea purpurea (L.) Moench and its endophytic communities on the production of alkamides is investigated. To mimic the in vivo conditions, we have set up an infection model of axenic in vitro E. purpurea plants inoculated with a pool of bacterial strains isolated from the E. purpurea stems and leaves. Here we show different alkamide levels between control (not-inoculated) and inoculated plants, suggesting that the alkamide biosynthesis may be modulated by the bacterial infection. Then, we have analysed the branched-chain amino acids (BCCA) decarboxylase gene (GenBank Accession #LT593930; the enzymatic source for the amine moiety formation of the alkamides) expression patterns. The expression profile shows a higher expression level in the inoculated E. purpurea tissues than in the control ones. These results suggest that the plant-endophyte interaction can influence plant secondary metabolism affecting the therapeutic properties of E. purpurea.

Oncogenic osteomalacia secondary to a hemangiopericytoma of the hip: case report

International Nuclear Information System (INIS)

Baronofsky, S.I.; Kalbhen, C.L.; Demos, T.C.; Sizemore, G.W.

1999-01-01

Osteomalacia is characterized by abnormally increased unmineralized osteoid within the bone matrix. This metabolic bone disease is usually the result of decreased uptake or abnormal metabolism of vitamin D or of renal tubular phosphate loss. Dietary deficiency, malabsorption, cirrhosis, renal tubular acidosis and certain drugs can cause osteomalacia., Oncogenic osteomalacia - osteomalacia secondary to tumours - is rare, and the exact mechanisms by which neoplasms induce osteomalacia are not known. We describe a patient with chronic osteomalacia of unknown origin who was subsequently found to have oncogenic osteomalacia secondary to a hemangiopericytoma of the hip. (author)

Oncogenic osteomalacia secondary to a hemangiopericytoma of the hip: case report

Energy Technology Data Exchange (ETDEWEB)

Baronofsky, S.I.; Kalbhen, C.L.; Demos, T.C.; Sizemore, G.W. [Loyola Univ. Medical Center, Dept. of Medicine, Maywood, IL (United States)

1999-02-01

Osteomalacia is characterized by abnormally increased unmineralized osteoid within the bone matrix. This metabolic bone disease is usually the result of decreased uptake or abnormal metabolism of vitamin D or of renal tubular phosphate loss. Dietary deficiency, malabsorption, cirrhosis, renal tubular acidosis and certain drugs can cause osteomalacia., Oncogenic osteomalacia - osteomalacia secondary to tumours - is rare, and the exact mechanisms by which neoplasms induce osteomalacia are not known. We describe a patient with chronic osteomalacia of unknown origin who was subsequently found to have oncogenic osteomalacia secondary to a hemangiopericytoma of the hip. (author)

Respiratory, cardiovascular and metabolic responses during different modes of overground bionic ambulation in persons with motor-incomplete spinal cord injury: A case series

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Jochen Kressler

2017-09-01

Full Text Available Objective: To investigate the effects of overground bionic ambulation with variable assistance on cardiorespiratory and metabolic responses in persons with motor-incomplete spinal cord injury. Design: Case series. Subjects: Four participants with chronic, motor-incomplete spinal cord injury. Methods: Subjects completed a maximal graded exercise test on an arm-ergometer and 3 6-min bouts of overground bionic ambulation using different modes of assistance, i.e. Maximal, Adaptive, Fixed. Cardiorespiratory (oxygen consumption and metabolic (caloric expenditure and substrate utilization measures were taken using a mobile metabolic cart at each overground bionic ambulation assistance. Results: Cardiorespiratory responses ranged from low (24% VO2peak for the least impaired and fittest individual to supramaximal (124% VO2peak for the participant with the largest impairments and the lowest level of fitness. Different overground bionic ambulation assistive modes elicited small (3–8% VO2peak differences in cardiorespiratory responses for 3 participants. One participant had a large (28% VO2peak difference in cardiorespiratory responses to different modes of overground bionic ambulation. Metabolic responses mostly tracked closely with cardiorespiratory responses. Total energy expenditure ranged from 1.39 to 7.17 kcal/min. Fat oxidation ranged from 0.00 to 0.17 g/min across participants and different overground bionic ambulation modes. Conclusion: Overground bionic ambulation with variable assistance can substantially increase cardiorespiratory and metabolic responses; however, these responses vary widely across participants and overground bionic ambulation modes.

Metabolomics Reveals Metabolically Healthy and Unhealthy Obese Individuals Differ in their Response to a Caloric Challenge.

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Flavia Badoud

Full Text Available To determine if metabolically healthy obese (MHO individuals have a different metabolic response to a standardized diet compared to lean healthy (LH and metabolically unhealthy obese (MUO individuals.Thirty adults (35-70 yrs were classified as LH, MHO, and MUO according to anthropometric and clinical measurements. Participants consumed a standardized high calorie meal (~1330 kcal. Blood glucose and insulin were measured at fasting, and 15, 30, 60, 90 and 120 min postprandially. Additional blood samples were collected for the targeted analysis of amino acids (AAs and derivatives, and fatty acids (FAs.The postprandial response (i.e., area under the curve, AUC for serum glucose and insulin were similar between MHO and LH individuals, and significantly lower than MUO individuals (p < 0.05. Minor differences were found in postprandial responses for AAs between MHO and MUO individuals, while three polyunsaturated FAs (linoleic acid, γ-linolenic acid, arachidonic acid showed smaller changes in serum after the meal in MHO individuals compared to MUO. Fasting levels for various AAs (notably branched-chain AA and FAs (e.g., saturated myristic and palmitic acids were found to correlate with glucose and insulin AUC.MHO individuals show preserved insulin sensitivity and a greater ability to adapt to a caloric challenge compared to MUO individuals.

Production of soybean isoflavone genistein in non-legume plants via genetically modified secondary metabolism pathway.

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Liu, Rongrong; Hu, Yuanlei; Li, Jialin; Lin, Zhongping

2007-01-01

Genetic modification of secondary metabolic pathways to produce desirable natural products is an attractive approach in plant biotechnology. In our study, we attempted to produce a typical soybean isoflavone genistein, a well-known health-promoting metabolite, in non-legume plants via genetic engineering. Both overexpression and antisense suppression strategies were used to manipulate the expression of several genes encoding key enzymes in the flavonoids/isoflavonoids pathway in transgenic tobacco, lettuce, and petunia. Introducing soybean isoflavone synthase (IFS) into these plants, which naturally do not produce isoflavonoids due to a lack of this leguminous enzyme, resulted in genistein biosynthesis in tobacco petals, petunia leaves and petals, and lettuce leaves. In tobacco, when flavanone 3-hydroxylase (F3H) expression was suppressed by its antisense gene while soybean IFS was overexpressed at the same time, genistein yield increased prominently. In addition, overexpression of phenylalanine ammonia-lyase (PAL) also led to an enhanced genistein production in tobacco petals and lettuce leaves in the presence of IFS than in the plants that overexpressed only IFS.

Cytokines in tears during the secondary keratoconjunctival responses induced by allergic reaction in the nasal mucosa.

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Pelikan, Zdenek

2014-01-01

Allergic keratoconjunctivitis (KC) can occur in a primary form due to an allergic reaction taking place in the conjunctivae or in a secondary form induced by nasal allergy. To search for the cytokine changes in tears accompanying the secondary keratoconjunctival response types (SKCR), caused by the nasal allergy. In 43 KC patients developing 15 immediate (SIKCR), 16 late (SLKCR) and 12 delayed (SDYKCR) responses to nasal provocation tests with allergens (NPT), the NPTs were repeated with subsequent recording of cytokine concentrations in tears up to 72 h. The SIKCRs (ptears, suggesting involvement of different hypersensitivity mechanisms. These results also stress the diagnostic usefulness of NPTs combined with monitoring of ocular features in KC patients who did not respond satisfactorily to the topical ophthalmological treatment. © 2014 S. Karger AG, Basel.

The Factor Inhibiting HIF Asparaginyl Hydroxylase Regulates Oxidative Metabolism and Accelerates Metabolic Adaptation to Hypoxia.

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Sim, Jingwei; Cowburn, Andrew S; Palazon, Asis; Madhu, Basetti; Tyrakis, Petros A; Macías, David; Bargiela, David M; Pietsch, Sandra; Gralla, Michael; Evans, Colin E; Kittipassorn, Thaksaon; Chey, Yu C J; Branco, Cristina M; Rundqvist, Helene; Peet, Daniel J; Johnson, Randall S

2018-04-03

Animals require an immediate response to oxygen availability to allow rapid shifts between oxidative and glycolytic metabolism. These metabolic shifts are highly regulated by the HIF transcription factor. The factor inhibiting HIF (FIH) is an asparaginyl hydroxylase that controls HIF transcriptional activity in an oxygen-dependent manner. We show here that FIH loss increases oxidative metabolism, while also increasing glycolytic capacity, and that this gives rise to an increase in oxygen consumption. We further show that the loss of FIH acts to accelerate the cellular metabolic response to hypoxia. Skeletal muscle expresses 50-fold higher levels of FIH than other tissues: we analyzed skeletal muscle FIH mutants and found a decreased metabolic efficiency, correlated with an increased oxidative rate and an increased rate of hypoxic response. We find that FIH, through its regulation of oxidation, acts in concert with the PHD/vHL pathway to accelerate HIF-mediated metabolic responses to hypoxia. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Organ-Specific Differential NMR-Based Metabonomic Analysis of Soybean [Glycine max (L. Merr.] Fruit Reveals the Metabolic Shifts and Potential Protection Mechanisms Involved in Field Mold Infection

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Wen-yu Yang

2017-04-01

Full Text Available Prolonged, continuous rainfall is the main climatic characteristic of autumn in Southwest China, and it has been found to cause mildew outbreaks in pre-harvest soybean fields. Low temperature and humidity (LTH stress during soybean maturation in the field promotes pre-harvest mildew, resulting in damage to different organs of soybean fruits to different extents, but relatively little information on the resistance mechanisms in these fruits is available. Therefore, to understand the metabolic responses of soybean fruits to field mold (FM, the metabonomic variations induced by LTH were characterized using proton nuclear magnetic resonance spectroscopy (1H-NMR, and the primary metabolites from the pod, seed coat and cotyledon of pre-harvest soybean were quantified. Analysis of FM-damaged soybean germplasms with different degrees of resistance to FM showed that extracts were dominated by 66 primary metabolites, including amino acids, organic acids and sugars. Each tissue had a characteristic metabolic profile, indicating that the metabolism of proline in the cotyledon, lysine in the seed coat, and sulfur in the pod play important roles in FM resistance. The primary-secondary metabolism interface and its potential contribution to FM resistance was investigated by targeted analyses of secondary metabolites. Both the seed coat and the pod have distinct but nonexclusive metabolic responses to FM, and these are functionally integrated into FM resistance mechanisms.

The effect of environmental temperature on immune response and metabolism of the young chicken

NARCIS (Netherlands)

Henken, A.M.

1982-01-01

The effect of environmental temperature on immune response and metabolism was studied in young chickens. Immunization was performed by injecting intramuscularly 0.5 ml packed SRBC (sheep red blood cells) in both thighs of 32 days old pullets ( WarrenSSL ). The

Role of Glucocorticoids in the Response to Unloading of Muscle Protein and Amino Acid Metabolism

Science.gov (United States)

Tischler, M. E.; Jaspers, S. R.

1985-01-01

Intact control (weight bearing) and suspended rats gained weight at a similar rate during a 6 day period. Adrenaectomized (adx) weight bearing rats gained less weight during this period while adrenalectomized suspended rats showed no significant weight gain. Cortisol treatment of both of these groups of animals caused a loss of body weight. Results from these studies show several important findings: (1) Metabolic changes in the extensor digitorum longus muscle of suspended rats are due primarily to increased circulating gluccorticoids; (2) Metabolic changes in the soleus due to higher steroid levels are probably potentiated by greater numbers of receptors; and (3) Not all metabolic responses in the unloaded soleus muscle are due to direct action of elevated glucocorticoids or increased sensitivity to these hormones.

Growth platform-dependent and -independent phenotypic and metabolic responses of Arabidopsis and its halophytic relative, Eutrema salsugineum, to salt stress.

Science.gov (United States)

Kazachkova, Yana; Batushansky, Albert; Cisneros, Aroldo; Tel-Zur, Noemi; Fait, Aaron; Barak, Simon

2013-07-01

Comparative studies of the stress-tolerant Arabidopsis (Arabidopsis thaliana) halophytic relative, Eutrema salsugineum, have proven a fruitful approach to understanding natural stress tolerance. Here, we performed comparative phenotyping of Arabidopsis and E. salsugineum vegetative development under control and salt-stress conditions, and then compared the metabolic responses of the two species on different growth platforms in a defined leaf developmental stage. Our results reveal both growth platform-dependent and -independent phenotypes and metabolic responses. Leaf emergence was affected in a similar way in both species grown in vitro but the effects observed in Arabidopsis occurred at higher salt concentrations in E. salsugineum. No differences in leaf emergence were observed on soil. A new effect of a salt-mediated reduction in E. salsugineum leaf area was unmasked. On soil, leaf area reduction in E. salsugineum was mainly due to a fall in cell number, whereas both cell number and cell size contributed to the decrease in Arabidopsis leaf area. Common growth platform-independent leaf metabolic signatures such as high raffinose and malate, and low fumarate contents that could reflect core stress tolerance mechanisms, as well as growth platform-dependent metabolic responses were identified. In particular, the in vitro growth platform led to repression of accumulation of many metabolites including sugars, sugar phosphates, and amino acids in E. salsugineum compared with the soil system where these same metabolites accumulated to higher levels in E. salsugineum than in Arabidopsis. The observation that E. salsugineum maintains salt tolerance despite growth platform-specific phenotypes and metabolic responses suggests a considerable degree of phenotypic and metabolic adaptive plasticity in this extremophile.

Do diabetes and obesity affect the metabolic response to exercise?

DEFF Research Database (Denmark)

Plomgaard, Peter; Weigert, Cora

2017-01-01

control before an intervention can be a risk factor of reduced therapeutic benefit from exercise. But the acute metabolic response to exercise and the transcriptional profile of the working muscle is similar in healthy controls and type 2 diabetic patients, including but not limited to intact activation...... of skeletal muscle AMP-activated kinase signaling, glucose uptake and expression of peroxisome proliferator-activated receptor gamma coactivator 1α. The increase in plasma acylcarnitines during exercise is not influenced by type 2 diabetes or obesity. The hepatic response to exercise is dependent......PURPOSE OF REVIEW: Exercise is recommended as therapeutic intervention for people at risk to develop type 2 diabetes to prevent or treat the disease. Recent studies on the influence of obesity and type 2 diabetes on the outcome of exercise programs are discussed. RECENT FINDINGS: Poor glycemic...

Early metabolic response using FDG PET/CT and molecular phenotypes of breast cancer treated with neoadjuvant chemotherapy

International Nuclear Information System (INIS)

Keam, Bhumsuk; Moon, Woo Kyung; Kim, Tae-You; Park, In Ae; Noh, Dong-Young; Chung, June-Key; Bang, Yung-Jue; Im, Seock-Ah; Koh, Youngil; Han, Sae-Won; Oh, Do-Youn; Cho, Nariya; Kim, Jee Hyun; Han, Wonshik; Kang, Keon Wook

2011-01-01

This study was aimed 1) to investigate the predictive value of FDG PET/CT (fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography) for histopathologic response and 2) to explore the results of FDG PET/CT by molecular phenotypes of breast cancer patients who received neoadjuvant chemotherapy. Seventy-eight stage II or III breast cancer patients who received neoadjuvant docetaxel/doxorubicin chemotherapy were enrolled in this study. FDG PET/CTs were acquired before chemotherapy and after the first cycle of chemotherapy for evaluating early metabolic response. The mean pre- and post-chemotherapy standard uptake value (SUV) were 7.5 and 3.9, respectively. The early metabolic response provided by FDG PET/CT after one cycle of neoadjuvant chemotherapy was correlated with the histopathologic response after completion of neoadjuvant chemotherapy (P = 0.002). Sensitivity and negative predictive value were 85.7% and 95.1%, respectively. The estrogen receptor negative phenotype had a higher pre-chemotherapy SUV (8.6 vs. 6.4, P = 0.047) and percent change in SUV (48% vs. 30%, P = 0.038). In triple negative breast cancer (TNBC), the pre-chemotherapy SUV was higher than in non-TNBC (9.8 vs. 6.4, P = 0.008). The early metabolic response using FDG PET/CT could have a predictive value for the assessment of histopathologic non-response of stage II/III breast cancer treated with neoadjuvant chemotherapy. Our findings suggest that the initial SUV and the decline in SUV differed based on the molecular phenotype. ClinicalTrials.gov: http://www.clinicaltrials.gov/ct2/show/NCT01396655

The Role of Carbohydrate Response Element Binding Protein in Intestinal and Hepatic Fructose Metabolism

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Katsumi Iizuka

2017-02-01

Full Text Available Many articles have discussed the relationship between fructose consumption and the incidence of obesity and related diseases. Fructose is absorbed in the intestine and metabolized in the liver to glucose, lactate, glycogen, and, to a lesser extent, lipids. Unabsorbed fructose causes bacterial fermentation, resulting in irritable bowl syndrome. Therefore, understanding the mechanisms underlying intestinal and hepatic fructose metabolism is important for the treatment of metabolic syndrome and fructose malabsorption. Carbohydrate response element binding protein (ChREBP is a glucose-activated transcription factor that controls approximately 50% of de novo lipogenesis in the liver. ChREBP target genes are involved in glycolysis (Glut2, liver pyruvate kinase, fructolysis (Glut5, ketohexokinase, and lipogenesis (acetyl CoA carboxylase, fatty acid synthase. ChREBP gene deletion protects against high sucrose diet-induced and leptin-deficient obesity, because Chrebp−/− mice cannot consume fructose or sucrose. Moreover, ChREBP contributes to some of the physiological effects of fructose on sweet taste preference and glucose production through regulation of ChREBP target genes, such as fibroblast growth factor-21 and glucose-6-phosphatase catalytic subunits. Thus, ChREBP might play roles in fructose metabolism. Restriction of excess fructose intake will be beneficial for preventing not only metabolic syndrome but also irritable bowl syndrome.

Seasonal variations in the pattern of RNA metabolism of tuber tissue in response to excision and culture

International Nuclear Information System (INIS)

Macleod, A.J.; Mills, E.D.; Yeoman, M.M.

1979-01-01

Between December 1975 and June 1976 explants excised from Jerusalem artichoke tubers were cultured in the presence and in the absence of 2,4-D, the cells in the tissue dividing only in the presence of 2,4-D, in which the length of the first cell cycle increased nonlinearly from 18 hours to 40 hours as the tubers aged in storage at 4 0 C. Simultaneously the amount of RNA in the tissue declined linearly from 8 to 5 μg RNA per explant. Detailed examination of the RNA metabolism in dividing and in non-dividing cells during February and June 1976 revealed superimposed but independent responses to wounding during excision and to stimulation into growth by 2,4-D. The responses to wounding involved only a very low level of metabolic activity, were complete within a few hours of excision and changed very little with the storage of the tubers. Tissue treated with 2,4-D showed a much higher level of metabolic activity including the periodic accumulation of RNA coupled to its discontinuous synthesis. The features of these growth-related responses changed considerably during the investigation. (author)

Delaware Technical & Community College's response to the critical shortage of Delaware secondary science teachers

Science.gov (United States)

Campbell, Nancy S.

This executive position paper examines the critical shortage of Delaware high school science teachers and Delaware Technical & Community College's possible role in addressing this shortage. A concise analysis of economic and political implications of the science teacher shortage is presented. The following topics were researched and evaluated: the specific science teacher needs for Delaware school districts; the science teacher education program offerings at Delaware universities and colleges; the Alternative Route to Teacher Certification (ARTC); and the state of Delaware's scholarship response to the need. Recommendations for Delaware Tech's role include the development and implementation of two new Associate of Arts of Teaching programs in physics secondary science education and chemistry secondary science education.

Functional roles of FgLaeA in controlling secondary metabolism, sexual development, and virulence in Fusarium graminearum.

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Hee-Kyoung Kim

Full Text Available Fusarium graminearum, the causal agent of Fusarium head blight in cereal crops, produces mycotoxins such as trichothecenes and zearalenone in infected plants. Here, we focused on the function of FgLaeA in F. graminearum, a homolog of Aspergillus nidulans LaeA encoding the global regulator for both secondary metabolism and sexual development. Prior to gene analysis, we constructed a novel luciferase reporter system consisting of a transgenic F. graminearum strain expressing a firefly luciferase gene under control of the promoter for either TRI6 or ZEB2 controlling the biosynthesis of these mycotoxins. Targeted deletion of FgLaeA led to a dramatic reduction of luminescence in reporter strains, indicating that FgLaeA controls the expression of these transcription factors in F. graminearum; reduced toxin accumulation was further confirmed by GC-MS analysis. Overexpression of FgLaeA caused the increased production of trichothecenes and additional metabolites. RNA seq-analysis revealed that gene member(s belonging to ~70% of total tentative gene clusters, which were previously proposed, were differentially expressed in the ΔFgLaeA strain. In addition, ΔFgLaeA strains exhibited an earlier induction of sexual fruiting body (perithecia formation and drastically reduced disease symptoms in wheat, indicating that FgLaeA seems to negatively control perithecial induction, but positively control virulence toward the host plant. FgLaeA was constitutively expressed under both mycotoxin production and sexual development conditions. Overexpression of a GFP-FgLaeA fusion construct in the ΔFgLaeA strain restored all phenotypic changes to wild-type levels and led to constitutive expression of GFP in both nuclei and cytoplasm at different developmental stages. A split luciferase assay demonstrated that FgLaeA was able to interact with FgVeA, a homolog of A. nidulans veA. Taken together, these results demonstrate that FgLaeA, a member of putative FgVeA complex

The mediating role of secondary beliefs: enhancing the understanding of emotional responses and illness perceptions in arthritis.

Science.gov (United States)

McCracken, James; Lindner, Helen; Sciacchitano, Laura

2008-01-01

Chronic illnesses are a significant issue across many health professional domains, becoming an increasing burden on limited and costly resources. The current study investigated the relationship between secondary beliefs and emotional responses, beyond the relationship accounted for by illness perceptions, using the framework of Rational Emotive Behavior Therapy. Sixty-five adults with arthritis participated in the questionnaire-based study. Multivariate analysis found that different emotional representations of the illness were significantly predicted by the individual's secondary belief, above and beyond that predicted by the cognitive representation of their illness alone. The study found that individuals who utilized an achievement secondary belief experienced feelings of worry, whereas individuals who used an approval orientation to understand their arthritis experienced emotions such as depression, being upset, anger, anxiety, and fear. No significant pattern emerged for individuals who used a comfort secondary belief to understand their arthritis. These findings are in line with the theory of secondary beliefs, as articulated by Rational Emotive Behavior Therapy.

Maternal Diet, Metabolic State, and Inflammatory Response Exert Unique and Long-Lasting Influences on Offspring Behavior in Non-Human Primates

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Jacqueline R. Thompson

2018-04-01

Full Text Available Nutritional status influences brain health and gestational exposure to metabolic disorders (e.g. obesity and diabetes increases the risk of neuropsychiatric disorders. The aim of the present study was to further investigate the role of maternal Western-style diet (WSD, metabolic state, and inflammatory factors in the programming of Japanese macaque offspring behavior. Utilizing structural equation modeling, we investigated the relationships between maternal diet, prepregnancy adiposity, third trimester insulin response, and plasma cytokine levels on 11-month-old offspring behavior. Maternal WSD was associated with greater reactive and ritualized anxiety in offspring. Maternal adiposity and third trimester macrophage-derived chemokine (MDC exerted opposing effects on offspring high-energy outbursts. Elevated levels of this behavior were associated with low maternal MDC and increased prepregnancy adiposity. This is the first study to show that maternal MDC levels influence offspring behavior. We found no evidence suggesting maternal peripheral inflammatory response mediated the effect of maternal diet and metabolic state on aberrant offspring behavior. Additionally, the extent of maternal metabolic impairment differentially influenced chemokine response. Elevated prepregnancy adiposity suppressed third trimester chemokines, while obesity-induced insulin resistance augmented peripheral chemokine levels. WSD also directly increased maternal interleukin-12. This is the first non-human primate study to delineate the effects of maternal diet and metabolic state on gestational inflammatory environment and subsequent offspring behavior. Our findings give insight to the complex mechanisms by which diet, metabolic state, and inflammation during pregnancy exert unique influences on offspring behavioral regulation.

Exploring the Use of Audience Response Systems in Secondary School Science Classrooms

Science.gov (United States)

Kay, Robin; Knaack, Liesel

2009-10-01

An audience response systems (ARS) allows students to respond to multiple choice questions using remote control devices. Once the feedback is collected and displayed, the teacher and students discuss misconceptions and difficulties experienced. ARSs have been extremely popular and effective in higher education science classrooms, although almost no research has been done at the secondary school level. The purpose of this study was to conduct a detailed formative analysis of the benefits, challenges, and use of ARSs from the perspective of 213 secondary school science students. Perceived benefits were increased student involvement (engagement, participation, and attention) and effective formative assessment of student understanding. Perceived challenges included decreased student involvement and learning when ARSs were used for summative assessment, occasional technological malfunctions, resistance to using a new method of learning, and increased stress due to time constraints when responding to questions. Finally, students rated the use of ARSs significantly higher when it was used for formative as opposed to summative assessment.

Discriminating response groups in metabolic and regulatory pathway networks.

Science.gov (United States)

Van Hemert, John L; Dickerson, Julie A

2012-04-01

Analysis of omics experiments generates lists of entities (genes, metabolites, etc.) selected based on specific behavior, such as changes in response to stress or other signals. Functional interpretation of these lists often uses category enrichment tests using functional annotations like Gene Ontology terms and pathway membership. This approach does not consider the connected structure of biochemical pathways or the causal directionality of events. The Omics Response Group (ORG) method, described in this work, interprets omics lists in the context of metabolic pathway and regulatory networks using a statistical model for flow within the networks. Statistical results for all response groups are visualized in a novel Pathway Flow plot. The statistical tests are based on the Erlang distribution model under the assumption of independent and identically Exponential-distributed random walk flows through pathways. As a proof of concept, we applied our method to an Escherichia coli transcriptomics dataset where we confirmed common knowledge of the E.coli transcriptional response to Lipid A deprivation. The main response is related to osmotic stress, and we were also able to detect novel responses that are supported by the literature. We also applied our method to an Arabidopsis thaliana expression dataset from an abscisic acid study. In both cases, conventional pathway enrichment tests detected nothing, while our approach discovered biological processes beyond the original studies. We created a prototype for an interactive ORG web tool at http://ecoserver.vrac.iastate.edu/pathwayflow (source code is available from https://subversion.vrac.iastate.edu/Subversion/jlv/public/jlv/pathwayflow). The prototype is described along with additional figures and tables in Supplementary Material. julied@iastate.edu Supplementary data are available at Bioinformatics online.

Secondary and sucrose metabolism regulated by different light quality combinations involved in melon tolerance to powdery mildew.

Science.gov (United States)

Jing, Xin; Wang, Hui; Gong, Biao; Liu, Shiqi; Wei, Min; Ai, Xizhen; Li, Yan; Shi, Qinghua

2018-03-01

We evaluated the effect of different light combinations on powdery mildew resistance and growth of melon seedlings. Light-emitting diodes were used as the light source and there were five light combinations: white light (420-680 nm); blue light (460 nm); red light (635 nm); RB31 (ratio of red and blue light, 3: 1); and RB71 (ratio of red and blue light, 7: 1). Compared with other treatments, blue light significantly decreased the incidence of powdery mildew in leaves of melon seedlings. Under blue light, H 2 O 2 showed higher accumulation, and the content of phenolics, flavonoid and tannins, as well as expression of the genes involved in synthesis of these substances, significantly increased compared with other treatments before and after infection. Lignin content and expression of the genes related to its synthesis were also induced by blue light before infection. Melon irradiated with RB31 light showed the best growth parameters. Compared with white light, red light and RB71, RB31 showed higher accumulation of lignin and lower incidence of powdery mildew. We conclude that blue light increases melon resistance to powdery mildew, which is dependent on the induction of secondary metabolism that may be related to H 2 O 2 accumulation before infection. Induction of tolerance of melon seeds to powdery mildew by RB31 is due to higher levels of sucrose metabolism and accumulation of lignin. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Dopamine D4 receptors modulate brain metabolic activity in the prefrontal cortex and cerebellum at rest and in response to methylphenidate

Energy Technology Data Exchange (ETDEWEB)

Michaelides, M.; Wang, G.; Michaelides, M.; Pascau, J.; Gispert, J.-D.; Delis, F.; Grandy, D.K.; Wang, G.-J.; Desco, M.; Rubinstein, M.; Volkow, N.D.; Thanos, P.K.

2010-07-16

Methylphenidate (MP) is widely used to treat attention deficit hyperactivity disorder (ADHD). Variable number of tandem repeats polymorphisms in the dopamine D4 receptor (D{sub 4}) gene have been implicated in vulnerability to ADHD and the response to MP. Here we examined the contribution of dopamine D4 receptors (D4Rs) to baseline brain glucose metabolism and to the regional metabolic responses to MP. We compared brain glucose metabolism (measured with micro-positron emission tomography and [{sup 18}F]2-fluoro-2-deoxy-D-glucose) at baseline and after MP (10 mg/kg, i.p.) administration in mice with genetic deletion of the D{sub 4}. Images were analyzed using a novel automated image registration procedure. Baseline D{sub 4}{sup -/-} mice had lower metabolism in the prefrontal cortex (PFC) and greater metabolism in the cerebellar vermis (CBV) than D{sub 4}{sup +/+} and D{sub 4}{sup +/-} mice; when given MP, D{sub 4}{sup -/-} mice increased metabolism in the PFC and decreased it in the CBV, whereas in D{sub 4}{sup +/+} and D{sub 4}{sup +/-} mice, MP decreased metabolism in the PFC and increased it in the CBV. These findings provide evidence that D4Rs modulate not only the PFC, which may reflect the activation by dopamine of D4Rs located in this region, but also the CBV, which may reflect an indirect modulation as D4Rs are minimally expressed in this region. As individuals with ADHD show structural and/or functional abnormalities in these brain regions, the association of ADHD with D4Rs may reflect its modulation of these brain regions. The differential response to MP as a function of genotype could explain differences in brain functional responses to MP between patients with ADHD and healthy controls and between patients with ADHD with different D{sub 4} polymorphisms.

Ozone modifies the metabolic and endocrine response to glucose: Reproduction of effects with the stress hormone corticosterone.

Science.gov (United States)

Thomson, Errol M; Pilon, Shinjini; Guénette, Josée; Williams, Andrew; Holloway, Alison C

2018-03-01

Air pollution is associated with increased incidence of metabolic disease (e.g. metabolic syndrome, obesity, diabetes); however, underlying mechanisms are poorly understood. Air pollutants increase the release of stress hormones (human cortisol, rodent corticosterone), which could contribute to metabolic dysregulation. We assessed acute effects of ozone, and stress axis involvement, on glucose tolerance and on the metabolic (triglyceride), endocrine/energy regulation (insulin, glucagon, GLP-1, leptin, ghrelin, corticosterone), and inflammatory/endothelial (TNF, IL-6, VEGF, PAI-1) response to exogenous glucose. Male Fischer-344 rats were exposed to clean air or 0.8 ppm ozone for 4 h in whole body chambers. Hypothalamic-pituitary-adrenal (HPA) axis involvement in ozone effects was tested through subcutaneous administration of the glucocorticoid synthesis inhibitor metyrapone (50 mg/kg body weight), corticosterone (10 mg/kg body weight), or vehicle (40% propylene glycol) prior to exposure. A glucose tolerance test (2 g/kg body weight glucose) was conducted immediately after exposure, with blood samples collected at 0, 30, 60, 90, and 120 min. Ozone exposure impaired glucose tolerance, an effect accompanied by increased plasma triglycerides but no impairment of insulin release. Ozone diminished glucagon, GLP-1, and ghrelin responses to glucose, but did not significantly impact inflammatory/endothelial analytes. Metyrapone reduced corticosterone but increased glucose and triglycerides, complicating evaluation of the impact of glucocorticoid inhibition. However, administration of corticosterone reproduced the profile of ozone effects, supporting a role for the HPA axis. The results show that ozone-dependent changes in glucose tolerance are accompanied by altered metabolic and endocrine responses to glucose challenge that are reproduced by exogenous stress hormone. Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.

Impact of metal stress on the production of secondary metabolites in Pteris vittata L. and associated rhizosphere bacterial communities.

Science.gov (United States)

Pham, Hoang Nam; Michalet, Serge; Bodillis, Josselin; Nguyen, Tien Dat; Nguyen, Thi Kieu Oanh; Le, Thi Phuong Quynh; Haddad, Mohamed; Nazaret, Sylvie; Dijoux-Franca, Marie-Geneviève

2017-07-01

Plants adapt to metal stress by modifying their metabolism including the production of secondary metabolites in plant tissues. Such changes may impact the diversity and functions of plant associated microbial communities. Our study aimed to evaluate the influence of metals on the secondary metabolism of plants and the indirect impact on rhizosphere bacterial communities. We then compared the secondary metabolites of the hyperaccumulator Pteris vittata L. collected from a contaminated mining site to a non-contaminated site in Vietnam and identified the discriminant metabolites. Our data showed a significant increase in chlorogenic acid derivatives and A-type procyanidin in plant roots at the contaminated site. We hypothesized that the intensive production of these compounds could be part of the antioxidant defense mechanism in response to metals. In parallel, the structure and diversity of bulk soil and rhizosphere communities was studied using high-throughput sequencing. The results showed strong differences in bacterial composition, characterized by the dominance of Proteobacteria and Nitrospira in the contaminated bulk soil, and the enrichment of some potential human pathogens, i.e., Acinetobacter, Mycobacterium, and Cupriavidus in P. vittata's rhizosphere at the mining site. Overall, metal pollution modified the production of P. vittata secondary metabolites and altered the diversity and structure of bacterial communities. Further investigations are needed to understand whether the plant recruits specific bacteria to adapt to metal stress.

A dose-response strategy reveals differences between normal-weight and obese men in their metabolic and inflammatory responses to a high-fat meal.

Science.gov (United States)

Schwander, Flurina; Kopf-Bolanz, Katrin A; Buri, Caroline; Portmann, Reto; Egger, Lotti; Chollet, Magali; McTernan, Philip G; Piya, Milan K; Gijs, Martin A M; Vionnet, Nathalie; Pralong, François; Laederach, Kurt; Vergères, Guy

2014-10-01

A dose-response strategy may not only allow investigation of the impact of foods and nutrients on human health but may also reveal differences in the response of individuals to food ingestion based on their metabolic health status. In a randomized crossover study, we challenged 19 normal-weight (BMI: 20-25 kg/m(2)) and 18 obese (BMI: >30 kg/m(2)) men with 500, 1000, and 1500 kcal of a high-fat (HF) meal (60.5% energy from fat). Blood was taken at baseline and up to 6 h postprandially and analyzed for a range of metabolic, inflammatory, and hormonal variables, including plasma glucose, lipids, and C-reactive protein and serum insulin, glucagon-like peptide-1, interleukin-6 (IL-6), and endotoxin. Insulin was the only variable that could differentiate the postprandial response of normal-weight and obese participants at each of the 3 caloric doses. A significant response of the inflammatory marker IL-6 was only observed in the obese group after ingestion of the HF meal containing 1500 kcal [net incremental AUC (iAUC) = 22.9 ± 6.8 pg/mL × 6 h, P = 0.002]. Furthermore, the net iAUC for triglycerides significantly increased from the 1000 to the 1500 kcal meal in the obese group (5.0 ± 0.5 mmol/L × 6 h vs. 6.0 ± 0.5 mmol/L × 6 h; P = 0.015) but not in the normal-weight group (4.3 ± 0.5 mmol/L × 6 h vs. 4.8 ± 0.5 mmol/L × 6 h; P = 0.31). We propose that caloric dose-response studies may contribute to a better understanding of the metabolic impact of food on the human organism. This study was registered at clinicaltrials.gov as NCT01446068. © 2014 American Society for Nutrition.

Secondary osteoporosis.

Science.gov (United States)

Gennari, C; Martini, G; Nuti, R

1998-06-01

Generalized osteoporosis currently represents a heterogeneous group of conditions with many different causes and pathogenetic mechanisms, that often are variably associated. The term "secondary" is applied to all patients with osteoporosis in whom the identifiable causal factors are other than menopause and aging. In this heterogeneous group of conditions, produced by many different pathogenetic mechanisms, a negative bone balance may be variably associated with low, normal or increased bone remodeling states. A consistent group of secondary osteoporosis is related to endocrinological or iatrogenic causes. Exogenous hypercortisolism may be considered an important risk factor for secondary osteoporosis in the community, and probably glucocorticoid-induced osteoporosis is the most common type of secondary osteoporosis. Supraphysiological doses of corticosteroids cause two abnormalities in bone metabolism: a relative increase in bone resorption, and a relative reduction in bone formation. Bone loss, mostly of trabecular bone, with its resultant fractures is the most incapacitating consequence of osteoporosis. The estimated incidence of fractures in patients prescribed corticosteroid is 30% to 50%. Osteoporosis is considered one of the potentially serious side effects of heparin therapy. The occurrence of heparin-induced osteoporosis appeared to be strictly related to the length of treatment (over 4-5 months), and the dosage (15,000 U or more daily), but the pathogenesis is poorly understood. It has been suggested that heparin could cause an increase in bone resorption by increasing the number of differentiated osteoclasts, and by enhancing the activity of individual osteoclasts. Hyperthyroidism is frequently associated with loss of trabecular and cortical bone; the enhanced bone turnover that develops in thyrotoxicosis is characterized by an increase in the number of osteoclasts and resorption sites, and an increase in the ratio of resorptive to formative bone

Metabolomics reveals differences in postprandial responses to breads and fasting metabolic characteristics associated with postprandial insulin demand in postmenopausal women.

Science.gov (United States)

Moazzami, Ali A; Shrestha, Aahana; Morrison, David A; Poutanen, Kaisa; Mykkänen, Hannu

2014-06-01

Changes in serum metabolic profile after the intake of different food products (e.g., bread) can provide insight into their interaction with human metabolism. Postprandial metabolic responses were compared after the intake of refined wheat (RWB), whole-meal rye (WRB), and refined rye (RRB) breads. In addition, associations between the metabolic profile in fasting serum and the postprandial concentration of insulin in response to different breads were investigated. Nineteen postmenopausal women with normal fasting glucose and normal glucose tolerance participated in a randomized, controlled, crossover meal study. The test breads, RWB (control), RRB, and WRB, providing 50 g of available carbohydrate, were each served as a single meal. The postprandial metabolic profile was measured using nuclear magnetic resonance and targeted LC-mass spectrometry and was compared between different breads using ANOVA and multivariate models. Eight amino acids had a significant treatment effect (P insulin. Women with higher fasting concentrations of leucine and isoleucine and lower fasting concentrations of sphingomyelins and phosphatidylcholines had higher insulin responses despite similar glucose concentration after all kinds of bread (cross-validated ANOVA, P = 0.048). High blood concentration of branched-chain amino acids, i.e., leucine and isoleucine, has been associated with the increased risk of diabetes, which suggests that additional consideration should be given to bread proteins in understanding the beneficial health effects of different kinds of breads. The present study suggests that the fasting metabolic profile can be used to characterize the postprandial insulin demand in individuals with normal glucose metabolism that can be used for establishing strategies for the stratification of individuals in personalized nutrition. © 2014 American Society for Nutrition.

Measuring general and specific stress causes and stress responses among beginning secondary school teachers in the Netherlands

OpenAIRE

Harmsen, R; Helms-Lorenz, M.; Maulana, R; van Veen, K; van Veldhoven, M.J.P.M.

2018-01-01

The main aim of this study was to adjust the Questionnaire on the Experience and Evaluation of Work (QEEW) in order to measure stress causes and stress responses of beginning secondary school teachers in the Netherlands. First, the suitability of the original QEEW stress scales for use in the beginning teachers (BTs) context was investigated using a sample of 356 beginning teachers from 52 different secondary school locations in the Netherlands. Confirmatory Factor Analyses, Principal Compone...

Measuring general and specific stress causes and stress responses among beginning secondary school teachers in the Netherlands.

OpenAIRE

Harmsen, Ruth; Helms-Lorenz, Michelle; Maulana, Ridwan; van Veen, Klaas; van Veldhoven, M.J.P.M.

2018-01-01

The main aim of this study was to adjust the Questionnaire on the Experience and Evaluation of Work (QEEW) in order to measure stress causes and stress responses of beginning secondary school teachers in the Netherlands. First, the suitability of the original QEEW stress scales for use in the beginning teachers (BTs) context was investigated using a sample of 356 beginning teachers from 52 different secondary school locations in the Netherlands. Confirmatory Factor Analyses, Principal Compone...

Differential RNA-seq, Multi-Network Analysis and Metabolic Regulation Analysis of Kluyveromyces marxianus Reveals a Compartmentalised Response to Xylose.

Directory of Open Access Journals (Sweden)

Du Toit W P Schabort

Full Text Available We investigated the transcriptomic response of a new strain of the yeast Kluyveromyces marxianus, in glucose and xylose media using RNA-seq. The data were explored in a number of innovative ways using a variety of networks types, pathway maps, enrichment statistics, reporter metabolites and a flux simulation model, revealing different aspects of the genome-scale response in an integrative systems biology manner. The importance of the subcellular localisation in the transcriptomic response is emphasised here, revealing new insights. As was previously reported by others using a rich medium, we show that peroxisomal fatty acid catabolism was dramatically up-regulated in a defined xylose mineral medium without fatty acids, along with mechanisms to activate fatty acids and transfer products of β-oxidation to the mitochondria. Notably, we observed a strong up-regulation of the 2-methylcitrate pathway, supporting capacity for odd-chain fatty acid catabolism. Next we asked which pathways would respond to the additional requirement for NADPH for xylose utilisation, and rationalised the unexpected results using simulations with Flux Balance Analysis. On a fundamental level, we investigated the contribution of the hierarchical and metabolic regulation levels to the regulation of metabolic fluxes. Metabolic regulation analysis suggested that genetic level regulation plays a major role in regulating metabolic fluxes in adaptation to xylose, even for the high capacity reactions, which is unexpected. In addition, isozyme switching may play an important role in re-routing of metabolic fluxes in subcellular compartments in K. marxianus.

Metabolomics by proton nuclear magnetic resonance spectroscopy of the response to chloroethylnitrosourea reveals drug efficacy and tumor adaptive metabolic pathways.

Science.gov (United States)

Morvan, Daniel; Demidem, Aicha

2007-03-01

Metabolomics of tumors may allow discovery of tumor biomarkers and metabolic therapeutic targets. Metabolomics by two-dimensional proton high-resolution magic angle spinning nuclear magnetic resonance spectroscopy was applied to investigate metabolite disorders following treatment by chloroethylnitrosourea of murine B16 melanoma (n = 33) and 3LL pulmonary carcinoma (n = 31) in vivo. Treated tumors of both types resumed growth after a delay. Nitrosoureas provoke DNA damage but the metabolic consequences of genotoxic stress are little known yet. Although some differences were observed in the metabolite profile of untreated tumor types, the prominent metabolic features of the response to nitrosourea were common to both. During the growth inhibition phase, there was an accumulation of glucose (more than x10; P < 0.05), glutamine (x3 to 4; P < 0.01), and aspartate (x2 to 5; P < 0.01). This response testified to nucleoside de novo synthesis down-regulation and drug efficacy. However, this phase also involved the increase in alanine (P < 0.001 in B16 melanoma), the decrease in succinate (P < 0.001), and the accumulation of serine-derived metabolites (glycine, phosphoethanolamine, and formate; P < 0.01). This response witnessed the activation of pathways implicated in energy production and resumption of nucleotide de novo synthesis, thus metabolic pathways of DNA repair and adaptation to treatment. During the growth recovery phase, it remained polyunsaturated fatty acid accumulation (x1.5 to 2; P < 0.05) and reduced utilization of glucose compared with glutamine (P < 0.05), a metabolic fingerprint of adaptation. Thus, this study provides the proof of principle that metabolomics of tumor response to an anticancer agent may help discover metabolic pathways of drug efficacy and adaptation to treatment.

The immunoglobulin class of anti-hapten antibody secreted during secondary responses in vitro and in vivo.

Science.gov (United States)

North, J R; Dresser, D W

1977-05-01

A comparison has been made of the in vitro and in vivo response of primed mouse spleen cells to the hapten DNP. The responses were analysed in terms of six classes (sub-classes) of humoral antibody directed against the cross-reacting hapten TNP. By comparison with the response in intact mice the adoptive secondary response is delayed by 3 days in addition to being somewhat lesser in magnitude. The timing of the response in vitro is similar to that observed in intact mice. The preponderant class in all three responses was gammaG1 with gammaA and gammaG3 secreting cells consistently comprising the smallest proportion of the total of antibody-secreting cells.

Microbial Composition in Decomposing Pine Litter Shifts in Response to Common Soil Secondary Minerals

Science.gov (United States)

Welty-Bernard, A. T.; Heckman, K.; Vazquez, A.; Rasmussen, C.; Chorover, J.; Schwartz, E.

2011-12-01

A range of environmental and biotic factors have been identified that drive microbial community structure in soils - carbon substrates, redox conditions, mineral nutrients, salinity, pH, and species interactions. However, soil mineralogy has been largely ignored as a candidate in spite of recent studies that indicate that minerals have a substantial impact on soil organic matter stores and subsequent fluxes from soils. Given that secondary minerals and organic colloids govern a soil's biogeochemical activity due to surface area and electromagnetic charge, we propose that secondary minerals are a strong determinant of the communities that are responsible for process rates. To test this, we created three microcosms to study communities during decomposition using pine forest litter mixed with two common secondary minerals in soils (goethite and gibbsite) and with quartz as a control. Changes in bacterial and fungal communities were tracked over the 154-day incubation by pyrosequencing fragments of the bacterial 16S and fungal 18S rRNA genes. Ordination using nonmetric multidimensional scaling showed that bacterial communities separated on the basis of minerals. Overall, a single generalist - identified as an Acidobacteriaceae isolate - dominated all treatments over the course of the experiment, representing roughly 25% of all communities. Fungal communities discriminated between the quartz control alone and mineral treatments as a whole. Again, several generalists dominated the community. Coniochaeta ligniaria dominated communities with abundances ranging from 29 to 40%. The general stability of generalist populations may explain the similarities between treatment respiration rates. Variation between molecular fingerprints, then, were largely a function of unique minor members with abundances ranging from 0.01 to 8%. Carbon availability did not surface as a possible mechanism responsible for shifts in fingerprints due to the relatively large mass of needles in the

Role of secondary metabolites/antioxidants in vitro

Science.gov (United States)

In literature, secondary metabolites are described as natural products, waste, phytopharmaceuticals, bioactive constituents or by-products of the primary metabolism. They occur in many plant genera and microorganisms in vivo and in vitro, and have complex chemical structures specific to the plants w...

Space radiation-induced bystander effect: kinetics of biologic responses, mechanisms, and significance of secondary radiations

International Nuclear Information System (INIS)

Gonon, Geraldine

2011-01-01

more cells than expected based on the fraction of cells traversed through the nucleus by an iron or silicon ion. The effect was expressed as early as 15 min after exposure, peaked at 1 h and decreased by 24 h. A similar tendency occurred after exposure to a mean absorbed dose of 0.2 cGy of 3.7 MeV a particles, but not after 0.2 cGy of 290 MeV/u carbon ions.Analyses in dishes that incorporate a CR-39 solid state nuclear track detector bottom identified the cells irradiated with iron or silicon ions and further supported the participation of bystander cells in the stress response. Mechanistic studies indicated that gap junction intercellular communication, DNA repair, and oxidative metabolism participate in the propagation of the induced effects. We also considered the possible contribution of secondary particles produced along the primary particle tracks to the biological responses. Simulations with the FLUKA multi-particle transport code revealed that fragmentation products, other than electrons, in cells cultures exposed to HZE particles comprise ≤1 % of the absorbed dose. Further, the radial spread of dose due to secondary heavy ion fragments is confined to approximately 10-20 μm. Thus, the latter are unlikely to significantly contribute to the stressful effects in cells not targeted by primary HZE particles. (author)

Identification and Functional Characterization of Monofunctional ent-Copalyl Diphosphate and ent-Kaurene Synthases in White Spruce Reveal Different Patterns for Diterpene Synthase Evolution for Primary and Secondary Metabolism in Gymnosperms1[W][OA

Science.gov (United States)

Keeling, Christopher I.; Dullat, Harpreet K.; Yuen, Mack; Ralph, Steven G.; Jancsik, Sharon; Bohlmann, Jörg

2010-01-01

The biosynthesis of the tetracyclic diterpene ent-kaurene is a critical step in the general (primary) metabolism of gibberellin hormones. ent-Kaurene is formed by a two-step cyclization of geranylgeranyl diphosphate via the intermediate ent-copalyl diphosphate. In a lower land plant, the moss Physcomitrella patens, a single bifunctional diterpene synthase (diTPS) catalyzes both steps. In contrast, in angiosperms, the two consecutive cyclizations are catalyzed by two distinct monofunctional enzymes, ent-copalyl diphosphate synthase (CPS) and ent-kaurene synthase (KS). The enzyme, or enzymes, responsible for ent-kaurene biosynthesis in gymnosperms has been elusive. However, several bifunctional diTPS of specialized (secondary) metabolism have previously been characterized in gymnosperms, and all known diTPSs for resin acid biosynthesis in conifers are bifunctional. To further understand the evolution of ent-kaurene biosynthesis as well as the evolution of general and specialized diterpenoid metabolisms in gymnosperms, we set out to determine whether conifers use a single bifunctional diTPS or two monofunctional diTPSs in the ent-kaurene pathway. Using a combination of expressed sequence tag, full-length cDNA, genomic DNA, and targeted bacterial artificial chromosome sequencing, we identified two candidate CPS and KS genes from white spruce (Picea glauca) and their orthologs in Sitka spruce (Picea sitchensis). Functional characterization of the recombinant enzymes established that ent-kaurene biosynthesis in white spruce is catalyzed by two monofunctional diTPSs, PgCPS and PgKS. Comparative analysis of gene structures and enzyme functions highlights the molecular evolution of these diTPSs as conserved between gymnosperms and angiosperms. In contrast, diTPSs for specialized metabolism have evolved differently in angiosperms and gymnosperms. PMID:20044448

Ionomic and metabolic responses to neutral salt or alkaline salt stresses in maize (Zea mays L.) seedlings.

Science.gov (United States)

Guo, Rui; Shi, LianXuan; Yan, Changrong; Zhong, Xiuli; Gu, FengXue; Liu, Qi; Xia, Xu; Li, Haoru

2017-02-10

Soil salinity and alkalinity present a serious threat to global agriculture. However, most of the studies have focused on neutral salt stress, and the information on the metabolic responses of plants to alkaline salt stress is limited. This investigation aimed at determining the influence of neutral salt and alkaline salt stresses on the content of metal elements and metabolites in maize plant tissues, by using mixtures of various proportions of NaCl, NaHCO 3 , Na 2 SO 4 , and Na 2 CO 3 . We found that alkaline salt stress suppressed more pronouncedly the photosynthesis and growth of maize plants than salinity stress. Under alkaline salt stress conditions, metal ions formed massive precipitates, which ultimately reduced plant nutrient availability. On the other hand, high neutral salt stress induced metabolic changes in the direction of gluconeogenesis leading to the enhanced formation of sugars as a reaction contributing to the mitigation of osmotic stress. Thus, the active synthesis of sugars in shoots was essential to the development of salt tolerance. However, the alkaline salt stress conditions characterized by elevated pH values suppressed substantially the levels of photosynthesis, N metabolism, glycolysis, and the production of sugars and amino acids. These results indicate the presence of different defensive mechanisms responsible for the plant responses to neutral salt and alkaline salt stresses. In addition, the increased concentration of organic acids and enhanced metabolic energy might be potential major factors that can contribute to the maintenance intracellular ion balance in maize plants and counteract the negative effects of high pH under alkaline salt stress.

Primary, Secondary Metabolites, H2O2, Malondialdehyde and Photosynthetic Responses of Orthosiphon stimaneus Benth. to Different Irradiance Levels

Directory of Open Access Journals (Sweden)

Mohd Hafiz Ibrahim

2012-01-01

Full Text Available The resource availability hypothesis predicts an increase in the allocation to secondary metabolites when carbon gain is improved relative to nutrient availability, which normally occurs during periods of low irradiance. The present work was carried out to confirm this hypothesis by investigating the effects of decreasing irradiance on the production of plant secondary metabolites (flavonoids and phenolics in the herbal plant Orthosiphon stamineus, and to characterize this production by carbohydrate, H2O2, and malondialdehyde (MDA levels, net photosynthesis, leaf chlorophyll content and carbon to nitrogen ratio (C/N. Four levels of irradiance (225, 500, 625 and 900 µmol/m2/s were imposed onto two-week old seedlings for 12 weeks in a randomized complete block design experiment. Peak production of total flavonoids, phenolics, soluble sugar, starch and total non-structural carbohydrate ocurred under low irradiance of 225 µmol/m2/s, and decreased with increasing irradiance. The up-regulation of secondary metabolites could be explained by the concomitant increases in H2O2 and MDA activities under low irradiance. This condition also resulted in enhanced C/N ratio signifying a reduction in nitrogen levels, which had established significant negative correlations with net photosynthesis, total biomass and total chlorophyll content, indicating the possible existence of a trade-off between growth and secondary metabolism under low irradiance with reduced nitrogen content. The competition between total chlorophyll and secondary metabolites production, as exhibited by the negative correlation coefficient under low irradiance, also suggests a sign of gradual switch of investment from chlorophyll to polyphenols production.

Biosynthesis and Metabolic Fate of Phenylalanine in Conifers

OpenAIRE

Pascual, María B.; El-Azaz, Jorge; de la Torre, Fernando N.; Cañas, Rafael A.; Avila, Concepción; Cánovas, Francisco M.

2016-01-01

The amino acid phenylalanine (Phe) is a critical metabolic node that plays an essential role in the interconnection between primary and secondary metabolism in plants. Phe is used as a protein building block but it is also as a precursor for numerous plant compounds that are crucial for plant reproduction, growth, development, and defense against different types of stresses. The metabolism of Phe plays a central role in the channeling of carbon from photosynthesis to the biosynthesis of pheny...

Molecular and physiological responses to titanium dioxide ...

Science.gov (United States)

- Changes in tissue transcriptomes and productivity of Arabidopsis thaliana were investigated during exposure of plants to two widely-used engineered metal oxide nanoparticles, titanium dioxide (nano-titanium) and cerium dioxide (nano-cerium). Microarray analyses confirmed that exposure to either nanoparticle altered the transcriptomes of rosette leaves and roots, with comparatively larger numbers of differentially expressed genes (DEGs) found under nano-titania exposure. Nano-titania induced more DEGs in rosette leaves, whereas roots had more DEGs under nano-ceria exposure. MapMan analyses indicated that while nano-titania up-regulated overall and secondary metabolism in both tissues, metabolic processes under nano-ceria remained mostly unchanged. Gene enrichment analysis indicated that both nanoparticles mainly enriched ontology groups such as responses to stress (abiotic and biotic), and defense responses (pathogens), and responses to endogenous stimuli (hormones). Nano-titania specifically induced genes associated with photosynthesis, whereas nano-ceria induced expression of genes related to activating transcription factors, most notably those belonging to the ethylene responsive element binding protein family. Interestingly, there were also increased numbers of rosette leaves and plant biomass under nano-ceria exposure, but not under nano-titania. Other transcriptomic responses did not clearly relate to responses observed at the organism level. This may b

Deciphering the Differential Effective and Toxic Responses of Bupleuri Radix following the Induction of Chronic Unpredictable Mild Stress and in Healthy Rats Based on Serum Metabolic Profiles

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Xiaoxia Gao

2018-01-01

Full Text Available The petroleum ether fraction of Bupleuri Radix which is contained in the traditional Chinese medicine prescription of Xiaoyaosan (XYS may have a therapeutic effect in depressed subjects based on the results of our previous study. It has been reported that Bupleuri Radix can cause liver toxicity following overdosing or long-term use. Therefore, this study aimed to decipher the differential effective and toxic responses of Bupleuri Radix in chronic unpredictable mild stress (CUMS (with depression and healthy rats based on serum metabolic profiles. Serum metabolic profiles were obtained using the UHPLC- Q Exactive Orbitrap-MS technique. Our results demonstrated that the petroleum ether fraction of Bupleuri Radix (PBR produces an antidepressant effect through regulating glycometabolism, amino acid metabolism, sphingolipid metabolism, glycerophospholipid metabolism, and fatty acid metabolism. It also induces more severe toxic reactions in the liver or kidney in healthy rats than in CUMS rats, which exhibited a comparatively mild drug-induced toxic reaction. The altered lysine degradation, sphingolipid metabolism, glycerophospholipid metabolism, fatty acid metabolism, and bile acid metabolism could be at least partly responsible for the PBR toxic responses in healthy rats. The differential effective and toxic response of PBR in CUMS rats and healthy rats provide a new standard for the more rational and safer application of clinical drugs in the future.

Time course of the response of carbohydrate metabolism to unloading of the soleus

Science.gov (United States)

Henriksen, Erik J.; Tischler, Marc E.

1988-01-01

The time course of the response of carbohydrate metabolism to unloading was studied in the soleus muscle of rats subjected to tail-cast suspension. In the fresh soleus, 12 hours of unloading led to higher concentrations of glycogen and lower activity ratios of both glycogen synthase and glycogen phosphorylase. These changes were still evident on day three. Thereafter, the increased glycogen concentration apparently diminished the activity ratio of glycogen synthase, leading to a subsequent fall in the total glycogen content after day one. After 24 hours of unloading, when no significant atrophy was detectable, there was no differential response to insulin for in vitro glucose metabolism. On day three, the soleus atrophied significantly and displayed a greater sensitivity to insulin for most of these parameters compared to the weight-bearing control muscle. However, insulin sensitivity for glycogen synthesis was unchanged. These results showed that the increased sensitivity to insulin of the unloaded soleus is associated with the degree of muscle atrophy, likely due to an increased insulin binding capacity relative to muscle mass. This study also showed that insulin regulation of glucose uptake and of glycogen synthesis is affected differentially in the unloaded soleus muscle.

Activation of SAT1 engages polyamine metabolism with p53-mediated ferroptotic responses.

Science.gov (United States)

Ou, Yang; Wang, Shang-Jui; Li, Dawei; Chu, Bo; Gu, Wei

2016-11-01

Although p53-mediated cell-cycle arrest, senescence, and apoptosis remain critical barriers to cancer development, the emerging role of p53 in cell metabolism, oxidative responses, and ferroptotic cell death has been a topic of great interest. Nevertheless, it is unclear how p53 orchestrates its activities in multiple metabolic pathways into tumor suppressive effects. Here, we identified the SAT1 (spermidine/spermine N 1 -acetyltransferase 1) gene as a transcription target of p53. SAT1 is a rate-limiting enzyme in polyamine catabolism critically involved in the conversion of spermidine and spermine back to putrescine. Surprisingly, we found that activation of SAT1 expression induces lipid peroxidation and sensitizes cells to undergo ferroptosis upon reactive oxygen species (ROS)-induced stress, which also leads to suppression of tumor growth in xenograft tumor models. Notably, SAT1 expression is down-regulated in human tumors, and CRISPR-cas9-mediated knockout of SAT1 expression partially abrogates p53-mediated ferroptosis. Moreover, SAT1 induction is correlated with the expression levels of arachidonate 15-lipoxygenase (ALOX15), and SAT1-induced ferroptosis is significantly abrogated in the presence of PD146176, a specific inhibitor of ALOX15. Thus, our findings uncover a metabolic target of p53 involved in ferroptotic cell death and provide insight into the regulation of polyamine metabolism and ferroptosis-mediated tumor suppression.

Metabolic Profiling of Dendrobium officinale in Response to Precursors and Methyl Jasmonate

Directory of Open Access Journals (Sweden)

Chunyan Jiao

2018-03-01

Full Text Available Alkaloids are the main active ingredients in the medicinal plant Dendrobium officinale. Based on the published genomic and transcriptomic data, a proposed terpenoid indole alkaloid (TIA biosynthesis pathway may be present in D. officinale. In this study, protocorm-like bodies (PLBs with a high-yielding production of alkaloids were obtained by the optimization of tryptophan, secologanin and methyl jasmonate (MeJA treatment. The results showed that the total alkaloid content was 2.05 times greater than that of the control group when the PLBs were fed with 9 µM tryptophan, 6 µM secologanin and 100 µM MeJA after 36 days. HPLC analysis showed that strictosidine synthase (STR activity also increased in the treated plants. A total of 78 metabolites were identified using gas chromatography-mass spectrometry (GC-MS in combination with liquid chromatography-mass spectrometry (LC-MS methods; 29 differential metabolites were identified according to the multivariate statistical analysis. Among them, carapanaubine, a kind of TIA, exhibited dramatically increased levels. In addition, a possible underlying process of the metabolic flux from related metabolism to the TIA biosynthetic pathway was enhanced. These results provide a comprehensive view of the metabolic changes related to alkaloid biosynthesis, especially TIA biosynthesis, in response to tryptophan, secologanin and MeJA treatment.

Effects of energy restriction on acute adrenoceptor and metabolic responses to exercise in obese subjects

NARCIS (Netherlands)

Kempen, K.P.G.; Saris, W.H.M.; Senden, J.M.G.; Menheere, P.P.C.A.; Blaak, E.E.; van Baak, M.A.

1994-01-01

Effects of energy restriction on acute adrenoceptor and metabolic responses to exercise in obese subjects. Kempen KP, Saris WH, Senden JM, Menheere PP, Blaak EE, van Baak MA. Department of Human Biology, University of Limburg, Maastricht, The Netherlands. This study was intended to investigate the

Uptake, accumulation and metabolic response of ferricyanide in weeping willows.

Science.gov (United States)

Yu, Xiao-Zhang; Gu, Ji-Dong

2009-01-01

The remediation potential and metabolic responses of plants to ferricyanide were investigated using pre-rooted weeping willows (Salix babylonica L.) grown hydroponically in growth chambers and treated with potassium ferricyanide. Positive responses were observed for the plants exposed to cyanide recovered in plant biomass was constant in all treatments, indicating that transport is a major limiting step for the uptake of ferricyanide by plants. The majority of the ferricyanide taken up from the growth media was possibly assimilated during transport through plants. The velocity of the removal processes can be described by Michaelis-Menten kinetics, and the half-saturation constant (K(M)) and the maximum removal capacity (v(max)) were estimated to be 228.1 mg CN L(-1) and 36.43 mg CN kg(-1) d(-1), respectively, using non-linear regression methods. These results suggest that weeping willows can take up, transport and assimilate ferricyanide; and phytoremediation is an option for cleaning up the environmental sites contaminated with cyanide complexes.

Similar metabolic responses in pigs and humans to breads with different contents and compositions of dietary fibers: a metabolomics study

DEFF Research Database (Denmark)

Nielsen, Kirstine Lykke; Hartvigsen, Merete; Hedemann, Mette Skou

2014-01-01

Background: In nutritional studies, pigs are often used as models for humans because of nutritional and physiologic similarities. However, evidence supporting similar metabolic responses to nutritional interventions is lacking. Objective: The objective was to establish whether pigs and humans...... respond similarly to a nutritional intervention. Using metabolomics, we compared the acute metabolic response to 4 test breads between conventional pigs (growing) and adult human subjects (with the metabolic syndrome). Design: Six catheterized pigs and 15 human subjects were tested in a randomized...... different basal metabolome concentrations in the plasma of pigs and humans. Humans had higher contents of phosphatidylcholines, oleic acid, and carnitine in plasma, possibly reflecting a higher intake of meats and fats. In pigs, betaine, choline, creatinine, tryptophan, and phenylalanine were higher...

A Dose-Response Strategy Reveals Differences between Normal-Weight and Obese Men in Their Metabolic and Inflammatory Responses to a High-Fat Meal123

Science.gov (United States)

Schwander, Flurina; Kopf-Bolanz, Katrin A.; Buri, Caroline; Portmann, Reto; Egger, Lotti; Chollet, Magali; McTernan, Philip G.; Piya, Milan K.; Gijs, Martin A. M.; Vionnet, Nathalie; Pralong, François; Laederach, Kurt; Vergères, Guy

2014-01-01

A dose-response strategy may not only allow investigation of the impact of foods and nutrients on human health but may also reveal differences in the response of individuals to food ingestion based on their metabolic health status. In a randomized crossover study, we challenged 19 normal-weight (BMI: 20–25 kg/m2) and 18 obese (BMI: >30 kg/m2) men with 500, 1000, and 1500 kcal of a high-fat (HF) meal (60.5% energy from fat). Blood was taken at baseline and up to 6 h postprandially and analyzed for a range of metabolic, inflammatory, and hormonal variables, including plasma glucose, lipids, and C-reactive protein and serum insulin, glucagon-like peptide-1, interleukin-6 (IL-6), and endotoxin. Insulin was the only variable that could differentiate the postprandial response of normal-weight and obese participants at each of the 3 caloric doses. A significant response of the inflammatory marker IL-6 was only observed in the obese group after ingestion of the HF meal containing 1500 kcal [net incremental AUC (iAUC) = 22.9 ± 6.8 pg/mL × 6 h, P = 0.002]. Furthermore, the net iAUC for triglycerides significantly increased from the 1000 to the 1500 kcal meal in the obese group (5.0 ± 0.5 mmol/L × 6 h vs. 6.0 ± 0.5 mmol/L × 6 h; P = 0.015) but not in the normal-weight group (4.3 ± 0.5 mmol/L × 6 h vs. 4.8 ± 0.5 mmol/L × 6 h; P = 0.31). We propose that caloric dose-response studies may contribute to a better understanding of the metabolic impact of food on the human organism. This study was registered at clinicaltrials.gov as NCT01446068. PMID:24812072

Relative Quantitative Proteomic Analysis of Brucella abortus Reveals Metabolic Adaptation to Multiple Environmental Stresses.

Science.gov (United States)

Zai, Xiaodong; Yang, Qiaoling; Yin, Ying; Li, Ruihua; Qian, Mengying; Zhao, Taoran; Li, Yaohui; Zhang, Jun; Fu, Ling; Xu, Junjie; Chen, Wei

2017-01-01

Brucella spp. are facultative intracellular pathogens that cause chronic brucellosis in humans and animals. The virulence of Brucella primarily depends on its successful survival and replication in host cells. During invasion of the host tissue, Brucella is simultaneously subjected to a variety of harsh conditions, including nutrient limitation, low pH, antimicrobial defenses, and extreme levels of reactive oxygen species (ROS) via the host immune response. This suggests that Brucella may be able to regulate its metabolic adaptation in response to the distinct stresses encountered during its intracellular infection of the host. An investigation into the differential proteome expression patterns of Brucella grown under the relevant stress conditions may contribute toward a better understanding of its pathogenesis and adaptive response. Here, we utilized a mass spectrometry-based label-free relative quantitative proteomics approach to investigate and compare global proteomic changes in B. abortus in response to eight different stress treatments. The 3 h short-term in vitro single-stress and multi-stress conditions mimicked the in vivo conditions of B. abortus under intracellular infection, with survival rates ranging from 3.17 to 73.17%. The proteomic analysis identified and quantified a total of 2,272 proteins and 74% of the theoretical proteome, thereby providing wide coverage of the B. abortus proteome. By including eight distinct growth conditions and comparing these with a control condition, we identified a total of 1,221 differentially expressed proteins (DEPs) that were significantly changed under the stress treatments. Pathway analysis revealed that most of the proteins were involved in oxidative phosphorylation, ABC transporters, two-component systems, biosynthesis of secondary metabolites, the citrate cycle, thiamine metabolism, and nitrogen metabolism; constituting major response mechanisms toward the reconstruction of cellular homeostasis and metabolic

Oxidative stress protection and glutathione metabolism in response to hydrogen peroxide and menadione in riboflavinogenic fungus Ashbya gossypii.

Science.gov (United States)

Kavitha, S; Chandra, T S

2014-11-01

Ashbya gossypii is a plant pathogen and a natural overproducer of riboflavin and is used for industrial riboflavin production. A few literature reports depict a link between riboflavin overproduction and stress in this fungus. However, the stress protection mechanisms and glutathione metabolism are not much explored in A. gossypii. In the present study, an increase in the activity of catalase and superoxide dismutase was observed in response to hydrogen peroxide and menadione. The lipid peroxide and membrane lipid peroxide levels were increased by H2O2 and menadione, indicating oxidative damage. The glutathione metabolism was altered with a significant increase in oxidized glutathione (GSSG), glutathione peroxidase (GPX), glutathione S transferase (GST), and glutathione reductase (GR) and a decrease in reduced glutathione (GSH) levels in the presence of H2O2 and menadione. Expression of the genes involved in stress mechanism was analyzed in response to the stressors by semiquantitative RT-PCR. The messenger RNA (mRNA) levels of CTT1, SOD1, GSH1, YAP1, and RIB3 were increased by H2O2 and menadione, indicating the effect of stress at the transcriptional level. A preliminary bioinformatics study for the presence of stress response elements (STRE)/Yap response elements (YRE) depicted that the glutathione metabolic genes, stress genes, and the RIB genes hosted either STRE/YRE, which may enable induction of these genes during stress.

Energetic and metabolic transient response of Saccharomyces cerevisiae to benzoic acid.

Science.gov (United States)

Kresnowati, M T A P; van Winden, W A; van Gulik, W M; Heijnen, J J

2008-11-01

Saccharomyces cerevisiae is known to be able to adapt to the presence of the commonly used food preservative benzoic acid with a large energy expenditure. Some mechanisms for the adaptation process have been suggested, but its quantitative energetic and metabolic aspects have rarely been discussed. This study discusses use of the stimulus response approach to quantitatively study the energetic and metabolic aspects of the transient adaptation of S. cerevisiae to a shift in benzoic acid concentration, from 0 to 0.8 mM. The information obtained also serves as the basis for further utilization of benzoic acid as a tool for targeted perturbation of the energy system, which is important in studying the kinetics and regulation of central carbon metabolism in S. cerevisiae. Using this experimental set-up, we found significant fast-transient (< 3000 s) increases in O(2) consumption and CO(2) production rates, of approximately 50%, which reflect a high energy requirement for the adaptation process. We also found that with a longer exposure time to benzoic acid, S. cerevisiae decreases the cell membrane permeability for this weak acid by a factor of 10 and decreases the cell size to approximately 80% of the initial value. The intracellular metabolite profile in the new steady-state indicates increases in the glycolytic and tricarboxylic acid cycle fluxes, which are in agreement with the observed increases in specific glucose and O(2) uptake rates.

Responsive eLearning exercises to enhance student interaction with metabolic pathways.

Science.gov (United States)

Roesler, William J; Dreaver-Charles, Kristine

2018-05-01

Successful learning of biochemistry requires students to engage with the material. In the past this often involved students writing out pathways by hand, and more recently directing students to online resources such as videos, songs, and animated slide presentations. However, even these latter resources do not really provide students an opportunity to engage with the material in an active fashion. As part of an online introductory metabolism course that was developed at our university, we created a series of twelve online interactive activities using Adobe Captivate 9. These activities targeted glycolysis, gluconeogenesis, the pentose phosphate pathway, glycogen metabolism, the citric acid cycle, and fatty acid oxidation. The interactive exercises consisted of two types. One involved dragging objects such as names of enzymes or allosteric modifiers to their correct drop locations such as a particular point in a metabolic pathway, a specific enzyme, and so forth. A second type involved clicking on objects, locations within a pathway, and so forth, in response to a particular question. In both types of exercises, students received feedback on their decisions in order to enhance learning. The student feedback received on these activities was very positive, and indicated that they found them to increase their confidence in the material and that they had learned the key principles of each pathway. © 2018 by The International Union of Biochemistry and Molecular Biology, 46(3):223-229, 2018. © 2018 The International Union of Biochemistry and Molecular Biology.

The Interplay between Adolescent Needs and Secondary School Structures: Fostering Developmentally Responsive Middle and High School Environments across the Transition

Science.gov (United States)

Ellerbrock, Cheryl R.; Kiefer, Sarah M.

2013-01-01

Understanding the developmental responsiveness of secondary school environments may be an important factor in supporting students as they make the transition from one school to the next. Students' needs may or may not be met depending on the nature of the fit between their basic and developmental needs and secondary school structures at the middle…

It must be my metabolism: Metabolic control of mind

Directory of Open Access Journals (Sweden)

Dana M Small

2014-07-01

relationship between the reinforcing potency of sugared solutions and the metabolic effects that follow their consumption (16, also see the abstract of I. de Araujo. We therefore hypothesized that metabolic response provides the critical signal necessary to condition preference. To test this prediction in humans we designed a flavor nutrient conditioning study in which participants first rated their liking for novel flavored beverages and then, over a three week-long conditioning protocol, alternately ingested one of the flavored beverages with 112.5 kcal from maltodextrin, a tasteless and odorless polysaccharide that breaks down into glucose, and another flavored beverage with no calories added. Plasma glucose was measured before and after each of the drinks’ consumption as a proxy measure of metabolic response, assuming that glucose oxidation depends upon the level of circulating glucose. For each participant flavor-calorie pairings were held constant but the identity of the conditioned flavors were counterbalanced across participants. Following the exposure phase, participants’ liking of, and brain responses to, non-caloric versions of the flavors were assessed. We predicted that change in plasma glucose produced by beverage consumption during the exposure sessions would be associated with neural responses in dopamine source and target regions to the calorie predictive flavor. As predicted, response in the ventral striatum and hypothalamus to the calorie-predictive flavor (CS+ vs. non the noncaloric-predictive flavor (CS- was strongly associated with the changes in plasma glucose levels produced by ingestion of these same beverages when consumed previously either with (CS+ or without (CS- calories (17. Specifically, the greater the increase in circulating glucose occurring post ingestion of the beverage containing 112.5 kcal from maltodextrin versus the noncaloric drink, the stronger was the brain response to the CS+ compared to the CS- flavor. Importantly, because each

Functional imaging to monitor vascular and metabolic response in canine head and neck tumors during fractionated radiotherapy.

Science.gov (United States)

Rødal, Jan; Rusten, Espen; Søvik, Åste; Skogmo, Hege Kippenes; Malinen, Eirik

2013-10-01

Radiotherapy causes alterations in tumor biology, and non-invasive early assessment of such alterations may become useful for identifying treatment resistant disease. The purpose of the current work is to assess changes in vascular and metabolic features derived from functional imaging of canine head and neck tumors during fractionated radiotherapy. Material and methods. Three dogs with spontaneous head and neck tumors received intensity-modulated radiotherapy (IMRT). Contrast-enhanced cone beam computed tomography (CE-CBCT) at the treatment unit was performed at five treatment fractions. Dynamic (18)FDG-PET (D-PET) was performed prior to the start of radiotherapy, at mid-treatment and at 3-12 weeks after the completion of treatment. Tumor contrast enhancement in the CE-CBCT images was used as a surrogate for tumor vasculature. Vascular and metabolic tumor parameters were further obtained from the D-PET images. Changes in these tumor parameters were assessed, with emphasis on intra-tumoral distributions. Results. For all three patients, metabolic imaging parameters obtained from D-PET decreased from the pre- to the inter-therapy session. Correspondingly, for two of three patients, vascular imaging parameters obtained from both CE-CBCT and D-PET increased. Only one of the tumors showed a clear metabolic response after therapy. No systematic changes in the intra-tumor heterogeneity in the imaging parameters were found. Conclusion. Changes in vascular and metabolic parameters could be detected by the current functional imaging methods. Vascular tumor features from CE-CBCT and D-PET corresponded well. CE-CBCT is a potential method for easy response assessment when the patient is at the treatment unit.

Acute Cardiorespiratory and Metabolic Responses During Exoskeleton-Assisted Walking Overground Among Persons with Chronic Spinal Cord Injury

Science.gov (United States)

Hartigan, Clare; Kandilakis, Casey; Pharo, Elizabeth; Clesson, Ismari

2015-01-01

Background: Lower extremity robotic exoskeleton technology is being developed with the promise of affording people with spinal cord injury (SCI) the opportunity to stand and walk. The mobility benefits of exoskeleton-assisted walking can be realized immediately, however the cardiorespiratory and metabolic benefits of this technology have not been thoroughly investigated. Objective: The purpose of this pilot study was to evaluate the acute cardiorespiratory and metabolic responses associated with exoskeleton-assisted walking overground and to determine the degree to which these responses change at differing walking speeds. Methods: Five subjects (4 male, 1 female) with chronic SCI (AIS A) volunteered for the study. Expired gases were collected during maximal graded exercise testing and two, 6-minute bouts of exoskeleton-assisted walking overground. Outcome measures included peak oxygen consumption (V̇O2peak), average oxygen consumption (V̇O2avg), peak heart rate (HRpeak), walking economy, metabolic equivalent of tasks for SCI (METssci), walk speed, and walk distance. Results: Significant differences were observed between walk-1 and walk-2 for walk speed, total walk distance, V̇O2avg, and METssci. Exoskeleton-assisted walking resulted in %V̇O2peak range of 51.5% to 63.2%. The metabolic cost of exoskeleton-assisted walking ranged from 3.5 to 4.3 METssci. Conclusion: Persons with motor-complete SCI may be limited in their capacity to perform physical exercise to the extent needed to improve health and fitness. Based on preliminary data, cardiorespiratory and metabolic demands of exoskeleton-assisted walking are consistent with activities performed at a moderate intensity. PMID:26364281

Acute Cardiorespiratory and Metabolic Responses During Exoskeleton-Assisted Walking Overground Among Persons with Chronic Spinal Cord Injury.

Science.gov (United States)

Evans, Nicholas; Hartigan, Clare; Kandilakis, Casey; Pharo, Elizabeth; Clesson, Ismari

2015-01-01

Lower extremity robotic exoskeleton technology is being developed with the promise of affording people with spinal cord injury (SCI) the opportunity to stand and walk. The mobility benefits of exoskeleton-assisted walking can be realized immediately, however the cardiorespiratory and metabolic benefits of this technology have not been thoroughly investigated. The purpose of this pilot study was to evaluate the acute cardiorespiratory and metabolic responses associated with exoskeleton-assisted walking overground and to determine the degree to which these responses change at differing walking speeds. Five subjects (4 male, 1 female) with chronic SCI (AIS A) volunteered for the study. Expired gases were collected during maximal graded exercise testing and two, 6-minute bouts of exoskeleton-assisted walking overground. Outcome measures included peak oxygen consumption (V̇O2peak), average oxygen consumption (V̇O2avg), peak heart rate (HRpeak), walking economy, metabolic equivalent of tasks for SCI (METssci), walk speed, and walk distance. Significant differences were observed between walk-1 and walk-2 for walk speed, total walk distance, V̇O2avg, and METssci. Exoskeleton-assisted walking resulted in %V̇O2peak range of 51.5% to 63.2%. The metabolic cost of exoskeleton-assisted walking ranged from 3.5 to 4.3 METssci. Persons with motor-complete SCI may be limited in their capacity to perform physical exercise to the extent needed to improve health and fitness. Based on preliminary data, cardiorespiratory and metabolic demands of exoskeleton-assisted walking are consistent with activities performed at a moderate intensity.

Liquid scintillation vial for radiometric assay of lymphocyte carbohydrate metabolism in response to mitogens

International Nuclear Information System (INIS)

Tran, N.; Wagner, H.N. Jr.

1978-01-01

We have demonstrated that mitogens--i.e., PHA and Con.A--stimulate lymphocyte carbohydrate metabolism using a liquid-scintillation vial with conventional liquid-scintillation detectors. The results showed that this enclosed system can be useful for development of rapid in vitro tests of lymphocytes immune responsiveness, as well as for radiometric detection of bacterial growth in various gaseous atmospheres

Basal metabolic regulatory responses and rhythmic activity of ...

African Journals Online (AJOL)

... Rattus sp. Low concentrations of kola nut extract stimulated the heart by increasing rate and force of contraction as well as metabolic rate. Higher concentrations reduced rate and amplitude of beat resulting, at still higher concentrations in heart failure. Keywords: Kolanut, extract, basal metabolic rate, mammalian heart ...

Etiological classification of depression based on the enzymes of tryptophan metabolism.

Science.gov (United States)

Fukuda, Katsuhiko

2014-12-24

Viewed in terms of input and output, the mechanisms of depression are still akin to a black box. However, there must be main pivots for diverse types of depression. From recent therapeutic observations, both the serotonin (5-HT) and kynurenine pathways of tryptophan metabolism may be of particular importance to improved understanding of depression. Here, I propose an etiological classification of depression, based on key peripheral and central enzymes of tryptophan metabolism. Endogenous depression is caused by a larger genetic component than reactive depression. Besides enterochromaffin and mast cells, tryptophan hydroxylase 1 (TPH1), primarily expressed in the gastrointestinal tract, is also found in 5-hydroxytryptophan-producing cells (5-HTP cells) in normal intestinal enterocytes, which are thought to essentially shunt 5-HT production in 5-HT-producing cells. Genetic studies have reported an association between TPH1 and depression, or the responsiveness of depression to antidepressive medication. Therefore, it is possible that hypofunctional 5-HTP cells (reflecting TPH1 dysfunction) in the periphery lead to deficient brain 5-HT levels. Additionally,it has been reported that higher TPH2 expression in depressed suicides may reflect a homeostatic response to deficient 5-HT levels. Subsequently, endogenous depression may be caused by TPH1 dysfunction combined with compensatory TPH2 activation. Reactive depression results from life stresses and involves the hypothalamic-pituitary-adrenal axis, with resulting cortisol production inducing tryptophan 2,3-dioxygenase (TDO) activation. In secondary depression, caused by inflammation, infection, or oxidative stress, indoleamine 2,3-dioxygenase (IDO) is activated. In both reactive and secondary depression, the balance between 3-hydroxykynurenine (3-HK) and kynurenic acid may shift towards 3-HK production via kynurenine-3-monooxygenase (KMO) activation. By shifting the equilibrium position of key enzymes of tryptophan

Regulatory network of secondary metabolism in Brassica rapa : insight into the glucosinolate pathway

NARCIS (Netherlands)

Pino Del Carpio, Dunia; Basnet, Ram Kumar; Arends, Danny; Lin, Ke; De Vos, Ric C H; Muth, Dorota; Kodde, Jan; Boutilier, Kim; Bucher, Johan; Wang, Xiaowu; Jansen, Ritsert; Bonnema, Guusje

2014-01-01

Brassica rapa studies towards metabolic variation have largely been focused on the profiling of the diversity of metabolic compounds in specific crop types or regional varieties, but none aimed to identify genes with regulatory function in metabolite composition. Here we followed a genetical

Transcriptomic Changes in Response to Putrescine Production in Metabolically Engineered Corynebacterium glutamicum

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Zhen Li

2017-10-01

Full Text Available Putrescine is widely used in industrial production of bioplastics, pharmaceuticals, agrochemicals, and surfactants. Although engineered Corynebacterium glutamicum has been successfully used to produce high levels of putrescine, the overall cellular physiological and metabolic changes caused by overproduction of putrescine remains unclear. To reveal the transcriptional changes that occur in response to putrescine production in an engineered C. glutamicum strain, a comparative transcriptomic analysis was carried out. Overproduction of putrescine resulted in transcriptional downregulation of genes involved in glycolysis; the TCA cycle, pyruvate degradation, biosynthesis of some amino acids, oxidative phosphorylation; vitamin biosynthesis (thiamine and vitamin 6, metabolism of purine, pyrimidine and sulfur, and ATP-, NAD-, and NADPH-consuming enzymes. The transcriptional levels of genes involved in ornithine biosynthesis and NADPH-forming related enzymes were significantly upregulated in the putrescine producing C. glutamicum strain PUT-ALE. Comparative transcriptomic analysis provided some genetic modification strategies to further improve putrescine production. Repressing ATP- and NADPH-consuming enzyme coding gene expression via CRISPRi enhanced putrescine production.

Transcriptomic Changes in Response to Putrescine Production in Metabolically Engineered Corynebacterium glutamicum

Science.gov (United States)

Li, Zhen; Liu, Jian-Zhong

2017-01-01

Putrescine is widely used in industrial production of bioplastics, pharmaceuticals, agrochemicals, and surfactants. Although engineered Corynebacterium glutamicum has been successfully used to produce high levels of putrescine, the overall cellular physiological and metabolic changes caused by overproduction of putrescine remains unclear. To reveal the transcriptional changes that occur in response to putrescine production in an engineered C. glutamicum strain, a comparative transcriptomic analysis was carried out. Overproduction of putrescine resulted in transcriptional downregulation of genes involved in glycolysis; the TCA cycle, pyruvate degradation, biosynthesis of some amino acids, oxidative phosphorylation; vitamin biosynthesis (thiamine and vitamin 6), metabolism of purine, pyrimidine and sulfur, and ATP-, NAD-, and NADPH-consuming enzymes. The transcriptional levels of genes involved in ornithine biosynthesis and NADPH-forming related enzymes were significantly upregulated in the putrescine producing C. glutamicum strain PUT-ALE. Comparative transcriptomic analysis provided some genetic modification strategies to further improve putrescine production. Repressing ATP- and NADPH-consuming enzyme coding gene expression via CRISPRi enhanced putrescine production. PMID:29089930

Dynamical feedback between circadian clock and sucrose availability explains adaptive response of starch metabolism to various photoperiods

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Francois Gabriel Feugier

2013-01-01

Full Text Available Plants deal with resource management during all their life. During the day they feed on photosynthetic carbon, sucrose, while storing a part into starch for night use. Careful control of carbon partitioning, starch degradation and sucrose export rates is crucial to avoid carbon starvation, insuring optimal growth whatever the photoperiod. Efficient regulation of these key metabolic rates can give an evolutionary advantage to plants. Here we propose a model of adaptive starch metabolism in response to various photoperiods. We assume the three key metabolic rates to be circadian regulated in leaves and that their phases of oscillations are shifted in response to sucrose starvation. We performed gradient descents for various photoperiod conditions to find the corresponding optimal sets of phase shifts that minimize starvation. Results at convergence were all consistent with experimental data: i diurnal starch profile showed linear increase during the day and linear decrease at night; ii shorter photoperiod tended to increase starch synthesis speed while decreasing its degradation speed during the longer night; iii sudden early dusk showed slower starch degradation during the longer night. Profiles that best explained observations corresponded to circadian regulation of all rates. This theoretical study would establish a framework for future research on feedback between starch metabolism and circadian clock as well as plant productivity.

Comparative transcriptome analysis unveils the tolerance mechanisms of Citrus hystrix in response to 'Candidatus Liberibacter asiaticus' infection.

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Yan Hu

Full Text Available Citrus Huanglongbing (HLB, a highly devastating citrus disease, is associated with 'Candidatus Liberibacter asiacitus' (CLas, a member of phloem-inhabiting α-proteobacteria. HLB can affect all cultivated citrus and no cure is currently available. Previous studies showed that Kaffir lime (Citrus hystrix, primarily grown in South Asia and Southeast Asia, was tolerant to HLB but the molecular mechanism remains unknown. In this study, gene expression profiling experiments were performed on HLB-tolerant C. hystrix and HLB-susceptible C. sinensis three months after inoculation with CLas using RNA-seq data. Differentially expressed genes (DEGs in the two citrus cultivars were mainly involved in diverse cellular functions including carbohydrate metabolism, photosynthesis, cell wall metabolism, secondary metabolism, hormone metabolism and oxidation/reduction processes. Notably, starch synthesis and photosynthesis process were not disturbed in CLas-infected C. hystrix. Most of the DEGs involved in cell wall metabolism and secondary metabolism were up-regulated in C. hystrix. In addition, the activation of peroxidases, Cu/Zn-SOD and POD4, may also enhance the tolerance of C. hystrix to CLas. This study provides an insight into the host response of HLB-tolerant citrus cultivar to CLas. C. hystrix is potentially useful for HLB-tolerant/resistant citrus breeding in the future.

Response of melanoma tumor phospholipid metabolism to chloroethyle nitrosourea: a high resolution proton NMR spectroscopy study.

Science.gov (United States)

Morvan, Daniel; Demidem, Aïcha; Madelmont, Jean-Claude

2003-07-01

Phospholipid metabolism is tightly involved in tumor growth regulation and tumor cell survival. The response of phospholipid metabolism to chloroethyle nitrosourea treatment is investigated in a murine B16 melanoma model. Measurements of phospholipid derivatives are performed on intact tumor tissue samples using one- and two-dimensional proton NMR spectroscopy. During the tumor growth inhibition phase under treatment, tumors overexpress phosphocholine, phosphoethanolamine, glycerophosphocholine and glycerophosphoethanolamine, whereas phosphatidylcholine and phosphatidylethanolamine levels are maintained to control levels. During re-growth, which remained quantitatively much below control growth, chloroethyle nitrosourea-treated melanoma tumors overexpress phosphocholine and phosphoethanolamine only. In treated melanoma, phosphatidylcholine levels show an inverse relationship with tumor growth rates. In conclusion, chloroethyle nitrosourea-treated melanoma tumors maintain their phosphatidylcholine levels and exhibit transformed phospholipid metabolism phenotype, by mechanisms that could participate in tumor cell survival.

Metabolic syndrome is associated with poor treatment response to antiviral therapy in chronic hepatitis C genotype 3 patients.

Science.gov (United States)

Aziz, Hafsa; Gill, Uzma; Raza, Abida; Gill, Muzaffar L

2014-05-01

Hepatitis C viral (HCV) infection is caused by an RNA virus. HCV infection is considered to induce systemic disease that causes steatosis, alters lipid metabolism, and results in metabolic syndrome. This study aimed to investigate the therapeutic outcome in HCV genotype 3 patients with metabolic syndrome. A total of 621 HCV-positive patients who visited the hospital for treatment were screened. Among these, 441 patients were enrolled for antiviral therapy. These enrolled patients were assessed for metabolic syndrome according to the International Diabetes Federation criteria. Group A included patients with metabolic syndrome and group B included patients without metabolic syndrome. All patients received peginterferon-α2a (180 μg/week) and ribavirin (10 mg/kg/day) for 6 months. The prevalence of metabolic syndrome in chronic HCV patients was 37.9%. We observed that metabolic syndrome was more common among female compared with male participants (43.9 vs. 28.8%, P=0.005). It was found that sustained virologic response (SVR) rates were significantly higher in the patients in group B (without metabolic syndrome) compared with the patients in group A who had metabolic syndrome (72.2 vs. 43.7%, Pmetabolic syndrome and a correlation of metabolic syndrome with nonresponse to antiviral therapy was observed. An interesting correlation among metabolic syndrome, age, and SVR was found: with age, SVR decreases, while metabolic syndrome increases. Metabolic syndrome has an influence on therapeutic outcomes in terms of SVR. Moreover, this information can identify patients who might have a low chance of attaining an SVR and a timely decision may protect the patients from the adverse effects of therapy.

Analysis of protective and cytotoxic immune responses in vivo against metabolically inactivated and untreated cells of a mutagenized tumor line (requirements for tumor immunogenicity)

International Nuclear Information System (INIS)

Wehrmaker, A.; Lehmann, V.; Droege, W.

1986-01-01

The immunogenicity of a mutagenized subline (ESb-D) of the weakly immunogenic T-cell lymphoma L 5178 Y ESb has been characterized. The injection of 10(6) ESb-D cells ip did not establish lethal tumors in untreated DBA/2 mice but established tumors in sublethally irradiated mice. Injection of ESb-D cells into otherwise untreated DBA/2 mice established also a state of protective immunity against the subsequent injection of otherwise lethal doses of ESb tumor cells. Protection was only obtained after injection of intact but not UV-irradiated or mitomycin-C-treated ESb-D cells. A direct T-cell-mediated cytotoxic activity was also demonstrable in the spleen cells of DBA/2 mice after injection of ESb-D cells but not ESb cells. The cytotoxic activity was variant specific for ESb-D target cells, and it was induced only with intact but not UV-irradiated or mitomycin C-treated ESb-D cells. This suggested that the induction of protective and cytotoxic immunity may require the persistence of the antigen or unusually high antigen doses. The in vivo priming for a secondary in vitro cytotoxic response, in contrast, was achieved with intact and also with mitomycin C-treated ESb-D cells but again not with UV-irradiated ESb-D cells. This indicated that the metabolic activity was a minimal requirement for the in vivo immunogenicity of the ESb-D tumor line. The secondary cytotoxic activity was demonstrable on ESb-D and ESb target cells and could be restimulated in vitro about equally well with ESb-D and ESb cells. But the in vivo priming was again only obtained with ESb-D cells and not with ESb cells. These experiments thus demonstrated that the requirements for immunogenicity are more stringent in vivo than in vitro, and more stringent for the induction of direct cytotoxic and protective immunity in vivo than for the in vivo priming for secondary in vitro responses

Acute metabolic and physiologic response of goats to narcosis

Science.gov (United States)

Schatte, C. L.; Bennett, P. B.

1973-01-01

Assessment of the metabolic consequences of exposure to elevated partial pressures of nitrogen and helium under normobaric and hyperbaric conditions in goats. The results include the finding that hyperbaric nitrogen causes and increase in metabolic rate and a general decrease in blood constituent levels which is interpreted as reflecting a shift toward fatty acid metabolism at the expense of carbohydrates. A similar but more pronounced pattern was observed with hyperbaric helium.

Metabolic Profile and Inflammatory Responses in Dairy Cows with Left Displaced Abomasum Kept under Small-Scaled Farm Conditions

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Fenja Klevenhusen

2015-10-01

Full Text Available Left displaced abomasum (LDA is a severe metabolic disease of cattle with a strong negative impact on production efficiency of dairy farms. Metabolic and inflammatory alterations associated with this disease have been reported in earlier studies, conducted mostly in large dairy farms. This research aimed to: (1 evaluate metabolic and inflammatory responses in dairy cows affected by LDA in small-scaled dairy farms; and (2 establish an Animals 2015, 5 1022 association between lactation number and milk production with the outcome of metabolic variables. The cows with LDA had lower serum calcium (Ca, but greater concentrations of non-esterified fatty acids (NEFA and beta-hydroxy-butyrate (BHBA, in particular when lactation number was >2. Cows with LDA showed elevated levels of aspartate aminotransferase, glutamate dehydrogenase, and serum amyloid A (SAA, regardless of lactation number. In addition, this study revealed strong associations between milk yield and the alteration of metabolic profile but not with inflammation in the sick cows. Results indicate metabolic alterations, liver damage, and inflammation in LDA cows kept under small-scale farm conditions. Furthermore, the data suggest exacerbation of metabolic profile and Ca metabolism but not of inflammation and liver health with increasing lactation number and milk yield in cows affected by LDA.

Metabolic Profile and Inflammatory Responses in Dairy Cows with Left Displaced Abomasum Kept under Small-Scaled Farm Conditions.

Science.gov (United States)

Klevenhusen, Fenja; Humer, Elke; Metzler-Zebeli, Barbara; Podstatzky-Lichtenstein, Leopold; Wittek, Thomas; Zebeli, Qendrim

2015-10-13

Left displaced abomasum (LDA) is a severe metabolic disease of cattle with a strong negative impact on production efficiency of dairy farms. Metabolic and inflammatory alterations associated with this disease have been reported in earlier studies, conducted mostly in large dairy farms. This research aimed to: (1) evaluate metabolic and inflammatory responses in dairy cows affected by LDA in small-scaled dairy farms; and (2) establish an Animals 2015, 5 1022 association between lactation number and milk production with the outcome of metabolic variables. The cows with LDA had lower serum calcium (Ca), but greater concentrations of non-esterified fatty acids (NEFA) and beta-hydroxy-butyrate (BHBA), in particular when lactation number was >2. Cows with LDA showed elevated levels of aspartate aminotransferase, glutamate dehydrogenase, and serum amyloid A (SAA), regardless of lactation number. In addition, this study revealed strong associations between milk yield and the alteration of metabolic profile but not with inflammation in the sick cows. Results indicate metabolic alterations, liver damage, and inflammation in LDA cows kept under small-scale farm conditions. Furthermore, the data suggest exacerbation of metabolic profile and Ca metabolism but not of inflammation and liver health with increasing lactation number and milk yield in cows affected by LDA.

Metabolic and Transcriptional Response to Cofactor Perturbations in Escherichia coli

DEFF Research Database (Denmark)

Holm, Anders Koefoed; Blank, L.M.; Oldiges, M.

2010-01-01

Metabolic cofactors such as NADH and ATP play important roles in a large number of cellular reactions, and it is of great interest to dissect the role of these cofactors in different aspects of metabolism. Toward this goal, we overexpressed NADH oxidase and the soluble F1-ATPase in Escherichia coli...... of redox and energy metabolism and should help in developing metabolic engineering strategies in E. coli....

Coordinated and interactive expression of genes of lipid metabolism and inflammation in adipose tissue and liver during metabolic overload.

Directory of Open Access Journals (Sweden)

Wen Liang

Full Text Available BACKGROUND: Chronic metabolic overload results in lipid accumulation and subsequent inflammation in white adipose tissue (WAT, often accompanied by non-alcoholic fatty liver disease (NAFLD. In response to metabolic overload, the expression of genes involved in lipid metabolism and inflammatory processes is adapted. However, it still remains unknown how these adaptations in gene expression in expanding WAT and liver are orchestrated and whether they are interrelated. METHODOLOGY/PRINCIPAL FINDINGS: ApoE*3Leiden mice were fed HFD or chow for different periods up to 12 weeks. Gene expression in WAT and liver over time was evaluated by micro-array analysis. WAT hypertrophy and inflammation were analyzed histologically. Bayesian hierarchical cluster analysis of dynamic WAT gene expression identified groups of genes ('clusters' with comparable expression patterns over time. HFD evoked an immediate response of five clusters of 'lipid metabolism' genes in WAT, which did not further change thereafter. At a later time point (>6 weeks, inflammatory clusters were induced. Promoter analysis of clustered genes resulted in specific key regulators which may orchestrate the metabolic and inflammatory responses in WAT. Some master regulators played a dual role in control of metabolism and inflammation. When WAT inflammation developed (>6 weeks, genes of lipid metabolism and inflammation were also affected in corresponding livers. These hepatic gene expression changes and the underlying transcriptional responses in particular, were remarkably similar to those detected in WAT. CONCLUSION: In WAT, metabolic overload induced an immediate, stable response on clusters of lipid metabolism genes and induced inflammatory genes later in time. Both processes may be controlled and interlinked by specific transcriptional regulators. When WAT inflammation began, the hepatic response to HFD resembled that in WAT. In all, WAT and liver respond to metabolic overload by

Altered drug metabolism during pregnancy: hormonal regulation of drug-metabolizing enzymes.

Science.gov (United States)

Jeong, Hyunyoung

2010-06-01

Medication use during pregnancy is prevalent, but pharmacokinetic information of most drugs used during pregnancy is lacking in spite of known effects of pregnancy on drug disposition. Accurate pharmacokinetic information is essential for optimal drug therapy in mother and fetus. Thus, understanding how pregnancy influences drug disposition is important for better prediction of pharmacokinetic changes of drugs in pregnant women. Pregnancy is known to affect hepatic drug metabolism, but the underlying mechanisms remain unknown. Physiological changes accompanying pregnancy are probably responsible for the reported alteration in drug metabolism during pregnancy. These include elevated concentrations of various hormones such as estrogen, progesterone, placental growth hormones and prolactin. This review covers how these hormones influence expression of drug-metabolizing enzymes (DMEs), thus potentially responsible for altered drug metabolism during pregnancy. The reader will gain a greater understanding of the altered drug metabolism in pregnant women and the regulatory effects of pregnancy hormones on expression of DMEs. In-depth studies in hormonal regulatory mechanisms as well as confirmatory studies in pregnant women are warranted for systematic understanding and prediction of the changes in hepatic drug metabolism during pregnancy.

[Metabolic myopathies].

Science.gov (United States)

Papazian, Óscar; Rivas-Chacón, Rafael

2013-09-06

To review the metabolic myopathies manifested only by crisis of myalgias, cramps and rigidity of the muscles with decreased voluntary contractions and normal inter crisis neurologic examination in children and adolescents. These metabolic myopathies are autosomic recessive inherited enzymatic deficiencies of the carbohydrates and lipids metabolisms. The end result is a reduction of intra muscle adenosine triphosphate, mainly through mitochondrial oxidative phosphorylation, with decrease of available energy for muscle contraction. The one secondary to carbohydrates intra muscle metabolism disorders are triggered by high intensity brief (fatty acids metabolism disorders are triggered by low intensity prolonged (> 10 min) exercises. The conditions in the first group in order of decreasing frequency are the deficiencies of myophosforilase (GSD V), muscle phosphofructokinase (GSD VII), phosphoglycerate mutase 1 (GSD X) and beta enolase (GSD XIII). The conditions in the second group in order of decreasing frequency are the deficiencies of carnitine palmitoyl transferase II and very long chain acyl CoA dehydrogenase. The differential characteristics of patients in each group and within each group will allow to make the initial presumptive clinical diagnosis in the majority and then to order only the necessary tests to achieve the final diagnosis. Treatment during the crisis includes hydration, glucose and alkalinization of urine if myoglobin in blood and urine are elevated. Prevention includes avoiding exercise which may induce the crisis and fasting. The prognosis is good with the exception of rare cases of acute renal failure due to hipermyoglobinemia because of severe rabdomyolisis.

Responses and damages during long-term continuous irradiation in plants

International Nuclear Information System (INIS)

Watanabe, Yoshito

2011-01-01

Effects of long-term continuous irradiation are relevant to studies in radiation ecotoxicology. To investigate plants biological responses to continuous irradiation, we performed metabolome and transcriptome analysis in a model plant, arabidopsis. Comprehensive analysis of primary metabolites using capillary electrophoresis mass spectrometry revealed extensive metabolic changes at early onset of growth inhibition in plants exposed to gamma rays at the dose rate of 20 Gy/day. The changes included elevated levels of B vitamins and second metabolites, commonly responsive to many abiotic and biotic stresses. Responses at early onset of growth inhibition were also observed in the transcriptome analysis using microarray, which showed up-regulation of 55 genes in plants exposed to gamma rays at 20 Gy/day. Although about a half of the up-regulated genes were also responsive just after acute irradiation, the other half was responsive only during long-term continuous irradiation. Database analyses showed that the specifically up-regulated genes to long-term continuous irradiation included genes relating to general stress responses and protein metabolism. The results of these analyses appear to reflect plants responses to progressive radiation damages, from radiation-specific responses, which repair primary DNA damage, to more general stress responses, which maintain homoeostasis against secondary damages. (author)

A single night light exposure acutely alters hormonal and metabolic responses in healthy participants

Directory of Open Access Journals (Sweden)

Mohammed S Albreiki

2017-01-01

Full Text Available Many animal studies have reported an association between melatonin suppression and the disturbance of metabolic responses; yet, few human studies have investigated bright light effects on metabolic and hormonal responses at night. This study investigated the impact of light on plasma hormones and metabolites prior to, and after, an evening meal in healthy participants. Seventeen healthy participants, 8 females (22.2 ± 2.59 years, mean ± s.d. and 9 males (22.8 ± 3.5 years were randomised to a two-way cross-over design protocol; dim light (DL (500 lux sessions, separated by at least seven days. Saliva and plasma samples were collected prior to and after a standard evening meal at specific intervals. Plasma non-esterified fatty acid (NEFA levels were significantly higher pre-meal in DL compared to BL (P < 0.01. Plasma glucose and insulin levels were significantly greater post-meal in the BL compared to DL session (P = 0.02, P = 0.001, respectively. Salivary melatonin levels were significantly higher in the DL compared to those in BL session (P = 0.005. BL at night was associated with significant increases in plasma glucose and insulin suggestive of glucose intolerance and insulin insensitivity. Raised pre-prandial NEFA levels may be due to changes in insulin sensitivity or the presence of melatonin and/or light at night. Plasma triglyceride (TAG levels were the same in both sessions. These results may explain some of the health issues reported in shift workers; however, further studies are needed to elucidate the cause of these metabolic changes.

Can narrow-bandwidth light from UV-A to green alter secondary plant metabolism and increase Brassica plant defenses against aphids?

Science.gov (United States)

Neugart, Susanne; Schreiner, Monika; Wu, Sasa; Poehling, Hans-Michael

2017-01-01

Light of different wavelengths is essential for plant growth and development. Short-wavelength radiation such as UV can shift the composition of flavonoids, glucosinolates, and other plant metabolites responsible for enhanced defense against certain herbivorous insects. The intensity of light-induced, metabolite-based resistance is plant- and insect species-specific and depends on herbivore feeding guild and specialization. The increasing use of light-emitting diodes (LEDs) in horticultural plant production systems in protected environments enables the creation of tailor-made light scenarios for improved plant cultivation and induced defense against herbivorous insects. In this study, broccoli (Brassica oleracea var. italica) plants were grown in a climate chamber under broad spectra photosynthetic active radiation (PAR) and were additionally treated with the following narrow-bandwidth light generated with LEDs: UV-A (365 nm), violet (420 nm), blue (470 nm), or green (515 nm). We determined the influence of narrow-bandwidth light on broccoli plant growth, secondary plant metabolism (flavonol glycosides and glucosinolates), and plant-mediated light effects on the performance and behavior of the specialized cabbage aphid Brevicoryne brassicae. Green light increased plant height more than UV-A, violet, or blue LED treatments. Among flavonol glycosides, specific quercetin and kaempferol glycosides were increased under violet light. The concentration of 3-indolylmethyl glucosinolate in plants was increased by UV-A treatment. B. brassicae performance was not influenced by the different light qualities, but in host-choice tests, B. brassicae preferred previously blue-illuminated plants (but not UV-A-, violet-, or green-illuminated plants) over control plants. PMID:29190278

Can narrow-bandwidth light from UV-A to green alter secondary plant metabolism and increase Brassica plant defenses against aphids?

Directory of Open Access Journals (Sweden)

Ole Rechner

Full Text Available Light of different wavelengths is essential for plant growth and development. Short-wavelength radiation such as UV can shift the composition of flavonoids, glucosinolates, and other plant metabolites responsible for enhanced defense against certain herbivorous insects. The intensity of light-induced, metabolite-based resistance is plant- and insect species-specific and depends on herbivore feeding guild and specialization. The increasing use of light-emitting diodes (LEDs in horticultural plant production systems in protected environments enables the creation of tailor-made light scenarios for improved plant cultivation and induced defense against herbivorous insects. In this study, broccoli (Brassica oleracea var. italica plants were grown in a climate chamber under broad spectra photosynthetic active radiation (PAR and were additionally treated with the following narrow-bandwidth light generated with LEDs: UV-A (365 nm, violet (420 nm, blue (470 nm, or green (515 nm. We determined the influence of narrow-bandwidth light on broccoli plant growth, secondary plant metabolism (flavonol glycosides and glucosinolates, and plant-mediated light effects on the performance and behavior of the specialized cabbage aphid Brevicoryne brassicae. Green light increased plant height more than UV-A, violet, or blue LED treatments. Among flavonol glycosides, specific quercetin and kaempferol glycosides were increased under violet light. The concentration of 3-indolylmethyl glucosinolate in plants was increased by UV-A treatment. B. brassicae performance was not influenced by the different light qualities, but in host-choice tests, B. brassicae preferred previously blue-illuminated plants (but not UV-A-, violet-, or green-illuminated plants over control plants.

Waterborne cadmium and nickel impact oxidative stress responses and retinoid metabolism in yellow perch

International Nuclear Information System (INIS)

Defo, Michel A.; Bernatchez, Louis; Campbell, Peter G.C.; Couture, Patrice

2014-01-01

Highlights: • Cd and Ni affected indicators of retinoid metabolism and oxidative stress in fish. • Liver rdh-2 transcription levels increase in fish exposed to waterborne Cd. • Liver REH and LdRAT activities increase with increasing kidney Cd concentration. • Changes at molecular levels do not always mean changes at the functional levels. • Multi-level biological approaches are needed when assessing fish metal toxicology. - Abstract: In this experiment, we studied the transcriptional and functional (enzymatic) responses of yellow perch (Perca flavescens) to metal stress, with a focus on oxidative stress and vitamin A metabolism. Juvenile yellow perch were exposed to two environmentally relevant concentrations of waterborne cadmium (Cd) and nickel (Ni) for a period of 6 weeks. Kidney Cd and Ni bioaccumulation significantly increased with increasing metal exposure. The major retinoid metabolites analyzed in liver and muscle decreased with metal exposure except at high Cd exposure where no variation was reported in liver. A decrease in free plasma dehydroretinol was also observed with metal exposure. In the liver of Cd-exposed fish, both epidermal retinol dehydrogenase 2 transcription level and corresponding enzyme activities retinyl ester hydrolase and lecithin dehydroretinyl acyl transferase increased. In contrast, muscle epidermal retinol dehydrogenase 2 transcription level decreased with Cd exposure. Among antioxidant defences, liver transcription levels of catalase, microsomal glutathione-S-transferase-3 and glucose-6-phosphate dehydrogenase were generally enhanced in Cd-exposed fish and this up-regulation was accompanied by an increase in the activities of corresponding enzymes, except for microsomal glutathione-S-transferase. No consistent pattern in antioxidant defence responses was observed between molecular and biochemical response when fish were exposed to Ni, suggesting a non-synchronous response of antioxidant defence in fish exposed to

Waterborne cadmium and nickel impact oxidative stress responses and retinoid metabolism in yellow perch

Energy Technology Data Exchange (ETDEWEB)

Defo, Michel A. [Institut national de la recherche scientifique (INRS), Centre Eau Terre Environnement, 490 de la Couronne, Québec, Québec G1K 9A9 (Canada); Bernatchez, Louis [Institut de Biologie Intégrative et des Systèmes (IBIS), Université Laval, Québec, Québec G1V 0A6 (Canada); Campbell, Peter G.C. [Institut national de la recherche scientifique (INRS), Centre Eau Terre Environnement, 490 de la Couronne, Québec, Québec G1K 9A9 (Canada); Couture, Patrice, E-mail: patrice.couture@ete.inrs.ca [Institut national de la recherche scientifique (INRS), Centre Eau Terre Environnement, 490 de la Couronne, Québec, Québec G1K 9A9 (Canada)

2014-09-15

Highlights: • Cd and Ni affected indicators of retinoid metabolism and oxidative stress in fish. • Liver rdh-2 transcription levels increase in fish exposed to waterborne Cd. • Liver REH and LdRAT activities increase with increasing kidney Cd concentration. • Changes at molecular levels do not always mean changes at the functional levels. • Multi-level biological approaches are needed when assessing fish metal toxicology. - Abstract: In this experiment, we studied the transcriptional and functional (enzymatic) responses of yellow perch (Perca flavescens) to metal stress, with a focus on oxidative stress and vitamin A metabolism. Juvenile yellow perch were exposed to two environmentally relevant concentrations of waterborne cadmium (Cd) and nickel (Ni) for a period of 6 weeks. Kidney Cd and Ni bioaccumulation significantly increased with increasing metal exposure. The major retinoid metabolites analyzed in liver and muscle decreased with metal exposure except at high Cd exposure where no variation was reported in liver. A decrease in free plasma dehydroretinol was also observed with metal exposure. In the liver of Cd-exposed fish, both epidermal retinol dehydrogenase 2 transcription level and corresponding enzyme activities retinyl ester hydrolase and lecithin dehydroretinyl acyl transferase increased. In contrast, muscle epidermal retinol dehydrogenase 2 transcription level decreased with Cd exposure. Among antioxidant defences, liver transcription levels of catalase, microsomal glutathione-S-transferase-3 and glucose-6-phosphate dehydrogenase were generally enhanced in Cd-exposed fish and this up-regulation was accompanied by an increase in the activities of corresponding enzymes, except for microsomal glutathione-S-transferase. No consistent pattern in antioxidant defence responses was observed between molecular and biochemical response when fish were exposed to Ni, suggesting a non-synchronous response of antioxidant defence in fish exposed to

Molecular mechanisms of plant response to ionising radiation. Exploration of the glucosinolate role in the anti-oxidative response

International Nuclear Information System (INIS)

Gicquel, M.

2012-01-01

Terrestrial organisms are exposed to low doses of ionising radiation from natural or anthropogenic sources. The major effects of the radiations are due to DNA deterioration and water radiolysis which generates an oxidative stress by free radical production. Plants constitute good models to study the effects of ionising radiations and the search of antioxidant molecules because of their important secondary metabolism. Thus this thesis, funded by the Brittany region, characterized the physiological and molecular response of the model plant Arabidopsis thaliana to low (10 Gy) and moderate (40 Gy) doses of ionising radiation, and was therefore interested in glucosinolates, characteristic compounds of the Brassicaceae family. The global proteomic and transcriptomic studies carried out on this model revealed (1) a common response for both doses dealing with the activation of DNA repair mechanisms, cell cycle regulation and protection of cellular structures; (2) an adjustment of the energetic metabolism and an activation of secondary compounds biosynthesis (i.e. glucosinolates and flavonoids) after the 10 Gy dose; (3) an induction of enzymatic control of ROS, the regulation of cellular components recycling and of programmed cell death after the 40 Gy dose. The potential anti-oxidative role of glucosinolates was then explored. The in vitro anti-oxidative power of some glucosinolates and their derivative products were demonstrated. Their modulating effects against irradiation-induced damages were then tested in vivo by simple experimental approaches. The importance of the glucosinolate level to give a positive or negative effect was demonstrated. (author)

Increased response to insulin of glucose metabolism in the 6-day unloaded rat soleus muscle

Science.gov (United States)

Henriksen, Erik J.; Tischler, Marc E.; Johnson, David G.

1986-01-01

Hind leg muscles of female rats were unloaded by tail cast suspension for 6 days. In the fresh-frozen unloaded soleus, the significantly greater concentration of glycogen correlated with a lower activity ratio of glycogen phosphorylase (p less than 0.02). The activity ratio of glycogen synthase also was lower (p less than 0.001), possibly due to the higher concentration of glycogen. In isolated unloaded soleus, insulin (0.1 milliunit/ml) increased the oxidation of D(U-C-14) glucose, release of lactate and pyruvate, incorporation of D-(U-C-14) glucose into glycogen, and the concentration of glucose 6-phosphate more (p less than 0.05) than in the weight-bearing soleus. At physiological doses of insulin, the percent of maximal uptake of 2-deoxy-D-(1,2-H-3) glucose/muscle also was greater in the unloaded soleus. Unloading of the soleus increased, by 50 percent the concentration of insuling receptors, due to no decrease in total receptor number during muscle atrophy. This increase may account for the greater response of glucose metabolism to insulin in this muscle. The extensor digitorum longus, which generally shows little response to unloading, displayed no differential response of glucose metabolism to insulin.

The metabolic syndrome in long-term cancer survivors, an important target for secondary preventive measures

NARCIS (Netherlands)

Nuver, J; Smit, AJ; Postma, A; Sleijfer, DT; Gietema, JA

With increasing numbers of cancer survivors, attention has been drawn to long-term complications of curative cancer treatment, including a range of metabolic disorders. These metabolic disorders often resemble the components of the so-called metabolic syndrome, or syndrome X, which is an important

Investigations into the influence of airborne pollutants on the metabolism of secondary phenolic substances and amino acids. Untersuchungen ueber den Einfluss von Luftschadstoffen auf den Stoffwechsel von phenolischen Sekundaerstoffen und Aminosaeuren

Energy Technology Data Exchange (ETDEWEB)

Strack, D.

1988-10-01

Quantitative analyses of secondary phenols, free amino acids, and of the enzyme activities arginase and asparaginase were carried out on spruce needles from six different forest sites in North-Rhine Westphalia. In addition, the effects of ozone on spruce aged seven to eight years were investigated. The aim of this was to find out whether there is a correlation between the phenol and amino acid metabolism and the damage rate in older spruce (31 to 60 years) and in younger spruce exposed to ozone. No correlation could be established with a single exception: In one site, the free amino acid pattern showed a 10-fold increase of arginine and an accumulation of ornithine and lysine. This indicates a disturbed nitrogen metabolism, in particular a stimulation of the urea cycle, which may be caused by anthropogenic over fertilizing with nitrogen. The findings for the spruce exposed to ozone indicate a more complex effect on the needle metabolism, which affects both the phenol metabolism (strong decrease of the catechine concentration) and the amino acid metabolism (increase of the alanine concentration). This may be caused by damaged membranes (i.e. higher permeability accompanied by sensitive changes in the metabolic compartmenting) or by a potential increase of transaminase activities. (orig./MG).

Physiological and metabolic changes of purslane (Portulaca oleracea L. in response to drought, heat and combined stresses

Directory of Open Access Journals (Sweden)

Rui eJin

2016-01-01

Full Text Available Purslane (Portulaca oleracea L. is a fleshy herbaceous plant. So far, little information is available on the response of this plant to combined drought and heat stress. In this study, changes in physiological and metabolic levels were characterized after treatments with drought, heat and combined stresses. Both individual and combined stress treatments increased malondialdehyde (MDA, electrolyte leakage (EL, O2•− and activities of superoxide dismutase (SOD, peroxidase (POD, while declined chlorophyll content. No significant differences were found between control and treatments in leaf water content (LWC and catalase (CAT activity. Additionally, 37 metabolic compounds were detected in purslane. Through pathway analysis, 17 metabolites were directly involved in the glycolysis metabolic pathway. The present study indicated that combined drought and heat stress caused more serious damage in purslane than individual stress. To survive, purslane has a high capability to cope with environmental stress conditions through activation of physiological and metabolic pathways.

Physiological and Metabolic Changes of Purslane (Portulaca oleracea L.) in Response to Drought, Heat, and Combined Stresses

Science.gov (United States)

Jin, Rui; Wang, Yanping; Liu, Ruijie; Gou, Junbo; Chan, Zhulong

2016-01-01

Purslane (Portulaca oleracea L.) is a fleshy herbaceous plant. So far, little information is available on the response of this plant to combined drought and heat stress. In this study, changes in physiological and metabolic levels were characterized after treatments with drought, heat and combined stresses. Both individual and combined stress treatments increased malondialdehyde (MDA), electrolyte leakage (EL), O2•− and activities of superoxide dismutase (SOD), peroxidase (POD), while declined chlorophyll content. No significant differences were found between control and treatments in leaf water content (LWC) and catalase (CAT) activity. Additionally, 37 metabolic compounds were detected in purslane. Through pathway analysis, 17 metabolites were directly involved in the glycolysis metabolic pathway. The present study indicated that combined drought and heat stress caused more serious damage in purslane than individual stress. To survive, purslane has a high capability to cope with environmental stress conditions through activation of physiological and metabolic pathways. PMID:26779204

Transcriptional, proteomic, and metabolic responses to lithium in galactose-grown yeast cells

DEFF Research Database (Denmark)

Bro, Christoffer; Regenberg, Birgitte; Lagniel, G.

2003-01-01

Lithium is highly toxic to yeast when grown in galactose medium mainly because phosphoglucomutase, a key enzyme of galactose metabolism, is inhibited. We studied the global protein and gene expression profiles of Saccharomyces cerevisiae grown in galactose in different time intervals after addition...... of lithium. These results were related to physiological studies where both secreted and intracellular metabolites were determined. Microarray analysis showed that 664 open reading frames were down-regulated and 725 up-regulated in response to addition of lithium. Genes involved in transcription, translation......-regulated proteins were also identified as being changed on the mRNA level. Functional clusters obtained from proteome data were coincident with transcriptional clusters. Physiological studies showed that acetate, glycerol, and glycogen accumulate in response to lithium, as reflected in expression data, whereas...

[The participation of ethanol in induction of carbohydrates metabolism disturbances].

Science.gov (United States)

Orywal, Karolina; Jelski, Wojciech; Szmitkowski, Maciej

2009-07-01

Alcohol and products of its metabolism lead to impairment of many organs functions, what cause systemic and local carbohydrates metabolism disturbances. Abusing of alcohol induces changes in pancreatic digestive enzymes secretion, what contributes to development of chronic alcoholic pancreatitis. Alcohol can cause secondary diabetes, what is result of pancreatic beta-cells damage and is a risk factor for type 2 diabetes. Alcohol cause liver cells degeneration and induction of many metabolic disturbances especially carbohydrates.

Stress hormone release is a key component of the metabolic response to lipopolysaccharide (LPS): studies in hypopituitary and healthy subjects

DEFF Research Database (Denmark)

Bach, Ermina; Møller, Andreas Buch; Jørgensen, Jens Otto Lunde

2016-01-01

OBJECTIVE: Lipopolysaccharide (LPS) generates acute and chronic inflammatory and metabolic responses during acute illness and in the pathogenesis of the metabolic syndrome, type 2 diabetes and cardiovascular disease, but it is unclear whether these responses depend on intact pituitary release...... but not in HP. LPS increased whole body palmitate fluxes (3-fold) and decreased palmitate specific activity 40-50 % in CTR, but not in HP. G(0)/G(1) Switch Gene 2 (G0S2 - an inhibitor of lipolysis) adipose tissue mRNA was decreased in CTR. LPS increased phenylalanine fluxes significantly more in CTR, whereas...

Analysis of requirements for teaching materials based on the course bioinformatics for plant metabolism

Science.gov (United States)

Balqis, Widodo, Lukiati, Betty; Amin, Mohamad

2017-05-01

A way to improve the quality of learning in the course of Plant Metabolism in the Department of Biology, State University of Malang, is to develop teaching materials. This research evaluates the needs of bioinformatics-based teaching material in the course Plant Metabolism by the Analyze, Design, Develop, Implement, and Evaluate (ADDIE) development model. Data were collected through questionnaires distributed to the students in the Plant Metabolism course of the Department of Biology, University of Malang, and analysis of the plan of lectures semester (RPS). Learning gains of this course show that it is not yet integrated into the field of bioinformatics. All respondents stated that plant metabolism books do not include bioinformatics and fail to explain the metabolism of a chemical compound of a local plant in Indonesia. Respondents thought that bioinformatics can explain examples and metabolism of a secondary metabolite analysis techniques and discuss potential medicinal compounds from local plants. As many as 65% of the respondents said that the existing metabolism book could not be used to understand secondary metabolism in lectures of plant metabolism. Therefore, the development of teaching materials including plant metabolism-based bioinformatics is important to improve the understanding of the lecture material in plant metabolism.

Affordances of the Cultural Inquiry Process in Building Secondary Mathematics Teachers' Capacity for Cultural Responsiveness

Science.gov (United States)

Parker, Frieda; Bartell, Tonya; Novak, Jodie D.

2017-01-01

Over the last couple of decades, there has been a growing call for teachers to become more responsive to the increasing cultural diversity of students as a means of improving students' experiences in school and their learning outcomes. Challenges exist in working with secondary mathematics teachers due to the common belief that math is…

The metabolic syndrome and related characteristics in major depression: inpatients and outpatients compared metabolic differences across treatment settings

NARCIS (Netherlands)

Luppino, F.S.; Bouvy, P.F.; Giltay, E.J.; Penninx, B.W.J.H.; Zitman, F. G.

2014-01-01

Objective: We aimed to systematically compare patients with major depressive disorder from three different treatment settings (a primary care outpatient, a secondary care outpatient and one inpatient sample), with regard to metabolic syndrome (MetSyn) prevalences, individual MetSyn components and

The metabolic syndrome and related characteristics in major depression : inpatients and outpatients compared Metabolic differences across treatment settings

NARCIS (Netherlands)

Luppino, Floriana S.; Bouvy, Paul F.; Giltay, Erik J.; Penninx, Brenda W. J. H.; Zitman, Frans G.

Objective: We aimed to systematically compare patients with major depressive disorder from three different treatment settings (a primary care outpatient, a secondary care outpatient and one inpatient sample), with regard to metabolic syndrome (MetSyn) prevalences, individual MetSyn components and

Response of lactate metabolism in brain glucosensing areas of rainbow trout (Oncorhynchus mykiss) to changes in glucose levels.

Science.gov (United States)

Otero-Rodiño, Cristina; Librán-Pérez, Marta; Velasco, Cristina; Álvarez-Otero, Rosa; López-Patiño, Marcos A; Míguez, Jesús M; Soengas, José L

2015-12-01

There is no evidence in fish brain demonstrating the existence of changes in lactate metabolism in response to alterations in glucose levels. We induced in rainbow trout through intraperitoneal (IP) treatments, hypoglycaemic or hyperglycaemic changes to assess the response of parameters involved in lactate metabolism in glucosensing areas like hypothalamus and hindbrain. To distinguish those effects from those induced by peripheral changes in the levels of metabolites or hormones, we also carried out intracerebroventricular (ICV) treatments with 2-deoxy-D-glucose (2-DG, a non-metabolizable glucose analogue thus inducing local glucopenia) or glucose. Finally, we also incubated hypothalamus and hindbrain in vitro in the presence of increased glucose concentrations. The changes in glucose availability were in general correlated to changes in the amount of lactate in both areas. However, when we assessed in these areas the response of parameters related to lactate metabolism, the results obtained were contradictory. The increase in glucose levels did not produce in general the expected changes in those pathways with only a minor increase in their capacity of lactate production. The decrease in glucose levels was, however, more clearly related to a decreased capacity of the pathways involved in the production and use of lactate, and this was especially evident after ICV treatment with 2-DG in both areas. In conclusion, the present results while addressing the existence of changes in lactate metabolism after inducing changes in glucose levels in brain glucosensing areas only partially support the possible existence of an astrocyte-neuron lactate shuttle in hypothalamus and hindbrain of rainbow trout relating glucose availability to lactate production and use.

Towards systems metabolic engineering of streptomycetes for secondary metabolites production

DEFF Research Database (Denmark)

Robertsen, Helene Lunde; Weber, Tilmann; Kim, Hyun Uk

2017-01-01

Streptomycetes are known for their inherent ability to produce pharmaceutically relevant secondary metabolites. Discovery of medically useful, yet novel compounds has become a great challenge due to frequent rediscovery of known compounds and a consequent decline in the number of relevant clinical...

Multicompartmental nontargeted LC-MS metabolomics: explorative study on the metabolic responses of rye fiber versus refined wheat fiber intake in plasma and urine of hypercholesterolemic pigs

DEFF Research Database (Denmark)

Nørskov, Natalja; Hedemann, Mette Skou; Lærke, Helle Nygaard

2013-01-01

A multicompartmental nontargeted LC–MS metabolomics approach was used to study the metabolic responses on plasma and urine of hypercholesterolemic pigs after consumption of diets with contrasting dietary fiber composition (whole grain rye with added rye bran versus refined wheat). To study...... the metabolic responses, we performed a supervised multivariate data analyses used for pattern recognition, which revealed marked effects of the diets on both plasma and urine metabolic profiles. Diverse pools of metabolites were responsible for the discrimination between the diets. Elevated levels of phenolic...... compounds and dicarboxylic acids were detected in urine of pigs after rye consumption compared to refined wheat. Furthermore, consumption of rye was characterized by lower levels of linoleic acid derived oxylipins and cholesterol in the plasma metabolic profiles. These results indicate that higher...

Adaptive responses to cefotaxime treatment in ESBL-producing Escherichia coli and the possible use of significantly regulated pathways as novel secondary targets

DEFF Research Database (Denmark)

Møller, Thea S. B.; Rau, Martin Holm; Bonde, Charlotte S

2016-01-01

The aim of the study was to determine how ESBL-producing Escherichia coli change the expression of metabolic and biosynthesis genes when adapting to inhibitory concentrations of cefotaxime. Secondly, it was investigated whether significantly regulated pathways constitute putative secondary targets......-fold). Inhibition and/or mutations in other genes that were significantly regulated, belonging to energy synthesis, purine synthesis, proline uptake or potassium uptake, also rendered the resistant bacteria more susceptible to cefotaxime. The results show that ESBL-producing E. coli adapt to treatment...

Genome-Wide Identification of MicroRNAs in Response to Cadmium Stress in Oilseed Rape (Brassica napus L. Using High-Throughput Sequencing

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Hongju Jian

2018-05-01

Full Text Available MicroRNAs (miRNAs have important roles in regulating stress-response genes in plants. However, identification of miRNAs and the corresponding target genes that are induced in response to cadmium (Cd stress in Brassica napus remains limited. In the current study, we sequenced three small-RNA libraries from B. napus after 0 days, 1 days, and 3 days of Cd treatment. In total, 44 known miRNAs (belonging to 27 families and 103 novel miRNAs were identified. A comprehensive analysis of miRNA expression profiles found 39 differentially expressed miRNAs between control and Cd-treated plants; 13 differentially expressed miRNAs were confirmed by qRT-PCR. Characterization of the corresponding target genes indicated functions in processes including transcription factor regulation, biotic stress response, ion homeostasis, and secondary metabolism. Furthermore, we propose a hypothetical model of the Cd-response mechanism in B. napus. Combined with qRT-PCR confirmation, our data suggested that miRNAs were involved in the regulations of TFs, biotic stress defense, ion homeostasis and secondary metabolism synthesis to respond Cd stress in B. napus.

Seaweed supplements normalise metabolic, cardiovascular and liver responses in high-carbohydrate, high-fat fed rats.

Science.gov (United States)

Kumar, Senthil Arun; Magnusson, Marie; Ward, Leigh C; Paul, Nicholas A; Brown, Lindsay

2015-02-02

Increased seaweed consumption may be linked to the lower incidence of metabolic syndrome in eastern Asia. This study investigated the responses to two tropical green seaweeds, Ulva ohnoi (UO) and Derbesia tenuissima (DT), in a rat model of human metabolic syndrome. Male Wistar rats (330-340 g) were fed either a corn starch-rich diet or a high-carbohydrate, high-fat diet with 25% fructose in drinking water, for 16 weeks. High-carbohydrate, high-fat diet-fed rats showed the signs of metabolic syndrome leading to abdominal obesity, cardiovascular remodelling and non-alcoholic fatty liver disease. Food was supplemented with 5% dried UO or DT for the final 8 weeks only. UO lowered total final body fat mass by 24%, systolic blood pressure by 29 mmHg, and improved glucose utilisation and insulin sensitivity. In contrast, DT did not change total body fat mass but decreased plasma triglycerides by 38% and total cholesterol by 17%. UO contained 18.1% soluble fibre as part of 40.9% total fibre, and increased magnesium, while DT contained 23.4% total fibre, essentially as insoluble fibre. UO was more effective in reducing metabolic syndrome than DT, possibly due to the increased intake of soluble fibre and magnesium.

Seaweed Supplements Normalise Metabolic, Cardiovascular and Liver Responses in High-Carbohydrate, High-Fat Fed Rats

Directory of Open Access Journals (Sweden)

Senthil Arun Kumar

2015-02-01

Full Text Available Increased seaweed consumption may be linked to the lower incidence of metabolic syndrome in eastern Asia. This study investigated the responses to two tropical green seaweeds, Ulva ohnoi (UO and Derbesia tenuissima (DT, in a rat model of human metabolic syndrome. Male Wistar rats (330–340 g were fed either a corn starch-rich diet or a high-carbohydrate, high-fat diet with 25% fructose in drinking water, for 16 weeks. High-carbohydrate, high-fat diet-fed rats showed the signs of metabolic syndrome leading to abdominal obesity, cardiovascular remodelling and non-alcoholic fatty liver disease. Food was supplemented with 5% dried UO or DT for the final 8 weeks only. UO lowered total final body fat mass by 24%, systolic blood pressure by 29 mmHg, and improved glucose utilisation and insulin sensitivity. In contrast, DT did not change total body fat mass but decreased plasma triglycerides by 38% and total cholesterol by 17%. UO contained 18.1% soluble fibre as part of 40.9% total fibre, and increased magnesium, while DT contained 23.4% total fibre, essentially as insoluble fibre. UO was more effective in reducing metabolic syndrome than DT, possibly due to the increased intake of soluble fibre and magnesium.

Seaweed Supplements Normalise Metabolic, Cardiovascular and Liver Responses in High-Carbohydrate, High-Fat Fed Rats

Science.gov (United States)

Kumar, Senthil Arun; Magnusson, Marie; Ward, Leigh C.; Paul, Nicholas A.; Brown, Lindsay

2015-01-01

Increased seaweed consumption may be linked to the lower incidence of metabolic syndrome in eastern Asia. This study investigated the responses to two tropical green seaweeds, Ulva ohnoi (UO) and Derbesia tenuissima (DT), in a rat model of human metabolic syndrome. Male Wistar rats (330–340 g) were fed either a corn starch-rich diet or a high-carbohydrate, high-fat diet with 25% fructose in drinking water, for 16 weeks. High-carbohydrate, high-fat diet-fed rats showed the signs of metabolic syndrome leading to abdominal obesity, cardiovascular remodelling and non-alcoholic fatty liver disease. Food was supplemented with 5% dried UO or DT for the final 8 weeks only. UO lowered total final body fat mass by 24%, systolic blood pressure by 29 mmHg, and improved glucose utilisation and insulin sensitivity. In contrast, DT did not change total body fat mass but decreased plasma triglycerides by 38% and total cholesterol by 17%. UO contained 18.1% soluble fibre as part of 40.9% total fibre, and increased magnesium, while DT contained 23.4% total fibre, essentially as insoluble fibre. UO was more effective in reducing metabolic syndrome than DT, possibly due to the increased intake of soluble fibre and magnesium. PMID:25648511

Uncooked rice of relatively low gelatinization degree resulted in lower metabolic glucose and insulin responses compared with cooked rice in female college students.

Science.gov (United States)

Jung, Eun Young; Suh, Hyung Joo; Hong, Wan Soo; Kim, Dong Geon; Hong, Yang Hee; Hong, In Sun; Chang, Un Jae

2009-07-01

Cooking processes that gelatinize granules or disrupt structure might increase the glucose and insulin responses because a disruption of the structure of starch by gelatinization increases its availability for digestion and absorption in the small intestine. We hypothesized that the uncooked form of rice, which has a relatively low degree of gelatinization even though in powder form, would result in lower metabolic glucose and insulin responses compared with cooked rice (CR). To assess the effects of the gelatinization of rice on metabolic response of glucose and insulin, we investigated the glucose and insulin responses to 3 rice meals of different gelatinization degree in female college students (n = 12): CR (76.9% gelatinized), uncooked rice powder (UP; 3.5% gelatinized), and uncooked freeze-dried rice powder (UFP; 5.4% gelatinized). Uncooked rice powders (UP and UFP) induced lower glucose and insulin responses compared with CR. The relatively low gelatinization degree of UPs resulted in low metabolic responses in terms of the glycemic index (CR: 72.4% vs UP: 49.7%, UFP: 59.8%) and insulin index (CR: 94.8% vs UP: 74.4%, UFP: 68.0%). In summary, UPs that were less gelatinized than CR induced low postprandial glucose and insulin responses.

Measuring general and specific stress causes and stress responses among beginning secondary school teachers in the Netherlands

NARCIS (Netherlands)

Harmsen, R; Helms-Lorenz, M.; Maulana, R; van Veen, K; van Veldhoven, M.J.P.M.

2018-01-01

The main aim of this study was to adjust the Questionnaire on the Experience and Evaluation of Work (QEEW) in order to measure stress causes and stress responses of beginning secondary school teachers in the Netherlands. First, the suitability of the original QEEW stress scales for use in the

Systemic responses to inhaled ozone in mice: cachexia and down-regulation of liver xenobiotic metabolizing genes

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Last, Jerold A [Pulmonary and Critical Care Medicine, School of Medicine, Toxic Substances Program, 1131 Surge I, University of California, Davis, CA 95616-8723 (United States); Gohil, Kishorchandra [Pulmonary and Critical Care Medicine, School of Medicine, Toxic Substances Program, 1131 Surge I, University of California, Davis, CA 95616-8723 (United States); Mathrani, Vivek C [Pulmonary and Critical Care Medicine, School of Medicine, Toxic Substances Program, 1131 Surge I, University of California, Davis, CA 95616-8723 (United States); Kenyon, Nicholas J [Pulmonary and Critical Care Medicine, School of Medicine, Toxic Substances Program, 1131 Surge I, University of California, Davis, CA 95616-8723 (United States)

2005-10-15

Rats or mice acutely exposed to high concentrations of ozone show an immediate and significant weight loss, even when allowed free access to food and water. The mechanisms underlying this systemic response to ozone have not been previously elucidated. We have applied the technique of global gene expression analysis to the livers of C57BL mice acutely exposed to ozone. Mice lost up to 14% of their original body weight, with a 42% decrease in total food consumption. We previously had found significant up-regulation of genes encoding proliferative enzymes, proteins related to acute phase reactions and cytoskeletal functions, and other biomarkers of a cachexia-like inflammatory state in lungs of mice exposed to ozone. These results are consistent with a general up-regulation of different gene families responsive to NF-{kappa}B in the lungs of the exposed mice. In the present study, we observed significant down-regulation of different families of mRNAs in the livers of the exposed mice, including genes related to lipid and fatty acid metabolism, and to carbohydrate metabolism in this tissue, consistent with a systemic cachexic response. Several interferon-dependent genes were down-regulated in the liver, suggesting a possible role for interferon as a signaling molecule between lung and liver. In addition, transcription of several mRNAs encoding enzymes of xenobiotic metabolism in the livers of mice exposed to ozone was decreased, suggesting cytokine-mediated suppression of cytochrome P450 expression. This finding may explain a previously controversial report from other investigators more than 20 years ago of prolongation of pentobarbital sleeping time in mice exposed to ozone.

Systemic responses to inhaled ozone in mice: cachexia and down-regulation of liver xenobiotic metabolizing genes

International Nuclear Information System (INIS)

Last, Jerold A.; Gohil, Kishorchandra; Mathrani, Vivek C.; Kenyon, Nicholas J.

2005-01-01

Rats or mice acutely exposed to high concentrations of ozone show an immediate and significant weight loss, even when allowed free access to food and water. The mechanisms underlying this systemic response to ozone have not been previously elucidated. We have applied the technique of global gene expression analysis to the livers of C57BL mice acutely exposed to ozone. Mice lost up to 14% of their original body weight, with a 42% decrease in total food consumption. We previously had found significant up-regulation of genes encoding proliferative enzymes, proteins related to acute phase reactions and cytoskeletal functions, and other biomarkers of a cachexia-like inflammatory state in lungs of mice exposed to ozone. These results are consistent with a general up-regulation of different gene families responsive to NF-κB in the lungs of the exposed mice. In the present study, we observed significant down-regulation of different families of mRNAs in the livers of the exposed mice, including genes related to lipid and fatty acid metabolism, and to carbohydrate metabolism in this tissue, consistent with a systemic cachexic response. Several interferon-dependent genes were down-regulated in the liver, suggesting a possible role for interferon as a signaling molecule between lung and liver. In addition, transcription of several mRNAs encoding enzymes of xenobiotic metabolism in the livers of mice exposed to ozone was decreased, suggesting cytokine-mediated suppression of cytochrome P450 expression. This finding may explain a previously controversial report from other investigators more than 20 years ago of prolongation of pentobarbital sleeping time in mice exposed to ozone

Metabolic Response on Post-therapy FDG-PET Predicts Patterns of Failure After Radiotherapy for Cervical Cancer

International Nuclear Information System (INIS)

Schwarz, Julie K.; Siegel, Barry A.; Dehdashti, Farrokh; Grigsby, Perry W.

2012-01-01

Purpose: To determine the patterns of failure in patients with cervical cancer treated with definitive radiotherapy and evaluated for metabolic response with early posttherapy 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET). Methods and Materials: The records of 238 patients with cervical cancer were reviewed. All patients were treated with a combination of external radiotherapy and intracavitary brachytherapy. Two hundred and nineteen patients (92%) received concurrent chemotherapy. All patients underwent pretreatment FDG-PET, and posttherapy FDG-PET was performed within 8–16 weeks of the completion of radiotherapy. Posttherapy FDG-PET results were categorized as complete metabolic response (CMR), partial metabolic response (PMR), and progressive disease (PD). Failure patterns were categorized as none, isolated local failure (central pelvis ± pelvic lymph nodes), distant failure, or combined local plus distant failure. Results: Of the 91 patients (38%) who had a recurrence, 22 had isolated local failures, and 69 had distant failures (49 distant failures and 20 combined local plus distant failures). Of the 173 patients with a CMR, 40 (23%) experienced treatment failure. All 25 patients with PD experienced treatment failure, which was distant in 24 patients (96%). Among the 40 patients with PMR, no failure has been observed for 14 patients (35%). Of the 26 failures within the PMR group, 15 (58%) were limited to the pelvis. Differences in the patterns of failure between the three groups (CMR, PMR, PD) were statistically significant (chi-square test; p < 0.0001). Conclusions: The majority of failures after definitive radiotherapy for cervical cancer include distant failures, even in the setting of concurrent chemotherapy. PMR within the cervix or lymph nodes is more commonly associated with isolated local recurrence.

The effects of handling and anesthetic agents on the stress response and carbohydrate metabolism in northern elephant seals.

Directory of Open Access Journals (Sweden)

Cory D Champagne

Full Text Available Free-ranging animals often cope with fluctuating environmental conditions such as weather, food availability, predation risk, the requirements of breeding, and the influence of anthropogenic factors. Consequently, researchers are increasingly measuring stress markers, especially glucocorticoids, to understand stress, disturbance, and population health. Studying free-ranging animals, however, comes with numerous difficulties posed by environmental conditions and the particular characteristics of study species. Performing measurements under either physical restraint or chemical sedation may affect the physiological variable under investigation and lead to values that may not reflect the standard functional state of the animal. This study measured the stress response resulting from different handling conditions in northern elephant seals and any ensuing influences on carbohydrate metabolism. Endogenous glucose production (EGP was measured using [6-(3H]glucose and plasma cortisol concentration was measured from blood samples drawn during three-hour measurement intervals. These measurements were conducted in weanlings and yearlings with and without the use of chemical sedatives--under chemical sedation, physical restraint, or unrestrained. We compared these findings with measurements in adult seals sedated in the field. The method of handling had a significant influence on the stress response and carbohydrate metabolism. Physically restrained weanlings and yearlings transported to the lab had increased concentrations of circulating cortisol (F(11, 46 = 25.2, p<0.01 and epinephrine (F(3, 12 = 5.8, p = 0.01. Physical restraint led to increased EGP (t = 3.1, p = 0.04 and elevated plasma glucose levels (t = 8.2, p<0.01. Animals chemically sedated in the field typically did not exhibit a cortisol stress response. The combination of anesthetic agents (Telazol, ketamine, and diazepam used in this study appeared to alleviate a

Calcium metabolism in birds.

Science.gov (United States)

de Matos, Ricardo

2008-01-01

Calcium is one of the most important plasma constituents in mammals and birds. It provides structural strength and support (bones and eggshell) and plays vital roles in many of the biochemical reactions in the body. The control of calcium metabolism in birds is highly efficient and closely regulated in a number of tissues, primarily parathyroid gland, intestine, kidney, and bone. The hormones with the greatest involvement in calcium regulation in birds are parathyroid hormone, 1,25-dihydroxyvitamin D(3) (calcitriol), and estrogen, with calcitonin playing a minor and uncertain role. The special characteristics of calcium metabolism in birds, mainly associated with egg production, are discussed, along with common clinical disorders secondary to derangements in calcium homeostasis.

Whole-transcriptome analysis of verocytotoxigenic Escherichia coli O157:H7 (Sakai suggests plant-species-specific metabolic responses on exposure to spinach and lettuce extracts.

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Louise Crozier

2016-07-01

Full Text Available Verocytotoxigenic Escherichia coli (VTEC can contaminate crop plants, potentially using them as secondary hosts, which can lead to food-borne infection. Currently, little is known about the influence of the specific plant species on the success of bacterial colonisation. As such, we compared the ability of the VTEC strain, E. coli O157:H7 ‘Sakai’, to colonise the roots and leaves of four leafy vegetables: spinach (Spinacia oleracea, lettuce (Lactuca sativa, vining green pea (Pisum sativum and prickly lettuce (L. serriola, a wild relative of domesticated lettuce. Also, to determine the drivers of the initial response on interaction with plant tissue, the whole transcriptome of E. coli O157:H7 Sakai was analysed following exposure to plant extracts of varying complexity (spinach leaf lysates or root exudates, and leaf cell wall polysaccharides from spinach or lettuce. Plant extracts were used to reduce heterogeneity inherent in plant-microbe interactions and remove the effect of plant immunity. This dual approach provided information on the initial adaptive response of E. coli O157:H7 Sakai to the plant environment together with the influence of the living plant during bacterial establishment and colonisation. Results showed that both the plant tissue type and the plant species strongly influence the short-term (1 hour transcriptional response to extracts as well as longer-term (10 days plant colonisation or persistence. We show that propagation temperature (37 versus 18 oC has a major impact on the expression profile and therefore pre-adaptation of bacteria to a plant-relevant temperature is necessary to avoid misleading temperature-dependent wholescale gene-expression changes in response to plant material. For each of the plant extracts tested, the largest group of (annotated differentially regulated genes were associated with metabolism. However, large-scale differences in the metabolic and biosynthetic pathways between treatment types

Dynamic decoupling of secondary systems

International Nuclear Information System (INIS)

Gupta, A.K.; Tembulkar, J.M.

1984-01-01

The dynamic analysis of primary systems must often be performed decoupled from the secondary system. In doing so, one should assure that the decoupling does not significantly affect the frequencies and the response of the primary systems. The practice consists of heuristic algorithms intended to limit changes in the frequencies. The change in response is not considered. In this paper, changes in both the frequencies and the response are considered. Rational, but simple algorithms are derived to make accurate predictions. Material up to MDOF primary-SDOF secondary system is presented in this paper. MDOF-MDOF systems are treated in a companion paper. (orig.)

Circadian rhythms in glucose and lipid metabolism in nocturnal and diurnal mammals

NARCIS (Netherlands)

Kumar Jha, Pawan; Challet, Etienne; Kalsbeek, Andries

2015-01-01

Most aspects of energy metabolism display clear variations during day and night. This daily rhythmicity of metabolic functions, including hormone release, is governed by a circadian system that consists of the master clock in the suprachiasmatic nuclei of the hypothalamus (SCN) and many secondary

Early prediction of therapy response and disease free survival after induction chemotherapy in stage III non-small cell lung cancer by FDG-PET: Correlation between tumor FDG-metabolism and morphometric tumor response

International Nuclear Information System (INIS)

Baum, R.P.; Schmuecking, M.; Niesen, A.; Przetak, C.; Griesinger, F.

2002-01-01

Aim: Chemotherapy with Docetaxel and Carboplatin (DC) has shown high response rates in advanced non-small cell lung cancer (NSCLC). Histologic tumor response after chemotherapy or combined chemoradiotherapy is strongly associated with systemic tumor control and potentially cure. Metabolic tumor response assessed by FDG-PET after induction VIP-chemotherapy has been shown to be predictive of outcome in NSCLC. The aim of the present study was to correlate the tumor FDG metabolism as measured by F-18 FDG-PET with morphometric findings after DC induction chemotherapy plus Erythropoietin (10,000 IU Epo s.c. three times a week). Material and Methods: In this prospective multicenter study, 54 patients with NSCLC stage IIIA (9 patients) or IIIB (45 patients) were enrolled and received neoadjuvant treatment with D 100 mg/m 2 d1 and C AUC 7.5 d2 q21 days for 4 cycles prior to surgery. Postoperatively, all patients received adjuvant radiotherapy. WB-PET-studies (ECAT Exact 47) were obtained p.i. of 400 MBq F-18 FDG. Standardized uptake values (SUV), metabolic tumor diameter (MTD) and metabolic tumor index (MTI SUV x MTD) were assessed. Image fusion of PET and CT data was applied on a HERMES computer. Results: Of 54 enrolled patients, 46 were evaluable for response by CT. 30/46 patients (65%) achieved complete remission (CR, 1 patient) or partial remission (PR 29 patients.). Of the 46 patients, 37 patients completed neoadjuvant chemotherapy (Chx) and were studied before and after Chx by FDG-PET. 14 (30% of the 46 evaluable patients) had SUV < 2.5, corresponding to metabolic complete remission (mCR), 23 had PR or stable disease (non-mCR); in 9 patients, PET was not performed because of progressive disease demonstrated by CT. The R0-resection rate was 56% (27/48 evaluable patients). Of the 14 patients with metabolic CR, 9 were evaluated by morphometry. All had regression grades III (no vital tumor cells) or grade IIB (< 10% vital tumor cells and induced apoptosis). With a median

Protein kinase N2 regulates AMP kinase signaling and insulin responsiveness of glucose metabolism in skeletal muscle.

Science.gov (United States)

Ruby, Maxwell A; Riedl, Isabelle; Massart, Julie; Åhlin, Marcus; Zierath, Juleen R

2017-10-01

Insulin resistance is central to the development of type 2 diabetes and related metabolic disorders. Because skeletal muscle is responsible for the majority of whole body insulin-stimulated glucose uptake, regulation of glucose metabolism in this tissue is of particular importance. Although Rho GTPases and many of their affecters influence skeletal muscle metabolism, there is a paucity of information on the protein kinase N (PKN) family of serine/threonine protein kinases. We investigated the impact of PKN2 on insulin signaling and glucose metabolism in primary human skeletal muscle cells in vitro and mouse tibialis anterior muscle in vivo. PKN2 knockdown in vitro decreased insulin-stimulated glucose uptake, incorporation into glycogen, and oxidation. PKN2 siRNA increased 5'-adenosine monophosphate-activated protein kinase (AMPK) signaling while stimulating fatty acid oxidation and incorporation into triglycerides and decreasing protein synthesis. At the transcriptional level, PKN2 knockdown increased expression of PGC-1α and SREBP-1c and their target genes. In mature skeletal muscle, in vivo PKN2 knockdown decreased glucose uptake and increased AMPK phosphorylation. Thus, PKN2 alters key signaling pathways and transcriptional networks to regulate glucose and lipid metabolism. Identification of PKN2 as a novel regulator of insulin and AMPK signaling may provide an avenue for manipulation of skeletal muscle metabolism. Copyright © 2017 the American Physiological Society.

The FGF21 response to fructose predicts metabolic health and persists after bariatric surgery in obese humans

NARCIS (Netherlands)

ter Horst, Kasper W.; Gilijamse, Pim W.; Demirkiran, Ahmet; van Wagensveld, Bart A.; Ackermans, Mariette T.; Verheij, Joanne; Romijn, Johannes A.; Nieuwdorp, Max; Maratos-Flier, Eleftheria; Herman, Mark A.; Serlie, Mireille J.

2017-01-01

Objective: Fructose consumption has been implicated in the development of obesity and insulin resistance. Emerging evidence shows that fibroblast growth factor 21 (FGF21) has beneficial effects on glucose, lipid, and energy metabolism and may also mediate an adaptive response to fructose ingestion.

Telling metabolic stories to explore metabolomics data -- A case study on the Yeast response to cadmium exposure

NARCIS (Netherlands)

P.V. Milreu (Paulo); C.C. Klein (Cecilia); L. Cottret; V. Acuña (Vicente); E. Birmele; M. Borassi; C. Junot; A. Marchetti Spaccamela (Alberto); A. Morino; L. Stougie (Leen); F. Jourdan; P. Crescenzi; V. Lacroix; M.-F. Sagot (Marie-France)

2014-01-01

htmlabstractMotivation: The increasing availability of metabolomics data enables to better understand the metabolic processes involved in the immediate response of an organism to environmental changes and stress. The data usually come in the form of a list of metabolites whose concentrations

Predictive value of PET response combined with baseline metabolic tumor volume in peripheral T-cell lymphoma patients

DEFF Research Database (Denmark)

Cottereau, Anne-Segolene; El-Galaly, Tarec C; Becker, Stéphanie

2018-01-01

Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of aggressive non-Hodgkin lymphomas with poor outcomes with current therapy. We investigated if response assessed with Positron Emission Tomography/computed tomography (PET/CT) combined with baseline total metabolic tumor volume (TMTV) co...

Relative Quantitative Proteomic Analysis of Brucella abortus Reveals Metabolic Adaptation to Multiple Environmental Stresses

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Xiaodong Zai

2017-11-01

Full Text Available Brucella spp. are facultative intracellular pathogens that cause chronic brucellosis in humans and animals. The virulence of Brucella primarily depends on its successful survival and replication in host cells. During invasion of the host tissue, Brucella is simultaneously subjected to a variety of harsh conditions, including nutrient limitation, low pH, antimicrobial defenses, and extreme levels of reactive oxygen species (ROS via the host immune response. This suggests that Brucella may be able to regulate its metabolic adaptation in response to the distinct stresses encountered during its intracellular infection of the host. An investigation into the differential proteome expression patterns of Brucella grown under the relevant stress conditions may contribute toward a better understanding of its pathogenesis and adaptive response. Here, we utilized a mass spectrometry-based label-free relative quantitative proteomics approach to investigate and compare global proteomic changes in B. abortus in response to eight different stress treatments. The 3 h short-term in vitro single-stress and multi-stress conditions mimicked the in vivo conditions of B. abortus under intracellular infection, with survival rates ranging from 3.17 to 73.17%. The proteomic analysis identified and quantified a total of 2,272 proteins and 74% of the theoretical proteome, thereby providing wide coverage of the B. abortus proteome. By including eight distinct growth conditions and comparing these with a control condition, we identified a total of 1,221 differentially expressed proteins (DEPs that were significantly changed under the stress treatments. Pathway analysis revealed that most of the proteins were involved in oxidative phosphorylation, ABC transporters, two-component systems, biosynthesis of secondary metabolites, the citrate cycle, thiamine metabolism, and nitrogen metabolism; constituting major response mechanisms toward the reconstruction of cellular

VISCOSITY DICTATES METABOLIC ACTIVITY of Vibrio ruber

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Maja eBoric

2012-07-01

Full Text Available Little is known about metabolic activity of bacteria, when viscosity of their environment changes. In this work, bacterial metabolic activity in media with viscosity ranging from 0.8 to 29.4 mPas was studied. Viscosities up to 2.4 mPas did not affect metabolic activity of Vibrio ruber. On the other hand, at 29.4 mPas respiration rate and total dehydrogenase activity increased 8 and 4-fold, respectively. The activity of glucose-6-phosphate dehydrogenase increased up to 13-fold at higher viscosities. However, intensified metabolic activity did not result in faster growth rate. Increased viscosity delayed the onset as well as the duration of biosynthesis of prodigiosin. As an adaptation to viscous environment V. ruber increased metabolic flux through the pentose phosphate pathway and reduced synthesis of a secondary metabolite. In addition, V. ruber was able to modify the viscosity of its environment.

Induction of resistance to gray mold with benzothiadiazole modifies amino acid profile and increases proanthocyanidins in grape: primary versus secondary metabolism.

Science.gov (United States)

Iriti, Marcello; Rossoni, Mara; Borgo, Michele; Ferrara, Luigia; Faoro, Franco

2005-11-16

Field treatments of grapevine (cv. Merlot) with the plant activator benzothiadiazole (BTH, 0.3 mM) induced resistance against gray mold caused by Botrytis cinerea. Both incidence and severity of the disease were reduced. The resistance was associated with an increase of total polyphenols in berry skins, in particular, the proanthocyanidin fraction, that increased up to 36%. The amino acid profile of leaves was also modified by treatments, particularly lysine, that augmented 4-fold. Other amino acids involved in resistance mechanisms to either biotic or abiotic stress increased as well. These results indicate that BTH treatments can be used to control gray mold, thereby limiting an excessive use of fungicides, and could be exploited to increase the content of micronutrients of high nutritional value, arising from both primary and secondary metabolisms.

Metabolomics reveals metabolic targets and biphasic responses in breast cancer cells treated by curcumin alone and in association with docetaxel.

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Mathilde Bayet-Robert

Full Text Available BACKGROUND: Curcumin (CUR has deserved extensive research due to its anti-inflammatory properties, of interest in human diseases including cancer. However, pleiotropic even paradoxical responses of tumor cells have been reported, and the mechanisms of action of CUR remain uncompletely elucidated. METHODOLOGY/PRINCIPAL FINDINGS: (1H-NMR spectroscopy-based metabolomics was applied to get novel insight into responses of MCF7 and MDA-MB-231 breast cancer cells to CUR alone, and MCF7 cells to CUR in cotreatment with docetaxel (DTX. In both cell types, a major target of CUR was glutathione metabolism. Total glutathione (GSx increased at low dose CUR (≤ 10 mg.l(-1-28 µM- (up to +121% in MCF7 cells, P<0.01, and +138% in MDA-MB-231 cells, P<0.01, but decreased at high dose (≥ 25 mg.l(-1 -70 µM- (-49%, in MCF7 cells, P<0.02, and -56% in MDA-MB-231 cells, P<0.025. At high dose, in both cell types, GSx-related metabolites decreased, including homocystein, creatine and taurine (-60 to -80%, all, P<0.05. Together with glutathione-S-transferase actvity, data established that GSx biosynthesis was upregulated at low dose, and GSx consumption activated at high dose. Another major target, in both cell types, was lipid metabolism involving, at high doses, accumulation of polyunsaturated and total free fatty acids (between ×4.5 and ×11, P<0.025, and decrease of glycerophospho-ethanolamine and -choline (about -60%, P<0.025. Multivariate statistical analyses showed a metabolic transition, even a biphasic behavior of some metabolites including GSx, between low and high doses. In addition, CUR at 10 mg.l(-1 in cotreatment with DTX induced modifications in glutathione metabolism, lipid metabolism, and glucose utilization. Some of these changes were biphasic depending on the duration of exposure to CUR. CONCLUSIONS/SIGNIFICANCE: Metabolomics reveals major metabolic targets of CUR in breast cancer cells, and biphasic responses that challenge the widely accepted

Metabolic Adaptation to Muscle Ischemia

Science.gov (United States)

Cabrera, Marco E.; Coon, Jennifer E.; Kalhan, Satish C.; Radhakrishnan, Krishnan; Saidel, Gerald M.; Stanley, William C.

2000-01-01

Although all tissues in the body can adapt to varying physiological/pathological conditions, muscle is the most adaptable. To understand the significance of cellular events and their role in controlling metabolic adaptations in complex physiological systems, it is necessary to link cellular and system levels by means of mechanistic computational models. The main objective of this work is to improve understanding of the regulation of energy metabolism during skeletal/cardiac muscle ischemia by combining in vivo experiments and quantitative models of metabolism. Our main focus is to investigate factors affecting lactate metabolism (e.g., NADH/NAD) and the inter-regulation between carbohydrate and fatty acid metabolism during a reduction in regional blood flow. A mechanistic mathematical model of energy metabolism has been developed to link cellular metabolic processes and their control mechanisms to tissue (skeletal muscle) and organ (heart) physiological responses. We applied this model to simulate the relationship between tissue oxygenation, redox state, and lactate metabolism in skeletal muscle. The model was validated using human data from published occlusion studies. Currently, we are investigating the difference in the responses to sudden vs. gradual onset ischemia in swine by combining in vivo experimental studies with computational models of myocardial energy metabolism during normal and ischemic conditions.

Heat dissipation does not suppress an immune response in laboratory mice divergently selected for basal metabolic rate (BMR).

Science.gov (United States)

Książek, Aneta; Konarzewski, Marek

2016-05-15

The capacity for heat dissipation is considered to be one of the most important constraints on rates of energy expenditure in mammals. To date, the significance of this constraint has been tested exclusively under peak metabolic demands, such as during lactation. Here, we used a different set of metabolic stressors, which do not induce maximum energy expenditures and yet are likely to expose the potential constraining effect of heat dissipation. We compared the physiological responses of mice divergently selected for high (H-BMR) and low basal metabolic rate (L-BMR) to simultaneous exposure to the keyhole limpet haemocyanin (KLH) antigen and high ambient temperature (Ta). At 34°C (and at 23°C, used as a control), KLH challenge resulted in a transient increase in core body temperature (Tb) in mice of both line types (by approximately 0.4°C). Warm exposure did not produce line-type-dependent differences in Tb (which was consistently higher by ca. 0.6°C in H-BMR mice across both Ta values), nor did it result in the suppression of antibody synthesis. These findings were also supported by the lack of between-line-type differences in the mass of the thymus, spleen or lymph nodes. Warm exposure induced the downsizing of heat-generating internal organs (small intestine, liver and kidneys) and an increase in intrascapular brown adipose tissue mass. However, these changes were similar in scope in both line types. Mounting a humoral immune response in selected mice was therefore not affected by ambient temperature. Thus, a combined metabolic challenge of high Ta and an immune response did not appreciably compromise the capacity to dissipate heat, even in the H-BMR mice. © 2016. Published by The Company of Biologists Ltd.

Mixed acid-base disorder secondary to topiramate use in traumatic brain injury

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S Golla

2016-01-01

Full Text Available We report a case of a man with traumatic brain injury. He was started on to prophylactic topiramate which led to a mixed acid-base disorder. He had severe metabolic acidosis secondary to renal tubular acidification defect and respiratory alkalosis secondary to hyperventilation. Withdrawal of the offending drug led to the prompt resolution of the acid-base disturbance.

Metabolic responses of Eisenia fetida after sub-lethal exposure to organic contaminants with different toxic modes of action

Energy Technology Data Exchange (ETDEWEB)

McKelvie, Jennifer R.; Wolfe, David M.; Celejewski, Magda A. [Department of Physical and Environmental Sciences, University of Toronto, 1265 Military Trail Toronto, ON M1C 1A4 (Canada); Alaee, Mehran [Environment Canada, 867 Lakeshore Rd., P.O. Box 5050, Burlington, ON L7R 4A6 (Canada); Simpson, Andre J. [Department of Physical and Environmental Sciences, University of Toronto, 1265 Military Trail Toronto, ON M1C 1A4 (Canada); Simpson, Myrna J., E-mail: myrna.simpson@utoronto.ca [Department of Physical and Environmental Sciences, University of Toronto, 1265 Military Trail Toronto, ON M1C 1A4 (Canada)

2011-12-15

Nuclear magnetic resonance (NMR) - based metabolomics has the potential to identify toxic responses of contaminants within a mixture in contaminated soil. This study evaluated the metabolic response of Eisenia fetida after exposure to an array of organic compounds to determine whether contaminant-specific responses could be identified. The compounds investigated in contact tests included: two pesticides (carbaryl and chlorpyrifos), three pharmaceuticals (carbamazephine, estrone and caffeine), two persistent organohalogens (Aroclor 1254 and PBDE 209) and two industrial compounds (nonylphenol and dimethyl phthalate). Control and contaminant-exposed metabolic profiles were distinguished using principal component analysis and potential contaminant-specific biomarkers of exposure were found for several contaminants. These results suggest that NMR-based metabolomics offers considerable promise for differentiating between the different toxic modes of action (MOA) associated with sub-lethal toxicity to earthworms. - Highlights: > NMR-based earthworm metabolomic analysis of the toxic mode of action of various environmental contaminants. > Organic chemicals with different toxic modes of action resulted in varied metabolomic responses for E. fetida. > NMR-based metabolomics differentiates between the different modes of action associated with sub-lethal toxicity. - {sup 1}H NMR metabolomics was used to identify potential biomarkers of organic contaminant exposure in Eisenia fetida earthworms.

Abdominal obesity in adolescent girls attending a public secondary ...

African Journals Online (AJOL)

Background: Deposition of excess fat in the abdominal region is strongly associated with the metabolic disturbances thought to underlie many obesity related complications. Aim: To determine the prevalence of abdominal obesity using waist circumference inadolescents' girls attending a public secondary school in Port ...

Necrosis-Driven Systemic Immune Response Alters SAM Metabolism through the FOXO-GNMT Axis

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Fumiaki Obata

2014-05-01

Full Text Available Sterile inflammation triggered by endogenous factors is thought to contribute to the pathogenesis of acute and chronic inflammatory diseases. Here, we demonstrate that apoptosis-deficient mutants spontaneously develop a necrosis-driven systemic immune response in Drosophila and provide an in vivo model for studying the organismal response to sterile inflammation. Metabolomic analysis of hemolymph from apoptosis-deficient mutants revealed increased sarcosine and reduced S-adenosyl-methionine (SAM levels due to glycine N-methyltransferase (Gnmt upregulation. We showed that Gnmt was elevated in response to Toll activation induced by the local necrosis of wing epidermal cells. Necrosis-driven inflammatory conditions induced dFoxO hyperactivation, leading to an energy-wasting phenotype. Gnmt was cell-autonomously upregulated by dFoxO in the fat body as a possible rheostat for controlling energy loss, which functioned during fasting as well as inflammatory conditions. We propose that the dFoxO-Gnmt axis is essential for the maintenance of organismal SAM metabolism and energy homeostasis.

Secondary metabolism responses in two Pisum sativum L. cultivars ...

African Journals Online (AJOL)

Both cultivars were grown in the absence or presence of Fe with the addition of bicarbonate for twelve days. Higher concentrations of phenols and flavonoids were observed in Fe-deficient tissues of both cultivars; however, the increase was greater in the tolerant cultivar than in the susceptible one. The activity of shikimate ...

Metabolic consequences of resistive-type exercise

Science.gov (United States)

Dudley, G. A.

1988-01-01

This brief review concerns acute and chronic metabolic responses to resistive-type exercise (RTE) (i.e., Olympic/power weight lifting and bodybuilding). Performance of RTE presents power output substantially greater (10-15-fold) than that evident with endurance-type exercise. Accordingly, RTE relies heavily on the anaerobic enzyme machinery of skeletal muscle for energy supply, with alterations in the rate of aerobic metabolism being modest. Hydrolysis of high energy phosphate compounds (PC, ATP), glycogenolysis, and glycolysis are evident during an acute bout of RTE as indicated by metabolic markers in mixed fiber type skeletal muscle samples. The type of RTE probably influences the magnitude of these responses since the increase in blood lactate is much greater during a typical "bodybuilding" than "power lifting" session. The influence of RTE training on acute metabolic responses to RTE has received little attention. An individual's inherent metabolic characteristics are apparently sufficient to meet the energy demands of RTE as training of this type does not increase VO2max or substantially alter the content of marker enzymes in mixed fiber type skeletal muscle. Analyses of pools of fast- vs slow-twitch fibers, however, indicate that RTE-induced changes may be fiber type specific. Future studies should better delineate the metabolic responses to RTE and determine whether these are related to the enhanced performance associated with such training.

Transcriptome Analysis Identifies Key Metabolic Changes in the Hooded Seal (Cystophora cristata Brain in Response to Hypoxia and Reoxygenation.

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Mariana Leivas Müller Hoff

Full Text Available The brain of diving mammals tolerates low oxygen conditions better than the brain of most terrestrial mammals. Previously, it has been demonstrated that the neurons in brain slices of the hooded seal (Cystophora cristata withstand hypoxia longer than those of mouse, and also tolerate reduced glucose supply and high lactate concentrations. This tolerance appears to be accompanied by a shift in the oxidative energy metabolism to the astrocytes in the seal while in terrestrial mammals the aerobic energy production mainly takes place in neurons. Here, we used RNA-Seq to compare the effect of hypoxia and reoxygenation in vitro on brain slices from the visual cortex of hooded seals. We saw no general reduction of gene expression, suggesting that the response to hypoxia and reoxygenation is an actively regulated process. The treatments caused the preferential upregulation of genes related to inflammation, as found before e.g. in stroke studies using mammalian models. Gene ontology and KEGG pathway analyses showed a downregulation of genes involved in ion transport and other neuronal processes, indicative for a neuronal shutdown in response to a shortage of O2 supply. These differences may be interpreted in terms of an energy saving strategy in the seal's brain. We specifically analyzed the regulation of genes involved in energy metabolism. Hypoxia and reoxygenation caused a similar response, with upregulation of genes involved in glucose metabolism and downregulation of the components of the pyruvate dehydrogenase complex. We also observed upregulation of the monocarboxylate transporter Mct4, suggesting increased lactate efflux. Together, these data indicate that the seal brain responds to the hypoxic challenge by a relative increase in the anaerobic energy metabolism.

Maternal high-fat diet intensifies the metabolic response to stress in male rat offspring.

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Karbaschi, Roxana; Zardooz, Homeira; Khodagholi, Fariba; Dargahi, Leila; Salimi, Mina; Rashidi, FatemehSadat

2017-01-01

The mother's consumption of high-fat food can affect glucose metabolism and the hypothalamic-pituitary-adrenal axis responsiveness in the offspring and potentially affect the metabolic responses to stress as well. This study examines the effect of maternal high-fat diet on the expression of pancreatic glucose transporter 2 and the secretion of insulin in response to stress in offspring. Female rats were randomly divided into normal and high-fat diet groups and were fed in accordance with their given diets from pre-pregnancy to the end of lactation. The offspring were divided into control (NC and HFC) and stress (NS and HFS) groups based on their mothers' diet and exposure to stress in adulthood. After the two-week stress induction period was over, an intraperitoneal glucose tolerance test (IPGTT) was performed and plasma glucose and insulin levels were assessed. The pancreas was then removed for measuring insulin secretion from the isolated islets as well as glucose transporter 2 mRNA expression and protein levels. According to the results obtained, plasma corticosterone concentrations increased significantly on days 1 and 14 of the stress induction period and were lower on the last day compared to on the first day. In both the NS and HFS groups, stress reduced plasma insulin concentration in the IPGTT without changing the plasma glucose concentration, suggesting an increased insulin sensitivity in the NS and HFS groups, although more markedly in the latter. Stress reduced insulin secretion (at high glucose concentrations) and increased glucose transporter 2 mRNA and protein expression, especially in the HFS group. Mothers' high-fat diet appears to intensify the stress response by changing the programming of the neuroendocrine system in the offspring.

Secondary and tertiary hyperparathyroidism.

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Jamal, Sophie A; Miller, Paul D

2013-01-01

We reviewed the etiology and management of secondary and tertiary hyperparathyroidism. Secondary hyperparathyroidism is characterized by an increase in parathyroid hormone (PTH) that is appropriate and in response to a stimulus, most commonly low serum calcium. In secondary hyperparathyroidism, the serum calcium is normal and the PTH level is elevated. Tertiary hyperparathyroidism is characterized by excessive secretion of PTH after longstanding secondary hyperparathyroidism, in which hypercalcemia has ensued. Tertiary hyperparathyroidism typically occurs in men and women with chronic kidney disease usually after kidney transplant. The etiology and treatment of secondary hyperparathyroidism is relatively straightforward whereas data on the management of tertiary hyperparathyroidism is limited to a few small trials with short follow-up. Copyright © 2013 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

Analysis of Aspergillus nidulans metabolism at the genome-scale

DEFF Research Database (Denmark)

David, Helga; Ozcelik, İlknur Ş; Hofmann, Gerald

2008-01-01

of relevant secondary metabolites, was reconstructed based on detailed metabolic reconstructions available for A. niger and Saccharomyces cerevisiae, and information on the genetics, biochemistry and physiology of A. nidulans. Thereby, it was possible to identify metabolic functions without a gene associated...... a function. Results: In this work, we have manually assigned functions to 472 orphan genes in the metabolism of A. nidulans, by using a pathway-driven approach and by employing comparative genomics tools based on sequence similarity. The central metabolism of A. nidulans, as well as biosynthetic pathways......, in an objective and systematic manner. The functional assignments served as a basis to develop a mathematical model, linking 666 genes (both previously and newly annotated) to metabolic roles. The model was used to simulate metabolic behavior and additionally to integrate, analyze and interpret large-scale gene...

Variations in insulin responsiveness in rat fat cells are due to metabolic differences rather than insulin binding

DEFF Research Database (Denmark)

Hansen, Finn Mølgård; Nilsson, Poul; Sonne, Ole

1983-01-01

-insulin to fat cells. Insulin binding was not correlated to the plasma insulin level which however was reflected in the lipoprotein lipase activity in the adipose tissue. In conclusion, these results indicate that variations in insulin responsiveness in fat cells are due to alterations in cellular metabolism...

Road transport and diet affect metabolic response to exercise in horses.

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Connysson, M; Muhonen, S; Jansson, A

2017-11-01

This study investigated the effects of transport and diet on metabolic response during a subsequent race-like test in Standardbred horses in training fed a forage-only diet and a 50:50 forage:oats diet. Six trained and raced Standardbred trotter mares were used. Two diets, 1 forage-only diet (FONLY) and 1 diet with 50% of DM intake from forage and 50% from oats (FOATS), were fed for two 29-d periods in a crossover design. At Day 21, the horses were subjected to transport for 100 km before and after they performed an exercise test (transport test [TT]). At Day 26, the horses performed a control test (CT), in which they were kept in their stall before and after the exercise test. Blood samples were collected throughout the study, and heart rate and water intake were recorded. Heart rate and plasma cortisol, glucose, and NEFA concentrations were greater for the TT than for the CT ( = 0.008, = 0.020, = 0.010, and = 0.0002, respectively) but were not affected by diet. Plasma acetate concentration was lower during the TT than during the CT ( = 0.034) and greater for the FONLY than for the FOATS ( = 0.003). There were no overall effects of the TT compared with the CT on total plasma protein concentration (TPP), but TPP was lower with the FONLY than with the FOATS ( = 0.016). There was no overall effect of the TT compared with the CT on water intake, but water intake was greater with the FONLY than the FOATS ( = 0.011). There were no overall effects of transport or diet on BW, plasma lactate, or plasma urea concentration. It was concluded that both transport and diet affect metabolic response during exercise in horses. Aerobic energy supply was most likely elevated by transportation and by the FONLY. The FONLY also decreased exercise-induced effects on extracellular fluid regulation. These results highlight the importance of experimental design in nutrition studies. If the aim is to examine how a diet affects exercise response in competition horses, transport should

Secondary metabolites in fungus-plant interactions

Science.gov (United States)

Pusztahelyi, Tünde; Holb, Imre J.; Pócsi, István

2015-01-01

Fungi and plants are rich sources of thousands of secondary metabolites. The genetically coded possibilities for secondary metabolite production, the stimuli of the production, and the special phytotoxins basically determine the microscopic fungi-host plant interactions and the pathogenic lifestyle of fungi. The review introduces plant secondary metabolites usually with antifungal effect as well as the importance of signaling molecules in induced systemic resistance and systemic acquired resistance processes. The review also concerns the mimicking of plant effector molecules like auxins, gibberellins and abscisic acid by fungal secondary metabolites that modulate plant growth or even can subvert the plant defense responses such as programmed cell death to gain nutrients for fungal growth and colonization. It also looks through the special secondary metabolite production and host selective toxins of some significant fungal pathogens and the plant response in form of phytoalexin production. New results coming from genome and transcriptional analyses in context of selected fungal pathogens and their hosts are also discussed. PMID:26300892

Cardiovascular and Metabolic Responses to the Ingestion of Caffeinated Herbal Tea: Drink It Hot or Cold?

Science.gov (United States)

Maufrais, Claire; Sarafian, Delphine; Dulloo, Abdul; Montani, Jean-Pierre

2018-01-01

Aim: Tea is usually consumed at two temperatures (as hot tea or as iced tea). However, the importance of drink temperature on the cardiovascular system and on metabolism has not been thoroughly investigated. The purpose of this study was to compare the cardiovascular, metabolic and cutaneous responses to the ingestion of caffeinated herbal tea (Yerba Mate) at cold or hot temperature in healthy young subjects. We hypothesized that ingestion of cold tea induces a higher increase in energy expenditure than hot tea without eliciting any negative effects on the cardiovascular system. Methods: Cardiovascular, metabolic and cutaneous responses were analyzed in 23 healthy subjects (12 men and 11 women) sitting comfortably during a 30-min baseline and 90 min following the ingestion of 500 mL of an unsweetened Yerba Mate tea ingested over 5 min either at cold (~3°C) or hot (~55°C) temperature, according to a randomized cross-over design. Results: Averaged over the 90 min post-drink ingestion and compared to hot tea, cold tea induced (1) a decrease in heart rate (cold tea: -5 ± 1 beats.min -1 ; hot tea: -1 ± 1 beats.min -1 , p hot tea: +3.7%, p hot tea while decreasing cardiac load as suggested by the decrease in the double product. Further experiments are needed to evaluate the clinical impact of unsweetened caffeinated herbal tea at a cold temperature for weight control.

Secondary school learners' perceptions of responsible citizenship as taught in the life orientation learning area: a case study

OpenAIRE

2008-01-01

In this study, secondary school learners perceptions of Responsible Citizenship as taught in the Life Orientation learning area are explored. Citizen Education, which is set out in Learning Outcome Two of the Life Orientation Curriculum, forms the basis of the programme used to conduct this study. An international as well as a national perspective of Responsible Citizenship and the teaching thereof is explicated with special reference being made to the Further Education and Training Band. The...

Comparative proteomic analyses reveal the proteome response to short-term drought in Italian ryegrass (Lolium multiflorum.

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Ling Pan

Full Text Available Drought is a major abiotic stress that impairs growth and productivity of Italian ryegrass. Comparative analysis of drought responsive proteins will provide insight into molecular mechanism in Lolium multiflorum drought tolerance. Using the iTRAQ-based approach, proteomic changes in tolerant and susceptible lines were examined in response to drought condition. A total of 950 differentially accumulated proteins was found to be involved in carbohydrate metabolism, amino acid metabolism, biosynthesis of secondary metabolites, and signal transduction pathway, such as β-D-xylosidase, β-D-glucan glucohydrolase, glycerate dehydrogenase, Cobalamin-independent methionine synthase, glutamine synthetase 1a, Farnesyl pyrophosphate synthase, diacylglycerol, and inositol 1, 4, 5-trisphosphate, which might contributed to enhance drought tolerance or adaption in Lolium multiflorum. Interestingly, the two specific metabolic pathways, arachidonic acid and inositol phosphate metabolism including differentially accumulated proteins, were observed only in the tolerant lines. Cysteine protease cathepsin B, Cysteine proteinase, lipid transfer protein and Aquaporin were observed as drought-regulated proteins participating in hydrolysis and transmembrane transport. The activities of phospholipid hydroperoxide glutathione peroxidase, peroxiredoxin, dehydroascorbate reductase, peroxisomal ascorbate peroxidase and monodehydroascorbate reductase associated with alleviating the accumulation of reactive oxygen species in stress inducing environments. Our results showed that drought-responsive proteins were closely related to metabolic processes including signal transduction, antioxidant defenses, hydrolysis, and transmembrane transport.

Food odors trigger an endocrine response that affects food ingestion and metabolism.

Science.gov (United States)

Lushchak, Oleh V; Carlsson, Mikael A; Nässel, Dick R

2015-08-01

Food odors stimulate appetite and innate food-seeking behavior in hungry animals. The smell of food also induces salivation and release of gastric acid and insulin. Conversely, sustained odor exposure may induce satiation. We demonstrate novel effects of food odors on food ingestion, metabolism and endocrine signaling in Drosophila melanogaster. Acute exposure to attractive vinegar odor triggers a rapid and transient increase in circulating glucose, and a rapid upregulation of genes encoding the glucagon-like hormone adipokinetic hormone (AKH), four insulin-like peptides (DILPs) and some target genes in peripheral tissues. Sustained exposure to food odors, however, decreases food intake. Hunger-induced strengthening of synaptic signaling from olfactory sensory neurons (OSNs) to brain neurons increases food-seeking behavior, and conversely fed flies display reduced food odor sensitivity and feeding. We show that increasing the strength of OSN signaling chronically by genetic manipulation of local peptide neuromodulation reduces feeding, elevates carbohydrates and diminishes lipids. Furthermore, constitutively strengthened odor sensitivity altered gene transcripts for AKH, DILPs and some of their targets. Thus, we show that food odor can induce a transient anticipatory endocrine response, and that boosted sensitivity to this odor affects food intake, as well as metabolism and hormonal signaling.

Cerebral glucose metabolism in Parkinson's disease

Energy Technology Data Exchange (ETDEWEB)

Martin, W R.W.; Beckman, J H; Calne, D B; Adam, M J; Harrop, R; Rogers, J G; Ruth, T J; Sayre, C I; Pate, B D [British Columbia Univ., Vancouver (Canada). TRIUMF Facility

1984-02-01

Local cerebral glucose utilization was measured in patients with predominantly unilateral Parkinson's disease using sup(18)F-2-fluoro-deoxyglucose and positron emission tomography. Preliminary results indicate the presence of asymmetric metabolic rates in the inferior basal ganglia. The structure comprising the largest portion of basal ganglia at this level is globus pallidus. These findings are consistent with metabolic studies on animals with unilateral nigrostriatal lesions in which pallidal hypermetabolism on the lesioned side has been demonstrated. Increased pallidal activity is likely secondary to a loss of inhibitory dopaminergic input to the striatum from substantia nigra.

Cerebral glucose metabolism in Parkinson's disease

International Nuclear Information System (INIS)

Martin, W.R.W.; Beckman, J.H.; Calne, D.B.; Adam, M.J.; Harrop, R.; Rogers, J.G.; Ruth, T.J.; Sayre, C.I.; Pate, B.D.

1984-01-01

Local cerebral glucose utilization was measured in patients with predominantly unilateral Parkinson's disease using sup(18)F-2-fluoro-deoxyglucose and positron emission tomography. Preliminary results indicate the presence of asymmetric metabolic rates in the inferior basal ganglia. The structure comprising the largest portion of basal ganglia at this level is globus pallidus. These findings are consistent with metabolic studies on animals with unilateral nigrostriatal lesions in which pallidal hypermetabolism on the lesioned side has been demonstrated. Increased pallidal activity is likely secondary to a loss of inhibitory dopaminergic input to the striatum from substantia nigra

Association between textural and morphological tumor indices on baseline PET-CT and early metabolic response on interim PET-CT in bulky malignant lymphomas.

Science.gov (United States)

Ben Bouallègue, Fayçal; Tabaa, Yassine Al; Kafrouni, Marilyne; Cartron, Guillaume; Vauchot, Fabien; Mariano-Goulart, Denis

2017-09-01

We investigated whether metabolic, textural, and morphological tumoral indices evaluated on baseline PET-CT were predictive of early metabolic response on interim PET-CT in a cohort of patients with bulky Hodgkin and non-Hodgkin malignant lymphomas. This retrospective study included 57 patients referred for initial PET-CT examination. In-house dedicated software was used to delineate tumor contours using a fixed 30% threshold of SUV max and then to compute tumoral metabolic parameters (SUV max, mean, peak, standard deviation, skewness and kurtosis, metabolic tumoral volume (MTV), total lesion glycolysis, and area under the curve of the cumulative histogram), textural parameters (Moran's and Geary's indices, energy, entropy, contrast, correlation derived from the gray-level co-occurrence matrix, area under the curve of the power spectral density, auto-correlation distance, and granularity), and shape parameters (surface, asphericity, convexity, surfacic extension, and 2D and 3D fractal dimensions). Early metabolic response was assessed on interim PET-CT using the Deauville 5-point scale and patients were ranked according to the Lugano classification as complete or not complete metabolic responders. The impact of the segmentation method (alternate threshold at 41%) and image resolution (Gaussian postsmoothing of 3, 5, and 7 mm) was investigated. The association of the proposed parameters with early response was assessed in univariate and multivariate analyses. Their added predictive value was explored using supervised classification by support vector machines (SVM). We evaluated in leave-one-out cross-validation three SVMs admitting as input features (a) MTV, (b) MTV + histological type, and (c) MTV + histology + relevant texture/shape indices. Features associated with complete metabolic response were low MTV (P = 0.01), low TLG (P = 0.003), high power spectral density AUC (P = 0.007), high surfacic extension (P = 0.006), low 2D fractal dimension (P�

Unhealthy Lifestyle Behaviors in Korean People with Metabolic Syndrome.

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Moon, Seongmi

2017-01-01

This study identified factors associated with unhealthy lifestyle behaviors in people with metabolic syndrome in South Korea. The sample consisted of 1,207 subjects with metabolic syndrome from the Sixth Korea National Health and Nutrition Examination Survey conducted in 2014. High-risk alcohol consumption, smoking, aerobic physical activity, leisure physical activity, excessive carbohydrate intake, and fat intake were measured. A secondary data analysis was performed using chi-square tests and logistic regression. Gender was associated with all unhealthy behaviors. The number of metabolic syndrome components, a poor perceived health status, and attempts to control weight were associated with physical inactivity. Those findings may be helpful to develop a tailored lifestyle modification programs for people with metabolic syndrome.

Metabolic response of porcine colon explants to in vitro infection by Brachyspira hyodysenteriae : a leap into disease pathophysiology

NARCIS (Netherlands)

Welle, Thijs; Hoekstra, Anna T.; Daemen, Ineke A.J.J.M.; Berkers, Celia R.; de Oliveira Costa, Matheus

2017-01-01

Introduction: Swine dysentery caused by Brachyspira hyodysenteriae is a production limiting disease in pig farming. Currently antimicrobial therapy is the only treatment and control method available. Objective: The aim of this study was to characterize the metabolic response of porcine colon

Absorption and Metabolism of Xanthophylls

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Eiichi Kotake-Nara

2011-06-01

Full Text Available Dietary carotenoids, especially xanthophylls, have attracted significant attention because of their characteristic biological activities, including anti-allergic, anti-cancer, and anti-obese actions. Although no less than forty carotenoids are ingested under usual dietary habits, only six carotenoids and their metabolites have been found in human tissues, suggesting selectivity in the intestinal absorption of carotenoids. Recently, facilitated diffusion in addition to simple diffusion has been reported to mediate the intestinal absorption of carotenoids in mammals. The selective absorption of carotenoids may be caused by uptake to the intestinal epithelia by the facilitated diffusion and an unknown excretion to intestinal lumen. It is well known that β-carotene can be metabolized to vitamin A after intestinal absorption of carotenoids, but little is known about the metabolic transformation of non provitamin A xanthophylls. The enzymatic oxidation of the secondary hydroxyl group leading to keto-carotenoids would occur as a common pathway of xanthophyll metabolism in mammals. This paper reviews the absorption and metabolism of xanthophylls by introducing recent advances in this field.

Absorption and metabolism of xanthophylls.

Science.gov (United States)

Kotake-Nara, Eiichi; Nagao, Akihiko

2011-01-01

Dietary carotenoids, especially xanthophylls, have attracted significant attention because of their characteristic biological activities, including anti-allergic, anti-cancer, and anti-obese actions. Although no less than forty carotenoids are ingested under usual dietary habits, only six carotenoids and their metabolites have been found in human tissues, suggesting selectivity in the intestinal absorption of carotenoids. Recently, facilitated diffusion in addition to simple diffusion has been reported to mediate the intestinal absorption of carotenoids in mammals. The selective absorption of carotenoids may be caused by uptake to the intestinal epithelia by the facilitated diffusion and an unknown excretion to intestinal lumen. It is well known that β-carotene can be metabolized to vitamin A after intestinal absorption of carotenoids, but little is known about the metabolic transformation of non provitamin A xanthophylls. The enzymatic oxidation of the secondary hydroxyl group leading to keto-carotenoids would occur as a common pathway of xanthophyll metabolism in mammals. This paper reviews the absorption and metabolism of xanthophylls by introducing recent advances in this field.

Irradiation of protoporphyric mice induces down-regulation of epidermal eicosanoid metabolism

International Nuclear Information System (INIS)

He, D.; Lim, H.W.

1991-01-01

This study investigated the effect of radiation on clinical and histologic changes, and on cutaneous eicosanoid metabolism, in Skh:HR-1 hairless albino mice rendered protoporphyric by the administration of collidine. At 0.1-18 h after exposure to 12 kJ/m2 of 396-406 nm irradiation, thicknesses of back skin and ears were measured, and histologic changes were evaluated by using hematoxylin and eosin (H-E) and Giemsa's stains. Activities of eicosanoid-metabolizing enzymes in epidermal and dermal homogenates were assessed by incubating the tissue homogenates with 3H-AA, followed by quantitation of the eicosanoids generated by radio-TLC. In irradiated protoporphyric mice, an increase of back-skin thickness was noted at 0.1 h, reaching a peak at 18 h, whereas maximal increase in ear thickness was observed at 12 h. Histologic changes included dermal edema, increased mast cell degranulation, and mononuclear cells in the dermis. In these irradiated protoporphyric animals, generations of 6 keto-PGF1a, PGF2a, PGE2, PGD2, and HETE by epidermal eicosanoid-metabolizing enzymes were markedly suppressed at all the timepoints studied. Dermal eicosanoid-metabolizing enzymes of irradiated protoporphyric mice generated increased amounts of PGE2 and HETE at 18 h, probably reflecting the presence of dermal cellular infiltrates. The suppression of the activities of epidermal eicosanoid-metabolizing enzymes was prevented by intraperitoneal injection of WR-2721, a sulfhydryl group generator, prior to irradiation, suggesting that the suppression was secondary to photo-oxidative damage of the enzymes during the in vivo phototoxic response. These results suggest that the effect of protoporphyrin and radiation on cutaneous eicosanoid metabolism in this animal model in vivo is that of a down regulation of the activities of epidermal eicosanoid-metabolizing enzymes